Wednesday, October 27, 2004

Wednesday, October 27, 2004 Cardiovascular Diseases - Epidemiology 12:30 PM - 2:00 PM PREVALENCE OF ADEQUATE BLOOD PRESSURE CONTROL IN A UNIVERSITY CARDIOLOGY OR GENERAL MEDICINE CLINIC Glenn Gandelman, MD, MPH*; Wilbert S. Aronow, MD; Raja Varma, MD; New York Medical College, Valhalla, NY

EXERCISE LIMITATION IN MORBID OBESITY Prashant Grover, MBBS*; Judy D’Errico, RRT; Richard ZuWallack, MD; Bimalin Lahiri, MD; University of Connecticut and St. Francis Hospital, Farmington, CT

PURPOSE: The prevalence of adequate blood pressure (BP) control was investigated in patients with hypertension in a university cardiology or general medicine clinic. METHODS: We investigated in 344 women and 257 men with hypertension (27% white, 41% Black, 28% Hispanic, and 4% of other races), mean age 60⫾16 years, in a university cardiology or general medicine clinic the prevalence of adequate BP control. BP was considered adequately controlled if the last BP was ⬍140/90 mm/Hg and ⬍130/80 mm Hg in patients with diabetes or chronic renal insufficiency. RESULTS: In 601 patients, 1 antihypertensive drug was used in 202 patients (34%), 2 drugs in 197 patients (33%), 3 drugs in 153 patients (25%), 4 drugs in 40 patients (7%), and 5 drugs in 9 patients (1%). In 601 patients, diuretics were used in 363 patients (60%), beta blockers in 355 patients (59%), angiotensin-converting enzyme inhibitors in 354 patients (59%), angiotensin receptor blockers in 72 patients (12%), calcium channel blockers in 105 patients (17%), and other drugs in 11 patients (2%). BP was adequately controlled in 380 of 601 patients (63%), in 170 of 272 patients (63%) 65 years and older, and in 210 of 329 patients (64%) younger than 65 years (p not significant). BP was adequately controlled in 65% of whites, in 63% of Blacks, in 62% of Hispanics, and in 63% of patients of other races (p not significant). BP was adequately controlled in 336 of 484 Medicaid or private insurance patients (69%) versus 44 of 117 self pay or Medicare patients (38%) paying for their own drugs (p ⬍0.001). CONCLUSION: Hypertension was adequately controlled in 38% of patients who had to pay for their antihypertensive drugs versus 69% of patients who received their antihypertensive drugs because they were on Medicaid or had private insurance (p ⬍0.001). CLINICAL IMPLICATIONS: There is a significantly lower incidence of adequate BP control in patients with hypertension who have to pay for antihypertensive drugs prescribed by their physician. DISCLOSURE: G. Gandelman, None.

PURPOSE: Individuals with morbid obesity breathe at low lung volumes. This study determined whether flow limitation was present at these low lung volumes and, if so, whether it contributed to exercise limitation and dyspnea. METHODS: We studied 21 morbidly obese individuals without clinical lung disease, airflow limitation, or hypoxemia at rest. Following recording of maximal expiratory and inspiratory flow volume loops at rest, incremental cardiopulmonary exercise testing on a cycle ergometer was performed. Unloaded pedaling for three minutes was followed by 20 watt increments every minute to symptom limitation. Flow-volume loops and inspiratory capacity measurements were recorded every minute, and dyspnea/fatigue were measured every three minutes using a Borg scale. Flow limitation during peak exercise was defined as a greater than or equal to 50% overlap of the exercise flow volume loop with the maximal flow volume loop. RESULTS: Three males and 18 females were studied (age 34 ⫾ 8 years, BMI 49 ⫾ 6 kg/m2). Peak oxygen consumption (VO2) was 1.71 ⫾ 0.45 L/min, or 85 ⫾ 11 percent of predicted based on ideal body weight. When related to actual body weight, peak VO2 was 12.5 ⫾ 2.2 mL/kg/min, or 36 ⫾ 4 percent of predicted. Seven patients (33%) had flow limitation at peak exercise; these patients had lower end-expiratory lung volumes (EELV) than those without flow limitation at rest (0.42 vs 0.84 L, respectively, p. ⫽ 0.01) and at peak exercise (0.71 vs. 1.18 L, respectively p. ⫽ 0.015). Both groups had significant, similar increases in EELV at peak exercise (0.29 and 0.34 L, respectively, both, p. ⬍ 0.03). Flow limitation was not related to peak work rate or dyspnea/leg fatigue. CONCLUSION: Flow limitation during exercise is present in a minority of morbidly obese individuals without apparent lung disease, although a dynamic increase in end expiratory lung volumes is common. CLINICAL IMPLICATIONS: Only a minority of morbidly obese subjects have flow limitation during exercise. Flow limitation did not appear to be related to exercise capacity or exercise-limiting symptoms.

THE EXPRESSION OF APOPTOSIS IN CARDIAC MYXOMA Pao-Hsien Chu, MD*; Shih-Ming Jung, MD; Chang Gung Memorial Hospital and University, Taipei, Taiwan ROC PURPOSE: Cardiac myxoma, the most common primary tumor of the heart, has a variable clinical presentation. It has been proposed that apoptosis (programmed cell death) is critical in several cardiovascular diseases but not cardiac myxoma. This study was designed to identify and characterize apoptosis in cardiac myxoma. METHODS: A retrospective study was conducted between December 1976 and June, 2003, including 103 consecutive patients with cardiac myxoma whose tumors had been surgically excised. Apoptosis was studied using TUNEL and DNA fragmentation assays and by immunochemical studies for activation of caspase-3 and TNF␣] in tumor tissue. We analyzed samples from 32 randomly selected cardiac myxoma patients. RESULTS: Of the 103 myxoma patients, 58 were women, 45 men (age 39 ⫾ 21 y). Clinical presentations included asymptomatic (41%), dyspnea (33%), stroke (22%), chest pain (7%), fever (6%), syncope (5%) and tricuspid regurgitation (72%). Ninety-two myxomas were in left atrium, four recurrent myxomas and eight other myxomas were located elsewhere. These Myxomas did not differ in terms of pathological scores including vascular proliferation, inflammation, cellularity, hyaline, calcification and thrombosis. Most (85%) were characterized by extensive apoptosis but none involved activation of caspase-3. CONCLUSION: Apoptosis is very common in myxomas but does not involve caspase-3. Our results indicate that apoptosis has a novel pathological pattern in cardiac myxomas, a pattern that does not include activation of the caspase-3 pathway. These findings should help identify and characterize any possible role for apoptosis in the development of cardiac myxoma. CLINICAL IMPLICATIONS: The clinical implications of apoptosis in cardiac myxoma require further evaluation, this finding creates the possibility of treatments based on monoclonal antibodies or vaccination strategies, like those that already have been established for other tumor entities. DISCLOSURE: P. Chu, None.

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DISCLOSURE: P. Grover, None.

Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Cardiovascular Diseases - Epidemiology, continued SMOKING AND THE LINK TO CARDIAC DISEASE IN PATIENTS UNDERGOING TREATMENT FOR TOBACCO DEPENDENCE Virginia C. Reichert, NP*; Pat Folan, RN; Lynn Villano, NP; Nina Kohn, MA; Alan M. Fein, MD; Arunabh Talwar, MD; Center For Tobacco Control - NS-LIJ Health System, Great Neck, NY

PURPOSE: The Asian immigrant population from India, Pakistan and Bangladesh has been identified as one with higher prevalence of CAD. The aim was to study if at time of presentation with CAD, this ethnic group had more severe CAD as compared to all other patients with CAD seen in our institution. METHODS: Data on all Asian patients who presented to the Emergency Room of Coney Island Hospital and who underwent coronary angiography from 1998 to 2002 were evaluated and compared to that from non Asian patients in year 2002 with emphasis on the severity of CAD at the time of presentation. Assessment of severity of CAD was based on the need for coronary revascularization. RESULTS: 338 Asian patients and 251 non Asian patients were included. Significant CAD was noted in 218/338[64%] Asian patients vs. 152/251[60%] non Asian patients [p 0.3] suggesting no selection bias in recommending angiogram. 173/218[79%] of Asian patients and 98/152[64%] of non Asian patients needed coronary revascularization [p⬍0.05] either by CABG or PTCA/stent. Of these 112/218[51%] of Asian patients and 48/152[31%] of non Asian patients underwent CABG [p⬍0.05]. 61/218[28%] of Asian patients and 50/152[31%] of non Asian patients underwent PTCA/stent [p 0.3]. CONCLUSION: The Asian immigrant population from India, Pakistan and Bangladesh have more advanced CAD at the time of their initial presentation. CLINICAL IMPLICATIONS: This ethnic factor should be considered in risk stratification of patients with CAD. DISCLOSURE: V.A. Rupanagudi, None.

PURPOSE: Healthcare providers have long known smoking to be a risk factor in the development of heart disease. We studied the perceptions of smokers with and without self-reported cardiac co-morbidities enrolled in our tobacco dependence program. METHODS: Six weekly sessions emphasized behavior modification and pharmacological interventions. Innovative therapies of humor, grief counseling, and guided imagery were utilized. Data collected from cessation program questionnaires from 2000-2003 focusing on smoking and medical history were analyzed using SAS®. Quit status was biochemically verified with exhaled carbon monoxide levels. RESULTS: 1023 patients total; 375 reported a history of cardiac co-morbid conditions (43% males vs. 32% females p⬍0.0006) such as hypertension, angina, MI, arrhythmia. Mean age for patients reporting cardiac co-morbidities was higher (53.4 vs. 44.4 p⬍0.0001) as were the pack-years (39.4 vs. 31.9 p⬍0.0001). The Cardiac group was 2x as likely to have been hospitalized in the past year (p⬍0.02) and much more likely to report ’Depression’ as an additional co-morbidity (p⬍0.0001). Only a minority of the Cardiac group were more likely to cite ‘a recent change in health status’ (29.0% vs. 10.6%, p⬍0.0001), or ‘pressure from physician’ (26.1% vs. 15.7%, p⬍0.0001) as a reason for quitting. The quit success of both groups was similar (55.9% vs. 55.1%) at one month. CONCLUSION: Older smokers with greater pack-years, who were more frequently hospitalized, reported cardiac co-morbidities more often. With only a small minority of the cardiac group citing ’health reasons’/ ’physician input’ as factors in the impetus for their quit attempt, this indicates a need to put more emphasis on patient education. While advising smokers to quit, healthcare providers need to more thoroughly explain the connection between smoking and their heart disease. This issue, when properly addressed, can be useful as an additional tool to aid patients in quitting. CLINICAL IMPLICATIONS: Early intervention with effective treatment for tobacco dependence can reduce the prevalence of heart disease. Ultimately, this may also decrease the economic burden of treating cardiac illnesses. DISCLOSURE: V.C. Reichert, None.

CARDIAC LESIONS IN RHEUMATIOD ARTHRITIS AND THEIR EVOLUTION Dimitris P. Papadopoulos, DrPh; Ioannis Moyssakis, FESC*; E. J. Gialafos, Dr; P. Vlahoyannopoulos, Asst. Prof; G. Vayopoulos, Prof.; P. Sfikakis, Asst. Prof; V. Votteas, Asst. Prof.; Laiko Hospital, Athens, Greece PURPOSE: Rheumatoid arthritis (RA) is a systemic disease involving many organ systems and is accompanied by cardiac involvement. The aim of our study was to evaluate echocardiographically the incidence and progression of cardiac involvement in patients (pts) with RA. METHODS: Seventy nine (73 females – 6 males, aged 56⫾11 years) pts with RA were evaluated with M-mode, 2D and Doppler echocardiogram after a follow-up period of 56⫾14 months. The left ventricular (LV) fractional shortening (FS) and the velocity of tricuspid jet plus the right atrial pressure served as LV systolic function and pulmonary systolic pressure respectively. Organic valvular involvement was defined as valve thickening and/or regurgitation. Left ventricular (LV) mass index was calculated by the Penn convention formula. RESULTS: Depressed LV systolic function was present in 7 (8,9%) pts at the beginning and in 11 (13,9%) at the end. Pericardial effusion had 17 (21,5%) at the beginning and 15 (19%) pts at follow-up. Aortic regurgitation had 18 (22,8%) pts in the first study and in 7 it was due to aortic root or ascending aorta dilatation. In the last study aortic regurgitation had 24 (30,4%) pts and in 11 was due to aortic root or ascending aorta dilatation. Particularly in 5 cases the aortic regurgitation deteriorated. Likewise mitral regurgitation had 8 (10,1%) pts in the first study (causing from mitral valve prolapse in 3) and 11 (13,9%) at the end. Pulmonary hypertension also had 9 (11,4%) pts at the beginning and 12 (15,2%) at follow-up. The LV mass index was 109⫾22 g/m2 at the beginning and 118⫾26 at the end of our study (p⬍0.05). CONCLUSION: Our results show that cardiac abnormalities in pts with RA are frequently appeared with predominant lesions the aortic regurgitation and pericardial effusion.The most significant changes during the progression of the disease are aortic lesions and increased LV mass index. DISCLOSURE: I. Moyssakis, None.

INCIDENCE OF ECHOCARDIOGRPHIC LESIONS IN MIXED CONNECTIVE TISSUE DISEASE Ioannis Moyssakis, FESC*; Dimitris P. Papadopoulos, Dr; Cristoforos Georgakopoulos; V. Vasiliou; Panagiotis Marcos; Vassilios Votteas, Asst. Prof; Laiko Hospital, Athens, Greece PURPOSE: Mixed connective tissue disease (MCTD) is a syndrome with features of systemic lupus erythematosus, systemic sclerosis, polymyositis, and rheumatoid arthritis. High titers of circulating antibodies to nuclear ribonucleoprotein are frequently identified in affected patients (pts). METHODS: Forty seven ( 34 females-13 males, aged 53⫾12 years) pts with MCTD were evaluated with M-mode, 2D and Doppler echocardiography. Parameters measured included: Left ventricular (LV) dimensions and the peak velocity of the tricuspid regurgitant jet for the fractional shortening (FS) and pulmonary hypertension calculation respectively. Organic valvular involvement was defined as valve thickening and/or regurgitation. RESULTS: Depressed LV function (FS⬍29%) was present in 5 pts (10.6%) and was diffusely impaired. Valvular regurgitation was found in 6 pts (12,7%) and was mild mitral regurgitation (in two due to mitral valve prolapse). Pulmonary hypertension had 7 pts (15%), pericardial effusion 8 (17%) and LV hypertrophy 4 (8.5%) pts. CONCLUSION: In mixed connective tissue disease cardiac abnormalities are quite common with more frequent being pulmonary hypertension and pericardial effusion. DISCLOSURE: I. Moyssakis, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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POSTER PRESENTATIONS

ETHNICITY AS A PREDICTOR OF THE SEVERITY OF CORONARY ARTERY DISEASE [CAD] IN A CITY HOSPITAL WITH A SIZEABLE ASIAN IMMIGRANT POPULATION Vijay A. Rupanagudi, MBBS, MD*; Patel Umang, MD; Tejwant Dhillon, MD; Sanjay Shetty, MD; S Niranjan, MD; A Khanna, MD; Coney Island Hospital, Brooklyn, NY

Wednesday, October 27, 2004 Cardiovascular Diseases - Epidemiology, continued ETIOLOGY AND OUTCOMES IN PATIENTS WITH PERICARDIAL EFFUSION REQUIRING PERICARDIOCENTESIS Vijay Rupanagudi, MBBS, MD*; Hima Kona, MD; Karthikeyan Kanagarajan, MD; S. Niranjan, MD; Padmanabhan Krishnan, MD; Coney Island Hospital, Brooklyn, NY PURPOSE: We sought to study the clinical presentation, etiology and outcomes in patients with pericardial effusion requiring pericardiocentesis in our institution. METHODS: Medical records of all patients with pericardial effusion who required pericardiocentesis at Coney Island Hospital from July 1, 1997 to June 30, 2002 were reviewed for above data. RESULTS: Total number of patients were 29 (M:F⫽12:17). The age ranged from 32-92 years. The presenting symptom was dyspnea in 17 patients, chest pain in 7 patients, generalized weakness in 3 patients, syncope/near syncope in 3 patients, and cough in 3 patients. Diagnosis of pericardial effusion on initial evaluation was correctly made in only 13/29[45%] patients. All patients with correct initial diagnosis of pericardial effusion were discharged from hospital. When diagnosis of pericardial effusion was not made on initial evaluation, 4 patients died within 24 hours. In 15/29[52%], etiology of pericardial effusion was established during hospital stay. Carcinoma lung-6patients, Carcinoma Breast-3patients, Dressler syndrome-2patients, chronic renal failure-1patient, Rheumatoid arthritis-1patient. 2 patients had hemopericardium following complicated acute myocardial infarction. 14/29[48%] patients had no etiology identified as the cause of pericardial effusion. 15/29[52%] patients with established etiology for pericardial effusion had mean survival of ⬎23 months, with 1 and 2 year survival of 43% and 43% respectively. Patients with no etiology identified as cause of pericardial effusion had mean survival ⬎50 months, with 1 and 2 year survival of 93% and 85% respectively. CONCLUSION: Dyspnea and chest pain were the most common symptoms in patients with significant pericardial effusion. Carcinoma was the leading identified cause. Even in presence of significant pericardial effusion, diagnosis is often not made during the initial evaluation and such patients have a high early mortality. Patients with pericardial effusion with unknown etiology had better long-term survival than those with established etiology. CLINICAL IMPLICATIONS: A high index of suspicion is needed during the initial evaluation of patients with unexplained dyspnea and chest pain in order to promptly diagnose pericardial effusion. Idiopathic pericardial effusion even in patients requiring pericardiocentesis carries a good prognoses. DISCLOSURE: V. Rupanagudi, None. PREMATURE CORONARY ARTERY DISEASE [CAD] IN THE ASIAN IMMIGRANT POPULATION: DATA FROM A NEW YORK CITY HOSPITAL Tejwant Dhillon, MD; S. Niranjan, MD; A. Khanna, MD; Sanjay Shetty, MD; Umang Patel, MD*; Vijay Rupanagudi, MD; Coney Island Hospital, Brooklyn, NY

11[23%]. The mean total cholesterol was 210⫾48, mean LDL was 120⫾39, mean HDL was 36⫾58, mean triglycerides was 247⫾156. CONCLUSION: Premature severe CAD is a feature of the CAD seen in the immigrant population from India, Pakistan and Bangladesh. No unusual risk factors were noted in this group. CLINICAL IMPLICATIONS: A high index of suspicion for CAD is needed when evaluating young Asian patients presenting to Emergency Room with chest pain or angina equivalent. DISCLOSURE: U. Patel, None. DETERMINANTS OF CORONARY CALCIFICATION AND AORTIC CALCIFICATION IN PERIMENOPAUSAL WOMEN Vijay K. Verma, MD*; Steven M. Hollenberg, MD; Andrew Dumasius, MD; K. Matthews, MD; Kim Sutton-Tyrrell, MD; Lynda Powell, MD; Cooper Hospital/UMDNJ-Robert Wood Johnson Medical School, Camden, NJ PURPOSE: Elevations in coronary artery calcification (CAC) scores detected by electron beam computed tomography (EBCT) correlate with the extent of atherosclerosis. EBCT can also be used to assess calcification in the ascending aorta (AoC), another marker of vascular atherosclerosis. We measured CAC and AoC as part of a comprehensive analysis of vascular structure and function in perimenopausal women in the Study of Women’s Health Across the Nation (SWAN Heart study). METHODS: 213 women underwent EBCT for CAC and AoC. Brachial flow-mediated dilation (FMD), carotid average intimal-medial thickness (IMT), and pulse wave velocity (PWV) were measured using ultrasound. Studies were done fasting and off medications and tobacco. CAC scores were stratified by presence or absence of significant calcium (⬍10 or ⱖ10). RESULTS: Mean age was 49.9, mean arterial pressure (MAP) 95.0 mmHg, and mean body mass index (BMI) of 29.1; 5% were smokers. Mean CAC was 8.1, AoC 78.3, and FMD 6.1%. CAC correlated significantly with AoC (r⫽0.30, p⬍0.001). Subjects with CAC ⱖ or ⬍10 differed significantly in FMD (6.5 ⫾3.9 vs 4.9 ⫾3.5, p⫽0.03), average IMT (0.68 vs 0.63, p⫽0.01), maximum IMT (0.88 vs 0.82, p⫽0.03), log PWV (6.85 vs 6.60, p⬍0.01), BMI (34.4 vs 27.4, p⬍0.001), age, and HDL. Subjects with AoC ⱖ or ⬍10 differed significantly only in age and BMI (32.9 ⫾5.7 vs 25.7 ⫾3.6, p⬍0.001). CONCLUSION: The determinants of coronary and aortic calcification differed in this population of asymptomatic perimenopausal women. This suggests that mechanisms contributing to calcification differ between conduit vessels and coronary arteries. BMI was a strong predictor of both CAC and AoC. CLINICAL IMPLICATIONS: As a result of these findings, early preventive strategies in this population may be undertaken. DISCLOSURE: V.K. Verma, None. METABOLIC SYNDROME AND HS-CRP ASSOCIATION WITH ANGIOGRAPHIC CORONARY ARTERY DISEASE Kwame O. Akosah, MD*; Ana M. Schaper, PhD; Sharon I. Barnhart, BSN; Vicki L. McHugh, MS; Michelle A. Mathiason, MS; Gundersen Lutheran Health System, La Crosse, WI

PURPOSE: Physicians in our hospital have observed young patients with severe CAD among the Asian Immigrant population from India, Pakistan and Bangladesh. Our aim was to determine if premature CAD is a characteristic feature of CAD seen in this immigrant population. METHODS: Data of all Asian patients who presented to our institution with chest pain or angina equivalent who underwent coronary angiogram from 1998 to 2002 were collected and compared with non Asians during the year 2001. Premature CAD was defined as ⬎70% stenosis of at least one vessel on coronary angiography in males ⬍45 years of age. RESULTS: Data from 338 Asian patients and 251 non Asian patients was available for evaluation and comparison. Significant CAD was noted in 218/338[64%] Asian patients and in 152/251[60%] in non Asian patients [p⬎0.3] suggesting no selection bias in performing invasive cardiac work up. Average age of Asian patients with significant CAD was 54⫾9 years and 64.5⫾10 years among non Asian patients[p0.001]. Of the 218 Asian patients with CAD 45[21%] had premature CAD compared with only 9 out of 152 [6%] non Asian patients[p⬍0.05]. Among Asian patients, 9 were less than 40 years of age, and only 1 non Asian patient was less than 40 years of age. Of the 45 Asian patients with premature CAD, 25 needed CABG and 13 needed PTCA/stent, compared to 1 and 6 patient respectively among non Asian patients. Risk factors among Asian patients with premature CAD was smoking 25[57%], HTN 21[45%], DM

PURPOSE: Metabolic Syndrome (MS) and hs-CRP have been recommended for risk identification in coronary heart disease (CHD) prevention. However, it is not clear if information obtained by MS and hs-CRP is additive or redundant. We aimed to determine if MS and hs-CRP provide incremental information in coronary artery disease (CAD) risk. METHODS: Subjects scheduled for elective coronary angiography were prospectively evaluated for MS and hs-CRP. Exclusion criteria included older age (men ⬎ 55; women ⬎ 65), anti-lipid therapy, and prior CHD. MS was defined per NCEP III as the presence of ⱖ3 of the following traits: low HDL (men ⬍40 mg/dL, women ⬍50 mg/dL), high triglyceride (ⱖ150 mg/dL), hypertension (ⱖ130/85 mm Hg), fasting glucose (⬎/⫹110 mg/dL), and BMI ⱖ30. Elevated hs-CRP was defined as ⬎ 3mg/L. CAD was defined as stenosis ⱖ 50%. RESULTS: CAD was present in 77 (30%) of 253 subjects. Mean age was 51⫾8 (55% women). MS criteria was met by 75 subjects. Mean values for hs-CRP was similar among subjects with CAD compared to those without CAD (6.4⫾11.1 mg/L vs. 4.2⫾5.5 mg/L, p⫽NS), but significantly higher in subjects with MS compared to those without MS (6.4⫾9.5 mg/L vs. 3.7⫾5.4 mg/L, p⫽0.022). The odds associated with MS and CAD was 2.6 (CI:1.5-4.6, p⫽0.001). Among subjects without CAD, only 23% had MS, whereas 45% of

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Wednesday, October 27, 2004 Cardiovascular Diseases - Epidemiology, continued individuals with CAD met criteria for MS. When MS and hs-CRP status were considered, we found that the coexistence of MS and elevated hs-CRP was associated with increased risk (OR:3.0, CI:1.5-6.1; p⫽0.003). CONCLUSION: One-third of subjects evaluated for CAD met criteria for MS. Subjects with MS were more likely to have high-risk hs-CRP. MS is associated with coronary angiographic disease. The presence of highrisk hs-CRP in subjects with MS further increase CAD risk. CLINICAL IMPLICATIONS: Identifying subjects with MS as per NCEP III guidelines may help identify individuals at risk for CAD, and high-risk hs-CRP values may help identify subjects with MS at particularly high risk for CAD. DISCLOSURE: K.O. Akosah, None. DIAGNOSTIC PATTERNS IN THE EVALUATION OF PATIENTS HOSPITALIZED WITH SYNCOPE Shun Kohsaka, MD*; Takeki Suzuki, MD; Naohisa Matsunaga, MD; Michael Lanigan, MD; Gary R. Burke, MD; Texas Heart Institute, Baylor College of Medicine, Houston, TX

Table. Frequency of Abnormal Results for Various Inpatient Diagnostic Tests Vasovagal Vasovagal etiology All patients etiology not presenting suspected suspected with on on syncope admission admission (n⫽266) (n⫽126) (n⫽140) Cardiac, No. Telemetry (%) Monitoring Echocardiogram Stress Testing Tilt Table Testing Neurological, Brain CT Scan No. (%) Electroencephalography Carotid Doppler

12/229 (5) 10/208 (5) 9/51 (18) 8/14 (60)

1/103 (1)* 1/99 (1)* 1/22 (5)* 6/11 (55)

11/126 (9)

6/145 (4) 5/89 (6)

1/62 (2)* 5/83 (6) 1/31 (3) 4/58 (7)

4/60 (7)

2/34 (6)

9/109 (8) 8/29 (28) 2/3 (67)

2/26 (8)

* P⬍0.01, comparing the vasovagal to non-vasovagal group. DISCLOSURE: S. Kohsaka, None.

PURPOSE: Alcohol may decrease intimal proliferation, inflammation, and reduce atherosclerotic heart disease. However, coronary anatomy has not been well studied in alcoholic patients. The objective of this study was to compare angiographic results of patients presenting with angina with and without alcoholism. METHODS: We studied alcoholic patients (n ⫽ 60), diagnosed by alcoholism, alcoholic related pancreatitis or liver cirrhosis who presented with chest pain to the New York Harbor HealthCare System of the Brooklyn Veterans Affairs Medical Center (NYHBVA). Patients were compared to age and coronary risk factor matched controls (n⫽ 200) without alcoholism between 1994 and 2002. All patients were male and underwent diagnostic cardiac catheterization after an abnormal stress test. RESULTS: Baseline demographics were similar in both groups. The mean Canadian Cardiovascular Society Functional Classification was significantly higher in the alcoholic group compared to controls ( 2.8⫹0.7 vs. 1.3⫹0.3, p⬍0.05). The prevalence of coronary artery disease (CAD) (luminal diameter stenosis ⬎ 50%) was lower in alcoholic group than controls, 28% vs. 58%, p⬍0.05, OR 0.3 , 95% CI 0.16-0.54. Alcoholics had less extensive CAD, 1.7⫹0.2 vs. 2.3⫹0.3 stenosed vessels as compared to controls, p⬍0.05. The alcoholic group had lower mean left ventricular ejection fraction (LVEF) as compared to the controls, 31 ⫹ 4 % vs. 48 ⫹ 5 %, p⬍0.05. Left ventricular dysfunction (LVD) (LVEF ⬍ 40%) was more common in alcoholic group (80% vs. 40%, p⬍ 0.05). In patients with LVD, alcoholism associated with a lower prevalence of CAD (OR 0.015, 95% CI 0.004 - 0.047). In contrast, alcoholism associated with a higher prevalence of CAD in patients with preserved systolic function (OR 18, 95% CI 2.3-148.7). CONCLUSION: In this group of patients presenting with chest pain to the NYHBVA, alcoholism associated with a lower prevalence of and less extensive CAD despite worse anginal symptoms. LVD was more common in the alcoholic group and was associated with a lower prevalence of CAD. CLINICAL IMPLICATIONS: There appears to be an inverse relationship between CAD and LVD in alcoholic patients. DISCLOSURE: S. Kokolis, None.

Cardiovascular Disease - Assessment 12:30 PM - 2:00 PM INCREASED FASTING PLASMA INSULIN LEVELS ARE ASSOCIATED WITH THE SEVERITY OF ANGIOGRAPHIC CORONARY ARTERY DISEASE Wilbert S. Aronow, MD; Rishi Sukhija, MD*; Devraj Nayak, MD; Chul Ahn, PhD; Melvin B. Weiss, MD; New York Medical College, Valhalla, NY PURPOSE: We investigated the relationship between fasting plasma insulin levels and the severity of angiographic coronary artery disease(CAD). METHODS: Fasting plasma insulin levels were obtained in 51 men and 31 women, mean age 60 years, with an increased body mass index who underwent coronary angiography for suspected symptomatic CAD. RESULTS: Of 82 patients, 37 (45%) had left main or 3-vessel CAD, 22 (27%) had 2-vessel CAD, 9 (11%) had 1-vessel CAD, and 14 (17%) had no obstructive CAD. Among the 4 groups, there was no significant difference in gender, age, dyslipidemia, and smoking. Hypertension (p⫽0.0003), diabetes mellitus (p⫽0.035), and increased fasting plasma insulin level (p⬍0.0001) were significantly associated with the severity of CAD. Stepwise ordinal regression analysis identified increased fasting plasma insulin level as a significant independent risk factor for the severity of CAD (p⬍0.0001). CONCLUSION: Increased fasting plasma insulin level is a significant independent risk factor for the severity of angiographic CAD. CLINICAL IMPLICATIONS: Patients with increasedf fasting plasma insulin levels should be treated aggressively with risk factor modification. DISCLOSURE: R. Sukhija, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: It is estimated that up to 5% of hospital admissions are for evaluation of syncope. The etiology of syncope varies, and nonselective diagnostic evaluations to determine the cause of syncope are often inconclusive. We hypothesized that inpatient tests for syncope seldom provide additive information to achieve a correct diagnosis, especially in patients with suspected vasovagal syncope. METHODS: We retrospectively reviewed the medical records of consecutive adult patients with a principal diagnosis of syncope (ICD-9 Code 780.2) who were admitted through the emergency department of an 800-bed teaching hospital from January 1, 2000, through May 31, 2001. Two internists used standardized diagnostic criteria to determine the suspected cause of the syncope. RESULTS: A total of 266 patients (44% women) with a mean age of 72⫾27 were identified. On admission, vasovagal syncope was suspected in 47% of the patients. Other suspected causes included cardiac (20), metabolic (10%), and neurological disorders (6%); in the remaining 17%, the cause of syncope remained unexplained. Overall yield of inpatient diagnostic tests were low (5-18%; Table). Of note, telemetry monitoring, echocardiogram, stress testing and brain CT scan was significantly lower yielding in patients with suspected vasovagal syncope. CONCLUSION: Inpatient tests for syncope seldom achieve a correct diagnosis of syncope. Both cardiac and neurological tests are likely overused, especially when vasovagal syncope is suspected. CLINICAL IMPLICATIONS: Unselected use of inpatient diagnostic techniques is not only inefficient but also unwarranted, especially when vasovagal syncope is suspected on initial evaluation.

CORONARY ANGIOGRAPHIC FINDINGS OF ALCOHOLIC PATIENTS PRESENTING WITH ANGINAL CHEST PAIN Spyros Kokolis, MD*; Luther T. Clark, MD; Erdal Cavusoglu, MD; Jonathan D. Marmur, MD; Nabil El-Sherif, MD; Gioia Turitto, MD; Jason Lazar, MD; Downstate Medical Center, Brooklyn, NY

Wednesday, October 27, 2004 Cardiovascular Disease - Assessment, continued ASSESSMENT OF DIASTOLIC FUNCTION WITH TISSUE DOPPLER IMAGING AFTER CARDIAC SURGERY: EFFECTS OF THE “POSTOPERATIVE SEPTUM” IN ON-PUMP VERSUS OFF-PUMP PROCEDURES Philip Malouf, BS*; Michael Madani, MD; Anthony Perricone, MD; Thomas Waltman, MD; Ajit Raisinghani, MD; Anthony DeMaria, MD; Daniel Blanchard, MD; University of California, San Diego School of Medicine, La Jolla, CA PURPOSE: Tissue Doppler imaging (TDI) of the mitral annulus is now widely used in the assessment of LV diastolic function. There is not universal agreement, however, on the optimal site of TDI measurement: some centers record motion of the lateral mitral annulus (LMA) while others favor the septal mitral annulus (SMA). Abnormal septal motion (“post-op septum”) is often seen after cardiopulmonary bypass (CPB), though ejection fraction (EF), end-systolic, and end-diastolic volumes are generally unchanged. If TDI measurements of the SMA are selectively affected by CPB, assessment of diastolic function could be adversely affected. In this study, we analyzed mitral annular TDI measurements following CPB and compared these to changes in patients undergoing off-pump cardiac surgery. METHODS: We prospectively studied 8 CPB and 7 off-pump pts. Echocardiography was performed 4⫾3 days before surgery and again 31⫾7 days after. Velocity of early diastolic mitral annular motion (Em), transmitral E/A ratio, and ejection fraction (EF) were measured in the apical 4-chamber view & compared using Wilcoxon signed ranks test. Patients served as their own controls. RESULTS: SMA Em velocity in CPB pts decreased significantly after surgery, while there was a nonsignificant increase in off-pump patients. LMA Em, E/A, & EF were unaffected by CPB, while these parameters trended upward in the off-pump group (although the baseline systolic and diastolic parameters of the off-pump group were depressed compared to the CPB group). CONCLUSION: Cardiac surgery with CPB is associated with a statistically significant 20% decrease in SMA Em velocity, despite no change in LMA Em velocity, E/A, or EF. Of note, this decrease in SMA Em is not seen following off-pump cardiac surgery. CLINICAL IMPLICATIONS: Measurement of SMA Em velocity is not recommended for routine assessment of diastolic function after CPB. This parameter may, however, retain its clinical utility after off-pump cardiac surgery.

CPB Group PreOp SMA Em 8.1 (cm/s) LMA Em 10.3 (cm/s) EF 0.55 E/A 1.28

PostOp 6.4 10.0 0.56 1.11

Off-Pump Group P value

PreOp PostOp

P value

0.02

5.5

6.2

0.35(NS)

0.93(NS)

6.0

8.0

0.06(NS)

0.78(NS) 0.50(NS)

0.36 1.10

0.46 1.47

0.03 0.10(NS)

DISCLOSURE: P. Malouf, None. PERICARDIAL EFFUSION IN PATIENTS WITH LEFT VENTRICULAR DYSFUNCTION Mohammad Reza Movahed, MD*; Babak Kasravi, MD; Mastaneh Ahmadi-Kashani; Seyed Ahmad Samsam Shariat, MD; University of California, Irvine Medical Center, Orange, CA PURPOSE: Prevalence of pericardial effusion in patients with left ventricular dysfunction is not known. The goal of this study was to evaluate the prevalence and severity of pericardial effusion in patients with decreased fractional shortening (FS) using a large echocardiography data Base. METHODS: We retrospectively analyzed 24,265 echocardiograms performed at our institution between 1984 and 1998. FS were recorded in 18,015 echocardiograms. We correlated the occurrence of pericardial effusion with the degree of fractional shortening. We stratified FS in 4 groups ( 1. FS ⬎ 25%, 2. FS between 17.5 and 25%, 3. FS between 10 and

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17.5 % and 4. FS ⬍ 10%.) Effusion was divided in 3 groups (mild, moderate and severe). RESULTS: Pericardial effusion was present in 1,632 (9.1%) of echocardiograms with documented FS. Pericardial effusion was significantly more common in patients with FS ⬍ 25 % and correlated with the severity of decreased FS (group 1: 8.4%, group 2: 12,8%. group 3: 13.2%, group 4: 14.4%, p⬍0.0001). However, only mild pericardial effusion was correlated with low FS (group 1: 6.6%, group 2: 11.0%. group 3: 11.1%, group 4: 14.0%, p⬍0.0001). CONCLUSION: Decreased left ventricular systolic function correlates with only mild pericardial effusion. Therefore, moderate or severe pericardial effusion can not be explained by decreased LV systolic Function. CLINICAL IMPLICATIONS: Occurence of moderate to large effusion can not be secondery to left ventricular dysfunction. DISCLOSURE: M. Movahed, None. ACOUSTIC IMAGING OF THE LUNGS IN PATIENTS WITH CHF AND PULMONARY CONGESTION OF VARYING SEVERITY - REPORT OF PRELIMINARY OBSERVATIONS WITH THE PALISCOPE SYSTEM Gad Keren, MD*; Natali Bogomolni, MD; Lev Mendelevitch, MD; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel PURPOSE: The main methods used to assess Congestive Heart Failure (CHF) patients include clinical history, physical examination, pulse-oximetry and Chest-X-Ray (CXR). The PALIScope (Passive Acoustic Lung Imaging) is a bedside, noninvasive radiation-free device that provides dynamic functional and potentially structural lung imaging. Our purpose was to evaluate the PALIScope technology in the diagnosis, management and monitoring of CHF patients with various degrees of pulmonary congestion. METHODS: Nine patients (Age, avg. 66⫾11 y) with severe CHF due to systolic LV dysfunction (NYHA class II, III,) were enrolled. Each patient was assessed three times (on admission, 4 hours following treatment and before hospital discharge) by physician, pulse-oximetry and PALIScope. On admission and prior to discharge, CXR, Blood tests and Echocardiography were performed. The PALIScope images are based on the lungs acoustic response during a breathing cycle. The acoustic energy is collected simultaneously by 40 sensors that are adhered to the patient’s back. PALIScope images were compared to nine healthy controls. RESULTS: The underlying reason for CHF was acute MI (five patients) and dilated cardiomyopathy (four patients). All patients were dyspneic (RR 25⫾3/min). Lung crepitations, wheezing and peripheral edema were noted in nine, three and five patients respectively. CXR revealed Lung congestion and pleural effusion in seven and two patients respectively. Analysis of the PALIScope image by three independent observers revealed: On Admission: Lung ventilation was markedly reduced in all patients. Ventilation of lower lobes was intensely affected relative to other lobes. Sequence of lung air-flow was disynchronous. Ventilation of one lung in five patients was intensely affected as compared to the other lung. Effective treatment was associated with remarkable improvement in all aforementioned parameters. CONCLUSION: Acoustic lungs imaging may provide accurate noninvasive radiation-free method for diagnosis, management and monitoring CHF patients. CLINICAL IMPLICATIONS: Fluid retention and volume overload are implicit to CHF, therefore temporal changes evaluation in pulmonic vascular engorgement, interstitial and alveolar edema are desirable. The PALIScope technology may prove highly valuable and provide such an assessment technology. DISCLOSURE: G. Keren, Deep Breeze Ltd. VALUE OF THE 12-LEAD ELECTROCARDIOGRAM IN THE ASSESSMENT OF ACUTE CORONARY SYNDROMES RELATED TO THE LEFT CIRCUMFLEX ARTERY Diego Moguillansky, MD*; Angel Caldera, MD; Len Braitman, PhD; Natalia I. Markus, MD; D. L. Morris, MD; Albert Einstein Medical Center, Philadelphia, PA PURPOSE: The electrocardiogram (EKG) remains an essential tool in the evaluation of patients with acute coronary syndromes (ACS). The role of the EKG in assessing the severity of the coronary artery disease (CAD) in patients with a Left Circumflex artery (LCX) related ACS has not been well established. We evaluated the usefulness of the Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Cardiovascular Disease - Assessment, continued

APPLICATION OF ENERGY LOSS COEFFICIENT IN CLINICAL PRACTICE: THE ROLE OF PRESSURE RECOVERY IN AORTIC STENOSIS Sirin Apiyasawat, MD*; Jayashri Aragam, MD; Worcester Medical Center, University of Massachusetts, Worcester, MA PURPOSE: Discrepancies between measurements of aortic valve area by Doppler echocardiography and those by cardiac catheterization are largely due to the pressure recovery phenomenon. Recently, a study showed that calculating of energy loss coefficient (ELCO) from echocardiogram might resolve the discrepancies. This study is to evaluate the use of ELCO in clinical practice. METHODS: We retrospectively reviewed 71 patients (age 75.03 ⫾8.67, 54.9% male) who had cardiac catheterization and echocardiogram done less than 3 months apart for significant native aortic stenosis (AS). Aortic valve area by Doppler echocardiography (AVADop) and cardiac catheterization (AVAcath) were calculated using the standard continuity equation and Gorlin’s formula respectively. In order to account for pressure recovery phenomenon, AVADop was modified (ELCO) by using the following formula: ELCO ⫽ (AVADop x Aa) / (Aa - AVADop) ⫽ AVAcath , when Aa ⫽ cross-sectional area of the aorta at the level of sinotubular junction. The correlations between AVADop, ELCO, and AVAcath were analyzed. RESULTS: There was a fair correlation between AVADop and AVAcath (0.81⫾0.23 vs. 0.90⫾0.36 cm2, R⫽0.631, P⫽0.000000003). After substituting AVADop with ELCO, the correlation was improved (0.92⫾0.33 vs. 0.90⫾0.36 cm2, R⫽0.642, P⫽0.000000001). When AVADop was replaced by ELCO, 11 patients moved from the group of severe AS to moderate AS, and 4 patients moved from the group of moderate AS to mild AS. However, this correlation did not hold true in patients who had more than mild associated aortic insufficiency (AI). In patients with AI of at least mild to moderate degree (N⫽11), ELCO was poorly correlated with AVAcath (0.86⫾0.28 vs. 0.69⫾0.19 cm2, R⫽ 0.265, P⫽0.43). CONCLUSION: AVADop generally overestimates AVAcath which could be corrected by calculating ELCO from AVADop. However, this calculation only confines to patients without significant degree of AI. CLINICAL IMPLICATIONS: ELCO, instead of AVADop, correlates better with AVAcath and is probably a better representation of a true aortic valve area.

Correlation of large effusion with pulsus parodoxus, electrical alternans and low voltages in EKG Vol⬎500ml Vol⬍500ml Pulsus parodoxus present

5

0

Pulsus parodoxus absent 17 Electrical alternans 9 present

7 0

Electrical alternans absent Low voltages present

13

7

5

0

Low voltages absent

17

7

Sensitivity[SEN]23%,Specificity [SPE]-100%, Positive predictive value[PPV]100%,Negative predictive value[NPV]-29%. Average amount of fluid if pulsus parodoxus present was 800 ml SEN-41%,SPEC100%,PPV100%,NPV-35%. Average amount of fluid if electrical alternans present was 833ml

SEN-23%,SPE100%,PPV100%,NPV-29%. Average amount of fluid if low voltages present was 830 ml

Correlation of pulsus parodoxus and volume of pericardial effusion with echocardiographic evidence of tamponade Tamponade present

Tamponade absent

Pulsus parodoxus present

5

0

Pulsus parodoxus absent Vol⬎500ml

14 15

10 6

Vol⬍500ml

5

3

SEN-26%, SPE-100%,PPV100%,NPV-34% SEN-75%, SPEC-33%, PPV-71%, NPV-37%

DISCLOSURE: S. Apiyasawat, None.

CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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EKG at presentation to predict the angiographic results in patients who underwent emergent percutaneous coronary intervention (PCI) for a LCX related ACS. METHODS: Design: Retrospective chart review. Subjects: All documented LCX related ACS that underwent emergent PCI to the LCX between January 2001 and December 2002. Exclusion criteria: Elective PCI, thrombolytic therapy, PCI to multiple vessels, and history of coronary artery bypass graft. Patients were divided in two groups according to their EKG at admission: ischemic (T-wave inversion, ST-segment depression or elevation, left bundle branch block) and non-ischemic. Study outcomes: evidence of occlusive disease (OD) in the culprit vessel (TIMI flow 0-1), and severity of CAD in the remaining coronary arteries (Friesinger Index -FI). RESULTS: Of the 62 study patients, 36 (58.1%) had ischemic EKGs (T-wave inversion 21%, ST-segment depression 17.7%, ST-segment elevation 19.4%). Nineteen of 36 (53%) patients with ischemic EKGs had TIMI flow 0-1, compared to 14 of 26 (54%) in the non-ischemic EKG group (p⫽0.93). The sensitivity and specificity of an ischemic EKG for OD were 58% (95%CI, 39% to 75%) and 41% (95%CI, 24% to 61%), respectively. The positive likelihood ratio (LR) was 0.98 (pre-test probability⫽53%, post-test probability⫽52%), and the negative LR was 1.02 (pre-test probability⫽53%, post-test probability⫽53%). The mean values of the FI were similar in the ischemic (8.8) and non-ischemic (8.3) EKG groups, with a difference between the mean of 0.5 (95% CI: -0.6 to 1.6; p⫽0.38). CONCLUSION: In patients with LCX related ACS, the EKG was not useful in predicting the severity of the underlying CAD in the culprit vessel or in the remaining coronary arteries. CLINICAL IMPLICATIONS: A non-ischemic EKG should not deter PCI when otherwise clinically indicated. DISCLOSURE: D. Moguillansky, None.

Wednesday, October 27, 2004 Cardiovascular Disease - Assessment, continued RIGHT VENTRICULAR TEI-INDEX IN HYPERTROPHIC CARDIOMYOPATHY.THE INFLUENCE OF LEFT VENTRICULAR OBSTRUCTION Ioannis Moyssakis, FESC*; Dimitris P. Papadopoulos, Dr; Elias J. Gialafos, Dr; Urania G. Papazachou; Vassilios Votteas, Asst. Prof.; Laiko Hospital, Athens, Greece PURPOSE: This study was designed to compare the right ventricular (RV) myocardial performance index (Tei-index) in patients with hypertrophic cardiomyopathy(HCM) and normal control subjects, as well as between obstructive and non-obstructive HCM. METHODS: Thirty eight (25 males-13 females aged 49⫾11 years) pts with HCM which was obstructive in 16 pts and thirty five (25males-10 females,aged 50⫾9 years)normal subjects were echocardiographically evaluated. The RV Tei-index was calculated from the RV systolic outflow and tricuspid inflow velocity profiles as the sum of the RV systolic isovolumic contraction and relaxation times divided by the RV ejection time.. The left ventricular (LV) mass index was also calculated by the Penn convention formula. RESULTS: The mean RV Tei-index was 0,46⫾0,12 in HCM pts and 0,35⫾0,08 in normals,p⬍0.01. A significant correlation was observed on RV Tei-index and LV mass index(r⫽0,42, p⬍0.05). Between obstructive and non-obstructive HCM there was not significant difference on RV Tei-index (0,48⫾0,11 vs. 0,45⫾0,10 respectively,p⫽NS). CONCLUSION: Conclusion: Our results show that RV Tei-index is inpaired in pts with HCM possibly due to RV diastolic dysfunction and ventricular interdependence. However the LV outflow obstruction does not deteriorate the above index. DISCLOSURE: I. Moyssakis, None.

USEFULNESS OF CLINICAL PREDICTORS IN THE DETECTION OF SIGNIFICANT PERICARDIAL EFFUSION Mazen Alakhras, MD; Vijay Rupanagudi, MBBS, MD*; Karthikeyan Kanagarajan, MD; Raju Ailiani, MD; Padmanabhan Krishnan, MD; Coney Island Hospital, Brooklyn, NY PURPOSE: Several clinical predictors have been used to detect significant pericardial effusion. Our aim was to study their usefulness in diagnosing patients with significant pericardial effusion. METHODS: Medical records of all patients with pericardial effusion who required pericardiocentesis at Coney Island Hospital from July 1, 1997 to June 30, 2002 were reviewed. RESULTS: See Table below. (Table not provided) CONCLUSION: Clinical predictors of pericardial effusion like Pulsus Paradoxus, electrical alternans and low voltage complexes are specific but not-sensitive for detecting the presence of significant pericardial effusion, including tamponade. Volume of pericardial effusion at the time of pericardiocentesis was also not an accurate predictor of tamponade. CLINICAL IMPLICATIONS: Clinical predictors of pericardial effusion though accurate are not useful because of low sensitivity in identifying patients with significant pericardial effusion including those with tamponade. Therefore they cannot be relied on to detect even significant pericardial effusion and echocardiography is needed for this purpose. DISCLOSURE: V. Rupanagudi, None.

CHEST PAIN DISPLAY FACILITATES PHYSICIAN MONITORING OF PATIENTS’ PAIN IN THE EMERGENCY DEPARTMENT Emily L. Senecal, MD*; Bret P. Nelson, MD; Kevin Biese, MD; Stephen H. Thomas, MD; Massachusetts General Hospital, Boston, MA PURPOSE: Healthcare providers regularly use verbal pain scales to assess Emergency Department (ED) patients with acute chest pain; however, the efficacy of displaying pain scales has not been assessed. This study evaluated whether display of pain scores facilitates physician monitoring of ED patients’ chest pain. METHODS: A randomized, prospective convenience-sample study of 49 adult ED patients presenting with chest pain to an urban Level 1 Trauma center (annual census 70,000) was undertaken. Chest pain levels were assessed every five minutes for one hour using a verbal numeric scale. Pain scores were not displayed for the Control group (n⫽17). Pain scales were displayed at the bedside only in the Bedside group (n⫽16), and at both the bedside and a central ED workstation in the Bedside/

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Central group (n⫽16). At the conclusion of the one-hour monitoring period, physicians were surveyed as to the usefulness of the pain displays. RESULTS: Almost two-thirds (62.5%) of physicians caring for patients in the Bedside and Bedside/Central groups found the pain display provided useful information about their patient’s pain. Bedside/Central group physicians were nearly twice as likely as those in the Bedside group (81.3% versus 43.8%) to indicate that the pain display provided useful information about their patient’s pain (OR 5.6, 95% CI 1.1-27.5, p ⫽ 0.03). They were also more likely to indicate that the pain display made it easier to track their patient’s pain (OR 5.6, 95% CI 1.1-27.5, p ⫽ 0.03). CONCLUSION: Chest pain displays facilitate physician monitoring of chest pain in the acute care section of the ED. Physicians benefit the most from pain displays present both at the bedside and at a central workstation. CLINICAL IMPLICATIONS: Improving the assessment of acute chest pain will optimize patient care, especially treatment of timesensitive cardiac disease. Future studies are needed to evaluate whether the display of pain scales in a continuous fashion, such as on a cardiac monitor alongside heart rate and blood pressure, will improve outcomes. DISCLOSURE: E.L. Senecal, None.

EVALUATION OF LEFT VENTRICULAR EJECTION FRACTION WITH GATED SPECT AND ANGIOGRAPHIC MEASUREMENTS: RELATIONSHIP OF BODY SURFACE AREA Michael G. Reinig, DO*; Elias Iliadis, MD; Joseph E. Parrillo, MD; Rido Cha, MD; Cooper Heart Institute/Cooper University Hospital, Philadelphia, PA PURPOSE: Gated SPECT provides ejection fractions comparable to various modalities, however in patients with a smaller body surface area (BSA) this relationship is less consistent. METHODS: Retrospective analysis of myocardial perfusion images (MPI) was performed on 88 patients, each with Tc-99m sestamibi SPECT post-stress quantification software (Cedars Sinai). All underwent cardiac catheterization within a 30-day period with no major clinical events in the interim. Ventriculography was measured via planimetry averaging two consecutive beats. Nine patients were excluded from the study due to ventricular arrhythmias. The main indication for initial MPI was chest pain(63%), the majority of patients underwent exercise treadmill testing (60%) with the remaining undergoing vasodilator testing. RESULTS: 88 patients were divided in four groups based on sex and BSA. Forty-eight (55%) patients were male: 19 with a BSA⬍2.0 and 29 with a BSA⬎2.0. Forty (45%) patients were female: 25 with a BSA⬍1.8 and 15 with a BSA⬎1.8. For all patients in the study, comparison of SPECT and angiography revealed a high degree of correlation (correlation coefficient ⫽ 0.73 and p⬍0.005). The two groups with larger BSA had a much higher correlation coefficient:0.86 compared to the lower BSA groups with a correlation coefficient:0.44. CONCLUSION: This study demonstrates a high degree of correlation between results of SPECT analysis and those obtained by angiography in the group as a whole. However, gated SPECT does not consistently correlate to angiography when studying patients with smaller body surface areas. CLINICAL IMPLICATIONS: Although gated SPECT is an accepted modality in assessing ejection fraction, one needs to be aware of the disparities that exist in smaller patients.

Table 1. SPECT and Angiographic Correlation SPECT EF ANGIO EF Correlation Group Sex BSA N Mean(SD) Mean(SD) Coefficient P Value 1 2 3 4 Total

F F M M

⬍1.8 ⱖ1.8 ⬍2.0 ⱖ2.0

25 15 19 29 88

62(⫾10) 60(⫾8) 50(⫾9) 52(⫾12) 56(⫾11)

62(⫾6) 61(⫾8) 54(⫾11) 54(⫾12) 58(⫾10)

0.36 0.77 0.57 0.87 0.73

⬍0.005 ⬍0.005 ⬍0.005 ⫽0.001 ⬍0.005

DISCLOSURE: M.G. Reinig, None.


Wednesday, October 27, 2004 Cardiovascular Disease - Assessment, continued ESTIMATING MYOCARDIAL OXYGEN CONSUMPTION USING A PULMONARY ARTERY CATHETER Guillermo Gutierrez, MD, PhD*; Lakhmir S. Chawla, MD; The George Washington University Medical Center, Washington, DC

DISCLOSURE: G. Gutierrez, None.

SIGNIFICANT PHYSIOLOGIC AND HEMODYNAMIC DIFFERENCES BETWEEN ADENOSINE WITH AND WITHOUT LOWLEVEL TREADMILL EXERCISE IN PATIENTS COMPLAINING OF DYSPNEA Neeta Tripathi, MD*; Sherry Wilkinson, RN; Mitchell Somma, PA-C; Augustine Agocha, MD; Cooper Heart Institute, Robert Wood Johnson Medical School, Camden, NJ PURPOSE: Adenosine with low-level treadmill exercise is preferred due to superior images and favorable side-effect profile. Surprisingly, little data exists on the hemodynamic effects of additional exercise on adenosine infusion in largely sedentary patients. First Pass Radionuclide Angiography (FPRNA) can simultaneously evaluate both ventricles, and pulmonary function at rest and at peak stress using well-validated non-invasive hemodynamic parameters. We used adenosine testing with and without exercise to evaluate consecutive patients presenting with dyspnea to determine the hemodynamic effects of the additional exercise. METHODS: Adenosine was infused at 140 ug/kg/min for 6 minutes while sitting in a chair or walking on a treadmill (1.0 mph, 0% grade). Rest and stress FPRNA were obtained after 15-45 millicurie of sestamibi. Imaging was performed with Sim-400 multicrystal camera. RESULTS: 60 patients (60% female) with mean age 66.2 years were evaluated. 33 patients (55%) exercised (⫹EX) and 27 patients did not (-EX). Baseline variables were similar in both groups except age, cardiac index, and pulmonary mean transit time (PMTT). Adenosine infusion clearly changes most of the parameters measured (Table 1). Compared to

Table 1: Univariate comparison of hemodynamic parameters in patients with and without exercise Hemodynamic Variable (Change from rest to exercise) Cardiac output – mean (SD) Cardiac index – mean (SD) Time to peak flow – mean (SD) Peak flow rate– mean (SD) Pulmonary mean transit time – mean (SD)

Without Walk (N⫽27)

With Walk (N⫽33)

1.06 (0.39) 0.51 (0.20) 0.74 (12.06)

3.15 (0.35) 1.54 (0.17) - 37.70 (11.87)

t – 4.01, df 58, P ⬍ 0.001 t – 3.92, df 58, P ⬍ 0.001 t 2.25, df 58, P⫽0.03

0.10 (0.09) - 0.80 (0.42)

0.93 (0.18) - 1.27 (0.23)

t – 3.82, df 58, P ⬍ 0.001 t 1.04, df 58, P⫽0.30

Test of Significance

Table 2: Multivariate comparison of hemodynamic parameters in patients with and without exercise Dependent Variable (Change from rest to exercise)

Exercise vs No Exercise Groups

Cardiac output Cardiac index

P⫽0.002 P⫽0.03

Time to peak flow Peak flow rate pulmonary mean transit time

P⫽0.01 P⫽0.003 P⫽0.004

Variables Controlled Age,P⫽ 0.06 Age, P⫽ 0.06 Cardiac index at rest, P⫽0.001 Age, P⫽0.18 Age, P⫽0.07 Age, P⫽0.36 PMTT, P⬍0.001

DISCLOSURE: N. Tripathi, None.


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PURPOSE: A practical method to assess myocardial oxygen consumption (MVO2) would be a valuable adjunct to monitoring critically ill patients. Previously we reported a step-down in O2 saturation from atrial to pulmonary artery blood (Delta SO2), likely to result from mixing atrial with coronary sinus blood. We hypothesize that Delta SO2 bears a direct relationship to coronary sinus blood O2 saturation and by extension, to myocardial O2 consumption (MVO2). METHODS: An equation was developed using a two-compartment mass transport model relating MVO2 to DeltaSO2. The model was tested using data obtained from 45 patients with pulmonary artery (PA) catheters inserted during their stay in the ICU. We computed Delta SO2 from blood samples drawn from the proximal and distal ports of the PA catheter as Delta SO2 ⫽ (SO2)proximal- (SO2)distal. RESULTS: As shown in Figure 1, our model predicts a linear relationship between Delta SO2 and MVO2 (P ⬍ 0.0001; R2 ⫽ 0.76). CONCLUSION: There appears to be a robust linear relationship between Delta SO2 and MVO2. CLINICAL IMPLICATIONS: Further studies comparing calculated and direct measures of MVO2 are needed prior to advocating the use of Delta SO2 as an estimate of myocardial energy metabolism in critically ill patients.

-EX group, ⫹EX patients had significant augmentation (rest compared to stress) in cardiac output (P⬍ 0.001) and cardiac index (P⬍ 0.001). The addition of exercise significantly improved diastolic function due to increased peak filling rate (P ⬍ 0.001) and shortened time to peak filling (P ⬍ 0.05) in the ⫹EX group. These effects of exercise remained significant in multiple regression models (Table 2) that controlled for significant baseline differences in age, cardiac index, and pulmonary mean transit time. When controlling for significant difference in PMTT between the groups at rest, the change in PMTT was significantly different between the groups. CONCLUSION: Adenosine infusion alone has significant effects on non-invasive hemodynamic parameters measured by FPRNA. Additional low-level exercise results in improved images and significantly augments many functional parameters increasing the test’s utility. CLINICAL IMPLICATIONS: FPRNA is becoming the favored test to assess cardiovascular function in patients with dyspnea. Adenosine infusion and exercise provide additive benefits.

Wednesday, October 27, 2004 Pulmonary Function Testing 12:30 PM - 2:00 PM THE UTILITY OF THE FORCED OSCILLATION TECHNIQUE (FOT) IN ASSESSING BRONCHODILATOR RESPONSIVENESS IN PATIENTS WITH ASTHMA Michael J. Akerman, MD, FACP; Venkata A. Yalamanchili, MD; Vaidehi Kaza, MD; Jeremy Weedon, MD; Albert E. Heurich, MD; Makito Yaegashi, MD*; State University of New York, Health Science Center of Brook, Brooklyn, NY PURPOSE: To address the utility of the forced oscillation technique (FOT) in assessing bronchodilator responsiveness compared with FEV1 and PEF. METHODS: In 126 patients with clinical history of asthma, the following measures were obtained three times each, before and after two doses of pirbuterol 0.2mg inhalation. FOT measures: *the respiratory resistance at 5 Hz (R5) and at 20 Hz (R20), *R5-R20, *the total respiratory resistance (Rrs) *the total respiratory conductance (Grs). Spirometric measures: *FEV1 *peak expiratory flow (PEF) with spirometry. These measures were transformed into dimentionless subject-specific effect-size “d-scores” by dividing them by the estimated pooled within-subject standard deviation. RESULTS: Descriptive statistics for mean raw scores, delta scores and d-scores are presented in Table 1. The mean effect size among these measures were different between measures[omnibus test of difference, p⬍0.0001]. Post-hoc test analysis indicated that Grs,Rrs,R5 are most sensitive for changing in response to pirputrol inhalation, and that PEF & R5-R20 are least sensitive. [Tukey p⬍0.0001 in all cases]. The pattern of unadjusted p-values (p ⬍ 0.05) suggests three homogeneous sets of measures for sensitivity to change after pirputerol. In descending order of sensitivity they are: Grs, Rrs and R5; FEV1 and R20; and R5-R20 and PEF. CONCLUSION: Several forced oscillation measures, namely Grs, Rrs and R5, are very sensitive for detecting bronchodilator response in patients with asthma. CLINICAL IMPLICATIONS: Measurement of forced oscillation may be useful to detect bronchodilator response in asthmatic patients.

Table 1 Descriptive statistics for FOT measurement and FEV1 before and after pirbuterol Measure FEV1 (L)

Min.

Baseline Postdrug⌬d

0.50 4.18 N/A 0.55 4.01 -0.73 0.96 -6.72 8.90 0.93 3.82 p⫽0.0063 1.15 4.17 -0.74 1.68 -4.94 11.27 0.31 1.60 p⫽0.0095 0.27 1.31 -0.62 0.35 -5.31 9.55 0.26 1.08 p⫽0.0102 0.24 0.87 -0.37 0.25 -6.13 9.08

Grs (L䡠s-1 kPa-1) Baseline Postdrug⌬d R5 (kPa䡠L-1䡠s)


Rrs (kPa䡠L-1䡠s)


1.90 2.10 0.20 1.83 1.79 2.18 0.39 2.64 0.78 0.62 -0.16 2.52 0.60 0.50 -0.10 2.56

0.64 0.68 0.25 2.27 0.53 0.65 0.43 2.90 0.25 0.20 0.16 2.44 0.16 0.14 0.11 2.66

Max.

p value (vs FEV1)

Variable Mean SD

hypothesis, we studied normal subjects as well as subjects with COPD and asthma before and after inhalation of albuterol. METHODS: We measured lung mechanic parameters including FEV1, peak expiratory flow (PEF), expiratory lung resistance (Rle), esophageal pressure, and total lung capacity (TLC) before and after inhalation of 180 mcg of albuterol in the study subjects. We used a novel method to estimate FEV1 (NFEV1) corrected for effect of TGC. RESULTS: Our results demonstrate that bronchodilator inhalation reduced TGC and Rle; and increased PEF and FEV1. Furthermore, TGC reduction with bronchodilator explained 50% of increase in FEV1 post bronchodilator. CONCLUSION: We concluded that inhalation of bronchodilator decreased thoracic gas compression by improving expiratory flow limitation, and therefore, TGC reduction explains in part the improvement in FEV1 with bronchodilator. CLINICAL IMPLICATIONS: Special attention needs to be given to consitency in performing pulmonary function testing. Variable effort may alter the FEV1 without any true effect from bronchodilator. DISCLOSURE: A. Sharafkhaneh, None.

THE EFFECT OF VISUALLY OBSERVED EXPIRATORY DYNAMIC COLLAPSE OF THE AIRWAYS ON THE FLOW VOLUME LOOP Marivi Ora, MD*; David M. Murphy, MD; Deborah Heart and Lung Center, Browns Mills, NJ PURPOSE: Some patients with severe chronic obstructive pulmonary disease (COPD) exhibit significant dynamic expiratory collapse of the airways. This abnormality is sometimes seen during flexible fiberoptic bronchoscopy. We attempted to determine a physiologic abnormality characteristic of this finding. METHODS: We prospectively investigated ten subjects with visible dynamic collapse of the airways beyond the main carina identified at the time of bronchoscopy. All ten subjects were recorded on video. All subjects underwent forced expiratory maneuvers with recording of forced expiratory vital capacity (FVC), forced inspiratory vital capacity (FIVC), expiratory flows and flow volume loops with associated normal tidal volume inspiratory and expiratory loops. Maximum voluntary ventilation (MVV) maneuvers were recorded. An obstructive pattern was defined as an FEV1/FVC% less than 70%. The results obtained for the different parameters were compared to accepted normal values. RESULTS: When the data from the flow volume loops were evaluated, eight of ten subjects showed an obstructive pattern (FEV1/FVC% ⬍ 70%, range 52 to 68%). MVV (percent predicted) ranged from 24% to 102% (obstructed) and from 85 to 95% (non-obstructed). FIVC was less than the FVC in nine out of ten. The most characteristic finding was that the expiratory limb of the tidal volume tracing occurred at some point on the maximum expiratory curve of the flow volume loop. No abnormalities were observed in the inspiratory limb of the flow volume loop. CONCLUSION: 1. All subjects with demonstrable collapse identified at fiberoptic bronchoscopy showed that the expiratory limb of the normal tidal volume tracing occurred at some point on the maximum expiratory flow volume envelope. 2. Eight of ten subjects with dynamic collapse showed an obstuctive pattern. 3. Nine out of ten subjects showed an FIVC less than the FVC. 4. The two non-obstructed subjects did not show concave upward appearance of the flow volume loop. CLINICAL IMPLICATIONS: The presence of significant expiratory dynamic airways collapse and its accompanying flow volume loop changes do not necessarily indicate obstructive airways disease. DISCLOSURE: M. Ora, None.

DISCLOSURE: M. Yaegashi, None. THORACIC GAS COMPRESSION MODIFIES EFFECT OF BRONCHODILATOR ON EXPIRATORY FLOW Amir Sharafkhaneh, MD*; Todd M. Officer, MD; Joseph R. Rodarte, MD; Hossein Sharafkhaneh, MD; Aladin M. Boriek, PhD; Baylor College of Medicine, Houston, TX PURPOSE: In this study we hypothesized that bronchodilator inhalation reduces thoracic gas compression (TGC) and such a reduction explains in part the FEV1 improvement with a bronchodilator. To test this

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FLOW-VOLUME LOOPS IN STANDING AND SUPINE YOUNG MALES Christopher A. McCuller*; Terry M. Dwyer, MD, PhD; C. H. McCuller, MD; Marcy F. Petrini, PhD; Jackson Academy High School, Jackson, MS PURPOSE: Adult lung volumes depend on subject position, being less when supine than when standing. Two mechanisms may contribute to this Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Pulmonary Function Testing, continued

FVC FEV1/FVC

Standing

Supine

P

4.51⫾0.51 84 ⫾ 5

4.17⫾0.49 82 ⫾ 8

0.0001 0.15

DISCLOSURE: C.A. McCuller, None.

CAPILLARY VS ARTERIAL BLOOD GAS CORRELATION IN ADULT PATIENTS WITH CARDIOPULMONARY DISEASES Luis E. Santos-Martinez, MD, FCCP*; Jose Gotes, MD; ML MartinezGuerra, MD; Aida Duran, QFB; Arturo Carrillo, MD; Tomas Pulido, MD; Mateo Porres, MD; Gerardo Rojas, MD; Edgar Bautista, MD; Alicia Castan˜ on, RN; Alejandro Vazquez, MD; Julio Sandoval, MD; Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico

SaO2) Pearson correlation test (r) was used, the values are shown as mean ⫾ SD. The level of significance was established at p⬍ 0.05. RESULTS: We included 17 male and 23 female patients, with ages of 54 ⫾ 18. There were no incidents in the sampling. 160 simultaneous paired samples were obtained, 80 from the radial artery and 80 from the capillary bed of the distal phalanx. The pathologic conditions included were various Heart Disease (n⫽ 28), and Lung Diseases (n⫽ 12). The correlations obtained were:. CONCLUSION: Correlations are good, although, not as good as we expected. CLINICAL IMPLICATIONS: Capillary sampling could be a plausible and less invasive alternative for blood gas testing. DISCLOSURE: L.E. Santos-Martinez, None.

ABSOLUTE, RATHER THAN PERCENT DIFFERENCES, CAN BE USED TO ASSESS MEASUREMENT VARIABILITY FOR DLCO Robert O. Crapo, MD*; Neil R. MacIntyre, MD; Robert L. Jensen, PhD; LDS Hospital/University of Utah, Salt Lake City, UT PURPOSE: Punjabi reported test reproducibility for DLCO was best assessed by absolute differences of 2.0 to 2.5 DLCO units between tests (Chest 2003; 123:1082-89). This recommendation has been criticized because it was based on only one instrument manufacturer and one laboratory. METHODS: Using a retrospective design to avoid influencing laboratory procedure, 16 laboratories from the ATS lab registry program submitted complete data for two DLCO trials (DLCO, VI, VA) and patient demographic data from 50 consecutive laboratory reports (792 records). Data were obtained from 22 instruments representing nine different models and four manufacturers. The figure illustrates percent and absolute differences between the two DLCO measurements by average DLCO. RESULTS: There is strong nonlinear relationship between percent difference and average DLCO and a trivial linear relationship between absolute difference and average DLCO. After excluding four outliers, absolute differences for 70% of the tests were ⬍ 1 DLCO unit, 91.3% were ⬍ 2.0 units and 95.5% were ⬍ 2.5 units. These data confirm the Punjabi’s findings in 16 laboratories using a wide variety of instruments. CONCLUSION: Acceptable DLCO variability should be assessed as absolute differences less than 2 or 2.5 DLCO units. CLINICAL IMPLICATIONS: Doing so simplifies DLCO testing and may reduce the number of tests required to meet acceptability criteria.

PURPOSE: The correlation between Capillary Blood Gas Test (CBGT) vs Arterial Blood Gas Test (ABGT) has been previously reported as adequate in pediatric patients and anecdotic reports in adult. To our knowledge, this correlation has not been established in controlled studies of patients with stable cardiopulmonary diseases. METHODS: We studied 40 patients with known cardiopulmonary disease in the pulmonary function test lab. Demographic information was recorded from each patient. A modified Allen maneuver and capillary refill status was evaluated. After that, CBGT and ABGT were obtained from the non-dominant extremity with Inspired Oxygen Fraction of 21% (FiO2) and after 20 minutes of breathing oxygen with FiO2 of 100%. For each gasometric parameter (pH, PCO2, PO2, HCO3, TCO2, BE and

CBGT vs ABGT PH PCO2 PO2 HCO3 TCO2 BE SaO2

r / 21%

P⬍

r /100%

P⬍

.888 .766 .769 .669 .670 .589 .855

.000 .000 .000 .000 .000 .000 .000

.888 .891 .733 .833 .840 .829 .984

.000 .000 .000 .000 .000 .000 .000

DISCLOSURE: R.O. Crapo, None.


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change; 1) the lung may be compressed when the diaphragm is elevated; 2) the pulmonary blood volume may be increased, which, in turn, decreases compliance. In adult subject, this change in lung volume has also been associated with an increase in resistance and the change in compliance with an increase in closing volume. To determine whether this change in resistance would effect flow, we measured flow volume loops in young, non-obese subjects in whom closing volume should be minimal. We used flow-volume loops to obtain both a measure of lung volume and of flow (Forced Vital Capacity, FVC, and FEV1/FVC, the ratio of Forced Expired Flow in 1 second to FVC, respectively). METHODS: Flow-volume loops were performed in normal males ages 13 to 17 with BMI ⫽ 24.1 ⫾ 3.8 (mean ⫾ SD) who had no reported cardiopulmonary impairments. The Institutional Review Board approved this protocol. Measurements were made according to American Thoracic Society (ATS) standards in the standing and supine positions. By power analysis we determined that a sample size of 10 was sufficient to detect a 10% difference between the two positions when using the paired t-test, a P ⬍ 0.05, a power of 90% and a variability of 0.2 L. This variability was chosen because it is the ATS standard for reproducibility. The Bonferroni correction was used to adjust the P value for multiple variable comparisons, since two variables were measured, the FVC and the FEV1/FVC. RESULTS: Values are mean ⫾ S.D. in the table. CONCLUSION: In young adult males, we confirmed the small (7%) change in FVC when changing position from standing to supine. However, there was no difference in the FEV1/FVC, indicating that this small change in volume is not enough to cause an increase in airway resistance detectable by spirometry. CLINICAL IMPLICATIONS: Changes in lung volumes in young males do not effect flow.

Wednesday, October 27, 2004 Pulmonary Function Testing, continued EFFECT OF LUNG VOLUME HISTORY ON AIRWAY RESISTANCE AS MEASURED BY IMPULSE OSCILLOMETRY IN NORMAL INDIVIDUALS AND IN PATIENTS WITH VARIOUS PULMONARY FUNCTION ABNORMALITIES Hany F. Ghali Hana, MD*; Andrew Anyadiegwu, MD; Albert Heurich, MD; SUNY Downstate Medical Center at Brooklyn, Brooklyn, NY PURPOSE: The forced vital capacity (FVC) maneuver used in pulmonary function testing (PFT) allows the subject to inhale to total lung capacity (TLC) with a breath hold and then exhale forcibly. The maneuver of lung volume history done in Impulse Oscillometry (IOS) entails quiet deep inhalation to TLC followed by quiet exhalation. It is known that FVC maneuver results in decreased maximal expiratory flow especially in patients with COPD and hyper-reactive airways. The following questions were evoked; does the decrease in expiratory flow associated with FVC maneuver occur with lung volume history maneuver in IOS as well? Is that decrease in expiratory flow associated with a comparable increase in airway resistance measured in IOS? And if so, how do different pulmonary diseases influence its magnitude? The aim of this study is to determine if there is a significant difference in the indices of airway resistance measured in IOS during both normal and deep (lung volume history) breathing in normal individuals and in patients with abnormal PFT. METHODS: 163 patients were included in the study. All patients had a conventional PFT and IOS performed on the same day. Based on TLC, FEV1/FVC ratio, FEF25-75%, post-bronchodilator response; patients were categorized as; restrictive, obstructive, mixed, small airway disease, and normal. Indices of airway resistance in IOS (central and peripheral resistance, resonance frequency, Resistance at 5Hz and 20 Hz) were compared between act-1(normal breathing) and act-2(post- volume history) using wilcoxon signed ranks test. RESULTS: There was no statistically significant difference in resistance indices in the IOS between act-1 and act-2 neither in the total population nor in any of the categories (P ⬎0.05). CONCLUSION: Lung volume history maneuver neither increases central or peripheral airway resistance in normal individuals or in patients with pulmonary function abnormalities. CLINICAL IMPLICATIONS: IOS provides a technique for assessment of airway resistance without the technique significantly influencing the results. Lung volume history does not produce significant alteration in airway resistance and thus can be utilized in different pulmonary assessments. DISCLOSURE: H.F. Ghali Hana, None. CRACKLE POLARITY IS INFLUENCED BY RESPIRATORY CYCLE Raymond Murphy, MD*; Andrey Vyshedskiy, PhD; Ruqayyah Alhashem; Brigham and Women’s Faulkner Hospitals, Boston, MA

CONCLUSION: The reported findings are consistent with the hypothesis that sudden airway opening is responsible for inspiratory crackles and airway closing is responsible for expiratory crackles. CLINICAL IMPLICATIONS: While there are no immediate clinical benefits to knowing the polarity of a patient’s crackles, a clearer understanding of the mechanism of production of lung sounds offers the promise of improving noninvasive diagnosis of lung disorders. DISCLOSURE: R. Murphy, Stethographics, MEASURED LUNG VOLUMES IN HEALTHY AFRICAN AMERICANS VERSUS CAUCASIANS VERSUS PREDICTION EQUATION ESTIMATES Gene R. Pesola, MD, MPH*; Samuel Dartey-Heyford, MD; Gladstone Huggins; Yisa Sunmonu, MD; Jean G. Ford, MD; Harlem Hospital/ Columbia Univ., New York, NY PURPOSE: Lung volumes (LV) in African Americans (AA) are purported to be 10-15% less than Caucasians (C) for identical height (ht). To test this, 42 nonsmoking AA and 12 C controls with no history of lung disease underwent pulmonary function testing. METHODS: Spirometry and total lung capacity (TLC) by plethymography were obtained. Miller (M),Knudson (Kn),and Crapo (C) prediction equation estimates (PEE) for spirometry were used by entering age,sex,ht,and weight (wt) into appropriate equations. Body mass index (BMI) was also calculated. Results are mean ⫹ S.D. An abnormal LV was ⬍ 80% predicted. RESULTS: There were 20 female/22 male AA, mean age 35. There were 6 male/6 female C, average age 38. The average ht/wt/BMI were 68.2 ⫹ 3.6 inches/175.9 ⫹ 32.7 lbs/26.4 ⫹ 3.4 and 67.0 ⫹ 4.6 inches/ 153.9 ⫹ 35.2 lbs/23.5 for AA and C, respectively. The average FEV1, FVC and FEV1/FVC ratio were 3.23 ⫹ 0.68 liters, 3.90 ⫹ 0.84 liters, and 0.83 ⫹ 0.06 and 3.71 ⫹ 0.80 liters, 4.56 ⫹ 1.05 liters, and 0.82 ⫹ 0.06 for AA and Caucasian, respectively. There were significant difference in wt, BMI, FEV1, and FVC between AA and C (p ⬍ 0.05). The mean reductions in FEV1 and FVC were 12.9% and 14.5% in AA. TLC was 5.00 ⫹ 1.08 liters and 6.14 ⫹ 1.35 liters in AA/C, respectively. They were significantly different (p ⬍ 0.01) with an average reduction in TLC of 18.6% in AA. Using the C PEE on AA revealed abnormal FEV1 and/or FVC values in 16/42, 14/42, and 2/42 using the M, Kn, or C equations, respectively. When PEE were adjusted down by 15% for FVC and FEV1, all AA values were normalized. All C spirometric values were normal. CONCLUSION: Healthy AA of similar ht compared to C have smaller LV. This explains the etiology for the reduced diffusion noted in healthy AA compared to C(Pesola, et.al. Respiration, in press). CLINICAL IMPLICATIONS: Healthy AA can be defined as abnormal using PEE for LV derived from C unless adjustments are made. DISCLOSURE: G.R. Pesola, None.

PURPOSE: Although crackles are heard over the chests of patients with a number of common cardiopulmonary disorders, the mechanism of production of these sounds is poorly understood. Fredberg and Holford postulated that crackles were due to a stress relaxation quadrupole associated with sudden airway opening and closing. Their model predicted that the polarity of expiratory crackles would be the reverse of inspiratory crackles. The goal of this research was to examine systematically the relationship between crackle polarity and respiratory cycle. METHODS: Patients with pneumonia (PN), congestive heart failure (CHF) and interstitial fibrosis (IPF), with over 2 inspiratory crackles per breath (n⫽158), or over 2 expiratory crackles per breath (n⫽89) were examined using a 16-channel lung sound analyzer (Stethographics, Inc, Model STG1602). This device automatically analyzes crackles. Crackle polarity was defined as positive if the largest deflection of the crackle waveform was upward. Crackle polarity was defined as negative if the largest deflection was downward. RESULTS: The majority of patients had predominantly positive polarity of inspiratory crackles (88% of patients) and predominantly negative polarity of expiratory crackles (83% of patients). Seventy one percent of all inspiratory crackles had positive polarity (the total number of inspiratory crackles examined was 8,249). Seventy five percent of all expiratory crackles had negative polarity (the total number of expiratory crackles examined was 3,485). Inspiratory crackle polarity was significantly different between CHF and IPF (p⬍0.0008). It was slightly different between Pn and IPF (p⬍0.02), but not statistically different between PN and CHF. There were no significant differences in expiratory crackle polarity among the groups.

PURPOSE: Obesity alters the functional relationship between the lung, chest wall and diaphragm resulting in abnormal pulmonary function. We have noted a flow volume loop pattern {tidal flow volume loop (tFVL) touches or cuts across the forced expiratory flow-volume loop (fvcFVL)} suggestive of expiratory flow limitation in non-obstructed obese patients. We wished to study the relationship between this abnormal flow volume pattern with pulmonary function data obtained from obese and normal weight individuals. METHODS: A retrospective review of pulmonary function test (PFT) data of 420 consecutive patients over a four-month period was done. Exclusion criteria were Ageⱕ18, Fev1/VC⬍70 or incomplete data. PFT data on 152 patients was analyzed. Two groups of patients were identified, those patients in whom the tFVL touched or cut the fvcFVL (Group1) and those in whom it did not (Group2). Unpaired t tests were used to look for differences between the two groups. RESULTS: Age and Body Mass Index (BMI) were significantly higher in Group 1. Forced Vital Capacity (FVC), Forced expiratory volume 1(FEV1), Fev1/FVC, Forced expiratory flow 25-75% (FEF25-75%) were significantly lower in Group 1. Peak Expiratory Flow (PEF) and Peak

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EXPIRATORY FLOW LIMITATION IN NON OBSTRUCTED OBESE PATIENTS Thomas S. Kaleekal, MBBS*; Tilottama Majumdar, MBBS; Elizabeth Guy, MD; Amir Sharafkhaneh, MD; Baylor College of Medicine, Houston, TX

Wednesday, October 27, 2004 Pulmonary Function Testing, continued Inspiratory Flow (PIF), Total Lung Capacity (TLC), Vital Capacity (VC), Inspiratory Capacity (IC) and Functional Residual Capacity (FRC) showed no significant difference. Expiratory reserve volume (ERV) was significantly lower while Residual Volume (RV) and RV/TLC were increased in Group 1 and approached significant values. Logistic regression analysis with abnormal flow volume loop as the dependent variable correlated significantly with age, BMI and ERV. A multivariate regression analysis with ERV as the continuous dependent variable strongly correlated with flow volume loop pattern, age and BMI. CONCLUSION: Obesity (BMI ⬎ 30) is independently associated with significant expiratory flow limitation due to subtle small airway dysfunction, detected by an abnormal flow volume loop pattern (tFVL touching or cutting across the fvcFVL) in the absence of clinical obstruction. CLINICAL IMPLICATIONS: This abnormal flow volume loop pattern may indicate ventilatory limitation in clinically non-obstructed obese patients.

MAXIMAL PARTIAL EXPIRATORY FLOW IS MORE SENSITIVE THAT MAXIMAL FULL EXPIRATORY FLOW AND FEV1 IN DETERMINING BRONCHODILATOR RESPONSE Amir Sharafkhaneh, MD*; Burton Dickey, MD; Nicola A. Hanania, MD; Baylor College of Medicine, Houston, TX PURPOSE: The maximal full expiratory maneuver measures expired volume (FEV1) and flow following deep inhalation. In contrast,a maximal partial expiratory maneuver expiration starts at lower lung volume thus avoiding the need for deep inhalation,which may alter the true effect of bronchodilators on expiratory flow by inducing bronchodilation or bronchoconstriction. We therefore hypothesize that maximal partial expiratory flow (MEFP) is a more sensitive measure of bronchodilator response than maximal full expiratory flow (MEFF) and FEV1. To test this hypothesis, we compared the change in expiratory flow measured by MEFP and MEFF in response to cumulative doses of inhaled albuterol. METHODS: This was an open-labeled study in which we enrolled 18 subjects (8 normal, 5 with stable asthma and 5 with stable COPD). Each subject underwent measurements of lung mechanics including inspiratory and expiratory lung resistance (Rli and Rle), lung volumes (TLC) and FEV1. In addition expiratory flows were measured at 30% of vital capacity using MEFP and MEFF (Vp30 and Vm30, respectively). Serial measurements were obtained; at baseline, 20 minutes following the administration of inhaled placebo and cumulative doses of albuterol (180, 360, and 540 micrograms). ANOVA was used to compare responses, a p ⬍ 0.05 was considered as statistically significant. RESULTS: FEV1, Rli, Rle, Vp30 and Vm30 improved in all subjects following bronchodilator administration (comparing baseline to maximum albuterol dose). However, only Vp30 was able to to identify changes at each level of bronchodilator administration (p ⬍ 0.05). CONCLUSION: Our data suggest that MEFP is more sensitive than MEFF and FEV1 in detecting expiratory flow improvement in response to cumulative doses of inhaled albuterol. CLINICAL IMPLICATIONS: MEFP provides a sensitive method to measure the bronchodilator response in patients with expiratory flow

THE EFFECT OF OBESITY ON DIFFUSING CAPACITY (DLCO) AND THE DIFFUSING CAPACITY ADJUSTED FOR ALVEOLAR VOLUME (DL/VA) Hikmat N. Dagher, MD*; Thaddeus Bartter, MD; Jonathan Kass, MD; Melvin R. Pratter, MD; Cooper University Hospital, Voorhees, NJ PURPOSE: To define the effects of obesity on DLCO and DL/VA. METHODS: We retrospectively reviewed our pulmonary function testing (PFT) data for overweight individuals, defined as a body mass index (BMI) of ⬎25, who underwent PFTs. We selected for overweight non-smoking individuals who had a total lung capacity (TLC) ⬎ 80% of predicted, FEV1/FVC ⬎ 70%, and DL/VA ⬎60% of predicted. Miller non-smoking predicted values were used. Hemoglobin corrections were not performed. Nonparametric parameters were compared using Kendall’s tau. RESULTS: Out of 10,590 PFTs performed between Feb., 1999 and Feb., 2004 PFTs, 477 met criteria. Data are in Table 1. The DLCO % predicted and DL/VA % predicted were significantly different, with a p ⬍ .001. DLCO was decreased and was not correlated with BMI. DL/VA, however, was correlated with BMI (r ⫽ .15, p ⬍ .001). CONCLUSION: This is the largest study of diffusion in overweight individuals of which we are aware. Our results contradict some of those from other studies. Our results suggest that, 1) When using predicted values, the DLCO will tend to be low in overweight individuals; 2) In contrast, the DL/VA equation is not as “distorted” by weight; and 3) BMI is positively correlated with DL/VA in this population. CLINICAL IMPLICATIONS: The goal of predicted values in testing is to be able to use variance from the norm to identify the effect of a disease process upon function. In overweight individuals, DL/VA may be more accurate than DLCO in separating normal from abnormal physiology.

n ⫽ 477 Age BMI, kg/m2 FVC, % pred. FEV1, % pred. TLC, % pred. RV, % pred. ERV, % pred. DLCO, % pred. DL/VA, % pred.

Mean

SD

Range

54 33 81

⫾ 17 ⫾6.5 ⫾ 14

87 93 103 41 79 101

⫾ 16 ⫾ 12 ⫾ 29 ⫾ 24 ⫾ 19 ⫾ 18

8-93 25-60 141129 40-155 80-149 35-293 5-157 28-128 39-163

DISCLOSURE: H.N. Dagher, None.

Thoracic Surgical Interventions 12:30 PM - 2:00 PM REPAIR OF PECTUS EXCAVATUM IN ADULTS USING THE MINIMALLY INVASIVE TECHNIQUE Andre Hebra, MD*; Jeffrey Jacobs, MD; Alexander Feliz, MD; Claudia B. Moore, PA; All Children’s Hospital, University of South Florida, St. Petersburg, FL PURPOSE: Minimally invasive surgery (MIS) for repair of Pectus Excavatum (PE) has been widely used for pediatric patients. However, its CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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DISCLOSURE: T.S. Kaleekal, None.

limitation. This measurement may be useful in determining the optimal bronchodilator dose in patients with asthma or COPD. DISCLOSURE: A. Sharafkhaneh, None.

Wednesday, October 27, 2004 Thoracic Surgical Interventions, continued application in adult patients has been limited. We reviewed the outcomes of 30 patients treated with MIS. METHODS: Data was compiled from a survey of pediatric surgeons and combined with the main author’s experience in treating adult patients with PE. Thirty subjects (age range: 18 - 32 years of age, mean: 23 years; 75% males) with PE were treated with the MIS. The main indication for surgery was cosmetic (80%). Retrospective analysis of outcomes was conducted on the patients operated by the main authors and combined with survey results. RESULTS: In 60% of cases the operative time was between one and two hours. Thoracic epidural was successfully utilized for postoperative pain management in 90% of patients. Two Lorenz pectus bars were necessary in 16% and bilateral stabilizers were used in 53% of patients. Complications included: Seroma (10%), bar displacement (6%), pneumothorax requiring tube thoracostomy (6%), superficial wound infection (3%), and stabilizer bar fracture (3%). Two patients required conversion to modified Ravitch repair. Patient satisfaction was rated as Excellent (50%), Good (36%), and Fair (14%). Less than 50% of patients achieved 100% correction of their deformity. CONCLUSION: The MIS can be used safely for repair of PE in adult patients. The complication rate appears to be similar to previously reported series of pediatric patients. Two bars may be necessary for optimal results in selected cases. Postoperative pain appears to be more pronounced and prolonged compared to younger patients. This preliminary report suggests that adults are less likely to achieve complete correction of the pectus deformity and many have residual asymmetry of the chest. The overall results do not appear to be as good as reported for younger patients. CLINICAL IMPLICATIONS: The repair of pectus excavatum in adult patients can be sucessfully accomplished using the minimally invasive technique originaly described for pediatric patients. DISCLOSURE: A. Hebra, None.

COMPARATIVE STUDY OF SUBXIPHOID VERSUS VIDEOTHORACOSCOPIC PERICARDIAL “WINDOW” Larry R. Kaiser, MD; Patrick K. O’Brien, MD*; John C. Kucharczuk, MD; M. B. Marshall, MD; Joseph S. Friedberg, MD; Joseph B. Shrager, MD; University of Pennsylvania School of Medicine, Philadelphia, PA PURPOSE: When operation is indicated for the management of pericardial effusion, options include subxiphoid drainage (SXD) and thoracoscopic pericardial window (TPW), but it remains undefined which of these approaches is optimal. TPW creates a true “window” into the pleural space (unlike SXD) and permits the performance of simultaneous intra-pleural procedures, but it requires intercostal incisions, doublelumen intubation, and unilateral pulmonary collapse. We retrospectively reviewed our experience with TPW and SXW at the University of Pennsylvania Health System from 1992 to 2003 to compare indications, hospital course, and outcomes. METHODS: Records were reviewed for pertinent clinical information, including pre-operative and intra-operative variables, procedural morbidity, and recurrence of effusion. Echocardiographic evidence of tamponade was defined as right chamber collapse. Recurrence was defined as an effusion on follow-up echo that was moderate or greater, or hemodynamically significant. RESULTS: Fifteen patients underwent TPW, 56 underwent SXW. Prior percutaneous drainage was performed in 19 (27%). Echocardiographic evidence of tamponade present in 8 of 11 TPW patients (73%) and 43 of 56 SXD patients (81%). Concomitant procedures were performed in 10 (67%) and 18 (32%) patients, respectively (p⫽0.020). Anesthesia time was longer for TPW [117.1 ⫾ 32.4 vs. 81.1 ⫾ 25.5 minutes (p⬍0.001)]. Procedural morbidity was higher among TPW patients [4 (27%) vs. 1 (2%) (p⫽0.006)]. Hospital mortality related primarily to co-morbid illness and tended to be higher in SXD patients [7 (13%) vs. 0 (0%) (p⫽0.332)]“. (i.e. 7 patients, not 8, and the percentage now 13%). Follow up was complete for 67 patients (94%). Recurrences occurred in 1 TPW patient (8%) and 5 SXW patients (10%) (p⫽1.000). CONCLUSION: TPW and SXD appear to be equally effective in controlling pericardial effusions. TPW was more likely to be used when concomitant intra-pleural procedures were required. Operative time and procedural morbidity were higher following TPW.

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CLINICAL IMPLICATIONS: Since it simpler, faster, and less morbid, SXD is the more appropriate approach in the management of pericardial effusion except possibly in cases where a concomitant intrapleural process needs to be addressed. DISCLOSURE: P.K. O’Brien, None.

VIDEOASSISTED THORACIC SURGERY (VATS) FOR THE MANAGEMENT OF SPONTANEUS AND RECURRENT PNEUMOTHORAX Erich Hecker, MD*; Gudrun Eberhardt, MD; Thomas Muley, PhD; Felix J. Herth, MD; Hendrik Dienemann, Prof.; Klinikum Bremen-Ost, Bremen, Germany PURPOSE: In surgical management of spontaneous pneumothorax, both first episode and recurrences, videoassisted thoracoscopy (VATS) has gained acceptance as the procedure of choice. METHODS: After VATS treatment for pneumothorax, patients were followed up by questionnaire to assess perioperative morbidity, incidence of recurrence, persistence of postoperative pain, and how far the patients were satisfied with the complete management. The questionnaire was sended to every patient and results will be completed at August 2004. RESULTS: 404 operations for idiopathic pneumothorax were performed between 06/1996 and 12/2002. Surgery included atypical parenchyma resection and mechanical abrasion of the parietal pleura in all cases. Median follow-up was 22 month. Surgery was performed in 294 male (14-76 y, average 31.6 y) and 110 female patients (age 13-81 y, average 32.0 y) for 216 primary episodes and 188 recurrent pneumothoraces. Mean operation time was 54.5 minutes. Conversion to open thoracotomy treatment was necessary in 5 patients (1.2%) because of intraoperative situs. 17 patients (4.2%) had perioperative complications (bleeding: n⫽8, parenchyma fistula through more than one day: n⫽9), surgical revision was performed in 21 cases (5.2%) (thoracotomy: n⫽1; VATS n⫽5, chest tube: n⫽14). Average hospitalization was 8.8 d (4 41d).After evaluation of the questionnaire (return 87.3 % for the operation period till 12/2000) reccurence ocurred in 4.8% in patients primarily treated first episodes, 7.1% treated with VATS for second episodes. 6.3% complained of persistent pain at rest (n⫽3) or on strain (n⫽8), location varied widely. 91% expressed to be satisfied with treatment, 9% complained for most diverse reasons. CONCLUSION: Surgical management by VATS both for primary spontaneous pneumothorax and recurrent episodes proves to be a suitable therapeutic modality with low perioperative morbidity. CLINICAL IMPLICATIONS: We recommend VATS treatment for every spontaneous pneumothorax, both primary and recurrent. DISCLOSURE: E. Hecker, None.

AMIODARONE FOR ATRIAL FIBRILLATION PROPHYLAXIS IN PATIENTS UNDERGOING ESOPHAGECTOMY Thomas Fabian, MD*; Dennis J. Rassias, MD; Mani A. Daneshmand, MD; Riivo Ilves, MD; Albany Medical College, Albany, NY PURPOSE: Atrial fibrillation (AF) is a common occurrence following all chest surgery. AF following esophagectomy occurs in a third of patients and is associated with increased morbidity and mortality. We evaluated the efficacy of oral amiodarone as prophylaxis of AF. Eight patients were treated in a prospective fashion with postoperative amiodarone and were compared with 16 historical controls that received no prophylaxis. METHODS: During a 34-month period (May 2001-March 2004) 34 patients underwent thoracoabdominal esophagectomy. Eight patients received prophylactic amiodarone 200mg BID via jejunostomy immediately postoperatively and continued until time of discharge. Sixteen patients underwent esophagectomy and did not receive amiodarone, these patients served as historical controls. Ten patients were excluded because of previous history of AF, supraventricular arrhythmias, pacemaker implantation, or inadequate documentation. Primary endpoints were incidence of AF and length of stay. Fisher’s exact test was used to analyze data. RESULTS: Both groups were comparable in age, sex, comorbidities, and procedure performed. A total of 6/24 (25%) patients developed AF postoperatively.. In the experimental group 1/8 (12.5 %) developed AF compared to 5/16 in the control group (31.2%, p⫽0.32). Major compliAbstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Thoracic Surgical Interventions, continued cations occurred in 1/8 (12.5%) of the experimental group and 4/16 (25%, p⫽0.89) in the control group. Average length of stay was 11.7 days in the experimental group vs. 17 days in the control group p⫽0.15. CONCLUSION: Low dose amiodarone is relatively safe following esophagectomy. Although the reduction of AF postoperatively in the experimental group was not statistically significant there is clearly a trend toward a lower occurrence and shorter length of stay. This pilot study supports the need for a randomized prospective investigation. CLINICAL IMPLICATIONS: AF is a common occurrence following esophagectomy. Low dose amiodarone postoperatively has been used as prophylaxis in cardiac surgery, pulmonary resections, and now following esophagectomy. Prevention of AF may be useful in reducing high morbidity and mortality rates. DISCLOSURE: T. Fabian, None.

TRACHEOBRONCHIAL STENTS IN SELECTED PATIENTS WITH BENIGN AIRWAY DISEASE Anthony Lemaire, MD*; William R. Burfeind, MD; Stafford S. Balderson, MA; David H. Harpole, MD; Thomas A. D’Amico, MD; Duke University Medical Center, Durham, NC

EARLY OPEN THORACOTOMY AND MEDIASTINOPLEURAL IRRIGATION IS EFFECTIVE FOR SEVERE DESCENDING NECROTIZING MEDIASTINITIS Takekazu Iwata, MD*; Yasuo Sekine, MD; Kiyoshi Shibuya, MD; Hidehisa Hoshino, MD; Kazuhiro Yasufuku, MD; Akira Iyoda, MD; Yukio Saito, MD; Toshikazu Yusa, MD; Mitsutoshi Shiba, MD; Toshihiko Iizasa, MD; Takehiko Fujisawa, MD; Department of Thoracic Surgery, Chiba University Graduate School, Chiba, Japan PURPOSE: Descending necrotizing mediastinitis (DNM) is a severe infection spreading from cervical region to mediastinal connective tissue. The mortality rates have been reported between 25 and 40 % in the literature. Since DNM is uncommon, few reports of large series (more than 10 cases) of patients with DNM have been published. The aim was to evaluate our treatment strategy for DNM by retrospective chart review. METHODS: Retrospective chart review was performed in 10 patients with DNM between 1991 and 2003. Mean age was 53.8 ⫾ 23.3 years (median 58, range 16-82). The causes of DNM were primary peritonsillar or parapharyngeal abscess in 5 patients, odontogenic abscess of postextraction in 3, cervical abscess of post-tracheostomy in 1 and unknown in 1 patient. In 9 cases, the abscess extended from cervical region to the lower mediastinum, while in another case the abscess localized in the upper mediastinum above carina. Immediately after the diagnosis of

PERSONAL PROCEDURE OF THORACO-MEDIASTINAL PLICATION FOR TREATMENT OF POST-PNEUMONECTOMY EMPYEMA Alexandru M. Botianu, MD, PhD*; Surgical Clinic no. 4 (Abdominal and General Thoracic Surger, Targu-Mures, Romania PURPOSE: This study investigates the use of a personal procedure of thoraco-mediastinal-plication in treatment of post-pneumonectomy empyema. METHODS: The procedure consists of thoracotomy above the empyema cavity, topographical bone removal of its wall preserving the first rib, incision of the pachypleura following a central vertical line, creation of parietal pachypleura flaps in front of the bronchial fistula by ladder-like incisions through the bed of resected ribs respecting the blood supply and innervation, scraping and repeated lavages of the empyema pouch, suture of the bronchial fistulas (4 different personal techniques), creation of a closed-circuit irrigation-aspiration system using two drains, closure of muscular planes and of the skin in a single layer. The “padding” of the parietal and visceral pleura is completely replaced by external fixation in order to avoid any foreign material; the subscapulary space is not drained. During the last years we also used plombage with muscular flaps from the neighbourhood of the cavity. RESULTS: The procedure has been used in 26 patients with empyema after pneumonectomy. In 3 patients we performed one-stage pneumonectomy ⫹ thoraco-mediastinal plication. We had a 7,7 postoperative mortality (2 patients) and 2 small residual cavities solved by a modified open-window procedure. Most patients required an average 3 weeks of post-operative hospitalisation, with no need of further care after discharge. CONCLUSION: We believe that this procedure has certain advantages, as it is safe and ensures a quick healing, which we consider very important in patients with pmeumonectomy for lung cancer. Compared with other types of thoracoplasty/thoraco-mediastinal plication is safer, faster and less mutilant. CLINICAL IMPLICATIONS: We present a surgical solution for a very difficult and challenging problem of modern thoracic surgery. DISCLOSURE: A.M. Botianu, None. COMPLEX SURGICAL AND MEDICAL TREATMENT FOR SECONDARY THORACIC ECHINOCOCCOSIS Alexandru M. Botianu, MD*; Surgical Clinic no. 4 (Abdominal and Thoracic Surgery), Targu-Mures, Romania PURPOSE: Secondary thoracic echinococcosis is a rare condition due to the availability of both early diagnosis and effective treatment. This study analyses tactical and technical aspect of the complex treatment of this severe complication of hydatid disease. METHODS: During the last 20 years we have treated a total number of 12 patients with thoracic secondary echinococcosis. Primary location of hydatid cyst was pulmonary in 9 cases and hepatic in 3 cases (transdiaphragmatic migration). Most patients required complex procedures – multiple cystectomies associated with resection and decortication (8), CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Two hundred and twenty six tracheobronchial stents were placed in 173 patients for benign (N⫽33) and malignant (N⫽140) disease from January 1,1997 to May 31,2003. Although tracheobronchial stents are widely established in malignant disease as a palliative measure, their use in benign disease is controversial. The concern of long-term complications has been a deterrent to their use. We sought to identiy the benefits and risks of airway stents in selected patients with benign disease. METHODS: We retrospectively analyzed all tracheobronchial stents placed in patients aged 50⫾18 years old with benign disease from January 1, 1997 to May 31,2003. The stents placed were self-expandable metal (N⫽48) and rigid (N⫽6). The patient’s diagnosis included anastomotic stricture s/p lung transplantation(N⫽12), tracheomalacia(N⫽10), bronchomalacia(N⫽2), sarcoid(N⫽2), trauma(N⫽1), respiratory failure(N⫽2), tracheal stenosis(N⫽2), and bronchial stenosis(N⫽2). RESULTS: Eleven complications were identified in 54 stents placed in 33 patients with benign disease and included excessive granulation tissue(N⫽5), restenosis of stent(N⫽5), and migration of stent(N⫽1). The mean follow-up period was 604 days (range, 0-2673days). The complications required intervention including stent dilations(N⫽5), stent laser debridement(N⫽3), and stent removal(N⫽3). CONCLUSION: Tracheobronchial stents offer minimally invasive therapy for selected patients with benign disease with low complication risk. The major impediment is excessive granulation tissue formation and restenosis of stent often requiring intervention. CLINICAL IMPLICATIONS: Airway stents provide symptomatic improvement to patients with benign airway disease, and function as a bridge until more definitive treatment can be offered. DISCLOSURE: A. Lemaire, None.

DNM, broad spectrum antibiotics were administrated empirically and surgical treatments consisting of cervical drainage, thoracotomy with radical surgical debridement of the mediastinum with complete excision of the tissue necrosis, decortication and irrigation were performed in all cases. Postoperatively, mediastinopleural irrigation with saline was performed once or twice a day until culture of pleural effusion became negative. RESULTS: The mean duration of chest tube detention was 26.7⫾17.0 days, and their mean hospital stay was 62.3⫾33.9 days. Five patients suffered from severe complications including septic shock, acute respiratory distress syndrome, disseminated intravascular coagulation and panperitonitis due to duodenal perforation. The outcome was favorable in 8 patients. In patients with severe complications, two patients, who were older than 75 and had diabetes, died of multiple organ failure due to septic shock. (The mortality rate was 20 %). CONCLUSION: Our treatment strategy for severe DNM was feasible and reduced the mortality rate. CLINICAL IMPLICATIONS: Early detection of DNM and immediate thoracotomy and irrigation of mediastinum and thoracic cavity should be recommended. DISCLOSURE: T. Iwata, None.

Wednesday, October 27, 2004 Thoracic Surgical Interventions, continued decortication (2) and cure of hepatic lesion (3). In order to prevent hydatid recurrence we used pleural lavage with alcohol (3 patients) or formaldehide (1 patient), associated with postoperative treatment with mebendasole. RESULTS: We had one postoperative death through sepsis in a patient admitted to our unit in cardio-respiratory arrest. There was a significant morbidity, with 4 patients requiring re-operation: one drainage of a subphrenic abscess, one decortication and suture of a bronchial fistula, one thoracopleuroplasty and one wound debridation. We had one late lumbar recidive, solved through a lumbar approach. CONCLUSION: Secondary thoracic echinococcosis is a severe complication of hydatid disease due to the extent of lesions and associated infection, which requires complex surgical procedures and involves a high morbidity. CLINICAL IMPLICATIONS: Due to the complexity of the disease there is no clear standard for surgical approach of secondary thoracic echinococcosis and each patient must be very carefully analysed. This paper is also an argue for early diagnosis and treatment of hydatid disease. DISCLOSURE: A.M. Botianu, None. PULMONARY RESECTION FOR PARENCHYMAL INFECTION Norman J. Snow, MD*; Jacques Kpodonu, MD; Cimenga Tshibaka, MD; Malek G. Massad, MD; Alexander S. Geha, MD; University of Illinois at Chicago, Chicago, IL PURPOSE: Pulmonary resection for active infection has ben considered hazardous. However, the lung is often the source of the septic response and its attendant risks; therefore resection of the affected lung is often necessary and therapeutic. We saught to evaluate the risks and benefits of pulmonary parenchymal resection for infection. METHODS: We retrospectively reviewed the records of 39 patients, ages 16-68 who underwent pulmonary resection for an infectious process. Demographic, bacteriologic, radiologic and comorbid disease factors were analyzed for risks, perioperative variables and outcomes. We utlized chi square tables for categorical values and T tests between groups and Fisher’s exaxt t test. MS Excel 97 was used to copy the data to a STRATA file for analysis. RESULTS: 39 patients underwent 27 lobectomies, 7 pneumonectomies, 4 local excisions and one VATS wedge. Four patients died (10.2%). Factors influencing complications (bleeding, reoperation, prolonged air leak, reoperation empyema, respiratory failure and persistent sepsis) included preoperative weight loss, operative blood loss and transfusion, and active preoperative sepsis as a surgical indication. Factors influencing mortality include blood loss exceeding 1000cc, with trends toward significance of extent of resection (pneumonectomy). Sepsis and organ failure caused all deaths. Postoperative empyema occurred only twice, but postoperative sepsis comoplicated the recovery in 18% of patients. CONCLUSION: Active sepsis adversely affected outcomes following parenchymal resection of pulmonary infection. Efforts to control the sepsis and earlier surgical intervention may improve survival and limit the extend of resection. Semielective resections appears safe and effective. CLINICAL IMPLICATIONS: Earlier intervention for patients requiring surgical excision of parenchymal infectious processes may improve outcome. DISCLOSURE: N.J. Snow, None.

chest drainage was 11 days (range 2-67) and median hospital stay was 15 days (range 3-133). Positive pleural culture occurred at a median of 7 days (1-14). One patient was diabetic, 5 were on steroids and 11 were hypoalbuminemic pre-operatively. Thirteen patients were febrile when pleural fluid was sent. All patients had elevated white counts and/or pyrexia, except one patient on steroids who was neither. Empirical antibiotic treatment was initiated in 15 patients (with fever or elevated white counts). This was modified according to culture results when appropriate. The other 5 patients received culture-directed antibiotics after these results became available. Microscopy (with Gram staining) only detected organisms in 50% of culture positives. Most common organisms cultured were S. epidermidis (7) followed by Pseudomonas spp. (4) and E. faecalis (4). Of the 30 organisms isolated 15 were skin flora, 8 bowel commensals and 7 respiratory tract organisms. CONCLUSION: Pre-operative steroid administration and poor nutritional status (reflected by hypoalbuminemia) seem to be significant risk factors for post-operative pleural sepsis when chest drains remain in situ. These patients warrant close clinical surveillance. CLINICAL IMPLICATIONS: Pleural fluid culture is an investigation with a low yield if sent routinely. It is indicated in patients with pyrexia and/or neutrophilia. Microscopy is unreliable for predicting positive cultures. DISCLOSURE: L. Tang, None.

EFFICACY AND SAFETY OF MEDICAL THORACOSCOPIC LUNG BIOPSY OBTAINED BY STAPLER DEVICE Stylianos A. Michaelides, MD*; Nikolaos Anastasiou, MD, PhD; Dimitris Zachilas, MD; Nikolaos Thalassinos, MD; Department of Thoracic Medicine, A. Fleming General Hospital, Athens, Greece PURPOSE: To evaluate the diagnostic yield and the quality of biopsy in patients who underwent medical thoracoscopic lung biopsy (MTLB) using stapler device under regional anaesthesia, and neuroleptic analgesia for the evaluation of peripheral mass or diffuse interstitial lung disease. METHODS: From 6/2000-3/2004, 23 patients (16 males and 7 females) of mean age 58.5 yrs, (range 28-75 years) underwent MTLB. Biopsy samples were taken with the use of a stapler device. Anaesthesia was achieved with the use of midazolam and fentanyl. Intercostal block was performed in all patients with the use of ropivacain. RESULTS: Mean diameter of the biopsy specimens from stapler device was 3.2x1.7x0.9cm (mean volume: 3.61ccm). All lung biopsies were conclusive and diagnosis was established. Mean duration of the procedure was 30 min (15-35 min). There were no intraoperative or postoperative deaths or major complications. Successful analgesia was achieved in all patients. CONCLUSION: Stapler specimens received by MTLB have a high diagnostic accuracy in patients with peripheral tumors and diffuse interstitial lung disease. MTLB has also been shown to be a quick and safe diagnostic procedure for the evaluation of these cases. CLINICAL IMPLICATIONS: This method is highly diagnostic and does not seem to have significant complications.

HISTOLOGICAL ANALYSIS Malignancies

VALUE OF PLEURAL FLUID CULTURE POST THORACIC SURGERY Lydia Tang, MBBS*; John Pilling, BMBS; Caroline Parkin, BSc; Michael Dusmet, MD; Royal Brompton Hospital, London, United Kingdom PURPOSE: To investigate factors pertaining to positive microbiological cultures of pleural fluid post-operatively. METHODS: Six hundred fifty eight patients underwent surgery for non-infectious conditions over a 24 month period in a 3 thoracic surgeon unit; 224 (34%) had pleural fluid cultured. Twenty patients (3%) had positive pleural fluid cultures. Retrospective chart review recording length of hospital stay, duration of chest drainage, diagnosis, operation, factors predisposing to and clinical signs of infection, organisms cultured and antibiotic administration. RESULTS: Of the 20 patients with positive pleural fluid culture, 15 underwent pulmonary resection (10 lobectomies, 4 sublobar); 5 talc pleurodeses. Sixteen had underlying malignancies, 4 benign pathology. There were 14 thoracotomies and 6 VATS procedures. Median time of

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Lymphoma Non differential Metastatic adenocarcinoma Adenocarcinoma

Non Malignancies

2 2 1

Sarcoidosis NSIP UIP

1 1 7

3

BOOP DIP Pulmonary infarct Pneumonia

2 2 1 1

DISCLOSURE: S.A. Michaelides, None.


Wednesday, October 27, 2004 Thoracic Surgical Interventions, continued DESCENDING MEDIASTINAL INFECTION - PRESENTATIONS AND MANAGEMENT Alex Wohler, MD*; Marc Margolis, MBChB; Barbara Tempesta, CRNP; Matthew Facktor, MD; David Salter, MD; Nevin Katz, MD; Farid Gharagozloo, MD; Georgetown University Medical Center, Washington, DC

PURPOSE: Management of pneumothorax has traditionally been tube thoracostomy and -20 cmH20 suction. Our objective was to determine if underwater seal (WS) in iatrogenic and spontaneous pneumothoraces was safe and efficacious. METHODS: An IRB-approved, prospective, randomized trial enrolled patients with iatrogenic or spontaneous pneumothorax treated with small caliber tube thoracostomy (9fr). Large air leaks (⬎4/7) were treated with immediate operative intervention and excluded. For the rest, initial management was brief (1-2 hours) -20 cmH20 suction followed by chest radiography and randomization into one of three groups: -20 cmH20 suction, -10 cmH20 suction or WS. Tubes were discontinued at 48h if there was no pneumothorax and no air leak. Air leaks and recurrent pneumothoraces persisting for 5 days underwent pleurodesis. RESULTS: Thirty patients were enrolled from April of 2001 to September 2003, with none requiring immediate surgery. Seven were randomized to -20 cmH20, 12 to -10 cmH20 and 11 to WS. One patient had a persistent pneumothorax on WS and crossed over to -10 cmH20. The majority (N⫽18, 62%) of chest tubes were removed 48h after placement: 4/7 (57%) of -20cmH20, 9/13 (69%) of -10 cmH20, and 5/10 (50%) of WS (p⫽NS). Seven patients (23%) required pleurodesis: 2/7 (29%) in -20 cmH20, 3/13 (23%) in -10 cmH20, and 2/10 (20%) in WS (p⫽NS). CONCLUSION: The use of early WS is safe for the treatment of iatrogenic and spontaneous pneumothorax. It achieved similar frequencies of early chest tube removal and avoidance of surgery compared with traditional management strategy. CLINICAL IMPLICATIONS: Treatment of iatrogenic and spontaneous pneumothoraces may effectively incorporate the use of smallcaliber catheters and underwater seal. DISCLOSURE: J.M. Lyons, None.

PURPOSE: Descending mediastinal infections are usually associated with acute fulminant processes. Origins of infection include odontogenic, pharyngeal or cervical infections. Disease spreads into the mediastinum via fascial planes. Delays in diagnosis and management are frequent and may be associated with poorer outcomes. Ideal management varies according to acuity of presentation. METHODS: A retrospective review of all patients treated by thoracic surgeons at two teaching hospitals over an 18 month period was performed. The group was analysed for referral pattern, etiology of infection, clinical presentation, management approaches and outcome. RESULTS: Over the study period, 4 patients were treated surgically for descending mediastinal infections. All patients were referred after initial treatment with intravenous antibiotics at outside facilities resulted in progression of disease or failure of management. There were 3 males and 1 female. One patient presented with a fulminant course, one presented with an acute but stable course, and two patients were symptomatic but clinically stable. The two acute presentations resulted from presumed odontogenic infections. The other two patients had underlying pharyngeal infections. Those patients with odontogenic sources required more aggressive surgical debridement due to greater mediastinal involvement. These two patients underwent extensive mediastinal debridement via thoracotomies. The two patients with underlying pharyngeal infections were managed with mediastinal drainage via cervical approaches. There were no deaths. Patients were discharged on postoperative days 5, 6, 7, and 49 in the most acute case. All patients were discharged on intravenous or oral antibiotics. No patients had recurence of their disease process. CONCLUSION: Descending mediastinal infections may not present as acute descending mediastinitis. However, once the mediastinum is involved in the disease process, conservative management with intravenous antibiotics will fail. A high index of suspicion is needed in patients with the underlying etiological processes who fail to improve with conservative care. Surgical management is necessary but varies according to severity of disease. CLINICAL IMPLICATIONS: Appropriate initial management of descending mediastinal infections will decrease morbidity and mortality including the use of less invasive approaches when appropriate. DISCLOSURE: A. Wohler, None.

PULMONARY ALVEOLOCAPILLARY MEMBRANE PORE DIAMETER DILATATION AFTER LUNG RESECTION IN RATS Ilan Bar, MD*; Armand Molek, MD; Rafi Miler, MD; Assaf Harofeh Medical Center, Zerifin, Israel PURPOSE: Post-pneumonectomy pulmonary edema (PPE) is a wellknown postoperative complication, occurring in 8-10% of cases, with a high mortality rate of 60-80%. The cause of PPE has been extensively investigated and is widely believed to be multifactorial. An alteration in permeability and dilatation of alveolocapillary membrane pore diameter may contribute to the pathophysiology of PPE. The aim of this study was to determine dilatation of pore diameter after pulmonary resection. METHODS: Pulmonary resection was performed in twenty laboratory rats. Two hours prior to the pulmonectomy, fluorescein-isothiocyanate dextran 70,000 was injected. The concentration of dextran in the remaining and resected (control group) lung tissue was determined by the fluorescence method. RESULTS: The concentration of dextran was significantly higher in the remaining lung tissue, mean value 0.046, as compared to the control group (0.0278), p⫽0.001. CONCLUSION: Dextran is larger than alveolocapillary membrane pore diameter. Therefore the significant increase in the concentration of dextran in the remaining lung tissue after pulmonary resection indicates alterations in membrane permeability, an increase in alveolocapillary membrane pore diameter, and a possible contribution to the pathophysiology of PPE. CLINICAL IMPLICATIONS: If pulmonary alveolocapillary membrane pore diameter increases after resection, thus contributing to PPE, the treatment should be focused on these pores, and prostaglandins should be administered instead of diuretics. DISCLOSURE: I. Bar, None.

THORACOSCOPIC DRAINAGE OF EMPYEMA: AN IMPROVED SURGICAL APPROACH; PERSONAL EXPERIENCE WITH TWENTY SIX CONSECUTIVE CASES Carlos M. Chavez, MD*; Valley Regional Medical Center, Brownsville, TX PURPOSE: Thoracic empyema remains a challenge in medical and surgical management. Morbidity and mortality are still significant following open surgical drainage, due to the extent of the procedure. Thoracoscopy has provided a less invasive and effective modality for the surgical management of empyema. METHODS: Two database of patients who had undergone Thoracoscopy by one thoracic surgeon at two private community hospitals between June 1992 and June 2003 was analyzed as to age, sex and side of occurrence of empyema including comorbidities and bacteriological findings. Computerizedaxial tomography of the chest was done in each patient preoperatively. Routine cultures and sensitivities were obtained in all cases as well as cultures for TB and fungus. End results were compiled with clinical evaluation, Chest X-Rays and wound status. RESULTS: Two hundred twenty eight thoracoscopic procedures were performed by a single operator. From these twenty six (11.4%) were done for treatment of empyema. General Endotracheal anesthesia was used in all, and three ports were placed according to the location of the effusion. A 10mm. zero degree angle scope was utilized for visualization of the cavity. The ages were from 17 to 90 years. Seventeen were males (65.3%) and in sixteen (61.5%) the empyema occurred on the left side. There was only one death and was in a 90-year-old patient with severe COPD (3.84%). There were two tuberculous empyemas, but in many the cultures CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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A PROSPECTIVE, RANDOMIZED TRIAL OF UNDERWATER SEAL FOR SPONTANEOUS AND IATROGENIC PNEUMOTHORAX Jefferson M. Lyons, MD*; Micheal F. Reed, MD; Jeffrey A. Neu, MSN-FNP; Fred A. Luchette, MD; John A. Howington, MD; University of Cincinnati, Cincinnati, OH

Wednesday, October 27, 2004 Thoracic Surgical Interventions, continued were negative for TB or fungus or other bacteria as a result of the previous antibiotic therapy. (See below for the organisms cultured). CONCLUSION: Extensive debridment was feasible in all patients breaking loculations which are responsible for re-accumulation of fluid following simple tube thoracostomy. Partial decortication was possible in most of them. Chest tube drainage was used post-operatively. One or two chest tubes were utilized with an average time of drainage of 10 days. CLINICAL IMPLICATIONS: Minimal impairment of pulmonary mechanics with VATS as compared to formal thoracotomy allow for a more quickly recovery with reduced morbidity. DISCLOSURE: C.M. Chavez, None. METASTATIC NON-LUNG CANCER CARCINOMAS AND SARCOMAS TREATED WITH PHOTODYNAMIC THERAPY – A PHASE II STUDY Evelio Rodriguez, MD; Joseph S. Friedberg, MD; Shamus R. Carr, MD; Joshua P. Cantor, MD*; Dianna Stripp; James P. Stevenson, MD; Timothy Zhu, PhD; Debbie Smith, RN; Melissa Culligan, RN; Andrea Dimofte, PhD; Eli Glatstein, MD; Stephen M. Hahn, MD; Thomas Jefferson University, Philadelphia, PA PURPOSE: Malignant pleural metastasis occurs in 15-20% of patients with metastatic disease. The median survival for these patients is 4 months, with a 1-year survival of less than 15%. In an attempt to decrease local recurrence and increase overall survival, surgical debulking and intraoperative hemithoracic photodynamic therapy (PDT) was performed on patients with metastatic pleural malignancies. The objectives were to examine local control and effect on survival. METHODS: 10 patients (17-74 years old) with metastatic cancer (2 ovarian, 5 sarcoma, 1 thymoma, 1 pheochromocytoma, 1 breast) isolated to one pleural space were enrolled (9/10 bulk disease, 1 effusion alone). 9/10 were proven unresponsive to conventional therapy. Patients received porfirmer sodium (2mg/kg) 24 hours prior to surgery, underwent resection of all gross tumor and received intraoperative hemithoracic illumination with 30 J/cm2 630 nm light (9 thoracotomies, 1 thoracoscopy). Local recurrence was assessed with CT scans every three months. RESULTS: Due to intraoperative death, 2/5 patients with sarcoma did not receive PDT. One patient with sarcoma is alive at 2.0 months. The remaining 2/5 patients with sarcoma survived 1.9 and 6.5 months, both dying with local recurrences. The patient with pheochromocytoma is alive at 21.0 months postoperatively, but diagnosed with local recurrence at 20.0 months. The patient with thymoma is alive without recurrence at 20.4 months. The patient with metastatic breast cancer is alive at 14.7 months, but with recent brain metastases. One patient with ovarian cancer died after 7.7 months with locally recurrent disease and the other, treated thoracoscopically, was alive with abdominal recurrence at 25.5 months (then lost to follow-up). There were no significant PDT related complications. CONCLUSION: In select situations, combining surgery and PDT for patients with secondary cancers involving the pleura may be effective in controlling local recurrence and increasing overall survival. Patients with sarcomas appear to be the most difficult to treat and the least likely to derive significant benefit. CLINICAL IMPLICATIONS: PDT may be an effective adjuvant therapy to decrease local recurrence of pleural metastases. DISCLOSURE: J.P. Cantor, Photofrin

N-oxide, are pharmacologically active. Patients with COPD often receive warfarin for control of cardiovascular co-morbidity. This study determined whether pharmacodynamic or pharmacokinetic interactions exist between oral roflumilast and oral warfarin. METHODS: In this double-blind, randomized, placebo-controlled crossover study, healthy adult male subjects (N⫽24; age 19 to 45 years) received either oral roflumilast 500␮g or placebo once-daily for 12 consecutive days. All subjects were given each a single oral dose of warfarin sodium 25mg 14 days prior to roflumilast or placebo intake and on Day 8 concomitant with roflumilast or placebo. Washout periods between consecutive roflumilast or placebo treatments were 10 days. Serial blood samples were taken the day before and after warfarin administration. Prothrombin time, coagulation factor VII activity, and plasma concentrations of roflumilast, roflumilast N-oxide, and R- and S-warfarin were determined. Point estimates and 90% confidence intervals (CI) were used to evaluate pharmacokinetic equivalence between roflumilast co-administered with warfarin (Test, T) and placebo coadministered with warfarin (Reference, R). Safety parameters were monitored. RESULTS: There was no effect of roflumilast on warfarin pharmacodynamics. Point estimate ratios (T/R) for AUC(0-120h) for prothrombin time and factor VII activity were 0.99 (90%CI: 0.92, 1.07) and 1.02 (90%CI: 1.00, 1.05), respectively. Similarly, roflumilast did not affect the pharmacokinetics of racemic warfarin. Equivalence ratios for AUC(0-¥) were 1.02 (90%CI: 1.00, 1.05) and 1.03 (90%CI: 1.01, 1.05) for R-warfarin and S-warfarin, respectively. Likewise, roflumilast had no effect on Cmax, tmax, or t1/2 of warfarin. The pharmacokinetics of roflumilast or roflumilast N-oxide were not influenced by the single concomitant warfarin administration. Co-administration of roflumilast and warfarin was well tolerated. CONCLUSION: Oral, once-daily roflumilast 500␮g can be safely co-administered together with warfarin without altering the pharmacodynamic or pharmacokinetic profile of warfarin. CLINICAL IMPLICATIONS: In addition to roflumilast, patients may receive warfarin therapy without dose adjustments. DISCLOSURE: A. Huennemeyer, None.

ORAL, ONCE-DAILY ROFLUMILAST AND ITS ACTIVE N-OXIDE METABOLITE EXHIBIT DOSE-PROPORTIONAL PHARMACOKINETICS BETWEEN 250⌴G AND 500⌴G Andreas Huennemeyer, MD*; K. Zech, MD; T.D. Bethke, MD; G. Boehmer, MD; C.H. Gleiter, MD; ALTANA Pharma AG, Konstanz, Germany

PURPOSE: Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory activity that may be beneficial in the treatment of COPD. Roflumilast and its metabolite, roflumilast

PURPOSE: Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory activity, which may provide effective treatment of chronic obstructive pulmonary disease (COPD) and asthma. Both, roflumilast and its major metabolite, roflumilast N-oxide, are pharmacologically active. This study evaluated the pharmacokinetics of both, roflumilast and roflumilast N-oxide, and safety following single and repeated once-daily doses of oral roflumilast in healthy subjects. METHODS: This open-label, randomized, 2-period crossover study consisted of two treatment periods of 12 days each, separated by a 10- to 14-day washout period. During each treatment period, 19 healthy male subjects received oral roflumilast 250␮g or 500␮g once daily on Day 1 (single dose) and Days 5 to 12 (repeated dosing). Blood samples were collected on Days 1 and 12 of each treatment period. Adverse events, vital signs, and ECG were monitored throughout the study. RESULTS: Roflumilast and roflumilast N-oxide exhibited dose-proportional pharmacokinetics after single and repeated once-daily dosing with roflumilast 250␮g and 500␮g. After repeated dosing with roflumilast 250␮g and 500␮g (in steady-state), geometric mean AUCs of roflumilast were 17.0␮gxh/L and 33.7␮gxh/L, respectively; for roflumilast N-oxide, the respective geometric mean AUCs were 179.8␮gxh/L and 375.4␮gxh/L. Similarly, Cmax of roflumilast and roflumilast N-oxide showed a dose-proportional response. Repeated administration of either dose showed no relevant influence on the geometric means of the terminal half-life (t1/2) of roflumilast (roflumilast 250␮g: 16.0h; 500␮g: 18.0h) and roflumilast N-oxide (roflumilast 250␮g: 23.1h; 500␮g: 21.2h). Roflumilast was well tolerated. The majority of adverse events was mild to moderate in intensity, transient in duration and were not of any clinical concern. CONCLUSION: Roflumilast and roflumilast N-oxide showed doseproportional pharmacokinetics after single and repeated oral administra-

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COPD: Standard and Novel Therapies 12:30 PM - 2:00 PM ROFLUMILAST SHOWS NO PHARMACOKINETIC INTERACTION WITH WARFARIN IN HEALTHY SUBJECTS Andreas Huennemeyer, MD*; K. Zech, MD; J. Terblanche´ , MD; L. Duursema, MD; T.D. Bethke, MD; L. Venter, MD; ALTANA Pharma AG, Konstanz, Germany

Wednesday, October 27, 2004 COPD: Standard and Novel Therapies, continued tion of once-daily roflumilast 250␮g and 500␮g. Both roflumilast doses were well tolerated. CLINICAL IMPLICATIONS: Roflumilast given at 250␮g and 500␮g exhibits dose-proportional pharmacokinetics. The long terminal half-life of roflumilast and its active N-oxide metabolite supports the convenient once-daily dosing for optimal anti-inflammatory therapy. DISCLOSURE: A. Huennemeyer, None.

LONG-TERM SAFETY OF ROFLUMILAST IN THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE T.D. Bethke, MD; E.D. Bateman, MD; J.A. van Noord, MD*; H. Steffen, MD; C. Schmid-Wirlitsch, MD; D. Bredenbroeker, MD; M. Timar, MD; Atrium Medisch Centrum, Heerlen, the Netherlands

PURSED-LIPS BREATHING DECREASES DYSPNEA AND IMPROVES HEALTH-RELATED QUALITY OF LIFE IN 4-GROUP RANDOMIZED, CONTROLLED STUDY Margaret Nield, PhD*; Guy Soo Hoo, MD, MPH; Janice Roper, PhD, RN; Silverio Santiago, MD; VA, Greater Los Angeles, West LA VA, Los Angeles, CA PURPOSE: Chronic dyspnea is a distressing symptom that reduces health-related quality of life (HQOL). Breathing strategies such as pursed-lips breathing (PLB) are frequently encouraged by rehabilitation staff for dyspnea relief. However, contradictory evidence exists for breathing strategy efficacy. The study objective was to compare 3 methods for teaching a breathing strategy of prolonged, gentle exhalation on dyspnea relief and improved HQOL in patients with severe COPD. METHODS: 53 subjects (mean⫾sd age ⫽ 66⫾9 years, forced expiratory volume 1sec (FEV1)/ forced vital capacity ⫽ 47⫾11, FEV1% pred ⫽ 38 ⫾ 14, Body Mass Index (BMI) ⫽ 26⫾6, inspiratory muscle strength (PImax) ⫽ 71⫾22 cm H20) were randomized to either: 1) control; 2) inspiratory muscle training (IMT) at 30% PImax; 3) expiratory muscle training (EMT) at 10% PEmax; or 4) structured PLB with oxygen saturation level as feedback. Dyspnea measures of visual analogue scale, modified Borg, University of California, San Diego Shortness of Breath and HQOL measure of SF-36 were done at baseline, end of 4 weekly visits to the research laboratory, and 3 months. ANCOVA with planned post hoc analyses was used to explore differences among and between groups.

THE DETRIMENTAL EFFECTS OF HEAT ON FORMOTEROL DELIVERY Gregory T. Chu, MD*; Lynda M. Proctor, PharmD; Michael Gump, RPh; Allen R. Thomas, MD; Richard A. Robbins, MD; Carl T. Hayden Veterans Affairs Medical Center, Phoenix, AZ PURPOSE: The advent of centralized pharmacies has resulted in increased delivery of medications by mail. The climate of the Southwest combined with mailbox drug deposition poses the unique situation of prolonged drug exposure to potentially damaging heat. Based on anecdotal reports of formoterol degradation in this setting, our study examines the effect of heat on the formoterol capsule as well as its effects on drug delivery via inhalation. METHODS: Formoterol capsules in original blister packaging were heated at 70° C (158° F) for four hours. Capsules were removed from packaging and a vacuum setup was then used to dispense the formoterol into a filter tube using the inhalation technique and device provided by the manufacturer. Weights of the filter tube pre- and post-dispensation were obtained to calculate simulated drug delivery. These measurements were compared with those obtained from capsules which had not been exposed to heating. RESULTS: The change in filter weights from capsules that underwent heating were significantly less than those obtained from capsules that had not been heated (5.5 ⫾ 2.7 mg vs 12.7 ⫾ 1.5 mg, p⬍0.05). In addition, visual inspection of heated capsules revealed gross distortion of capsule as well as visible clumping of formoterol. Temperatures less than 70° C resulted in no clumping, whereas temperatures greater than 70° C resulted in increased clumping and capsule distortion. CONCLUSION: There is a significant decline in the amount of formoterol obtained through inhalation following simulated conditions inside a mailbox in Arizona heat. CLINICAL IMPLICATIONS: Current methods of medication delivery should be reexamined, and patients should be cautioned regarding other situations where medications may be exposed to temperatures equal to or greater than 70° C, such as car trunks and interiors. DISCLOSURE: G.T. Chu, None. EFFECT OF SYSTEMIC CORTICOSTEROIDS ON MECHANICALLY VENTILATED PATIENTS WITH ACUTE EXACERBATION OF COPD Ahmad M. Rashid, MBBS*; Ashok Fulambarker, MD, FCCP; Mark E. Cohen, PhD; Bhairvi Patel, PharmD; Vineet Sood, MD; Rosalind Franklin University of Medicine and Science, North Chicago, IL PURPOSE: Systemic corticosteroids (SCS) have been shown to be beneficial in Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). The beneficial effect of SCS in mechanically ventilated patients with AECOPD has not been thoroughly investigated. Objective: The goal of this study was to determine whether SCS have an effect on the duration of mechanical ventilation (MV) in patients with AECOPD. METHODS: We reviewed the records of 112 mechanically ventilated patients with AECOPD admitted to our Intensive Care Unit over five years. Patients with congestive heart failure, sepsis, cardiac arrest, stroke, terminal malignancies or “Do Not Resuscitate” orders were excluded. Patients receiving SCS one month prior to admission were also excluded. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: COPD is an inflammatory airway disease with progressive decline in lung function and health-related quality of life. Current treatments palliate clinical symptoms rather than target COPD pathophysiology. Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory activity, which may be beneficial in the treatment of COPD. The present study investigated long-term safety of roflumilast in COPD patients for up to 52 weeks. METHODS: After a 2-week single-blind, placebo run-in period, patients (postbronchodilator FEV1 35-75%; FEV1/FVC £ 70 predicted) received roflumilast 250 ␮g, or 500 ␮g or placebo for 26 weeks. Per-protocol patients (N⫽397) continued on to the open-label extension and received roflumilast 500 ␮g for another 26 weeks. Safety was assessed by monitoring adverse events (AEs), vital signs, ECG, and laboratory testing. RESULTS: Long-term treatment with roflumilast was well tolerated. The frequency of patients experiencing AEs was 49% during the doubleblind period (same frequency for all treatment groups), and 41% during the open-label extension. In both treatment periods, most AEs were mild to moderate in intensity and transient in duration; ⬎90% of all AEs were assessed as unrelated or unlikely related to study drug. During the open-label extension, AEs associated with the digestive, cardiovascular, or nervous systems were reported by few (⬍2%) of patients. Ten patients (2.5%) experienced 13 AEs that were assessed as likely or definitely related to study drug, and of these, 3 cases led to study discontinuation. No significant changes in laboratory parameters or vital signs occurred and there was no evidence of roflumilast-related effects on the QTc interval. CONCLUSION: One year of treatment with oral once-daily roflumilast was associated with a low overall incidence of drug-related, PDE4 inhibitor side effects. CLINICAL IMPLICATIONS: Roflumilast is an oral, well-tolerated anti-inflammatory agent with potential use in the long-term therapy of COPD. DISCLOSURE: J. van Noord, None.

RESULTS: Group effect was present for the modified Borg after 6-minute walk distance (6MWD) (p ⫽ 0.016) and SF-36 domains of mental health (p ⫽ 0.037) with covariate PImax and physical function (0.023) with covariate BMI. Dyspnea was significantly different (p ⫽ 0.015) for the PLB group after 6MWD, but not IMT or EMT, as compared to the control group. CONCLUSION: A significant decrease in dyspnea occurred with the PLB group after 6MWD at 3 months. The only group with sustained improvement in dyspnea, mental health and physical function occurred for the PLB group. CLINICAL IMPLICATIONS: Decreased dyspnea after activity and improved HQOL may result with regular use of PLB for those with COPD. DISCLOSURE: M. Nield, None.

Wednesday, October 27, 2004 COPD: Standard and Novel Therapies, continued 20 patients met the selected inclusion and exclusion criteria. 10 patients received SCS during the duration of MV. Both groups were matched for age, weight, sex, weight, body mass index, vasopressor and oxygen requirements in the first 24 hours and co-morbidities. All patients followed the standard ICU MV and weaning protocols. Primary end point was duration of MV and secondary end point was duration of ICU stay. RESULTS: The results of our study are summarized in the following table. The considerable differences in mean values between steroid and non-steroid groups were the result of a single steroid-group subject with an extremely long stay (MV and ICU both 95 days). When this outlier was eliminated, the remaining 9 steroid subjects had a mean of 5.0 MV days (SD⫽3.74) and a mean ICU stay of 7.56 days (SD⫽5.08), both values being less than comparable non-steroid group means. CONCLUSION: SCS do not seem to benefit mechanically ventilated patients with AECOPD. Larger well designed prospective studies are needed to confirm the findings of this study. CLINICAL IMPLICATIONS: More research is needed to define a role for SCS in mechanicaly ventilated patients with AECOPD.

Mean Duration of MV (days) No Steroids(n⫽10) Steroids(n⫽10) ICU Stay (days) No Steroids(n⫽10) Steroids(n⫽10)

SD

6.8 14.0

t-test 3.46 28.68

12.0 16.3

6.43 28.06

P-values Mann-

Whitney

0.441

0.353

0.642

0.165

DISCLOSURE: A.M. Rashid, None.

PATIENTS WITH OBSTRUCTIVE LUNG DISEASE PREFER RESPIMAT® SOFT MIST(TM) INHALER TO PMDI Richard V. Hodder, MD*; Wolfgang Schurmann, MD; Petra Moroni; Michael Barczok, MD; University of Ottawa, Ottawa, ON, Canada

COMPARISON OF TREATMENT DELIVERY METHODS WITH COMBINATION ALBUTEROL AND IPRATROPIUM MDI VERSUS (1)PREMIXED UD ALBUTEROL WITH IPRATROPIUM AND MDI VERSUS (2)CONCOMITANT USE OF NEBULIZER MORNING AND NIGHT WITH MDI DURING DAY AND EVENING Donald Tashkin, MD*; Richard ZuWallack, MD; Joe W. Ramsdell, MD; Gerald Klein, MD; Imtiaz Chaudry, PhD; Laura Wong, PharmD; Shoshana S. Colman, PhD; David Geffen School of Medicine, UCLA, Los Angeles, CA PURPOSE: Therapy with a beta2-agonist/anticholinergic combination via nebulization or MDI is commonly used to treat COPD. This study compared the use of fixed combination products with different modes of administration and the concomitant use of the two administration methods in the management of COPD. METHODS: Approximately 120 patients were enrolled in a 12-week, single-blinded study randomized across 15 sites into one of three parallel treatment arms: (1) albuterol 3.0mg/ ipratropium 500mcg premixed UD solution (alb/ipra UD) via nebulizer 4 times daily or (2) alb/ipra MDI 4 times daily, or (3) alb/ipra UD via nebulizer in the morning and at bedtime with concomitant use of alb/ipra MDI afternoon and evening. The MDI group is compared to both the premixed UD solution and the concomitant group. The primary outcome is Quality of Life (QOL) measured by the St. George Respiratory Questionnaire (SGRQ) at baseline, 6-weeks, and 12-weeks. Secondary efficacy measures include 1-hr post-bronchodilator FEV1, peak flow, patient symptom scores, use of rescue medication, and a validated Treatment Satisfaction Questionnaire. RESULTS: Preliminary results from 20 patients who completed 6-weeks of treatment indicate that there was an 8-point difference between the mean SGRQ scores for 10 patients using the concomitant nebulizer/MDI treatment compared to 10 patients who used the MDI treatment, in favor of concomitant therapy. The use of rescue medication was also reduced in this group. Confirmation of the preliminary results and its statistical significance will be reported at the meeting. CONCLUSION: These preliminary data suggest that a therapeutic regimen of concomitant nebulizer/MDI can lead to meaningful QOL improvements in COPD patients. CLINICAL IMPLICATIONS: The QOL of COPD patients treated with alb/ipra MDI may be enhanced by concomitant use of premixed UD nebulized alb/ipra in the morning and night. DISCLOSURE: D. Tashkin, Study is sponsored by Dey, LP

PURPOSE: Respimat® Soft Mist(TM) Inhaler (SMI) is a novel, propellant-free device which produces a slow-moving, long-lasting aerosol that is easy to inhale and has excellent deposition efficiency. Satisfaction with and preference for Respimat® SMI was assessed in three randomised, open-label studies. METHODS: In study A (Canada; n⫽129; mean age 66.1), COPD patients received ipratropium bromide (IB; 20 or 40 ug) or placebo qid via Respimat® SMI for 6 months; in study B, (Germany; n⫽47; mean age 63.7) COPD patients received IB/fenoterol (10/25 or 20/50 ug) or placebo qid via Respimat® SMI for 12 weeks. In study C (Germany; n⫽245; mean age 55.3), COPD, asthma or mixed disease patients received, tid or qid, IB/fenoterol 20/50 ug via Respimat® SMI or 40/100 ug via pressurised metered dose inhaler (pMDI) for 7 weeks each in a crossover design. Questionnaires on device satisfaction, preference and willingness to continue were completed after each treatment period or at the end of the study. RESULTS: Most patients in studies A and B (94 and 85%, respectively) said they would prefer to use Respimat® SMI over their current inhaler. Willingness to continue using Respimat® SMI was high (A, 80%; B, 72%), as was overall satisfaction with Respimat® SMI, with 74% (A) and 64% (B) giving ratings of 9 or 10 (10 ⫽ “extremely satisfied”). Of the 201 patients in study C who completed an assessment of both devices and expressed a preference, 162 (81%) preferred Respimat® SMI (p⬍0.001). Preference was unaffected by age or co-existing conditions that might adversely affect inhaler handling. Willingness-to-continue scores were significantly higher for Respimat® SMI than pMDI (p⬍0.001). Mean scores for 13 of the 15 items in the satisfaction questionnaire were higher for Respimat® SMI. CONCLUSION: In these 3 studies, patients were highly satisfied with Respimat® SMI and the vast majority preferred this device to the pMDI. CLINICAL IMPLICATIONS: Adherence to inhaler therapy and thus disease control may be enhanced when patients are offered an inhaler device that they prefer over the pMDI. DISCLOSURE: R.V. Hodder, None.

PURPOSE: This retrospective analysis compares the onset of relief from COPD symptoms after initiating therapy with either Advair Diskus 250/50 BID or ipratropium/albuterol 36/206mcg QID via MDI (IB/ALB). METHODS: Patient-recorded diary data was evaluated from two randomized, double-blind, parallel group trials of COPD patients (n⫽726) randomized to FSC or IB/ALB for 8 weeks. Patients were ⱖ40 years of age with symptomatic COPD, had a FEV1/FVC ⬍0.7 and a FEV1 40 to 70% of predicted normal (baseline mean⫽43%), and did not use inhaled or oral corticosteriods for at least 30 days prior to randomization. Patients recorded a daily diary with AM peak expiratory flow (PEF), nighttime awakenings requiring albuterol, and day and sleep symptom scores using a Visual Analogue Scale (VAS). Data from treatment day 1 to day 7 were compared between treatment groups to evaluate the onset of COPD symptom relief. RESULTS: Overall, symptom improvement was noted in both treatment groups, however, patients treated with Advair 250/50 consistently indicated early and significantly greater improvements in symptoms compared with IB/ALB. These patients perceived improvements following the significant increase in mean AM PEF starting at day 1 for Advair 250/50 (17.7 L/min) compared with IB/ALB (5.4 L/min) (p⬍0.001). The improvements seen early were sustained throughout the 8-week study period. CONCLUSION: Patients perceive significantly greater improvement in COPD symptoms as early as day 1 after initiating treatment with Advair 250/50 BID compared to IB/ALB 36/206mcg QID.

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A COMPARISON OF PATIENT PERCEIVED IMPROVEMENT IN SYMPTOMS AFTER INITIATING THERAPY WITH EITHER ADVAIR DISKUS (FLUTICASONE PROPIONATE/SALMETEROL) 250/50 OR IPRATROPIUM/ALBUTEROL Katharine Knobil, MD*; Kunal Merchant, PhD; Chris Kalberg, PhD; Amanda Emmett, MS; Michael Cicale, MD; GlaxoSmithKline, Research Triangle Park, NC

Wednesday, October 27, 2004 COPD: Standard and Novel Therapies, continued CLINICAL IMPLICATIONS: Use of an inhaled corticosteroid and long acting beta-agonist together provides patient perceived improvement in COPD symptoms within one day of starting treatment. This may encourage patient compliance and therefore lead to improved efficacy.

Changes in FEV1 Responses From Day 1 to Week 8

Peak FEV1 change from baseline, mL FEV1AUC0-6, L-hr FEV1AUC0-4 , L-hr FEV1AUC0-2 , L-hr

FSC (n⫽303)

IB/ALB (N⫽299)

51.5 (18.3%)

-17.7 (-5.4%)

0.33(22.7%) 0.25(24.6%) 0.15(26.7%)

-0.22(-14.2%) -0.11(-10.9%) -0.03(-5.9%)

CLINICAL IMPLICATIONS: Use of a beta-agonist in combination with an inhaled corticosteroid maintains or enhances bronchodilator efficacy, while a loss of bronchodilator efficacy is observed when combined with an anticholinergic. DISCLOSURE: K. Knobil, None. EFFICACY OF ADVAIR DISKUS 250/50 (FLUTICASONE PROPIONATE/SALMETEROL) OR IPRATROPIUM/ALBUTEROL IN PATIENTS WITH COPD ASSOCIATED WITH CHRONIC BRONCHITIS AND/OR EMPHYSEMA Frank C. Sciurba, MD*; Chris Kalberg, PhD; Amanda Emmett, MS; Kunal Merchant, PhD; Christy Brown, PharmD; Katharine Knobil, MD; University of Pittsburgh, Pittsburgh, PA PURPOSE: Advair 250/50 via Diskus in COPD has been studied primarily in patients with COPD associated with chronic bronchitis (CB).

Mean Change (s.e.) From Baseline at Endpoint

DISCLOSURE: K. Knobil, None.

CB ⫹ Emphysema

MAINTENANCE OF BRONCHODILATOR RESPONSE FOR ADVAIR DISKUS 250/50 (FLUTICASONE PROPIONATE/SALMETEROL) BUT NOT IPRATROPIUM/ALBUTEROL IN PATIENTS WITH COPD Katharine Knobil, MD*; Chris Kalberg, PhD; Kunal Merchant, PhD; Amanda Emmett, MS; Michael Cicale, MD; GlaxoSmithKline, Raleigh, NC PURPOSE: The bronchodilator response for Advair 250/50 was compared with ipratropium/albuterol (IB/ALB) via metered-dose inhaler. This comparison was performed to determine if these treatments differed in the maintenance of bronchodilator efficacy following repeat dosing in COPD patients. METHODS: A post-hoc analysis of FEV1 data from two randomized, double-blind, parallel-group multicenter trials comparing Advair 250/50 BID and IB/ALB 36/206mcg QID in patients with COPD (n⫽602) was performed. Six hour serial spirometry was performed after the first (Day 1) and last (Week 8) dose of study medication. Spirometry was conducted pre-dose and at 0.5, 1.0, 2.0, 4.0, and 6.0hr post-dose. Mean bronchodilator response at Week 8 was compared to the Day 1 response for all patients who completed the study. RESULTS: The mean FEV1AUC0-6hr for Advair 250/50 significantly increased from 1.06L-hr at Day 1 to 1.39L-hr at Week 8 (p⬍0.001). For IB/ALB, the mean FEV1AUC0-6hr significantly decreased from 1.16L-hr to 0.95L-hr (p⬍0.001). The FVC AUC0-6hr for Advair 250/50 increased from 1.69L-hr to 1.91L-hr (p⬍0.027) compared with a decrease from 2.03L-hr to 1.69L-hr with IB/ALB (p⬍0.001). The Week 8 FEV1 and FVC AUC0-6 values for Advair 250/50 were significantly greater than those for IB/ALB (p⫽0.027), while Day 1 values were not significantly different. Changes in FEV1 responses from Day 1 to Week 8 are shown below. At individual time points over the 6hr, mean increases in serial FEV1 values for Advair 250/50 from Day 1 to Week 8 ranged from 35 to 83mL compared with decreases of –55 to -8mL for IB/ALB. CONCLUSION: After 8 weeks of treatment, a significant increase in bronchodilator response was observed with Advair 250/50 but not IB/ALB in patients with COPD.

Change in FEV1 From Day 1 to Week 8

Peak FEV1 change from baseline, mL FEV1AUC0-6, L-hr FEV1AUC0-4 , L-hr FEV1AUC0-2 , L-hr

FSC (n⫽303)

IB/ALB (N⫽299)

51.5 (18.3%)

-17.7 (-5.4%)

0.33(22.7%) 0.25(24.6%) 0.15(26.7%)

-0.22(-14.2%) -0.11(-10.9%) -0.03(-5.9%)

Predose 132.6 (16.8)* FEV1 (mL) 6hr Serial 0.36(0.084)* FEV1 AUC (L-hr) (Week 8–Day 1) AM PEF 36.2 (3.9)* (L/ min) Predose 160.6 (25.6)* Forced Vital Capacity (FVC) 6hr Serial 0.27(0.138)* FVC AUC (L-hr) (Week 8–Day 1) Dyspnea 2.8 (0.2)* Score (TDI) Daytime -51.6 (5.5)* Symptom Score (0-400 Scale) % 26.2 (3.5)* Symptom-Free Nights % 35.5 (3.1)* Rescue-Free Days

IB/ALB (n⫽192)

Advair 250/ 50 (n⫽142)

-1.8 (15.4) 93.6 (20.8)*

-0.14(0.70)

3.6 (3.0)

IB/ALB (n⫽156) -4.9 (15.9)

0.30(0.093)* -0.30(0.077)

36.9 (6.0)*

18.6 (25.4) 135.5 (33.0)*

7.7 (4.0)

15.6 (29.9)

-0.34(0.119) 0.16(0.149)* -0.35(0.146)

1.4 (0.2)

-24.3 (4.9)

2.4 (0.3)*

-48.5 (6.1)

1.3 (0.3)

-44.0 (5.3)

6.3 (2.7)

21.7 (3.9)*

11.7 (3.1)

28.0 (3.0)

36.3 (3.9)*

25.3 (3.4)

*p⬍0.047 for Advair 250/50 vs IB/ALB within subgroup CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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Advair 250/50 (n⫽209)

Emphysema

Wednesday, October 27, 2004 COPD: Standard and Novel Therapies, continued This post hoc analysis evaluated treatment effects in patients with CB ⫹ emphysema or emphysema alone. METHODS: Two multicenter, randomized, double-blind studies comparing the efficacy and safety of Advair 250/50 BID with ipratropium/ albuterol 36/206 mcg QID (IB/ALB) over 8 weeks. Patients were identified by study investigators as having COPD associated with CB, emphysema, or both. RESULTS: Patients had similar mean baseline characteristics, including age (63-66 years), FEV1 (1.24-1.33 L; 42-44% predicted), FEV1/FVC ratio (0.50-0.52) and reversibility to albuterol (16.6-18.4%). After 8 weeks of treatment, patients with emphysema had a lower response in predose FEV1 to Advair 250/50. For Advair 250/50, all other efficacy parameters were similar regardless of COPD type. The responses to IB/ALB were more variable between disease types. CONCLUSION: Patients with emphysema generally had the same response to Advair 250/50 as did those with CB or mixed disease, with the exception of a small difference in predose FEV1. CLINICAL IMPLICATIONS: These data show that Advair and IB/ALB are efficacious regardless of type of COPD; Advair 250/50 provided greater efficacy in both groups compared with IB/ALB. DISCLOSURE: F.C. Sciurba, None.

ASSESSMENT OF IN VITRO DELIVERED DOSE OF FORMOTEROL VIA A NEW MULTI-DOSE DRY POWDER INHALER: RELIABLE DELIVERY OVER A RANGE OF CLINICALLY RELEVANT INSPIRATORY FLOW RATES D. Singh, PhD; P. Gilchrist, PhD; C. Niederlander, PhD; B. Haeberlin, PhD; U. Yegen, MD*; G. Geba, MD, MPH; Novartis Pharmaceuticals Corp., E. Hanover, NJ PURPOSE: Developing a reliable multiple-dose dry powder inhaler (MDDPI) that can be adapted by patients would potentially improve dose delivery by use of the correct technique and dosing compliance. Adequate inspiratory flow rate (IFR) is required for optimal delivery of drugs formulated in dry powder. This study assessed the peak inspiratory flow rates (PIFR) of patients with asthma and chronic obstructive pulmonary disease (COPD) using a novel MDDPI (ForadilR CertihalerTM) to determine the effect of IFR on expected drug delivery. METHODS: In vivo and in vitro evaluations were performed. PIFR was assessed in children (5-19 yrs; n⫽42) and adults (20-76 yrs; n⫽41) with mild-severe asthma, and in adults with moderate-severe COPD (FEV1⬍60% predicted; 59-84 yrs; n⫽13) using an inhalation profile recorder. The highest of three successive inhalations was recorded. Delivered dose (DD) and fine particle fraction (FPF) were determined. Aerodynamic particle size distribution was assessed using an Anderson Cascade Impactor. RESULTS: Mean (range) PIFRs in L/min were 63 (44-79), 70 (56-95), 63 (45-80) for children, adolescents and adults with asthma and 61 (51-78) for COPD patients. The release threshold for breath actuation was approximately 35 L/minute. Testing over inspiratory flow rates of 30-90 L/min showed that the in vitro delivered dose (DD) and fine particle fraction (FPF) were consistent over the entire range. DD in the range of observed PIFR of 40-90 L/min was 98.8-106.8% of an asthma label claim. Aerodynamic particle size distribution was marginally affected by flow rates. There was also little flow rate dependence of the FPF over clinically relevant ranges of IFR. CONCLUSION: In vitro delivery characteristics of ForadilR CerthalerTM over clinically relevant flow rates were consistent and reproducible. CLINICAL IMPLICATIONS: These findings suggest that delivery of formoterol via a novel MDDPI is reliable over a range of clinically relevant flow rates in patients with mild-moderate asthma and moderatesevere COPD. DISCLOSURE: U. Yegen, Novartis Pharmaceuticals AG and SkyePharma

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EFFICACY OF ADVAIR DISKUS 250/50 (FLUTICASONE PROPIONATE/SALMETEROL) IN PATIENTS PREVIOUSLY NAı¨VE TO COPD MAINTENANCE THERAPY Antonio R. Anzueto, MD*; Wendy Sense, MS; Julie Yates, BS; Christy Brown, PharmD; Katharine Knobil, MD; VA Medical Center, San Antonio, TX PURPOSE: Determining when to begin therapy with a long-acting bronchodilator and inhaled corticosteroid in patients with COPD is challenging since no clinical trials have been conducted to specifically answer this question. This analysis was conducted to evaluate the efficacy of a long-acting bronchodilator, an anti-inflammatory agent, or the two together compared with placebo in patients previously not receiving maintenance COPD medications. METHODS: Data was obtained from a 24-week clinical trial comparing twice daily Advair 250/50 with fluticasone propionate (FP) 250mcg, salmeterol 50mcg or placebo in patients with COPD. Patients were at least 40 years of age, had at least a 20 pack year history of smoking, and had symptoms of chronic bronchitis. RESULTS: Three hundred seventy-eight patients were previously naı¨ve to COPD therapy. The patients had similar mean baseline characteristics, including age (61-63 years), FEV1 (1.28-1.38L; 43-45% predicted), Baseline Dyspnea Index (BDI; 5.7-6.6) and reversibility to albuterol (19.9-22.0%). CONCLUSION: Advair 250/50 BID provided significant improvements in lung function when used as first line maintenance therapy in patients naı¨ve to COPD maintenance medications. Improvements were also seen in TDI and CRDQ though they did not reach statistical significance. CLINICAL IMPLICATIONS: These data, demonstrating the efficacy of initial maintenance therapy with Advair 250/50 in patients previously naı¨ve to COPD maintenance therapy, are consistent with efficacy results seen in the overall study population (Hanania, Chest 2003).

Mean Change From Advair Baseline at Endpoint 250/50 (SEM) (n⫽91) Pre-dose FEV1, mL 2-Hour Post-dose FEV1, mL Transition Dyspnea Index (TDI) Chronic Respiratory Disease Questionnaire (CRDQ)

171 (29.9)* 280 (32.0)† 2.0 (0.37) 12.1 (1.85)

FP (n⫽101)

Salmeterol (n⫽95)

109 (26.7)

86 (27.2)

149 (26.7)

209 (27.6)

1.9 (0.31)

1.3 (0.33)

13.0 (1.57)

7.0 (1.87)

Placebo (n⫽91) 15 (23.0) 57 (24.0) 1.3 (0.38) 7.9 (1.81)

*p⬍0.044 Advair vs Placebo, salmeterol; †p⬍0.0068 Advair vs Placebo, FP DISCLOSURE: A.R. Anzueto, None.

Asthma Evaluation 12:30 PM - 2:00 PM THE OPINION OF IRANIAN ASTHMATICS REGARDING THE EFFECT OF FOOD AND DIET ON ASTHMA ACTIVITY Amir Soltani Abhari, MD*; Shaghayegh Kaidi Majd, MD; Sari Medical School, Sari, Iran PURPOSE: Experience has shown that Iranians deeply believe that food modifies asthma activity. To evaluate this experience and it’s determining factors, we conducted this study.


Wednesday, October 27, 2004 Asthma Evaluation, continued

ELECTROLYTE DISTURBANCE IN ACUTE ASTHMA Keng Leong Tan, MBBS, FCCP*; Shakina Rauff, MBBS; Stephanie Fook-Chong, MSc; Philip Eng, MBBS, FCCP; Singapore General Hospital, Singapore, Singapore PURPOSE: Electrolyte disturbances in acute asthma may be due to many factors, although the underlying mechanisms remain unknown. The aim of our study was to determine the prevalence of electrolyte disturbance in patients admitted with acute asthma to our institution and to examine the association between electrolyte disturbance and the length of stay. METHODS: A retrospective, observational, hospital-based case-series study was carried out. The casenotes of 150 admissions for acute asthma were reviewed retrospectively. The initial serum electrolyte levels (sodium, potassium, magnesium, calcium and phosphate), the initial and current medications and the length of stay of each admission were noted. Statistical analysis was performed using Statistical Package for Social Sciences version 10.0.5. RESULTS: Electrolyte disturbance was present in 45.3% of the admissions. Among these, 70.6% had one electrolyte disturbance, 25% had 2 electrolyte disturbances and 4.4% had 3 electrolyte disturbances. Electrolyte disturbance was not significantly associated with an increased length of stay of the admissions. Logistic regression analysis showed significant association between steroid therapy and hypokalaemia (p⫽0.046), and between steroid therapy and the number of electrolyte disturbances (p⫽0.005). There was no significant association between beta2-agonist therapy and electrolyte disturbance. CONCLUSION: Electrolyte disturbance was common among admissions presenting with acute asthma. Electrolyte disturbance was not associated with increased length of stay. CLINICAL IMPLICATIONS: The high prevalence of electrolyte disturbance serves to highlight the importance of maintenance of electrolyte balance that is emphasised in the supportive treatment of acute asthma. DISCLOSURE: K. Tan, None.

point is scored in a range of 0-6 with the overall score expressed as the average of all questions. While this provides useful information, we propose scoring the questionnaire differently, looking at the objective versus the subjective scores. We believe this will predict a population of “poor perceivers” or patients who unreliably judge the severity of their asthma. METHODS: A retrospective chart review of patient records from our Asthma Clinic. Patients included had ICD 9 codes for asthma and were over the age of 18. Data was abstraced from the Juniper QOL questionnaire looking at the difference between the average score on the 6 subjective questions and the objective (spirometry)score. RESULTS: Of 100 charts reviewed, 97 had completed QOL questionnaires. Subjective scores were greater than objective scores by more than one data point in 28 (28.9%) of patients. Subjective and objective scores were matched within one data point in 23 (23.7%) of patients. Subjective scores were lower than objective scores by more than one data point in 46 (47%) of patients. CONCLUSION: This adjusted QOL scoring reveals that the majority of asthma patients’ perception of dyspnea does not correlate with their spirometric data. CLINICAL IMPLICATIONS: Patients with poor perception of dyspnea need further education to better judge the severity of their asthma. DISCLOSURE: R.L. Shriver, None.

USE OF HYPERTONIC SALINE IN BRONCHOPROVOCATION FOR THE DIAGNOSIS OF BRONCHIAL ASTHMA Abdullah A. Mamun, MD*; Mostafizur Rahman, FRCP; NIDCH, Dhaka, Bangladesh PURPOSE: To find out a simple ,chief, standard & easily available agent for bronchoprovocatiuon & also to determine the provocating dose of hypertonic saline , which will reduce at least 20% of FEV1 in bronchial asthma patient. METHODS: A prospective case control study was carried out among 50 patients with bronchial asthma and 50 normal healthy control at Asthma center in NIDCH, Bangladesh. Hypertonic saline of different concentration in doubling doses(1.8% , 3.6%, 7.2% ), sequentially from lower to higher concentration was inhaled to both group by nebulizer and the test was terminated when drop of at least 20% FEV1 had occurred. Patients were selected according to prefixed inclusion & exclusion criteria. Structured questioneer was filled-up by each patient. Written consent was taken from every patient & control after proper explanation about the procedure & its outcome. RESULTS: In the control group M/F ratio was 1.27:1,age ranged from 11 years to 50 years and of 5 different occupations (student, service holder, businessman, housewife and worker). In patient group M:F was 1.38:1, age range from 11 to 50 years and 5 different occupation was same as control. There were no statistically significant differences between the two groups regarding age, sex and occupation. In control, graded amount of hypertonic saline (1.8%, 3.6%, 7.2%) was given by nebulizer inhalation. None of them showed fall of FEV1 significantly (20%). But in patient group, with similar concentration of hypertonic saline inhalation, there was highly significant fall in FEV1, chi- square X2 test showed highly significant value, X2 ⫽75.42 and P⬍ 0.001. CONCLUSION: Hypertonic saline induced bronchoprovocation is actually very safe,simple & cheap. So the people of third world countries can afford this test in minimum cost. Provcative dose of Hypertonic saline is 7.2% (20% fall of FEV1). CLINICAL IMPLICATIONS: For the diagnosis of cough variant asthma & also in the suspected cases of bronchial asthma, we can performed this test confidently. DISCLOSURE: A.A. Mamun, None.

THE ADJUSTED QUALITY OF LIFE SCORE CORRELATES WITH POOR PERCEPTION OF DYSPNEA IN THE ADULT ASTHMA POPULATION Rebecca L. Shriver, MD*; Rita Mangold, RN; Steve Krantz, PhD; University of Missouri-Kansas City School of Medicine, Kansas City, MO

INHALATION PERFORMANCE INDEX IN ASTHMATICS INSTRUCTED BY VARIOUS HEALTH CARE PROVIDERS Hans Lee, MD; Robert Fleming, MD; Vasilios Sierros, MD; Raymond Khan, MD*; New York Hospital and Medical Center of Queens, Richmond Hill, NY

PURPOSE: The Juniper Quality of Life (QOL) questionnaire is the standard used for assessing dyspnea in asthma patients. It consists of 7 questions, 6 subjective and one objective (spirometry)in nature. Each data

PURPOSE: To assess the efficacy of medication delivery via MDI and Diskus in asthmatics instructed by different educators and to evaluate technique after months of training. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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METHODS: 120 consecutive adult asthmatics (50 male, 70 female; 77% city and 23% village residents; 29% illiterate, 36% below high-school diploma, and 35% high-school diploma and university educations) filled a questionnaire containing these questions: 1-Do they believe that diet modifies asthma activity? 2-What kinds of foods are responsible for their attacks? 3-Does fasting (to avoid drinking and eating for 12-17 hours) have any effect on their asthma? RESULTS: 110 (92%) believed that some foods aggravate their asthma. 85% mentioned their personal experience and 15% physicians advice as the source of this idea. This belief was stronger in older than 40 years (P⬍0.05), but unrelated to gender,level of education and place of living. Foods mostly named were: Pickles and sour taste (77% of answers), spice and pepper (68%), fried foods (68%), melon (61%), butter and fat (50%), garlic (36%), and onion (30%). 51% believed that fasting has no effect on their disease, 28% mentioned some kind of relief and 21% aggravation by fasting. CONCLUSION: Most our patients believe that diet has an effect on their disease. Personal experience is the main source of their idea. This belief is not related to level of education, gender,and to place of living, but is more prevalent in older patients. Most of them denied any major effect of fasting on asthma. CLINICAL IMPLICATIONS: Most Iranian asthmatics avoid some kinds of foods. This may result in inappropriate nutrition, and depletion of some necessary nutrients. This is especially important for young children that suffer from asthma. Experimental studies are needed to confirm the effect of diet on asthma, and if proved otherwise, educational programs are needed for patients and physicians. DISCLOSURE: A. Soltani Abhari, None.

Wednesday, October 27, 2004 Asthma Evaluation, continued METHODS: 102 consecutive patients admitted to an adult medical service with the diagnosis of bronchial asthma were entered into a prospective study to grade medication technique with MDI and/or Diskus and instruction source (pulmonologist, internist). The patients were scored on an Inhalation Performance Index (IPI): a set of 9 (discus) or 10 (MDI) pre-set criteria used by interviewers. 58 patients were divided into 4 groups and followed in clinic every 2 months for 10 months. Each visit patients received instructions on technique from either a pulmonologist/ fellow, internist/resident, nurse or no one. IPIs were reevaluated at the end of 10 months. RESULTS: Pulmonologist trained IPI for MDI 6.28/10 (62.8%) vs. 7.07/9(78%) for Diakus. Internist trained IPI for MDI 5.9/10(59%) vs. 6.6/9 (73%) for Diskus. 10-month follow-up group: pulmonologist/fellow trained IPIs were MDI 8.17/10 (81.7%) vs. 7.43/9 (82.6%) for Diskus. Internist/resident trained IPIs were MDI 7.82/10 (78.2%) vs. 7.23/9 (80.2%) for Diskus. The Nurse group IPIs were MDI 7.68/10 (76.8%) vs. 6.78/9 (75.3%) for Diskus. The non-taught group IPIs for MDI and Diskus were 5.84/10 (58.4%) and 5.86/9 (65.1%) respectively. The number of emergency visit and admission for asthma in the follow-up patients were 11 (23.9%) and 6 (13%) respectively, while non-follow-up group had 4 (40%) and 3 (30%) respectively. CONCLUSION: The Diskus users had a higher mean IPI score regardless of instruction source. Pulmonologist trained IPIs were better compared to internist or nurse trained groups. With proper instruction and close follow-up improved IPI scores were obtained. Increased IPI translated into fewer ER visits and hospitalization. Thus, proper use of MDI/Diskus can be achieved with persistent training and may improve asthma stability. CLINICAL IMPLICATIONS: Better technique would enhance treatment efficacy and reduce both ER visits and hospitalization. This will greatly decrease the overall cost of asthma management and improve quality of life for asthmatics. DISCLOSURE: R. Khan, None.

IMPACT OF INNOVATIVE MODEL OF PRIMARY CARE-CENTERED ASTHMA DISEASE MANAGEMENT PROGRAM ON PERSISTENT ASTHMA William F. Bria, MD*; Vivian Knieper; University of Michigan, Ann Arbor, MI PURPOSE: Asthma Disease Management Programs (ADMP) have been demonstrated to improve asthma symptom control and decrease the need for hospitalizations, ER visits and days out of work/school. However availability of ADMP in primary care settings has been limited due to costs and available practitioner time.This is a report of a collaborative model of Family Physician (FP) directed ADMP employing an asthma educator acting as the agent for the FP. METHODS: 25 patients (average age 47 yrs (range 18-60 yrs), F/M ratio 4:1) with moderate persistent asthma (NAEPP guidelines) were enrolled in an ADMP including the development of an asthma written care plan (WCP) codeveloped with the patients FP, and including audit of the plan by an asthma pulmonary specialist (See Diagram). Baseline information of asthma control and healthcare resource utilization (hospitalizations, ER visits etc) were obtained by questionnaire. Patient education was delivered both by the asthma educator and the FP during the course of routine office visits. Followup data was collected by phone contact. RESULTS: Patients received one in-person contact from the AE and 3 phone contacts for further education reinforcement during the 6 month followup period. Patients experienced an average of 1.2 hospitalizations and 2.8 ER visits in the 12 months prior to the ADMP intervention. At 6 months post intervention, none of the 25 study patients required either hospitalization nor ER care. Urgent office visits also decreased from an average of 6/patient to 3 visits. All patient reported significant improvement in asthma control post ADMP. Using regional average charges for ER and hospital visits for asthma the average cost savings is estimated at $12,000 per patient. CONCLUSION: We conclude that a structured ADMP can be delivered in a primary care setting employing an AE, with asthma specialist audit, resulting in improvements in healthcare resource utilization and patient reported asthma control. CLINICAL IMPLICATIONS: Primary Care delivered ADMP can be effectively accomplished with the aid of an AE to create a information interchange between patient, primary care provider and specialist.

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DISCLOSURE: W.F. Bria, None. IMPACT OF THE ASTHMA MORBIDITY USING THE NATIONAL GUIDELINES IN NUEVA ESPARTA, VENEZUELA Guillermo J. Isturiz, MD*; Rodrigo Ordaz, MD; Miguel Palenque, MD; Lorenzo Rodriguez, MD; Garcia Alexis, MD; Gur Levy, MD; FUNDASNE, Nueva Esparta, Venezuela PURPOSE: The prevalence of asthma in Venezuela is high (1), an approximate rate of 3,562 x 100,000 people (2), With the intention to impact the morbidity from asthma, we decided to apply the National Guidelines (3) in one of the regions of greater prevalence (Nueva Esparta, 30% according to the ISAAC statistics) (1) and very high index of morbidity (2), and began to apply said program throughout the state maintaining a permanent supply of medicines (Salbutamol, oral corticosteroids, Beclometasone, and spacers) and information to patients and communities through clubs of asthmatic patients where we stimulate sports and cultural activities. METHODS: We started to implement the asthma program in 1998, in Nueva Esparta (morbidity was up to 3,713 x 100,000 persons). We decided to measure such morbidity and to permanently supply medication and equipment to treat asthma attack (i.e., Salbutamol, Prednisona, Presnisolona, nebulizers and spacers) as well as inter-crises (Salbutamol, Beclometasone), and to provide proper education. RESULTS: When we started to implement the National Guidelines in 1998, it was the second cause for consultation. In 1999 it falls to the fourth place, in 2001 it occupied the eighth place and by 2002 it had disappeared from the list of the ten first causes of morbidity. Furthermore, if in 1998 the morbidity index was 2,713 x 100,000 persons, for the year 2002 the index had fallen to 1,089 x 100,000 people. CONCLUSION: We believe that with very simple rules, such as educating the asthmatic population, having them participate in their own problems, and supplying them in a regular way with the medication they need, it will be possible to obtain an important impact in the morbidity. In addition, we must insist using national guidelines. CLINICAL IMPLICATIONS: Our objective was to reduce the prevalence of asthma in Nueva Esparta using the Mational Guidelines. DISCLOSURE: G.J. Isturiz, None. GENETIC ALTERATIONS AT THE MICROSATELLITE DNA LEVEL IN NASAL ASPIRATES FROM COPD AND ASTHMATIC PATIENTS: PRELIMINARY RESULTS Alexandros D. Karatzanis, MD*; Katerina D. Samara, MD; Maria I. Zervou, MD; Eleni G. Tzortzaki, PhD; George A. Velegrakis, MD; Nikolaos M. Siafakas, MD, PhD; University General Hospital, Heraklion, Crete, Greece PURPOSE: Previous studies showed that Microsatellite DNA Instability is a common genetic alteration in sputum cells of COPD and Asthmatic patients. The aim of this study was to investigate the presence of the phenomenon in nasal aspirates from COPD and Asthmatic patients. METHODS: Nasal aspirates and peripheral blood from 3 COPD and 4 asthmatic patients were analyzed. For nasal aspirates 1ml of phosphate buffered saline was inserted directly into nasal cavity via a tapered end syringe and the secretions were aspirated back into the syringe. DNA was extracted using QIAamp tissue and blood kits according to manufacturer’s instructions with some modification. Microsatellite DNA amplification was peformed using primers D14S588, G29802, D6S344, D5S207, D13S71, harboring susceptibility genes for Asthma, Allergy and irreversible airway obstruction. PCR was carried out to amplify Microsatellite DNA sequences. The presence of MSI and/or LOH were scored using a Licor 2400 DNA Sequencer. RESULTS: Microsatellite Instability and/or Loss of Heterozygosity (LOH) are detectable phenomena in nasal aspirates in humans. LOH was detected at the Asthma group in one Microsatellite marker, namely Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Asthma Evaluation, continued D14S588 located at chromosome 14 related up to now with a1-antitrypsine gene. CONCLUSION: Our preliminary results showed that genetic alterations could easily be detected in nasal aspirates from COPD and Asthmatic patients, at the Microsatellite DNA level. CLINICAL IMPLICATIONS: Moreover, nasal aspirates can be safely and noninvasively obtained. Thus could potentialy be used to evaluate somatic mutations in the upper airways of those patients. DISCLOSURE: A.D. Karatzanis, None.

BRONCHIAL HYPERRESPONSIVENESS IN PATIENTS WITH GASTROESOPHAGEAL REFLUX Elie Fiss, MD*; Monica Lapa, MD; Roberto Rodrigues Junior, MD; Faculdade de Medicina da ABC, Santo Andre´ , Brazil

SPUTUM CELL SORTING VIA MAGNETIC MICROBEADS IN COPD AND ASTHMATIC PATIENTS Katerina Samara, MD*; Eleni Tzortzaki, PhD; Alexandros Karatzanis, MD; Maria Zervou, MD; Nikolaos Tzanakis, MD; Nikolaos Siafakas, MD, PhD; University of Crete, Heraklion, Crete, Greece PURPOSE: To determine whether it is possible to isolate sputum cell subpopulations for further molecular biology applications. METHODS: Seven (7) patients were studied, three (3) with COPD and four (4) withy Asthma. Sputum was induced via inhalation of a hypertonic saline aerosol, generated by an ultrasonic nebulizer (Ultraneb 2000; DeVilbiss) according to standard methods. The viscid portions of the expectorated sample were separated from the sputum. The cell pellet was processed with magnetic beads columns in order to separate antibodyspecific cell subpopulations, (CD45⫹) for white blood cells (macrophages, eosinophils, neutrophils, lymphocytes) and (HEA) for squamous and non-squamous epithelial cells. The selected cells were stained with a fluorochrome conjugated antibody (FITC) and the subpopulation’s purity was confirmed using flow cytometry. RESULTS: All seven (7) sputum samples were succesfully processed and separated. The purity of the positive selected samples calculated by flow cytometry was median (min-max) 92% (84-99)%. Furthermore, efficient DNA extraction was performed from each sputum cell subpopulation. CONCLUSION: Magnetic labeling of sputum cell subpoppulations with MicroBeads and separation via Macs Columns is an efficient and easy method that could allow to target each cell subpopulation for further molecular analysis. CLINICAL IMPLICATIONS: Separating sputum cell subpopulations via magnetic labeling could enable us to design cell-specific research involved in the pathogenesis of obstuctive airway disease. DISCLOSURE: K. Samara, None.

PURPOSE: The severity of bronchospasm is assessed by forced breathing maneuver that depends on coordination and motivation and is difficult to obtain during severe asthma. The PALIScope may provide an alternative, free of these limitations. METHODS: The PALIScope records tidal breath sounds from the chest surface, by a set of 42 microphones that are attached to the patient back. Signals at each sensor are converted to energy at intervals of 0.17 seconds, and presented as a dynamic, single breath image of the lungs. The acoustic energy throughout the breath (that correlates with ventilation) can be calculated for any lung region by integrating the energy over the matching sensor(s). 8 asthmatics (3 males) 32 years of age (range, 19-54) with baseline FEV1 of 60⫾ 24% of predicted. Testing: Auscultation, spirometry and PALIscopic examination, before and 30 min following nebulized 0.5 ml 0.5% salbutamol, and 2 ml ipratropium bromide, 0.25 mg/ml. RESULTS: FEV1 improved after bronchodilatation by 13⫾12% (P⬍0.01) and the corresponding total acoustic energy during tidal breath increased by 29⫾30% (p⫽0.02). The individual ratios, FEV1after/ FEV1before bronchodilatation tended to correlate with the corresponding ratios of the total acoustic energy, after/before, R⫽0.68, but this correlation did not reached significance. Interestingly, the acoustic energy wasn’t distributed symmetrically between the lungs and between lung regions. In one patient the left lung shared only 11% of the total energy at baseline and this increased to 21% following bronchodilatation. Images 1-2. CONCLUSION: Summation of the acoustic energy of tidal breath during asthma could reflect improvement following bronchodilatation, as could standard forced maneuvers. Furthermore, sounds were markedly asymmetrically distributed during the bronchospastic state and it approached normality after bronchodilation. CLINICAL IMPLICATIONS: By integrating and imaging the acoustic signals and their distribution, the PALIScope provides a simple method to assess the course of asthma. This image does not require maximal maneuver. The PALIScope is a bedside tool that may facilitate monitoring and treatment of asthma in a cost effective manner. Images are shown at: http://www.sheba.co.il/lung-image. DISCLOSURE: I. Ben-Dov, Deep Breeze Ltd. INCREASE IN AIRWAYS INFLAMMATION AND OXIDATIVE STRESS MARKERS IN SUBJECTS WITH GASTROESOPHAGEAL REFLUX (GER) AND GER ASSOCIATED WITH ASTHMA Giovanna E. Carpagnano, MD*; Giovanna E. Carpagnano, MD*; Maria P. Foschino Barbaro, MD; University of Medicine, Foggia, Bari, Italy PURPOSE: The aim of this work was to verify i) whether GER may worsen asthma by exacerbating the pre-existing airways inflammation and oxidative stress and ii) investigate the validity of breath condensate analysis in the study of the airways of subjects with GER. METHODS: We enrolled fourteen patients affected by mild asthma associated with GER (49⫾13 yr), nine with mild persistent asthma (39⫾13 yr), eight with GER (35⫾11 yr) and seventeen healthy subjects (33⫾9 yr). Sputum cells count and levels of IL-4, IL-6 and 8-isoprostane in breath condensate and supernatant were measured. RESULTS: A high airways neutrophilic inflammation has been observed in the airways of subjects with GER and GER and asthma, as assessed by the elevated concentrations of IL-6 observed in their breath condensate and supernatant of sputum and by cell’s sputum analysis. A concomitant increase in 8-isoprostane, as a marker of oxidative stress, has been found in the airways of these subjects. We conclude that GER is characterized by an oxidative stress that seem to worsen that already existing in asthma and by an airways neutrophilic inflammation. CONCLUSION: The measurement of inflammatory and oxidant markers in the breath condensate of subjects with GER mirrors that observed in the induced sputum. CLINICAL IMPLICATIONS: We believe that the use of breath condensate may be very useful in the study and monitoring of respiratory damage due to GER. DISCLOSURE: G.E. Carpagnano, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: The gastroesophageal reflux disease has been associated with cough and asthma. Studies of asthmatic patients have proven the existence of a esophagus-bronchial vagal reflex that would provoke the augment of airways responsiveness. Goals: To investigate this vagal reflex with a bronchial provocation in patients with gastroesophageal reflux. METHODS: All the patients went through an upper digestive endoscopy. 11 patients with no evidences of GER or hiatal hernia (HH) were the control group and 10 patients with HH or GER were the test group. They all were submitted to a bronchial provocation with Carbacol. RESULTS: The provocation was positive in 4 (44%) of the test group and in 3 (27%) of the control group (p⫽ 0,64). CONCLUSION: These data suggest that lungs of patients with GER with no respiratory symptoms might be more reactive than lungs of patients without GER, which would classify the GER disease as a risk factor for bronchial-constrictive diseases. CLINICAL IMPLICATIONS: More studies must be made to confirm this suggestions. DISCLOSURE: E. Fiss, None.

ASSESSING GLOBAL AND REGIONAL TIDAL VENTILATION IN ASTHMA, DURING BRONCHOSPASM AND FOLLOWING BRONCHODILATION, USING A DYNAMIC ACOUSTIC IMAGE OF THE LUNG, ASSEMBLED BY THE PALISCOPE Issahar Ben-Dov, MD*; Pnina Yaron, MSc; Ariela Velner, MT; Hector Roizin, MD; Chaim Sheba Medical Center, Tel Hashomer, Israel

Wednesday, October 27, 2004 Asthma Evaluation, continued THE ASSOCIATION BETWEEN STRESSFUL LIFE EVENTS AND ASTHMA-SPECIFIC QUALITY OF LIFE Connie Archea, BS*; Patricia P. Katz, PhD; Irene H. Yen, PhD; Gillian Earnest, MS; Edward H. Yelin, PhD; Mark D. Eisner, MD; Paul D. Blanc, MD; UCSF, San Francisco, CA PURPOSE: Exposure to stressful life events increases the risk for physical health problems in general, but has not been well studied in asthma specifically. We evaluated the relationship of a subset of stressful life events with asthma quality of life outcomes. METHODS: We studied survey data from 190 adults with asthma (mean age 46⫹9 years; 69% female) participating in a larger study of airways disease. We examined the relationship between a subset of the 41-item version of the Life Events Survey (LES) and the Marks Asthma Quality of Life (AQOL) score. RESULTS: Seven events from the LES occurring in previous year were associated with significantly poorer AQOL (all p ⬍0.05) These were: serious illness or injury; surgery or hospitalization; death of a pet; someone moved out of the home; a major car accident involving self, a family member or friend; lack of money to pay bills; major argument(s) with a family member or friend. The mean decrement in AQOL (reflected in higher score) associated with these events ranged from 1.8 (death of a pet) to 7.7 points (serious illness or injury). Fifty-five (29%) of subjects experienced none of the 7 events; 50 (26%) reported 1 only; 35 (18%) 2 only; and 50 (26%) reported 3-7. Respondents with no events had a mean AQOL score of 9.5 ⫹ 10.6; those with one event, 13.5⫹11.7; those with two, 19.2⫹18.4; those with 3-7, 23.6 ⫹18.7 (ANOVA p⬍0.05). A sensitivity analysis excluding illness/injury and surgery hospitalization [cumulative response frequencies collapsed to 0, 1 or 2 or more events] continued to show an incremental worsening in AQOL with more stressful events (ANOVA p⬍ 0.05). CONCLUSION: Selected stressful life events are associated with impaired AQOL. Multiple events have an incremental impact on AQOL. CLINICAL IMPLICATIONS: Certain stressful life events may linked to poorer AQOL; some of these may be clinical (serious illness, hospitalization), while other events may reflect psychological or social stress, including financial and emotional issues. DISCLOSURE: C. Archea, None.

ASTHMATICS WITH RESTRICTIVE VENTILATORY IMPAIRMENT Agnieszka Palecki, MD*; Albert Miller, MD; Kyungme Kim, MD; Anvita Bitta, MD; Michael Shulman; St. Vincent Catholic Medical Center, Jamaica, New York, NY PURPOSE: We have encountered a number of otherwise typical asthmatics who had restrictive ventilatory impairment in contrast to the expected obstructive pattern. We undertook the study to determine the percentage of asthma patients who had restrictive impairment, and to evaluate possible mechanisms. METHODS: Retrospective study designed to review full PFT’s of 443 patients with asthma from January 2000 to September 2003. All PFT’s were divided into four categories- normal, obstruction, obstruction with restriction and restriction. PFT’s showing restriction were further classified based on other indicators of restrictive impairment, such as decreased diffusion capacity (DL) as an indication of occult ILD, and high body mass index (BMI). Spirometry and DL adhered to ATS standards. FRC was reviewed to exclude air trapping. PFT’s of patients with obesity (BMI⬎ 30) were further investigated. If FVC normalized either after BD or at another time when BMI remained elevated, restriction was attributed to asthma rather then to obesity. RESULTS: In our population of 443 patients, 311(70%) demonstrated either obstruction or normal PFT’s, 37 (8%) demonstrated a combined restrictive and obstructive pattern and 95 (21%) demonstrated only a restrictive pattern, which was the focus of our study. Of the restrictive population, 19 (20%) had normal BMI and normal DL, and 8 (8%) had high BMI with normalization of FVC as mentioned above. The remaining 68 patients (72%) with restriction had high BMI and/or low DL. There were 27 patients (68%) whose restrictive impairment was attributed to asthma, and could not be explained by other disorders (obesity, ILD, pleural effusion etc.). Plethysmographic FRC was increased in only 2 of these 27, demonstrating that “restriction” was not secondary to air trapping.

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CONCLUSION: Of all 443 asthmatics, restriction attributed to asthma was found in 27 (6 %) cases. Asthma may contribute to restriction in 105 additional patients, along with obesity and/or occult ILD. CLINICAL IMPLICATIONS: The finding of restriction does not contraindicate the diagnosis of asthma. Restriction may be explained by airway closure rather then narrowing. DISCLOSURE: A. Palecki, None.

REVERSABLE AIRWAY OBSTRUCTION IS PREVALENT IN MORBIDLY OBESE PATIENTS Akella Chendrasekhar, MD*; St.Vincent’s Mercy Medical Center, Toledo, OH PURPOSE: We assessed the incidence and degree of reversable airway obstruction in morbidly obese(BMI ⬎ 40)patients and the relationships between forced expiratory volume(FEV-1) and forced vital capacity(FVC) and the body mass index in these patients so as to determine the utility of pulmonary function testing in this population. METHODS: We performed a retrospective chart review and detailed analysis of spiromentric data on 60 morbidly obese patients without a diagnosis of obstuctive sleep apnea and with a compaint of shortness of breath with activity. We evaluated the data by comparing patients with BMI between 40-50 (group 1)and BMI ⬎ 50(group 2). RESULTS: The average age for the overall study population was 44 years. The average values of FEV-1, FVC as a % predicted value were significantly lower in the higher BMI group(group 2). The percentage of patients showing improvement in response to bronchodilators in the higher BMI group(group 2) was significantly greater. The average percentage improvement for each patient was also significantly higher in the higher BMI group(group 2). CONCLUSION: Reversable obstructive airway disease is prevalent among morbidly obese patients. Patients with higher BMIs respond more often and have a better response to brochodilator therapy. CLINICAL IMPLICATIONS: Spirometric analysis and bronchodilator therapy improves pulmonary outcome in morbidly obese patients.

Table 1: Relationship between degree of obesity pulmonary function % of group % showing FEV1 (% FVC (% improvement improvement of of in FEV1 with with predicted predicted bronchodilators bronchodilators value) value) (avg./patient) (BD) Age Group 1 92.2 ⫾ (BMI 40- 2.2 50) n⫽33 Group 2 84.7 ⫾ (BMI ⬎ 2.5 50) n⫽27 P value 0.027

94.5 ⫾ 2.3

4.79 ⫾ 1.26

36.4 ⫾ 8.4

43.1

87.3 ⫾ 2.6

11.74 ⫾ 1.39

66.7 ⫾ 9.3

45.4

0.041

0.0005

0.019

0.422

Values are Mean (⫾ standard error of the mean), N.S.⫽ Not Significant DISCLOSURE: A. Chendrasekhar, None.

TIME SEQUENCE OF AIRWAY REMODELING IN A MOUSE MODEL OF CHRONIC ASTHMA Jin Woo Kim, MD*; Young Hyeun Kim, MD; Sang Haak Lee, MD; Seung Joon Kim, MD; Young-Kyoon Kim, MD; Kwan-Hyoung Kim, MD; Hwa-Sik Moon, MD; Jeong-Sup Song, MD; Sung-Hak Park, MD; The Catholic University of Korea, Seoul, South Korea PURPOSE: The purpose of this study was to establish the animal model of chronic human asthma characterized by airway remodeling. During the course of making animal model, the author tried to elucidate Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Asthma Evaluation, continued

CORRELATION OF ERYTHROCYTE SEDIMENTATION RATE, SERUM ALKALINE PHOSPHATASE AND SERUM POTASSIUM LEVEL TO DURATION OF HOSPITAL STAY IN HOSPITALIZED ADULT ASTHMA PATIENTS Nepal S. Raj, PharmD*; R. Guleria, MD; A. Mishra, MD; All India Institute of Medical Sciences, New Delhi, India PURPOSE: To examine the correlation of erythrocyte sedimentation rate, serum alkaline phosphatase and serum potassium level to duration of hospital stay in hospitalized adult asthma patients. METHODS: We studied 44 asthma patients (18 males, 26 females; age 43⫹-17 years; weight 60⫹-11 kg) admitted in medical ward of hospital for treatment of acute asthma. Erythrocyte sedimentation rate, serum alkaline phosphatase and serum potassium level were estimated at the time of admission. Patients were treated with normal adult doses of salbutamol nebuliser (33 - number of patients), beclomethasone inhaler (18), salbutamol inhaler (15), ipratropium inhaler (12), injection terbutaline (14), injection cortisone (17), injection aminophylline (15), tablet prednisolone (15), tablet theophylline (23). All patients were discharged when their condition was stable for 24 hours. Average, standard deviation (sd), correlation coefficient (r) and p values were calculated by Ms.Excel 97 in Win.Me using P4. RESULTS: Average (⫹-sd) values of duration of hospital stay (7.2⫹4.5 days), erythrocyte sedimentation rate (34⫹-14 mm / hour), serum alkaline phosphatase (180⫹-132 units /L) and serum potassium level (3.8⫹-0.5 mEq / L) were observed. The correlation between erythrocyte sedimentation rate and duration of hospital stay (r⫽0.52; p⬍0.05) was observed. The correlation between serum alkaline phosphatase and duration of hospital stay (r⫽0.36; p ⬍0.05) and the correlation between serum potassium level and duration of hospital stay (r⫽0.35; p ⬍0.05) was also observed. CONCLUSION: There was significant positive correlation between erythrocyte sedimentation rate and duration of hospital stay, between serum alkaline phosphatase and duration of hospital stay, between serum potassium level and duration of hospital stay. CLINICAL IMPLICATIONS: Higher erythrocyte sedimentation rate, serum alkaline phosphatase and serum potassium level may predict prolonged duration of hospital stay in adult asthma patients. DISCLOSURE: N.S. Raj, None.

CHARACTERISTICS OF NEWLY DIAGNOSED ASTHMA PATIENTS LIVING IN ZONGULDAK PROVINCE OF TURKEY Meltem M. Tor, MD*; Suna Akbulut, MD; Remzi Altin, MD; Levent Kart, MD; Zonguldak Karaelmas University Hospital Department of Pulmon, Zonguldak, Turkey PURPOSE: In this study, we aimed to assess the characteristics in a group of newly diagnosed asthma patients living in Zonguldak province of Turkey, located in western Black Sea region which is one of the mostly polluted areas in Turkey and to determine whether any of the factors were associated with more severe disease. METHODS: We conducted a retrospective chart review of 51 newly diagnosed patients (mean age 42.8⫾12.7 (18-75), 16 (31.4%) male, 35(68.6%) females, 70.6% nonsmokers) seen in our institution’s asthma clinic in 2003 and recorded the patient characteristics and laboratory and clinical data including the severity of asthma in each patient. RESULTS: We found allergen sensitization(either by skin prick test and/or specific IgE) in 16 of 51 patients(31.4%): house dust mite in 13.5%, pollen in 7.7% and mixed allergen sensitization in 9.6% respectively. Mean duration of symptoms was 5.8 years, and mean %predicted FEV1 was 81.9⫾20.36. Of 24(47%) nonsmoking females, all housewives, 83%(20/24) were nonatopic. Patients were grouped as mild, moderate and severe asthma (27 mild(%52.9), 16 moderate(31.4%) and 8 severe(15.7%)). We compared these factors by chi square analysis and used pearson correlation to determine whether any of these characteristics were associated with more severe asthma. Rhinitis, chronic sinusitis, gastroesophageal reflux disease, bronchiectasis and psychiatric problems were reported in 15(29.4%), 16(31.4%), 10(19.6%), 9(17.6%) and 5(9.8%) patients respectively. Increasing age, symptom duration, and chronic sinusitis were independently associated with more severe asthma (p⫽0.004, p⫽0.04 and p⫽0.025 respectively). Chronic sinusitis was also correlated with lower FEV1 predicted (p⫽0.029). We did not find any correlation between asthma severity and atopy, cigarette smoking, gastroesophageal reflux disease and other factors. CONCLUSION: This study confirms earlier studies showing that chronic sinusitis is an important comorbid condition in patients with asthma being associated with greater asthma severity. CLINICAL IMPLICATIONS: The fact that majority of our patients were nonatopic and female housewives led us to consider especially indoor and outdoor pollution as an important risk factor that need to be further investigated in our population. DISCLOSURE: M.M. Tor, None.

Asthma Therapy 12:30 PM - 2:00 PM EFFECT OF FLUTICASONE/SALMETEROL AND MONTELEUKAST ON TOTAL EXHALED, BRONCHIAL, AND ALVEOLAR NITRIC OXIDE IN ASTHMATICS Arthur F. Gelb, MD*; Colleen F. Taylor, MA; Joel D. Epstein, MD; Chris Shinar, PharmD; Carlos Gutierrez, MD; Noe Zamel, MD; Lakewood Regional Medical Center, Lakewood, CA PURPOSE: Evaluate the role of therapeutic intervention on endogenous markers of inflammation in asthma. METHODS: Spirometry and total exhaled nitric oxide at 100ml/s (FENO), bronchial NO flux and alveolar NO were measured using the technique of Tsoukias and George(JAP 2001;91:477⫽487). We studied 7 non-smoking, stable asthmatics (4M) age 60⫾23 yr (mean⫾SD) after 3 weeks of fluticasone 250ug(F)/salmeterol 50ug (S) bid, after 3 weeks of S, after 3 weeks of S plus monteleukast 10mg (M) daily, and after 3 weeks of FS plus M. RESULTS: After 3 weeks of FS the FEV 1 was 2.2⫾0.7L (82⫾25%pred) and did not change with different regimens.After 3 weeks of FS the FENO was 38⫾15ppb (normal value:12⫾15ppb) and increased with S and S ⫹ M and unchanged with FS⫹M. Bronchial NO flux after 3 weeks of FS was 3.1⫾1.7 nl/s (normal value:0.85⫾0.55nl/s) and increased with S and S⫹M but unchanged with FS ⫹ M. Alveolar NO after 3 weeks of FS was 7.5⫾4.6ppbCHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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the time sequence of airway hyperresponsiveness, airway inflammation, airway remodeling. METHODS: 7-week-old female BALB/c mice were studied for chronic asthma model using ovalbumin(OVA), and they were divided 3 asthma groups depending on the duration of OVA inhalation(group I; 4 weeks, group II; 8 weeks, group III; 12 weeks) and a control group. Airway resistance was measured for airway hyperresponsiveness, serum total IgE, IgG1, IgG2a were measured. PAS and Masson’s trichrome stain in the lung tissue were measured. RESULTS: 1. Airway hyperresponsiveness was significantly increased in all asthma groups than control group. 2. Serum total IgE was significantly increased in all asthma groups, group I, group II, group III(0.99⫾0.30 ␮g/ml, 2.66⫾1.16 ␮g/ml, 2.42⫾0.92 ␮g/ml, respectively) than control group(0.41⫾0.16 ␮g/ml)(P⬍0.01). And among asthma groups, total IgE was significantly increased in group II and group III than group I(P⬍0.01). 3. OVA specific IgG1, IgG2a were not detected in control group. In asthma groups, OVA specific IgG1 was significantly increased in group II(9.58⫾0.13 A.U.) than group I(9.33⫾0.23 A.U.), and group III(11.22⫾1.51 A.U.) than group II(9.58⫾0.13 A.U.)(P⬍0.01). 4. In the lung tissue stained with PAS, goblet cell hyperplasia was significantly increased in all asthma groups than control group(P⬍0.01). 5. In the lung tissue stained with Masson’s trichrome, peribronchial fibrosis was increased in all asthma groups than control group(P⬍0.01). Among asthma groups, time dependent increase in peribronchial fibrosis was observed. CONCLUSION: In this ovalbumin induced murine model, airway inflammation as well as airway hyperresponsiveness was sustained and airway remodeling was developed, so chronic asthma was achieved. In this process, the author thought that IgE, IgG1, IgG2a as well as inflammatory cells were continuously attributed for the pathogenesis of chronic asthma. CLINICAL IMPLICATIONS: Chronic asthma model in mouse. DISCLOSURE: J. Kim, None.

Wednesday, October 27, 2004 Asthma Therapy, continued (normal value:3.2⫾2.0 ppb)and increased with S and S⫹M but reduced with FS ⫹M. CONCLUSION: Stable non-smoking asthmatics with mild to moderate reduction in FEV 1 despite being on FS have elevated FENO,bronchial NO flux and alveolar NO.The combination of FS ⫹ M reduced the alveolar NO. CLINICAL IMPLICATIONS: Combination of FS ⫹ M may have an important role in reducing alveolar NO in clinically stable asthmatics. DISCLOSURE: A.F. Gelb, None. THERAPUTIC RESPPONSE PATTERNS OF SEVERE ACUTE ASTHMA PATIENTS TO HIGH AND CUMULATIVE DOSES OF SALBUTAMOL Mostafizur Rahman, MBBS, FRCP*; Adnan Y. Choudhury, MBBS; S.M. Abdullah A. Mamun, MBBS, MD; NIDCH, Dhaka, Bangladesh PURPOSE: Nebulized b2 adrenergic agonists are still the first line drugs for a rapid bronchodilatation & an easily adminstered drug during acute asthma attack. Purpose of this study is to assess theraputic response patterns of severe acute asthma patients to high and cumulative doses of salbutamol. METHODS: 70 patients with sign symptoms of severe acute asthma (PEFR⬍50% but ⬎30% of predicted), who were previously diagnosed and registered as suffering from bronchial asthma in Asthma Centre, NIDCH Dhaka were enrolled in this study. All patients were treated with salbutamol delivered with a metered dose inhaler into a spacer device in 4 puffs(400mg) at 10 min intervale for 2 hours. Variable were recorded at 0,30,60,90& 120 min & compared to each other for statistical significanse. RESULTS: Among the 70 patients included in the study 53 (75.7%) achieved the discharge threshold(eg,PEFR⬎70%) after the end of 2 hours of treatment. 17 patients (24.3%) failed to reach the discharge threshold and 2(2.8%) of them can not complete the protocol treatment due to intolarable side effects. Analysis of the variables reveals statistically significant decrease in respiratory rate, use of accessory muscles, wheezing & dyspnoea. Heart rate was increased significantly but there were very little change in systolic & diastolic pressures. SaO2 increased significantly but the most significant improvement was noted in PEFR both in L/min and % predicted. CONCLUSION: High and cumulative doses of salbutamol delivered through an MDI with spacer device is an effective, well tolerated modality of treatment for severe acut attack. CLINICAL IMPLICATIONS: This effective low tech single drug treatment modality can be an option for treatment of severe acute asthma in emergency situation at home condition as well as during patient transport to hospital. As more then 75% patient responded well to this treatment it may reduce hospital admission in patients with severe acute asthma. DISCLOSURE: M. Rahman, None. AZITHROMYCIN REDUCED THE INFLAMMATION BY BRONCHOSCOPY Kazuyuki Yamaguchi, MD*; Shigenori Kanazawa, MD; Mikiko Muramatsu, MD; Shosaku Nomura, MD; Kansai Medical University, Osaka, Japan PURPOSE: An anti-inflammatory action of macrolides has recently been detected in diffuse panbronchiolitis. Inflammatory cells and cytokines/chemokines seem to play an important role in the ful-like reaction to bronchoscopy. We measured the plasma interleukin-6 and soluble CD14 levels in patients who underwent bronchoscopy with or without administration of azithromycin. METHODS: Patients underwent bronchoscopy with or without azithromycin were recruited. Blood samples were collected before and after bronchoscopy (4 hour and next day). Peripheral blood cell count was measured and plasma soluble CD14 (sCD14) and interleukin-6 (IL-6) levels were measured with a monoclonal antibody-based ELISA kits. RESULTS: In patients who were not administered azithromycin, there was a significant increase of interleukin-6 at 4 hours after bronchoscopy (15.477 ⫾ 28.896 versus 44.763 ⫾ 69.315, p⬍0.001, n⫽30), sCD14 on the day after bronchoscopy (4.534 ⫾ 1.411 versus 5.575 ⫾ 2.769, p⬍0.05, n⫽30), and neutrophils and monocytes at 4 hours and the day after bronchoscopy (monocytes: 349 ⫾ 133 versus 475 ⫾ 142, p⬍0.05, n⫽12 versus 451 ⫾ 147, n⫽12, p⬍0.05). In contrast, the increase of these parameters except neutrophils was suppressed in patients who treated

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with azithromycin (IL-6: 10.750 ⫾ 9.321 versus 17.410 ⫾ 13.446, p⬎0.05, n⫽10; sCD14: 4.396 ⫾ 1.232 versus 4.522 ⫾ 1.288, p⬎0.05, n⫽10; monocytes: 341 ⫾ 120 versus 385 ⫾ 215, p⬎0.05, n⫽8; versus 328 ⫾ 165, p⬎0.05, n⫽8). CONCLUSION: We conclude that activated monocytes/macrophages are heavily involved in bronchial events. Azithromycin had anti-inflammatory effect, especially on monocytes/macrophages. CLINICAL IMPLICATIONS: The anti-inflammatory effect, especially on monocytes/macrophages of azithromycin may help to prevent for bronchial events in which activated monocytes have a role. DISCLOSURE: K. Yamaguchi, None.

ADDITIVE EFFECTS OF MONTELUKAST ON BRONCHIAL HYPERRESPONSIVENESS TO MCH AND LTE4 URINE LEVELS IN MILD-PERSISTENT ATOPIC ASTHMATICS ASSUMING ICS Silvia Tognella, MD; Claudio Micheletto, MD; Maria P. Visconti, Biologist; Roberto W. Dal Negro, MD*; Bussolengo General Hospital, Bussolengo, Italy PURPOSE: Inhaled corticosteroids (ICS) are regarded as the first-line treatment in patients with persistent asthma, resulting lung function, bronchial hyperresponsiveness and eosinophilic inflammation significantly improved. Nonetheless, many patients receiving ICS continue to experience asthma symptoms, and both the synthesis and the release of cys-leucotrienes (LTs) are not inhibited completely. Montelukast, a selective cys-LT1 receptor antagonist, has been found to reduce airway eosinophilic inflammation in patient with asthma, and it would then provide additional benefit for symptomatic patients already receiving ICS. Aim: to assess and compare the 6-week efficacy of ICS alone and of ICS⫹Montelukast on bronchial hyperresponsiveness to MCh and on the LTE4 urine levels in mild-persistent asthma. METHODS: After informed consent, 18 mild-persistent atopic (prick test positive for inhalants) asthmatics (18-62y; mean basal FEV1⫽103.2%pred⫾15.4sd; mean PD20FEV1 to MCh⫽89.8mcg⫾102.6sd) were randomized. Nine subjects received only Fluticasone p. 250mcg o.d. (group FP), and the remaining 9 Fluticasone p. 250mcg o.d. plus Montelukast 10mg o.d. (FP⫹M), for 6 weeks according to a double-dummy, double-blind design. PD20 FEV1 to MCh and LTE4 urinary levels were assessed in bsln and at the end of treatments. Urine were collected in the morning and processed by an immunoenzimatic method (Cayman Chemical, Mi, USA). Statistics: t test vs basal and between treatments; p⬍ 0.05 accepted. RESULTS: In tab. 1. CONCLUSION: 1) unlike ICS, only the addition of Montelukast enables a substantial decrease of urinary LTE4; 2) the LTs-mediated inflammation confirms its relevant role in atopic asthma. CLINICAL IMPLICATIONS: Montelukast provides a consistent additional control on bronchial hyperresponsiveness when added to ICS in mild persistent asthma.

Tab,1 FP basal FP⫹M basal FP 6 wks FP⫹M6 wks

FEV1 (%pred) 95.1⫾8.2 98.5⫾9.1 103.2⫾15.4 101.2⫾11.4

MCh (mcg)

LTE4 g/ml)

61.2⫾70.1 118.5⫾125.1 395.7⫾109.1* 638.7⫾155.3§ ^

488.1⫾290.3 430.3⫾288.1 366.6⫾278.4 179.7⫾126.1°

* p⬍0.001 vs FPbasal; § p⬍0.001 vs FP⫹M basal; ^ p⬍0.002 vs FP 6 weeks; DISCLOSURE: R.W. Dal Negro, None.


Wednesday, October 27, 2004 Asthma Therapy, continued AEROSOLIZED BUDESONIDE THERAPY IN ACUTE MODERATE EXACERBATIONS OF ASTHMA Sudhir K. Agarwal, MD*; Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

TREATMENT OF PATIENTS WITH DIFFICULT-TO-CONTROL ASTHMA IN A MULTI-DISCIPLINARY ASTHMA CENTER IMPROVES QUALITY OF LIFE OUTCOME SCORES Andrew G. Villanueva, MD*; Leslie Mitchell, PharmD; Lahey Clinic Medical Center, Burlington, MA PURPOSE: Our institution has a fully operational multi-disciplinary Asthma Center (“Full Asthma Center” or FAC) in which patients with difficult-to-control asthma (DTCA) are evaluated and treated. We measured quality of life outcomes at baseline, one month and six months to determine whether patients showed improvement. METHODS: Patients with DTCA who were evaluated in the FAC were assessed by a pulmonologist, allergist, nurse and pharmacist (LM). Treatment decisions were made after a group meeting of the FAC team. The patient received intensive asthma education. We assessed patients using the Asthma Quality of Life Questionnaire (AQLQ) and classified the severity of their asthma using the 1997 NAEP guidelines: mild intermittent (1), mild persistent (2), moderate persistent (3) and severe persistent (4). Other measures included inhaled corticosteroid (ICS) use, compliance with medications and the use of an action plan. Data were collected before or during the first visit, after one month and after six months. RESULTS: AQLQ scores and NAEP severity of asthma classification scores are summarized in the attached table. The overall AQLQ score improved from 3.8 to 5.0 at one month and 5.1 at six months. The overall NAEP classification improved from 3.4 at baseline to 2.8 at one month and 2.6 at six months. Patients using ICS increased from 72% at baseline to 92% at one month and 82% at six months. 66% were found to be compliant with their medications at baseline, compared to 88% at one month and 87% at six months. No patients used an action plan at baseline, compared to 98% at one month and 100% at six months. CONCLUSION: Patients with DTCA who underwent treatment at our FAC showed significant improvement over six months in AQLQ scores, severity of asthma, use of ICS and compliance with their medical regimen. CLINICAL IMPLICATIONS: A multi-disciplinary asthma center can improve the quality of life of patients with DTCA.

NHLBI Classification (1-4) (mean) Asthma symptoms (1-4) (mean) Rescue medication use (1-4) (mean) Peak flow (1-4) (mean)

One month

Six months

3.8 (1.6-6.6) n⫽69 Baseline 3.4 n⫽72

5.0 (2.1-6.8) n⫽43 One month 2.8 n⫽51

5.1 (2.6-6.7) n⫽34 Six months 2.6 n⫽39

3.0 n⫽76

2.0 n⫽54

1.9 n⫽39

2.9 n⫽70

1.7 n⫽51

1.9 n⫽38

2.6 n⫽69

2.6 n⫽49

2.4 n⫽29

DISCLOSURE: A.G. Villanueva, None. ASTHMA EDUCATION BY A PHARMACIST IN PATIENTS WITH MILD TO MODERATE PERSISTENT ASTHMA IMPROVES QUALITY OF LIFE OUTCOME SCORES Andrew G. Villanueva, MD; Leslie Mitchell, Pharm D*; Lahey Clinic Medical Center, Burlington, MA PURPOSE: In addition to a multi-disciplinary Asthma Center, our institution also has a “modified Asthma Center” (MAC) for patients with less severe asthma referred by their primary care physician. The MAC involves intensive patient education by a trained pharmacist (LM). We measured quality of life outcomes at baseline, one month and six months to determine whether patients showed improvement. METHODS: Referred patients who did not have difficult-to-control asthma were seen in the MAC. Intervention by the pharmacist included intensive asthma education. Any recommended changes in the patients’ medical regimens were discussed with and approved by a supervising physician. We assessed patients using the Asthma Quality of Life Questionnaire (AQLQ) and classified the severity of their asthma using the 1997 NAEP guidelines: mild intermittent (1), mild persistent (2), moderate persistent (3) and severe persistent (4). Other measures included

AQLQ score (1-7) (mean, range)

Baseline 4.4 (1.9-6.5) n⫽65

Baseline NHLBI 2.8 n⫽63 Classification (1-4) (mean) Asthma 2.5 n⫽70 symptoms (1-4) (mean) Rescue 2.4 n⫽63 medication use (1-4) (mean) Peak flow 2.1 n⫽48 (1-4) (mean)

One month 5.4 (2.1-7.0) n⫽43

Six months 5.6 (2.9-7.0) n⫽22

One month 2.2 n⫽24

Six months 2.1 n⫽10

1.8 n⫽45

1.6 n⫽21

1.6 n⫽22

1.4 n⫽9

2.3 n⫽15

1.8 n⫽5


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PURPOSE: To assess the utility of inhaled corticosteroids for the early management of acute exacerbations of asthma in the emergency room. METHODS: This randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of high dose inhaled budesonide with frequent beta-2-agonist therapy in patients of acute moderate exacerbations of asthma. Seventy patients between 15 and 40 years of age with acute moderate exacerbations of asthma were put on aerosolized 800 ␮g of budesonide at half hourly intervals for three doses with metered dose inhaler and spacer. All patients received humidified oxygen and nebulized salbutamol (0.15 mg/kg in 3 ml saline) prior to budesonide administration. The control group received placebo instead of inhaled budesonide. Patients who had received corticosteroids in the preceding 72 h were excluded from the study. If there was an inadequate response or no response to treatment at the end of 2 hour, oxygen and salbutamol therapy were continued and given one dose of intravenous hydrocortisone and was started on an aminophylline infusion. RESULTS: Both budesonide and control group showed a significant improvement in respiratory status at the end of 2 h. However, patients in the budesonide group showed greater improvement in PEFR ( p ⬍ 0.05) and significantly lower proportion of patients required oxygen improvement in PEFR ( p ⬍ 0.01). The length of stay was significantly shorter in the budesonide group than in the placebo group (p ⬍ 0.01). CONCLUSION: Aerosolized budesonide therapy with MDI and spacer together with salbutamol in the treatment of acute exacerbations of asthma helped in early recovery and decreased hospital stay. CLINICAL IMPLICATIONS: Inhaled budesonide may be given with MDI and spacer in the treatment of acute exacerbations of asthma. DISCLOSURE: S.K. Agarwal, None.

AQLQ score (1-7) (mean, range)

Baseline

Wednesday, October 27, 2004 Asthma Therapy, continued inhaled corticosteroid (ICS) use, compliance with medication and the use of an action plan. Data were collected before or during the first visit, after one month and after six months. RESULTS: AQLQ scores and NAEP severity of asthma classification scores are summarized in the attached table. The overall AQLQ score improved from 4.4 to 5.4 at one month and 5.6 at six months. The overall NAEP classification improved from 2.8 to 2.2 at one month and 2.1 at six months. Patients using ICS increased from 66% at baseline to 80% at one month and 91% at six months. 83% were found to be compliant with their medications at baseline, compared to 75% at one month and 100% at six months. No patients used an action plan at baseline, compared to 95% at one month and 100% at six months. CONCLUSION: Patients with mild to moderate persistent asthma who underwent asthma education in our MAC showed improvement over six months in AQLQ scores, severity of asthma, use of ICS and compliance with their medical regimen. CLINICAL IMPLICATIONS: Asthma education by a trained pharmacist results in improved quality of life of patients with asthma. DISCLOSURE: L. Mitchell, None.

IMPROVED AEROSOLIZATION OF SUSPENSIONS USING ELECTRONIC MICROPUMP TECHNOLOGY COMPARED TO CONVENTIONAL PNEUMATIC NEBULIZATION Andrew P. Bosco, BSc; Myrna B. Dolovich, PEng*; McMaster University, Hamilton, ON, Canada PURPOSE: Conventional jet nebulizers have been shown to be inefficient at generating drug-carrying droplets from aqueous suspensions. Aerosol delivery of two different aqueous suspensions was compared using a jet nebulizer and a device incorporating micropump technology, a design which may result in a more efficient production of suspension products. METHODS: Particle drug and radioactivity content of two aqueous suspensions were characterized using the Andersen II cascade impactor (28.3 lpm), measuring mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD) and fine particle fraction (FPF; %⬍4.7 microns)). Two suspensions were compared - 99mTc-labeled human serum albumin microaggregates (MIA) produced in saline by the thermal denaturation and ultrasonication of 25% human serum albumin, and budesonide (BUD; Pulmicort Respules (0.5 mg/ml) AstraZeneca, CAN). The former was developed as a radioactive surrogate of BUD. Each suspension was delivered from the Aerodose 5.7 (AD5.7; Aerogen Inc., California), a liquid inhaler incorporating electronic micropump technology, and the LC Star (LCS; Pari GmbH, GER), a breath-enhanced conventional jet nebulizer operated with compressed O2 at 8 lpm. RESULTS: Compared to the LCS, the MMAD of MIA and BUD particles delivered from the AD5.7 were significantly smaller with a significantly greater GSD. For BUD only, the FPF was significantly greater from the AD5.7. The size characteristics of the MIA particles and BUD from the AD5.7 appear to be similar. CONCLUSION: Aerosols generated from two different aqueous suspensions using electronic micropump technology have a significantly smaller MMAD compared to a conventional jet nebulizer. Electronic micropump technology also generates a more heterodisperse suspension aerosol with a significantly greater % of steroid particles in the respirable range. CLINICAL IMPLICATIONS: There is potential for a greater fine particle dose to be delivered more distally in the lung when using electronic micropump technology compared to conventional jet nebulizers.

N⫽9 Mean (SD) MMAD GSD FPF (%)

BUD

99mTc-MIA

AD

LCS

P

AD

LCS

P

2.38 (0.16) 2.21 (0.33) 81.61 (4.61)

3.54 (0.26) 1.97 (0.49) 69.12 (3.68)

⬍0.001

2.15 (0.28) 2.51 (0.28) 80.08 (1.88)

2.96 (0.28) 1.73 (0.11) 79.99 (2.03)

⬍0.001

0.012 ⬍0.001

DISCLOSURE: M.B. Dolovich, Aerogen Inc.

816S

⬍0.001 0.926

SUCCESFUL OUTPATIENT TREATMENT OF BRONCHIAL ASTHMA Ramon F. Lebron, MD*; Asthma Management Center, San Juan, PR PURPOSE: To introduce a new tool to facilitate the uniformity and obtain better results than the ones obtained since the introduction of National Asthma Educational Management Program (NAEMP) guidelines. Our clinical experience with 736 patients, all of them referred because of their refractoriness in their course, confirms the usefulness of the Asthma Patient Bill of Rights (APBOR) is such a tool. METHODS: Age of patients was 16-60 years. A questionnaire describing symptoms and quality of life was filled at the first visit, together with a complete physical examination, laboratory, chest and paranasal X rays, electrocardiogram, spirometry and flow volume loop before and after broncodilators and oxymetry. Medications were prescribed following the guidelines according to status of the condition and after each was proficient in the use of the spacer and peak flow meter. Scheduled visits were every 2 weeks until improvement was ⬎50% of baseline; then every 6-10 weeks. All learned how to identify dangerous situations to access hospitas. RESULTS: After one year only 2.5% visited emergency departments and 1.8% were admitted with a lenght of stay between 7-15 days. The expenses of the admitted were almost equal to the amount paid in medications for the rest. CONCLUSION: The results obtain are significants; demostrating that adherence to the management guidelines is the only path to get better results than previous obtained in the last decade. CLINICAL IMPLICATIONS: To obtain better results we need a tool that simplifies and improve the compliance with the NAEMP guidelines. DISCLOSURE: R.F. Lebron, None.

NEBULIZATION OF STEROID SUSPENSION: AN IN VITRO EVALUATION OF THE AERONEB® GO AND THE PARI LC PLUS™ NEBULIZERS James B. Fink, MS, RRT*; Reginald Simmons, BS; Aerogen, Inc., Mountain View, CA PURPOSE: Pulmicort Respule®(AstraZeneca) contains a budesonide suspension approved for use with jet nebulizers based on registration trials with the LC Plus jet nebulizer (PARI). Ultrasonic nebulizers are not recommended for administration. The Aeroneb Go (Aerogen, Inc.), is an electronic micropump nebulizer that incorporates a piezo vibrational element to pump aerosol through an aperture plate. We wanted to determine ability of this technology to nebulize a suspension. METHODS: Budesonide suspension (Pulmicort Respules®; 0.5 mg/2 mL) was aerosolized with three LC Plus and three Aeroneb Go nebulizers To determine inhaled mass, aerosol was collected on a filter placed between the nebulizer mouthpiece and breathing simulator (Hans Rudolph; adult breathing pattern). The Mass Median Aerodynamic Diameter (MMAD) of the aerosol was determined with cascade impaction (Anderson Mk II). The amount of drug deposited was determined by HPLC. Treatment time was measured to the end of aerosol generation (Aeroneb Go) or one minute past sputter (LC Plus). All experiments were performed in triplicate. RESULTS: Performance data are shown in the table below. Both nebulizers had similar treatment times and inhaled mass of budesonide. The inhaled mass (%) for the LC Plus matches that previously reported by Smaldone et al (J Aerosol Med,1998;11:113-125.). CONCLUSION: We conclude that the Aeroneb Go was as efficient as the jet nebulizer in delivering aerosolized budesonide solution. CLINICAL IMPLICATIONS: New aerosol technologies, such as the electronic micropump, may deliver suspensions as well as the most efficient compressor nebulizer systems. Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Asthma Therapy, continued

Devices Aeroneb Go Pari LC Plus

Inhaled Mass (␮g)

Inhaled Mass (%)

MMAD (␮m)

GSD

Time (min)

115⫾13

22⫾3

3.1⫹0.1

1.6⫾0.1

6⫾0

91⫾14

18⫾3

3.8⫾0.4

2.3⫾1.1

6⫾0

DISCLOSURE: J.B. Fink, Aerogen, Inc.

MOMETASONE FUROATE DRY POWDER INHALER (MF-DPI) 400 MCG ONE PUFF, ONCE DAILY IN THE EVENING COMPARED WITH BUDESONIDE DRY POWDER INHALER (BUDDPI) 400 MCG TWICE DAILY IN SUBJECTS WITH ASTHMA PREVIOUSLY MAINTAINED ON BUDESONIDE Anthony D’Urzo, MD*; Jacques Hebert, MD; Vibeke Backer, DM; Lisa Ghaly, PharmD; Primary Care Asthma Clinic, Toronto, ON, Canada

EFFECT OF DELIVERY ANGLE ON AEROSOLIZED BRONCHODILATOR SOLUTION OUTPUT OF JET NEBULIZERS Ariel Berlinski, MD*; Umit Emre, MD; Long Island College Hospital, Brooklyn, NY PURPOSE: Inhalation therapy remains the cornerstone of treatment for many pediatric pulmonary diseases. Nebulizer therapy is widely prescribed by pediatricians particularly for younger patients. Since many patients receive these treatments in a supine position, thus tilting the nebulizer cup to an approximate 45 degree angle, we speculated that delivery angle might influence nebulizer solution output. In the present study we aim to evaluate the effects of nebulizer cup angle on bronchodilator solution output at different fill volumes, drug concentrations, and running times. METHODS: We tested 4 continuous jet nebulizer brands: MICRO MIST® & T UP-DRAFT® (Hudson RCI); Airlife™ Misty-Neb™ (Alle-

Micro Mist®

Nebulizer OC A B C D

90° 1.48 1.32 1.23 2.68

45° 1.34 1.34 1.40 2.80

T Up-DRAFT 90° *0.89 *0.88 0.73 *2.11

45° *0.63 *0.54 0.72 *1.49

MistyNeb™

Aeromist B&F

90° 45° 90° 45° 1.57 1.37 *1.29 *0.56 1.47 1.43 *1.10 *0.41 1.26 1.26 1.32 1.31 *3.05 *2.69 *2.57 *1.81

(expressed as ml) are shown below (夹P⬍0.05): DISCLOSURE: A. Berlinski, None.

Fiberoptic Bronchoscopy 12:30 PM - 2:00 PM BRONCHOALVEOLAR LAVAGE (BAL) IN PATIENTS WITH TREE-IN-BUD SIGN ON CT OF THE CHEST John W. Bloom, MD; Robert A. Barbee, MD*; Michael R. Blumhardt, MD; Richard E. Sobonya, MD; University of Arizona, Tucson, AZ PURPOSE: The tree-in-bud sign is a relatively new yet increasingly popular finding on chest CT. Tree-in-bud refers to radiographic opacification of usually invisible small, peripheral airways that typically results from infection. While multiple diseases have been associated with the tree-in-bud finding, no study to date has examined the yield of BAL in patients with this radiographic sign. We investigated BAL results in patients with tree-in-bud sign on CT of the chest. METHODS: We retrospectively reviewed radiograph reports of every adult patient who underwent fiberoptic bronchoscopy (FB) with BAL at the University of Arizona from January 1, 2001 through December 31, 2003. The BAL results of each patient with tree-in-bud sign were reviewed, as were the treatment plans instituted based on these results. Major comorbidities in this population were recorded. RESULTS: Five hundred BALs were performed during the study period. 24 patients had tree-in-bud sign on pre-FB CT scan. Eight of the 24 patients had bronchiectasis. Nine patients were immunosuppressed: diabetes (4), HIV/AIDS (1), collagen vascular disease (1), vasculitis (1), solid organ transplant (1), chemotherapy (1). Seventeen of the 24 patients (71%) had microorganisms isolated by BAL. Antibiotics were instituted based on BAL findings in 15 (62.5%). Mycobacteria were the most common organisms isolated: Mycobacterium avium-intracellulare (7), Mycobacterium tuberculosis (2), and Mycobacterium bovis (1). Fungal organisms were isolated in 3 patients: Scedosporium apiospermum (2) and coccidioidomycosis (1). Bacteria were isolated in 5 patients: Haemophilus influenzae (2), Burkholderia cepacia (1), mucoid pseudomonas (1), and Nocardia abscessus (1). Viruses were isolated in 3 patients: rhinovirus (1), cytomegalovirus (1), and parainfluenza virus type 3 (1). CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: To compare the efficacy and safety of MF-DPI administered once daily in the evening (qd PM) with BUD-DPI administered twice daily (bid) for 8 weeks. METHODS: This 8-week, randomized, open-label study compared MF-DPI 400 mcg qd PM with BUD-DPI 400 mcg bid in subjects (N ⫽ 178) ⱖ 12 years of age with moderate persistent asthma previously maintained on BUD 400 mcg/day or 800 mcg/day. The primary efficacy variable was change from baseline in FEV1 at endpoint. Secondary variables included AM and PM peak expiratory flow (PEF) rates, response to therapy, and subject satisfaction with their inhaler. RESULTS: Improvements in FEV1 were observed in both treatment groups. At the end of treatment, the mean change from baseline in FEV1 was 0.23 L (8.6%) with MF-DPI and 0.17 L (6.4%) with BUD-DPI (p ⫽ 0.307; 1-sided 95% CI, lower bound: -1.7%). No significant differences were observed in AM or PM PEF responses between the two treatment groups. Greater proportions of subjects in the MF-DPI group were rated by physicians as “improved” or “much improved” compared with the BUD-DPI group at Week 2 (62% vs 39%, respectively; p ⫽ 0.014) and Week 4 (67% vs 47%, respectively; p ⫽ 0.010). A significantly greater proportion of subjects in the MF-DPI group “liked the inhaler a lot” compared with subjects in the BUD-DPI group who “liked the inhaler a lot” (45% vs 22%, respectively; p ⫽ 0.016). Both treatments were well tolerated. CONCLUSION: Once-daily treatment with MF-DPI (400 mcg qd PM; one puff/day) was as effective as twice-daily treatment with BUDDPI (400 mcg bid) in moderate persistent asthma previously treated with BUD. CLINICAL IMPLICATIONS: MF-DPI maintains effective asthma control in patients whose asthma previously was controlled with BUD. DISCLOSURE: A. D’Urzo, Integrated Therapeutics Group

giance Healthcare Corp.); and Aeromist B&F Medical (Allied, Inc.). Nebulizers were operated at 10 LPM (compressed air at 50 PSI) and solution output was determined by gravimetric analysis at with delivery angles of 90 and 45 degrees (N⫽6, for each determination). Operating conditions (OC) were as follows: (A) albuterol nebulizer solution (2.5 mg/3ml) run for 5 minutes; (B) albuterol nebulizer solution (1.25 mg/3ml) run for 5 minutes; (C) operating condition (A) ⫹ ipratropium bromide nebulizer solution (0.5 mg/2.5ml) (fill volume 5.5 ml); and (D) operating condition (C) run for 9.2 minutes. Statistical analysis done by ANOVA for repeated measures. RESULTS: Please refer to the table. CONCLUSION: Aerosolized bronchodilator therapy in the supine position (thus tilting the nebulizer cup to a 45 degree angle), significantly decreases solution output for 2 of the 4 nebulizers tested. Increasing fill volume, but not bronchodilator concentration or run time, buffers this detrimental effect. CLINICAL IMPLICATIONS: Effects of treatment position on drug delivery and therapeutic outcomes should be considered when prescribing nebulized bronchodilators.

Wednesday, October 27, 2004 Fiberoptic Bronchoscopy, continued CONCLUSION: BAL is associated with a high recovery rate of microorganisms in patients with tree-in-bud sign. Bronchiectasis and immunosuppression were common in the study population. CLINICAL IMPLICATIONS: Fiberoptic bronchoscopy with BAL is effective for the diagnosis of infection in patients with tree-in-bud sign on CT scan of the chest. DISCLOSURE: R.A. Barbee, None. PULMONARY COMPLICATIONS OF ESOPHAGEAL STENT REQUIRING FIBER OPTIC BRONCHOSCOPY Sameer Rana, MBBS*; Eric S. Edell, MD; Baron H. Todd, MD; Mayo Clinic, Rochester, MN PURPOSE: Esophageal stents are increasingly being placed for palliation of malignant dysphagia. The present study was conducted to look at the pulmonary complications of esophageal stent necessitating fiberoptic bronchoscopy and to identify risk factors predicting the need for fiberoptic bronchoscopy. METHODS: We identified all patients who had an esophageal stent placed at Mayo Clinic between 1998 and 2002, and those who subsequently underwent Fiberoptic Bronchoscopy. Bronchoscopic findings and intervention required were noted. The Fischer exact test was applied to see if there were any factors which significantly increased the risk of a patient getting a fibreoptic bronchoscopy. RESULTS: A total of 103 patients’had an esophageal stent placed. Eighty-four (81%) patients had esophageal cancer. A total of 46(44%) had esophageal dilatation / laser therapy prior to esophageal stent placement. Tracheo-esophageal fistula was present prior to stent placement in 5(4.8%) patients. Treatment records were available for 68 patients of which 57(83%) received radiotherapy or chemotherapy. A total of 7 (6.7%) patients with esophageal stent required fibreoptic bronchoscopy. Dyspnea and cough were the main reason for bronchoscopy. Esophageal stent perforating into the trachea was seen in 4(3.8%) patients, 2(1.9%) required placement of airway stent. External airway compression was seen in 1 patient. Factors influencing the requirement of fibreoptic bronchoscopy in patients with esophageal stent were analyzed. Presence of tracheoesophageal fistula was a significant factor p ⫽ 0.001. Diagnosis, previous esophageal dilatations/laser therapy, treatment with either radiotherapy / chemotherapy, were not significantly associated with the need for fibreoptic bronchoscopy. CONCLUSION: In the present study a total of 7 patients (6.7%) with esophageal stent required fibreoptic bronchoscopy. The esophageal stent was seen perforating into the trachea in 4(3.8%) patients, of these 2(1.9%) had airway stent placed. External airway compression was seen in 1 patient.The presence of tracheoesophageal fistula at the time of esophageal stent placement predicted the need for fiberoptic bronchoscopy. CLINICAL IMPLICATIONS: Patients with tracheoesophageal fistulas treated with esophageal stent will likely develop airway compromise requiring airway intervention. DISCLOSURE: S. Rana, None. THE SAFETY AND EFFICACY OF TOPICAL COCAINE IN FLEXIBLE FIBEROPTIC BRONCHOSCOPY Emir Festic, MD*; Margaret M. Johnson, MD; Margaret M. Johnson, MD; Mayo Clinic, Jacksonville, FL

group. There was significantly less fentanyl use in the cocaine versus the control group (p⫽0.009, median 75 vs. 88 mcg, respectively). There was a nonsignificant trend towards less midazolam use in the cocaine versus the control group (p⫽0.48). Eleven patients had FFBs done both with and without topical cocaine use. There was a trend towards less midazolam use(median values 2 vs. 3 mg, p⫽0.07) and less fentanyl use(median values 50 vs. 75 mcg, p⫽0.24) in this subgroup when cocaine was used versus no cocaine use, respectively. CONCLUSION: Topical application of 4% cocaine to each piriform sinus in addition to standard xylocaine appears to be safe. Its’ use is associated with significantly less use of fentanyl and a trend towards less use of midazolam. CLINICAL IMPLICATIONS: The use of topical cocaine may allow FFB to be performed with less systemic narcotic use. DISCLOSURE: E. Festic, None. UTILITY OF FIBRE OPTIC BRONCHOSCOPY IN DIAGNOSIS OF LUNG CANCER Avanti Vigg, MBBS*; Chest Clinic, Hyderabad, India PURPOSE: To determine the current diagnostic yield of fibreoptic bronchoscopy (FOB) in the investigation of lung cancer. METHODS: This is a retrospective analysis of FOB performed between January 1998 and December 2003 for possible lung cancer at Apollo Hospitals, a tertiary care referral centre in Hyderabad, South India. RESULTS: One thousand four hundred and fourteen (1414) patients underwent FOB for possible lung cancer during the study period. There were 1081 males (76.4%) and 333 females (23.6%); mean age was 46.9 yrs ⫹ 2.84 SD. Out of 1414 patients, 1131 received a diagnosis of lung cancer (80%; 95% CI: 78-82). Amongst the 1131 diagnosed patients endobronchial tumour was seen in 724 patients (64%). Bronchoscopic appearances suspicious of malignancy was observed in 169 patients (15%) no endobronchial growth was seen in 226 patients (20%). Positive sampling rate when tumour was seen endobronchially was 90%; the yield was 80% by biopsy & 5% each by bronchoalveolar lavage, cytology, transbronchial needle aspiration & brushings. In patients without any endobronchial growth, BAL cytology was positive in 11 patients(5%) The diagnostic yield with transbronchial lung biopsy was 75%(n⫽170) & with transbronchial needle aspiration was 20% (n⫽45). Symptomatically, 792 patients (70%) presented with history of haemoptysis. Three hundred & thirty nine patients (30%) were referred because of abnormal Chest X Ray. Clinical correlation of patient’s history & bronchoscopic diagnosis showed a sensitivity of 88.7% and specificity of 66%. Radiological correlationship with diagnosis of lung cancer had a sensitivity of 86.6%; specificity of 51%; positive predictive value of 24.4% and negative predictive value of 93.1% with accuracy of 56%. CONCLUSION: Fibreoptic Bronchoscopy when performed for suspected lung cancer had a high overall diagnostic yield. Broncho alveolar lavage, transbronchial lung biopsy & transbronchial needle aspiration can further improve the diagnostic yield. CLINICAL IMPLICATIONS: Bronchoscopy performed for suspected lung cancer can yield high diagnostic rate provided it is combined with various modalities. DISCLOSURE: A. Vigg, None.

PURPOSE: Cocaine has been used topically as an anesthetic in flexible fiberoptic bronchoscopy (FFB). There are reports of cardiac ischemic and arrhythmic complications following intratracheal cocaine instillation. We propose that application of 4% cocaine-soaked cotton pledgets to each piriform sinus via Jackson forceps for one minute represents a safe and efficacious method of providing additional topical anesthesia for FFB. METHODS: We retrospectively reviewed all FFBs performed at Mayo Clinic Jacksonville from January, 1999 to April, 2004. Data abstracted included periprocedural complications and doses of midazolam and fentanyl used in the FFBs with or without topical cocaine application in addition to the usual anesthesia with topical xylocaine. For the subgroup of patients who had FFBs both with and without cocaine, doses of midazolam and fentanyl were compared. The Wilcoxon rank sum test was used for statistical analysis. RESULTS: We identified 60 FFBs where topical 4% cocaine use was documented. A random sample of 80 FFBs without cocaine use was obtained by reviewing every 16th FFB performed and served as the control group. There were no periprocedural complications in either

THERAPEUTIC IMPLICATIONS OF BRONCHOSCOPY IN THE EVALUATION OF PATIENTS WITH FEBRILE NEUTROPENIA AND PULMONARY INFILTRATES Tobias Peikert, MD*; Eric S. Edell, MD; Mayo Clinic College of Medicine, Rochester, MN

818S


PURPOSE: To investigate bronchoscopic findings, adjustments in management and survival benefits of bronchoscopy in patients with neutropenic fever. METHODS: With approval of the Institutional Review Board we quarried the medical record database and identified 416 broncho-alveolar lavages (BAL) in 2002. All patients with fever, moderate or severe neutropenia (absolute neutrophil count (ANC) ⬍1000/microliter) and chest-radiographic abnormalities at the time of BAL were included. RESULTS: 38 BALs evaluated pulmonary infiltrates in patients with febrile neutropenia. Underlying diagnoses included hematological malignancies (74.3%) and lymphomas (11.4%). Neutropenia was caused by chemotherapy (19 patients), hematopoetic stem cell transplantation (11

Wednesday, October 27, 2004 Fiberoptic Bronchoscopy, continued

EARLY LUNG CANCER DETECTION - A COMPARISON OF AUTOFLUORESCENCE-BRONCHOSCOPY AND VIDEOCHIPBRONCHOSCOPY Felix J. Herth, MD*; Ralf Eberhardt, MD; Heinrich D. Becker, MD; Armin Ernst, MD; Thoraxklinik, Heidelberg, Germany PURPOSE: Autofluorescense bronchoscopy (AF) is an established method to detect dysplasia and carcinoma in situ. Videochipbronchoscopy (VC) is new development in this field. VC allows a computer-based analysis of the bronchial mucosa. This study aimes to directly compare the D-light system and videochiptechnology in detection of early lung cancer. METHODS: In a prospective study we examined patients with risk factors for lung cancer who underwent bronchoscopy with both methods. The findings were classified in normal, abnormal and suspicious lesions by independent investigators and compared. RESULTS: 300 consecutive patients (208 male, 92 female, mean age 52,7 years, range (r) 40-85) were included. 21 patient had a class IV lesion, all detected by both systems. 17 (6%) pts had a histological controlled class III lesion (2x CIS, 8x servere dysplasia, 7x mild dysplasia). Thereof AF missed one mild dysplasia. 13 pts. showed with AF endoscopically a class III lesion, histological only inflammation. With VC 10 of this lesion were classified as class II lesions. The mean time for the both examination were similiar. CONCLUSION: Both system yielded comparable results. With VC the rate of false positive results is decreased compared to AF. CLINICAL IMPLICATIONS: Early lung cancer detection is also possible with the new videochiptechnology. DISCLOSURE: F.J. Herth, None. A RETROSPECTIVE REVIEW AND COMPARISON OF FLEXIBLE FIBEROPTIC BRONCHOSCOPY AT A UNIVERSITY TEACHING HOSPITAL AND A COMMUNITY BASED HOSPITAL Brian McNab, MD*; Rodmehr Hafezi, MD; Darcy Marciniuk, MD, FRCP(C); Robert Skomro, MD, FRCP(C); Karen Laframboise, MD, FRCP(C); David Todd, MD, FRCP(C); University of Saskatchewan, Saskatoon, SK, Canada PURPOSE: To compare flexible fiberoptic bronchoscopy (FFB) at a university teaching hospital and a community based hospital. METHODS: A retrospective review of FFB performed in a university teaching hospital and a community based hospital was done with comparison of indications and complications associated with this procedure. RESULTS: A total of 358 FFB procedures were reviewed – 181 at a university teaching hospital and 177 at a community based hospital. The age, gender, and smoking status of patients undergoing FFB in both hospitals did not differ significantly. The most common indications were

the presence of a lung mass on chest radiograph (31.8% university versus 34.5% community hospital) and hemoptysis (24.0% university hospital versus 20.9% community hospital). Indications for FFB differed somewhat between hospitals with chronic cough being a more common indication in the community based hospital (12.4% versus 4.5% university hospital) and diffuse lung disease a more common indication in the university hospital (9.4% versus 2.3% community hospital). The bronchoscopy procedures differed with transbronchial biopsy performed more frequently at the university hospital (12.8%) than the community hospital (1.1%). Complications associated with FFB were low at both hospitals, with slightly higher complication rates at the community hospital (4.5% community hospital versus 2.7% university hospital). CONCLUSION: The results suggest that except for small differences, the indications, conduct and complication rates associated with FFB are similar regardless of whether the procedure is undertaken at either a university teaching hospital or a community hospital. CLINICAL IMPLICATIONS: There is no increase in the complication rate associated with FFB at a university teaching hospital where the procedure is often performed by supervised trainees in comparison with a community based hospital. DISCLOSURE: B. McNab, None. INTERVENTIONAL BRONCHOSCOPY IN THE TREATMENT OF TRACHEAL OBSTRUCTION DUE TO THYROID CANCER Alessandro Ribechini, MD; Valeria Bottici, MD; Antonio Chella, MD; Rossella Elisei, MD; Paolo Vitti, MD; Aldo Pinchera, MD; Nicolino Ambrosino, MD*; Cardio-Thoracic Department. Pulmonary Unit, Pisa, Italy PURPOSE: Surgery is the treatment of choice of symptomatic tracheal obstruction due to malignant thyroid disease. Few additional therapeutic alternatives are available: Radiotherapy (RT), chemotherapy (CT) or radio-iodine therapy (131-I). Only few studies on interventional bronchoscopic procedures (IBP) as alternative procedures are reported so far. This study is a retrospective report of results of IBP performed in patients with severe tracheal obstruction due to thyroid cancer. METHODS: Since 1/1/2000 to 31/3/2004 14 consecutive patients (5 males, mean age: 62.2 yrs) underwent IBP due to tracheal obstruction for anaplastic (ATC : 7 patients), differentiated (DTC : 5), medullary (MTC : 1) and non epithelial malignant (NEMN: 1) thyroid cancer. 8/14 had local advanced inoperable disease ab initio, 6/14 had local relapse after surgery , 131-I or RT. Ten patients out of 14 were submitted to IB for severe dyspnoea. In 4 patients airways patency was maintained by insertion of a stent; in 3 the tracheal neoplasm was removed by Nd-YAG laser, in 7 both procedures were performed. RESULTS: All 10 patients with dyspnoea showed an improvement of symptom. Early and late complications were observed in 4 and in 3 patients respectively. All but 4 DTC patients died 11.9 ⫾ 14.2 months after the diagnosis (4.20 ⫾ 5.1 after IB). In 4 DTC patients still alive at follow up, 90.7 ⫹ 59.2 months since diagnosis and 16.7 ⫹ 9.2 since IB; the airways dilatations allowed following treatment like 131-I and/or RT. CONCLUSION: Interventional bronchoscopy, including Nd-YAG laser and airways stenting are alternatives to surgery in inoperable thyroid –induced tracheal obstruction. Moreover, the airway dilatation improve the dyspnea and allowed successive treatment. CLINICAL IMPLICATIONS: Interventional bronchoscopy should be considered as an option in the comprehensive treatment of thyroid cancer. DISCLOSURE: N. Ambrosino, None. CLINICAL UTILIZATION OF TRANSBRONCHIAL NEEDLE ASPIRATION BIOPSY(TBNA) OF MEDIASTINAL LYMPH NODES William C. Frey, MD; Dominic Gallo, MD*; William Conner, MD; David Bell, MD; Brooke Army Medical Center, San Antonio, TX PURPOSE: The accurate diagnosis of enlarged mediastinal lymph nodes is necessary for determining the most appropriate therapy in the treatment of both malignant and benign diseases. TBNA has been widely utilized as a nonoperative diagnostic tool. TBNA’s diagnostic accuracy ranges from 63-85%. The wide variation, mainly due to negative TBNA results(-TBNA), often requires mediastinoscopy(gold standard) for definitive diagnosis. Confident therapeutic decisions require knowledge of institutional diagnostic accuracy of TBNA before recommendations reCHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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patients) and manifestations of the underlying disease (7 patients). Neutropenia was moderate (ANC 1000-500/microliter) in 13 cases (34.2%) and severe (ANC ⬍500/microliter) in 25 cases. Ten patients also underwent Transbronchial biopsy (TBB). Procedure related complications were rare and limited to one intubation, two ICU admissions and the need for repeat-bronchoscopy in two patients because of inadequate samples. Bronchoscopic findings changed the management in 19 cases (50%). Glucocorticoids were added in 10 cases (9 patients with diffuse alveolar hemorrhage (DAH)), antibiotics were withdrawn in 6 patients and added in 4. In 19 patients (50%) bronchoscopy established a specific diagnosis. TBB contributed only one specific diagnosis not established by BAL and sputum analysis. Sputum sampling was infrequently utilized (9 patients) but provided diagnostic information in 6 cases of aspergillosis, supplementing BAL in 2 cases. Radiographic patterns did not predict the impact of bronchoscopy on diagnosis and management. Diagnosis and management changes had no impact on hospital-mortality. CONCLUSION: Bronchoscopy is a safe diagnostic procedure. It is a valuable tool to establish a diagnosis in patients with febrile neutropenia and chest-radiographic abnormalities. Bronchoscopic findings frequently result in alterations of management particularly if the diagnosis is DAH. TBB contributes very little to BAL and sputum analysis. Noninvasive techniques such as sputum analysis are underutilized. CLINICAL IMPLICATIONS: Even though survival benefits are not estabished bronchoscopy should be utilized to obtain a diagnosis and guide management of neutropenic patients. DISCLOSURE: T. Peikert, None.

Wednesday, October 27, 2004 Fiberoptic Bronchoscopy, continued garding mediastinoscopy can be made. Therefore, we reviewed our TBNA results and identified clinical predictors which yield positive TBNA(⫹TBNA). METHODS: We retrospectively reviewed data between 1997 and 2004. TBNA results were obtained and compared to pathologic diagnosis obtained from mediastinoscopy. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. ⫹TBNA was assumed to be a true positive, and did not undergo mediastinoscopy. Spearman correlation analysis, contingency testing, and multilogistic regression analysis was performed utilizing clinical variables that might predict a ⫹TBNA. A p-value less than 0.05 was considered significant. RESULTS: 92 TBNAs on 90 (49 male) patients were performed. Median age was 63 (range 27 -88). There were 71 malignant (60 NSCLC and 11 small cell) and 21 benign (16 sarcoidosis) diagnoses. Sensitivity was 76.6%, specificity 100%, positive predictive value 100%, negative predictive value 65%, and diagnostic accuracy 83%. Spearman coorelation indentified five risk factors that were important in predicting a ⫹TBNA. Contingency tests revealed the greater the number of risk factors present, the higher the probablility of a ⫹TBNA(Figure 1, p⬍.001). After multilogistic regression analysis, only lymph node size (⬎2.5cm) independently predicted a ⫹TBNA(p⬍0.05). CONCLUSION: TBNA at our institution has a diagnostic accuracy of 83%. Accumulation of defined risk factors predicts ⫹TBNA. Only lymph node size independently predicted an accurate diagnosis. Given low sensitivity and negative predicted value of TBNA, patients with a negative result should undergo mediastinoscopy. CLINICAL IMPLICATIONS: Patients with mediastinal adenopathy and a negative TBNA require mediastinoscopy for accurate diagnosis.

DISCLOSURE: D. Gallo, None. UTILITY OF LASER BRONCHOSCOPY AS ADJUNCT TO BALLOON DILATION FOR BENIGN TRACHEAL STENOSIS Maria del Mar Cirino-Marcano, MD*; Kathleen Williams, DO; Jennifer Greenheck, NP; Kevin L. Kovitz, MD; Tulane University School of Medicine, New Orleans, LA PURPOSE: Benign tracheal stenosis is a complication of endotracheal intubation and tracheostomy. Balloon dilation or laser bronchoscopy relieves symptoms and increasing airway lumen diameter. The benefit of the use of laser as an adjunct to balloon dilation deserves report. METHODS: Retrospective chart review of 53 patients with benign tracheal stenosis secondary to endotracheal intubation or tracheostomy treated with balloon dilation with or without laser bronchoscopy. All patients had refused or were not candidates for surgical resection. RESULTS: Twenty-six patients (17 women, 9 men) had interventions with balloon dilation with or without laser. All had symptomatic dyspnea. A total of 54 dilation interventions (mean 2.07) were performed (balloon dilation 38, balloon dilation with laser 16). All patients had immediate symptomatic relief. A total of 25 (65.8%) repeat interventions for repeat dilation were performed at one year in the balloon dilation group compared with 7 (43.8%) in the balloon dilation with laser group. There were 5 (13%) balloon dilation alone patients versus 4 (25%) in the balloon dilation and laser group who required only one procedure. Additionally, sixteen patients (50%) in the balloon dilation group needed a follow-up

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procedure for treatment of granulation tissue versus twelve patients (37.5%) in the laser and balloon dilation group. CONCLUSION: Laser bronchoscopy as adjunct to balloon dilation for benign tracheal stenosis results fewer interventions and less granulation tissue. CLINICAL IMPLICATIONS: Laser bronchoscopy should be considered as an adjunct to balloon dilation for the treatment of benign tracheal stenosis. A randomized, prospective trial is warranted. DISCLOSURE: M. Cirino-Marcano, None. EFFICACY AND SAFETY OF THE NEW EXCELON TRANBRONCHIAL NEEDLE: EXPERIENCE WITH THE FIRST 50 CASES Rex C. Yung, MD*; Johns Hopkins University, Baltimore, MD PURPOSE: Transbronchial Needle Aspiration (TBNA) is a effective minimally invasive bronchoscopic method to sample lung masses and intrathoracic adenopathy. It’s use amongst pulmonologists are limited by perceptions of technical difficulties including device failure, complications of bleeding and bronchoscope damage. We report our initial experience with a new TBNA needle (eXcelon) designed to address the above issues. METHODS: Patients with lung masses and intrathoracic adenopathy referred for bronchoscopy are studied. Lesions (lymph nodes and masses) are sequentially sampled with the potentially higest staged lesion sampled first. Separate needles are used for distinct lesions. Type of needle (caliber), samples aspirated and prepared on slides are identified sequentially. Bedside cytopathologyis available for all cases. Adequacy of sample and preliminary diagnosis is given at time of TBNA. Complications and adverse events: TBNA catheter kinking, failure of locking or retraction, airway bleeding or mucosa trauma, and bronchoscope damage are recorded. RESULTS: In this series of TBNA using the 21guage and 19guage eXcelon TBNA needles, yield of a positive diagnosis varies from 90% for primary lung cancer (100% for endobronchial tumor and 85% from lymph node and peripheral lung masses) to 87% adequate tissue sampling of benign lymph node or masses (sarcoid, aspergilloma and other granulomatous lesions). In the two to five month follow-up of non-malignant diseases, no new cancers were diagnosed. Complications include catheter kinking in 10%, dropped to 5% after use of the first ten needles. The eXcelon makes a larger entry hole, but there is no more than usual bleeding, and no pneumothoraces are noted. Overall ease of use is subjectively excellent because of design for single hand use of needle deployment and locking system. CONCLUSION: The new 21G and 19G eXcelon TBNA are easy to use, has excellent safety profile and have yield comparable to presently available needles. CLINICAL IMPLICATIONS: Improved end-user instrument compatibility and high yield may increase use of TBNA and improve diagnosis and staging of intrathoracic lesions. DISCLOSURE: R.C. Yung, Boston Scientific Microvasive

Pulmonary Interventional Procedures 12:30 PM - 2:00 PM DIRECT VISUAL GUIDANCE FOR CHEST TUBE PLACEMENT AFTER SINGLE-PORT THORACOSCOPY: A NOVEL TECHNIQUE Michael Zgoda, MD*; William Lunn, MD; Armin Ernst, MD; David Feller-Kopman, MD; Simon Ashiku, MD; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA PURPOSE: Thoracoscopy is a relatively simple and diagnostically useful procedure. Chest tube placement after medical thoracoscopy is necessary and placement of the tube in a specific location is challenging, as this is typically performed without real-time visual confirmation. A novel technique was devised to enable the placement of a chest tube under direct visualization without the need for a second port. METHODS: After performing pleuroscopy with a semi-rigid scope (Olympus, USA), a sterile Hopkins rod lens telescope (Karl Storz, Culver City, CA), was placed into the most proximal port of a twenty-eight French chest tube. The trocar was then removed, and under video Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Pulmonary Interventional Procedures, continued guidance, the chest tube was placed through the trochar site into the costodiaphragmatic gutter and the telescope was removed from the chest tube. A second chest tube was desired and again we utilized this technique to place the other tube along the posterior thorax toward the apex of the cavity. The chest tubes were sutured in place and a post procedure chest radiograph was taken to assure the tubes remained in their desired location after the lung was fully expanded. RESULTS: Two chest tubes were accurately placed under direct visual guidance into their respective desired locations without damage to surrounding structures. CONCLUSION: A rigid telescope can be utilized to enable and confirm accurate chest tube placement. CLINICAL IMPLICATIONS: This technique is a means of accomplishing accurate chest tube placement after thoracoscopy without increasing the risks associated with the addition of a second portal or prolonging procedure time. Future studies will investigate this method to reduce the incidence of malpositioned chest tubes inserted for other indications.

prone or sitting position; application of positive pressure support via facemask; administration of intravenous steroids if appropriate. 3)Awake fibreoptic bronchoscopic intubation is recommended if endobronchial intubation necessary. 4)Rigid bronchoscopy for endobronchial stenting should be accessible for immediate application if airway patency is not restored. 5)Standby ECMO as a temporizing life-saving measure. 6)Diagnosis should be established urgently so that specific therapy can be instituted, which includes surgery, chemotherapy, radiotherapy and palliative endobronchial stenting. CLINICAL IMPLICATIONS: A multidisciplinary approach using a flexible algorithm combining various modalities is required to optimize patient outcomes in this situation.

Table 1 – Clinical Characteristics and Interventions Patient/ Age(yr)/Sex

Lymphoma

2/20/M

Lymphoma

DISCLOSURE: M. Zgoda, None.

4/60/F

PURPOSE: Compression of the trachea, carina and main bronchi by mediastinal masses of benign or malignant pathologies may present as catastrophic airway obstruction. The situation may be inadvertently aggravated by conventional maneuvers intended to secure airway such as supine positioning of the patient and the use of paralytic agents during endobronchial intubation. We review the presentation, management and outcome of this group of patients in our institution. Various techniques to alleviate acute airway obstruction are discussed and an algorithm for the management of this life-threatening situation is proposed. METHODS: Retrospective review of the medical records of all patients who presented to our institution with life-threatening airway obstruction due to mediastinal masses, requiring urgent intervention and management in the Intensive Care Unit between March 1996 and December 2003. RESULTS: 8 patients with varied pathologies were identified (1 bronchogenic cyst, 3 lymphomas, 1 retrosternal goitre, 3 metastatic lymphadenopathies). The mean age was 37 years and 5 were females. 4 patients underwent successful endobronchial stenting; 1 patient failed stenting and required Extra-Corporeal Membrane Oxygenation(ECMO) whilst undergoing chemotherapy; 1 patient was supported with Continuous Positive Airway Pressure(CPAP) via facemask whilst undergoing chemotherapy; 2 patients went for curative surgery. All the patients were successfully weaned off the ventilator and transferred out of Intensive Care Unit. CONCLUSION: The following recommendations are made:1)Avoidance of airway manipulation, muscle paralysis and general anesthesia. 2)Immediate maneuvers include repositioning the patient in the lateral,

5/51/F 6/ 50/M 7/13/F

8/50/M

Intervention Failed endobronchial stenting via rigid bronchoscopy. Put on ECMO for 4 days while on chemotherapy.

Comment Airway obstruction precipitated by general anesthesia during open biopsy.

Endobronchial stenting via rigid bronchoscopy. Lymphoma CPAP via facemask whilst steroids and chemotherapy given. Metastatic Wall stenting via lymphadenopathy rigid bronchoscopy. Metastatic Wall stenting via lymphadenopathy rigid Metastatic bronchoscopy. lymphadenopathy Wall stenting via Bronchogenic rigid cyst bronchoscopy. Surgical resection. Retrosternal Surgical goiter resection.

* Etiologies of all cases except 4, 5, and 6 were undiagnosed at presentation with acute respiratory obstruction. DISCLOSURE: G. Phua, None.

AN EVALUATION OF SAFETY AND IMMEDIATE EFFICACY IN BRONCHIAL ARTERIAL EMBOLIZATION (BAE) FOR NONACUTE HAEMOPTYSIS Samuel Lee, MBBS*; Johnny W. Chan, MBBS, FCCP; C.K. Ng, MBBS; M.P. Lee, MBBS; W.L. Law, MBChB; T.L. Kwan, MBBS; Thomas Y. Mok, MBBS, FCCP; Queen Elizabeth Hospital, Kowloon, Hong Kong PRC PURPOSE: While bronchial arterial embolization(BAE) has been found to be useful in controlling acute massive hemoptysis, its role in non-acute cases has not been well studied. A study has been carried out CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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1/21/F

3/22/M

MULTI-MODALITY MANAGEMENT OF ACUTE AIRWAY OBSTRUCTION DUE TO EXTRINSIC COMPRESSION BY MEDIASTINAL MASSES Ghee Chee Phua, MBBS*; Philip Eng, MBBS, FCCP; Anne A.L. Hsu, MBBS, FCCP; Constance P.L. Lo, MBBS, MRCP; Singapore General Hospital, Singapore, Singapore

Etiology

Wednesday, October 27, 2004 Pulmonary Interventional Procedures, continued toevaluate the safety and efficacy of BAE performed on non-acute haemoptysis, in comparison to those performed during acute situations. METHODS: Hospital records of all patients undergone BAE in our hospital from 1999-2002 were studied. Cases were classified by the timing of the procedure in relation to their emergency admission for hemoptysis. Procedures performed more than 48 hours after admission and with hemoptysis subsided were classified as “non-acute”, which also included cases of chronic haemoptysis. Demographics data, co-morbidities, etiologies for hemoptysis, numbers of blood vessels embolized, immediate results and complications were recorded. Chi-square test was employed in statistical analysis for non-numerical variables, while independent t test and Mann-Whitney U test were used for numerical variables. RESULTS: Sixty-two bronchial arteriograms were performed in 59 patients. Forty-seven (75.8%) were classified as non-acute while 15 (24.2%) acute. Forty-eight (81.3%) were males (18.7%). Mean age was 64.1(SD⫽13.4). Bronchiectasis (59.6%) and pulmonary tuberculosis (59.6%) were the commonest underlying etiologies. Medical co-morbidities were present in 8 patients (13.4%), with no significance difference between two groups (p⫽0.234). BAE was performed in all but 5 cases: two had normal angiographic findings, two with failed attempts and one procedure terminated due to presence of hemomediastinum. Number of embolized blood vessels ranged from 1 to 5, without any signficant difference between the acute and non-acute groups (p⫽0.214). There were four episodes of complications (6.4%): three intimal dissections and one hemomediastinum. No mortality related to procedure was found. Although all complications occurred in non-acute cases, no statistical significant difference was found (p⫽0.56). No immediate recurrence of hemoptysis during that admission was found in all acute and non-acute procedures. CONCLUSION: BAE appeared to be safe and useful in the control of both acute and non-acute hemoptysis. CLINICAL IMPLICATIONS: BAE can be considered for cases of recurrent troublesome chronic hemoptysis. DISCLOSURE: S. Lee, None.

CUTANEOUS CARBON DIOXIDE TENSION MONITORING MIGHT ENHANCE PATIENT SAFETY DURING BRONCHOSCOPY AND MEDICAL THORACOSCOPY Prashant N. Chhajed, MD, FCCP*; Bruno Kaegi; Rajeevan Rajasekaran; Michael Tamm, MD; Division of Respiratory Medicine, University Hospital Basel, Basel, Switzerland

EBUS-TBNA – A NEW METHOD OF ENDOSCOPIC TRANSBRONCHIAL REAL TIME ULTRASOUND GUIDED BIOPSY FOR DIAGNOSIS OF MEDIASTINAL LYMPHNODES Felix J. Herth, MD*; Peter Vilmann, MD; Mark Krasnik, MD; Thoraxklinik, Heidelberg, Germany PURPOSE: TBNA is an established method for diagnosing mediastinal lymphadenopathy and staging of lung cancer. EBUS guidance seems to be beneficial in increasing the diagnostic yield. The auim of the present study was to gain experience with a new method of bronchoscopic ultrasound with direct, real time guided transbronchial needle aspiration. METHODS: Consecutive patients referred for TBNA of mediastinal lymph nodes were encluded in the trial. After detection of the node a ultrasound real time controlled puncture was performed. The results were compared to operative findings. Lymph node stations were classified after the recent ATS scheme. RESULTS: 214 patients (63 female, 151 male, mean age 53.9 years, range 22-79) were examined. Targeted were the lymphnodes region 2l, 3r, 3, 4r, 4l, 5, 7, 10r, 10l, 11r and 11l. The overall yield for was 89%. No complications were seen. CONCLUSION: EBUS TBNA is a promising new technique for lymph node staging. The yield increased to conventional TBNA. CLINICAL IMPLICATIONS: EBUS guidance should be considered as a routine adjunct to TBNA. DISCLOSURE: F.J. Herth, None.

BRONCHIAL THERMOPLASTY: LONG-TERM FOLLOW-UP AND PATIENT SATISFACTION Gerard Cox, MBBCh*; Miller D. John, MD; Annette McWilliams, MBBCh; Mark Fitzgerald, MBBCh; Lam Stephen, MD; St. Joseph’s Hospital, Hamilton, ON, Canada

PURPOSE: Oximetry is usually performed for patient monitoring during flexible bronchoscopy (FB) and medical thoracoscopy (MT). Monitoring of cutaneous carbon dioxide tension (PcCO2) may preceed severe hypoxemia by allowing intervention before the manifestation of severe hypoventilation. We examined the occurrence of hypoventilation during FB & MT by PcCO2 monitoring. METHODS: Following validation studies, PcCO2 was prospectively measured in 62 patients undergoing FB and 12 patients undergoing MT using a combined digital earlobe sensor measuring oxygen saturation (SpO2)(%) and PcCO2 (mm Hg) (Sentec, Therwil, Switzerland). All patients received supplemental oxygen. RESULTS: Mean duration of FB was 17 minutes and MT was 47 minutes. Mean midazolam dose administered during FB was 0.07 mg/kg and MT was 5.4 mg. Mean baseline and peak PcCO2 levels during FB were 38 mm Hg and 49 mm Hg and MT were 38.8 mm Hg and 50.2 mm Hg respectively. Mean increases in PcCO2 during FB and MT were 11 mm Hg and 11.4 mm Hg respectively. Mean duration from baseline to peak PcCO2 was 14 minutes for FB and 35 minutes for MT. During FB, 15 patients had SpO2 drop to ⱕ 90%. In 14 patients the SpO2 increased to ⬎ 90% with jaw support and in one patient a nasopharyngeal tube was inserted. Mean increase in PcCO2 in patients who did and did not manifest a lowest SpO2 ⱕ 90% during FB was 14.2 mm Hg and 9.5 mm Hg respectively (p⬍0.05). Mean fall in SpO2 during FB and MT was 4% and 5.2% respectively. During FB excessive coughing led to a transient artifactual decrease in pulse rate often accompanied by an artifactual drop in SpO2 whilst PcCO2 remained unchanged. CONCLUSION: Combined and continuous PcCO2 and SpO2 measurement permits monitoring of ventilation during FB and MT. CLINICAL IMPLICATIONS: Monitoring of ventilation during FB & MT may allow to better guide the administration of sedation and thus might improve patient safety. DISCLOSURE: P.N. Chhajed, None.

PURPOSE: Although there are many possible triggers, an acute asthma attack is usually characterized by contraction of the smooth muscle in the airway wall. Bronchial thermoplasty, a novel bronchoscopic treatment approach, aims to reduce smooth muscle contraction as a potential therapy for asthma. METHODS: We studied the safety of bronchial thermoplasty with the Alair System in 16 subjects with a range of asthma severity. Accessible airways distal to main bronchi and 3mm in diameter or greater were treated. Baseline and 12-week post treatment measurements included spirometry, methacholine challenge, and daily diary recording of peak flow, symptoms and rescue medication usage. The diary was maintained through 12 weeks. Objective measures of lung function were performed at subsequent annual visits. A patient survey designed to retrospectively assess the patient’s quality of life and satisfaction was administered after the one-year follow-up visit. RESULTS: Each patient was treated with approximately 120 total activations performed during three or four 30-minute treatment sessions. Side effects of the procedure were transient and typical of the types expected following bronchoscopy in patients with asthma. At 12 weeks, symptom-free days (p⫽0.012) and peak flow measurements (p⬍0.010) were improved over baseline. All patients had improvements in PC20 over baseline; the mean increase was 2.4 doubling doses (p⬍0.001). For the patients tested, PC20 values at the yearly follow-up demonstrated persistence of improvement over baseline out to 2 years. The patient survey was administered 14 to 36 months after the last treatment session. Seventyfive percent (75%) of patients believed they were less limited in their daily activities than they were before treatment; 25% believed they experienced no change. All 16 patients indicated that they would probably or definitely undergo the procedure again and would recommend the procedure to a friend or family member. CONCLUSION: This experience suggests that bronchial thermoplasty is well tolerated in selected subjects with asthma with follow-up to beyond one year. CLINICAL IMPLICATIONS: The efficacy of this procedure remains to be established through further controlled studies. DISCLOSURE: G. Cox, Asthmatx Inc.

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Wednesday, October 27, 2004 Pulmonary Interventional Procedures, continued SUCCESSFUL APPLICATION OF FLEXIBLE BRONCHOSCOPIC DILATATION AND TRACHEOBRONCHIAL STENTING WITH THE UTILIZATION OF NEWER HOLMIUM-YAG LASER IN THE RELIEF OF SYMPTOMS FROM TRACHEOBRONCHIAL OBSTRUCTIVE LESIONS Shamsuddin Khwaja, MD*; Alykhan S. Nagji, BS; Michelle C. Paul, BS; Rehal A. Bhojani, BS; John E. Hoopman, BS; Michael A. Wait, MD; J. M. DiMaio, MD; University of Texas Southwestern Medical Center, Dallas, TX

TWELVE-YEAR TREATMENT OF SEVERE TRACHEAL STENOSIS WITH SILICON PROSTHESIS Susana Padrones Sanchez, MD*; Alicia N. Rodriguez, MD; Teresa M. Argemi Coletas, MD; Pablo J. Diaz-Jimenez, MD; Bellvitge University Hospital, Bellvitge, Spain PURPOSE: To present an unusual case of severe tracheal stenosis treated with a silicon stent, left in place during 12 years. METHODS: Review of patient records. RESULTS: A 29-year-old female schisophrenic patient presented with a catatonic state when she was 17 years old, requiring long term mechanical ventilation. She needed a tracheotomy to wean from the ventilator. One year later she was hospitalized again with respiratory insufficiency requiring a second tracheotomy. She developed a tracheoesophagic fistula in the mid trachea, and underwent corrective surgery (resection and anastomosis). A Montgomery T tube was left in the trachea during 5 months, and then discontinued after and endoscopic examination showed satisfactory tracheal diameter.Three months later she presented to the emergency room complaining of progressive shortness of breath and stridor. A new bronchoscopy revealed a severe reduction in the tracheal lumen, with an 80% stenosis of approximately 2 cm in length. Significant retraction of both the lateral and posterior tracheal walls was observed; the soft tissue around had a great tendency to collapse (malacia). Since she was not considered a good candidate for a new surgery, a silicon stent (Dumon 13x50mm) was placed, with significant symptomatic improvement. The patient underwent periodical follow-up bronchoscopies, to assess both the status of the tracheal wall and the stent. The silicon prosthesis was changed approximately every two years. A progressive improvement in the malatic trachea was observed over time. Recently, it was decided to discontinue the prosthesis since the compromised tracheal segment was no longer stenotic and did not present wall

DISCLOSURE: S. Padrones Sanchez, None.

LONG-TERM COMPLICATIONS OF TRACHEOBRONCHIAL STENTING USING SELF-EXPANDING METALLIC STENTS–A SINGLE CENTER EXPERIENCE 1999-2003 Leonard C. Moses, MD*; McGuire Veterans Affairs Medical Center, Richmond, VA PURPOSE: The self-expanding metallic stent(SEMS) is an acceptable palliative therapy for advanced tracheobronchial disease in the absence of surgical alternatives. Immediate relief of symptoms and ease of administration makes stenting an attractive option for complicated tracheobronchial pathology. However, late complications related to granulation tissue, infection, and primary stent failure has been described. This study tracks our local experience over a four-year period for delayed stent complications requiring intervention or hospitalization. METHODS: Retrospective Study; single center; longitudinal tracking using the VAMC computerized patient record system/remote access system. RESULTS: 618 bronchoscopy procedures were performed by the Pulmonary Service at the Richmond VA Medical Center (1999-2003). 62 interventional procedures were performed, including 15 SEMS procedures in 12 patients for a total of 22 stents (Wallstent, Ultraflex; Boston Scientific Corporation). Primary diagnosis includes malignancy(4), transplant-related bronchial stenosis(3)or dehiscence(1), and benign tracheobronchial disorders with severe respiratory compromise(4). Immediate improvement was noted in 10/12 pts; survival beyond 30d was noted in 9/12. Patients still alive 5/9 (range 2mo-48mo post-SEMS). Late complications (beyond 30d) were seen in 7/9 pts. Patients with malignancy(4): no SEMS complications reported; deaths were related to pneumonia(1/4), underlying malignancy (2/4) or myocardial infarct (1/4). Transplantrelated disorders(4): one early death related to sepsis, one late death related to aspergillus. SEMS complications included recurrent infection with mucous plugging (3/4). Non-malignant tracheobronchial disease(4): no early deaths; one late death (11 months) due to COPD/hypercapneic respiratory failure. Late complications included recurrent infections (4/4), significant granulation tissue (3/4) and primary stent failure (2/4) requiring replacement SEMS. Multiple bronchoscopies were required in most patients, with ⬎5 procedures in 3/9; ⬎10 in 1/9; stent-related hospitalizations were common, including ⬎3 admissions in 5/9 pts. CONCLUSION: SEMS is a reasonable therapy, offering immediate palliation of symptoms if surgical treatment is not available. However, potential late complications may require multiple bronchoscopic interventions or hospitalizations. CLINICAL IMPLICATIONS: Further studies are recommended to determine the long-term benefits of tracheobronchial stenting. Newer stent designs and better patient selection may offer improved results with fewer late complications. DISCLOSURE: L.C. Moses, Boston CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Tracheobronchial obstructive lesions cause significant patient discomfort and increased morbidity. The Holmium-YAG laser has a depth of penetration and optic visualization that allows precise and controlled ablation of tissue. This is the largest case series describing the application of Holmium-YAG laser for tracheobronchial obstructive disease. METHODS: A retrospective analysis of patients undergoing surgical treatment of tracheobronchial obstruction from benign and malignant conditions. The study period was over 28 months. We utilized flexible bronchoscopy and Holmium-YAG laser. RESULTS: 34 patients were treated. Average age was 55.6 ⫾ 10.5 years (range 36-75). Twenty-seven (79%) had cancer, 18 had primary lung cancer. Seven patients had airway obstruction secondary to benign conditions. Eighty-five percent had American Society of Anesthesiologists (ASA) score of 3 or 4. Pre-operative pneumonia was present in 38% and 18% had lung consolidation. Total of 57 procedures were performed. Holmium-YAG laser was used in 46 procedures – 26 laser only and 20 with laser plus stenting. There was 1 (2.9%) operative death, 30-day mortality was 6/34 (17.6%), and hospital mortality was 7/34 (20.6%). Post-operative relief of symptoms was completely determined in 22 patients. Twenty patients had immediate improvement, 1 was worse, and 1 had no change in breathing. Average hospital stay was 3.6 ⫾ 8.4 days (range 0-59). CONCLUSION: Patients presenting with tracheobronchial obstruction in general have poor pre-operative functional status with significant discomfort. In this select group, symptomatic relief in breathing and functional status can be provided by the application of the newer Holmium-YAG laser combined with tracheobronchial dilation and stenting. CLINICAL IMPLICATIONS: This new technique enables a physician to open and maintain an airway that was previously inaccessible. It provides a reasonable technique that appears safe and effective. DISCLOSURE: S. Khwaja, None.

collapse. After six months, patient is stable and asymptomatic. Neither stenosis nor malacia have relapsed to present. CONCLUSION: To our knowledge, this is the first case a prosthesis has been left in place during a 12 year period. CLINICAL IMPLICATIONS: It is possible to keep a silicon prosthesis during prolonged periods of time to treat complex tracheal stenosis in selected patients. In such cases, periodical follow up bronchoscopies are mandatory, and regular prosthesis changes may be necessary.

Wednesday, October 27, 2004 Pulmonary Interventional Procedures, continued DIAGNOSIS OF PULMONARY DISEASES BY TRANSCUTANEOUS PULMONARY FINE-NEEDLE ASPIRATION IN A BRAZILIAN UNIVERSITY HOSPITAL Lucelia A. Henn, PhD*; Ellen A. Almeida; Fernanda B. Damian; Denise Manica; Gustavo B. Nabinger; Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil PURPOSE: To evaluate the applicability of Transcutaneous Pulmonary Fine-Needle Aspiration guided by ultrasonografy in the diagnosis of pulmonary lesions, including nodules, masses, inflamatory lesions and pleural effusions. METHODS: Transcutaneous Pulmonary Fine-Needle Aspiration guided by ultrasonografy was performed in 351 patients, from 1998 to 2002, with pulmonary lesions to obtain the diagnosis. Cytopathologic, histologic, microbiologic analysis were made. RESULTS: The diagnosis was obtained by the method in 240 cases (68,4%). Were analysed 247 pleural effusions/pleural samples, 74 masses, 18 nodules, 5 consolidations, 4 necrotising lesions and 1 lymph node. Among the pleural effusions/pleural samples, the diagnosis were obtained by the method in 129 cases, being: 42 pneumonias, 26 neoplasms, 20 tuberculosis, 11 empyema, 4 hemothorax, 1 cryptococcosis, 1 leishmaniasis and 22 cases of pleural effusion caused by non-pulmonary diseases. Among the masses, diagnosis was obtained in 66: 53 neoplasia, 4 pneumonias, 2 aspergillosis, 2 cryptococcosis, 2 cavitary lesions, 1 tuberculosis. Among the nodules, diagnosis was obtained in 15 cases: neoplasias in 1; 3 tuberculosis, 1 pneumonia. Consolidations showed diagnosis in all cases: 3 tuberculosis, 1 cryptococcosis, 1 pneumonia. Cavitary lesions: diagnosis in all cases, being 3 infections, 1 neoplasm. There were 1 case of hemothorax and 5 (1,42%) cases of pneumothorax after the exam. None needed of tube thoracostomy. CONCLUSION: Transcutaneous Pulmonary Fine-Needle Aspiration is useful in the diagnosis of pulmonary lesions and the risk of complications is very low. CLINICAL IMPLICATIONS: It is an important instrument of diagnosis for malignant lesions, however, it is also useful to diagnosis of benign lesions. Moreover, it can avoid to submitt patient to more invasive methods to obtain the diagnosis of pulmonary diseases. DISCLOSURE: L.A. Henn, None. HISTOLOGICAL EVALUATION OF BRONCHIAL AIRWAYS DURING IMPLANT AND AFTER REMOVAL OF INTRA-BRONCHIAL VALVES USED FOR VOLUME REDUCTION IN TWO ANIMAL MODELS David H. Dillard, BS*; Piper Treuting, DVM; Xavier Gonzalez, MD; Spiration Inc, Redmond, WA PURPOSE: Intra-bronchial valves (IBV) Spiration Inc. are being evaluated as palliative treatment for patients with advanced emphysema. Minimal tissue response around this non-stent device is highly desirable to maintain the valve function as well as allow for removal. In order to evaluate the tissue response to IBV devices, histological evaluation of implanted airways was performed in two species. METHODS: IBV devices were implanted in 8 sheep and 8 dogs. The animals were bronchoscopically observed at 1, 3 and 6-months. A scheduled number of devices were removed at each time-point from all but 2 of each species. At 1 and 3 months, 2 of each species were sacrificed; the remaining 6 animals were sacrificed at 6-months. For this analysis tissue samples were taken from the airways implanted with valves and from airways where devices had been removed in previous procedures. Each sample was graded on a 5-point scale (0-normal, 1-minimal, 2-mild, 3-moderate, 4-marked) for 8 response categories including mucosal changes (epithelial hyperplasia, cilia loss, metaplasia, ulceration), submucosal changes (edema, fibrosis, glandular hyperplasia) and inflammation. Average tissue response grades were calculated for each category and plotted against time and location to show trends. An average of all response category grades for the implanted airways was calculated for both species to determine the comparative level of tissue reaction for implant sites and removed device sites. RESULTS: The comparative level of tissue reaction reached a plateau approximately 1 month after implant (1-month: 2.1 ⫾0.8; 3-month: 2.26 ⫾0.81; 6-month: 2.39 ⫾0.85). After removal, resolution of changes occurred quickly, returning to near normal in 2-5 months (1-month removals: 0.45 ⫾0.53 at 3-months, 0.61 ⫾0.86 at 6-months; 3-month removals: 0.69 ⫾0.74 at 6-months). CONCLUSION: In these animal models, the average histological response to IBV implants was mild to moderate, preserving tissue and

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device functionality. Near complete resolution was observed after removal. CLINICAL IMPLICATIONS: In patients, limited tissue response may be a distinctive advantage of the IBV system to preserve function, facilitate removal and allow tissue recovery post-removal. DISCLOSURE: D.H. Dillard, Spiration Inc. SELF-EXPANDING METALLIC STENTS FOR MALIGNANT AERODIGESTIVE FISTULAE Gonzalo V. Gonzalez-Stawinski, MD*; Maria S. Rojas, MD; Thomas R. Gildea, MD; John A. Dumot, DO; Atul C. Mehta, MBBS; Sudish C. Murthy, MD, PhD; Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Malignant aerodigestive fistulae are rare but devasting sequelae of thoracic cancers. Most commonly associated with esophageal cancer, survival following fistula development is measured in weeks. Palliation is the primary goal of therapy and to this end, we report the use of self-expanding metallic stents (SEMS) as treatment of these fistulae. METHODS: Between May 1999 and January 2004, 12 patients were treated for malignant aerodigestive fistulae. The underlying diagnosis was esophageal cancer for 10 patients and non-small cell lung cancer in two others. All patients were symptomatic and fistulae were diagnosed by esophagoscopy in 7, bronchoscopy in 2, and esophagram in 3. Seven covered WallstentsTM (6 esophageal and 1 tracheal) and 8 covered UltraflexTM (5 tracheal and 3 esophageal) were used. RESULTS: A single stent was placed in 8 patients (6 esophageal and 2 tracheal). Three patients required esophageal and tracheal stents and one patient needed 2 tracheal stents. General anesthesia was required for 6 patients. There were no procedure-related complications. Symptoms were palliated in 100% (12/12) of patients and oral intake was reinstituted in 42% (5/12). All patients were discharged from hospital after SEMS placement and 1 patient returned for uneventful tracheal stent replacement secondary to mucus impaction 2 months later. CONCLUSION: SEMS placement is an effective strategy to palliate malignant aerodigestive fistulae. Complications are rare and symptoms are alleviated in most patients. CLINICAL IMPLICATIONS: SEMS have simplified the management of malignant aerodigestive fistulae. DISCLOSURE: G.V. Gonzalez-Stawinski, None.

Cardiovascular Diseases - Therapeutic Options 12:30 PM - 2:00 PM DUAL-CHAMBER RATE RESPONSIVE PACING INCREASES MORTALITY IN PATIENTS WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS Wilbert S. Aronow, MD; Rishi Sukhija, MD*; Carmine Sorbera, MD; Kiran Yalamanchili, MD; Martin Cohen, MD; New York Medical College, Valhalla, NY PURPOSE: To investigate in patients with automatic implantable cardioverter-defibrillators (AICDs) mortality at long-term follow-up of patients with dual-chamber rate responsive pacing at 70/minute (DDDR70) versus ventricular backup pacing at 40/minute (VVI-40). METHODS: We performed a retrospective study to determine allcause mortality in all patients at a university hospital who had AICDs without indications for antibradycardia pacing. Of 535 patients, mean age 70 years, 271 patients had backup ventricular pacing with a VVI-40, and 264 patients had dual-chamber rate responsive pacing with a DDDR-70. RESULTS: At 3.7-year mean follow-up, all-cause mortality was 19% (50 of 264 patients) in patients with DDDR-70 pacing versus 11% (29 of 271 patients) with VVI-40 pacing (p⬍0.01). CONCLUSION: Because of the increased mortality, increased costs, and complexity for dual-chamber rate responsive pacing in patients with AICDs, concomitant DDDR pacing at a rate of 70/minute in patients without an indication for antibradycardia pacing is not warranted. CLINICAL IMPLICATIONS: In patients with AICDs, concomitant DDDR pacing at a rate of 70/minute in patients without an indication for antibradycardia pacing is not warranted. DISCLOSURE: R. Sukhija, None. Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Cardiovascular Diseases - Therapeutic Options, continued EZETIMIBE AND COLESEVELAM ARE ADDITIVE IN THE MANAGEMENT OF HYPERCHOLESTEROLEMIA Michael J. Zema, MD*; Enoch Chan, MD; Brookhaven Memorial Hospital Medical Center, Patchogue, NY

ROLE OF INSULIN IN THE TREATMENT OF ACUTE MYOCARDIAL INFARCTION Avinash S. Bachwani, MD*; Anjali R. Kulkarni, MD; Mitesh G. Thakkar, MBBS; Sonali J. Patel, MD; St. Clare’s Hospital, Schenectady, NY PURPOSE: Metabolic Modulation as initially proposed by SodiPallares continues to remain an attractive option for adjunctive therapy in Myocardial Infarction. Although PCI/CABG have greatly improved the standard of care in the post-thrombolytic era, they may not fully exploit the potential for myocardial salvage by themselves. GIK serves to delay cell death until reperfusion can occur and optimize energy transfer in the post-ischemic heart. METHODS: 29 patients who sustained an Acute Myocardial Infarction were randomized to either Test or Control groups. In addition to standardized treatment, patients in the test group received High-dose Glucose-Insulin-Potassium infusion (Rackley Regime) while those in the control group received Normal-Saline. Apart from routine laboratory monitoring, levels of CK-MB were recorded at 0 & 24 hours. ST-segment scores, as measured by adding the total amount of ST elevation in mm in V1-V6 in Anterior Infarction & II-III-aVF in Inferior Infarction were also recorded at 0 & 24 hours. Complications relating to Angina, Arrhythmias, Heart-Failure, Biochemistry & other miscellaneous parameters were also recorded & compared amongst the 2 groups. RESULTS: Serum Insulin levels rose at 24 hours in both groups, although levels were expectedly much higher amongst test subjects due to the GIK infusion. CK-MB levels fell significantly (p⬍0.05) at 24 hrs compared to controls amongst both diabetic & non-diabetic sub-populations in the test group. ST-segment scores declined significantly (p⬍0.05) amongst non-diabetics while showing an encouraging trend amongst the diabetics. Glucose & Potassium levels were well controlled in test subjects reflecting the balance achieved in the milieu interior. Incidences of arrhythmias & angina were significantly lower (p⬍0.05) in the test group, although they had no statistical bearing on overall mortality. Only 1 patient experienced transient hypoglycemia.

Control Group

Test Group

‘t Test’ Values

Non Diabetics

40.8 (SD ⫽ 65.95) n ⫽ 5

Diabetics

50.28 (SD ⫽ 90.50) n ⫽ 7

-33.3 (SD ⫽ 46.20) n ⫽ 10 - 49 (SD ⫽ 63.791) n ⫽ 7

2.55; p ⬍ 0.05 * 2.3; p ⬍ 0.05*

Statistical Significance of Difference in ST Segment Scores at 24 Hrs. Control Group

Test Group

‘t Test’ Values

Non Diabetics

- 1.4 (SD ⫽ 7.127) n ⫽ 5

Diabetics

- 2.42 (SD ⫽ 5.940) n ⫽ 7

- 4.2 (SD ⫽ 2.201) n ⫽ 10 - 3.28 (SD ⫽ 2.870) n ⫽ 7

3.9024; p⬍ 0.05* 1.1713

Distribution of In-Hospital Events with Statistical Significance Event

Control Group

Test Group

Chi Square Test

Angina Reinfarction APC, VPC Bigeminy NSVT Ventricular Tachycardia Ventricular Fibrillation CHF Cardiogenic Shock Thromboembolic CVA Mortality

-2 (16.66%)

2 (11.76%) -

1 (8.33%) 1 (8.33%) -2 (16.66%) 1 (8.33%)

--1 (5.88%) 1 (5.88%) -

3.916, p⬍0.05* 1.777

2 (16.66%) 1 (8.33%)

2 (11.76%) -

3.27

-

1 (5.88%)

-

4 (33.33%)

2 (11.76%)

2.5

p ⬍ 0.05 - Significant CONCLUSION: GIK salvages ischemic myocardium, reduces complications & paves the way for both pharmacological & physical reperfusion. CLINICAL IMPLICATIONS: GIK is a cheap, reproducible & easily applicable adjunctive therapy devoid of the need for man-power or monitoring. With advances in Molecular & Cell-Biology techniques, Metabolic modulation has ample scope for research & implementation. DISCLOSURE: A.S. Bachwani, None. REDUCTION OF HIGH-SENSITIVITY C-REACTIVE PROTEIN AFTER TREATMENT WITH ANTI-SPASTIC AGENTS IN PATIENTS WITH CORONARY VASOSPASTIC ANGINA AND NO HEMODYNAMICALLY SIGNIFICANT CORONARY ARTERY DISEASE Ming-Jui Hung, MD*; Chang Gung Memorial Hospital, Keelung, Taiwan ROC PURPOSE: To assess whether treatment of coronary vasospastic angina with anti-spastic agents (calcium channel blockers and/or isosorbide dinitrate) can reduce the level of inflammation in patients with CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Recent studies suggest more rigorous lipid-lowering goals in comparison to previous guidelines. Statin Rx can be associated with bothersome side effects, and alternative treatment regimens must, therefore, be considered. METHODS: Twelve patients (PTS) (8 F, 4 M) mean age 64 yr (range 42-84 yr), average weight 176 lb (range 139-264 lb) with total cholesterol, LDL-C, HDL-C, non HDL-C and Triglycerides (TRIG) of 270, 192, 50, 220 and 147 mg/dl, respectively, were randomized open label to receive oral colesevelam (WEL) 1.875 g b.i.d. or ezetimibe (ZET) 10 mg q.d. After 6 weeks, the alternative agent was added (COMBORx). Six weeks later, the second agent only was withdrawn. Lipid panels, ALT and CK levels were obtained twice and averaged at baseline, on each mono Rx, on COMBORx, and again on mono Rx 6 weeks after washout of the second agent. RESULTS: Compared to baseline, LDL-C and non HDL-C fell by 20.3% (P⬍0.01) and 15.6% (p⬍0.01) and by 25.5% (p⬍0.001) and 22.5% (p⬍0.001), respectively, on mono Rx with WEL and ZET, respectively. In PTS on WEL, LDL-C and non HDL-C fell by an additional 19.1% (p⬍0.001) and 16.0% (p⬍0.001), respectively, when ZET was added. In PTS on ZET, LDL-C and non HDL-C fell by an additional 21.1% (p⬍0.005) and 16.4% (p⬍0.01), respectively, when WEL was added. Among the 8 PTS who took their WEL and ZET concomitantly, the additional decrease in LDL-C of 20.6% which occurred when the second drug was added did not differ from either the response of the remaining 4 PTS (19.1% decrease) or entire group of 12 PTS (20.1% decrease). WGT, HDL-C, TRIG, ALT, and CK were unchanged from baseline during any phase of study. CONCLUSION: WEL and ZET (COMBORx) are additive in lowering LDL-C and non HDL-C in hypercholesterolemic PTS. CLINICAL IMPLICATIONS: ComboRx is associated with a degree of LDL-C lowering [38.5%; (192 to 118 mg/dl)] and non HDL-C lowering [33.2%; (220 to 147 mg/dl)] which may represent an acceptable alternative for PTS intolerant of statin Rx. DISCLOSURE: M.J. Zema, None.

Statistical Significance of Fall in CK-MB Levels (mg/dl) at 24 Hrs.

Wednesday, October 27, 2004 Cardiovascular Diseases - Therapeutic Options, continued coronary vasospasm and no hemodynamically significant coronary artery disease. METHODS: Patients with a diagnosis of coronary vasospasm by intracoronary ergonovine testing were enrolled as the study group and patients who had no provoked coronary vasospasm as the control group. Highsensitivity C-reactive protein (hsCRP) levels were obtained before coronary angiography and 3 months after treatment with anti-spastic agents. RESULTS: There were 27 patients in the coronary vasospasm group and 29 patients in the control group. The proportions of the highest tertile of peripheral monocyte count and serum hsCRP level were significantly (p⬍0.001) elevated in the coronary vasospasm group. Multivariate analysis showed that hsCRP was independently associated with a diagnosis of coronary vasospastic angina (odds ratio ⫽ 5.44, 95% confidence interval ⫽ 1.60-18.47, p ⫽0.007). In the coronary vasospasm group, the initial mean level of hsCRP was 8.17 mg/l in the coronary vasospasm group and decreased significantly (p⫽0.001) to 2.95 mg/l 3 months after treatment. The level of hsCRP in the coronary vasospasm group after 3 months’ treatment was still significantly higher (p⬍0.001) than the baseline hsCRP level in the control group. CONCLUSION: This study demonstrated that treatment with antispastic agents decreases the inflammation status of coronary vasospasm in these patients as evidenced by hsCRP level. CLINICAL IMPLICATIONS: Coronary vasospasm with no hemodynamically significant coronary artery disease is an inflammatory coronary artery disease. DISCLOSURE: M. Hung, None. EVALUATION OF EFFICACY AND TOLERABILITY OF A FIXED DOSE COMBINATION OF LOSARTAN AND RAMIPRIL IN THE MANAGEMENT OF HYPERTENSIVE PATIENTS WITH ASSOCIATED DIABETES MELLITUS: LORD TRIAL (LOSARTAN RAMIPRIL IN DIABETIC HYPERTENSIVES) S. Joshi, MD, DM; M. Yeolekar, MD; Dilip R. Pawar, MD*; K. K. Tripathi, MD, DM; A. K. Maity, MD, DM; J. Giri, MD; M. Chopda, MD, DM; S. Maroli, MD; Unichem Laboratories Ltd, Mumbai, India PURPOSE: To evaluate efficacy and tolerability of combination of Losartan and Ramipril in the management of mild to moderate hypertensive patients with associated diabetes mellitus. The secondary objective was to evaluate the efficacy of the combination in reducing microalbuminuria. METHODS: The study was an open, non-comparative, multicentric clinical trial conducted in 7 centres in 325 patients. All the patients were treated with Losartan 50mg ⫹ Ramipril 2.5mg or Losartan 50mg ⫹ Ramipril 5mg once a day depending upon the baseline blood pressure for 12 weeks. RESULTS: The data was evaluated on a total of 315 patients. The mean prestudy systolic BP was 160.56⫹ 14.44 which was significantly reduced to 126.85 ⫹ 9.78 at the end of 12 weeks (P⬍0.001). Similarly the mean diastolic BP was 98.91 ⫹ 8.33 at baseline which was significantly reduced to 79.82 ⫹ 5.42 at the end of 12 weeks (P⬍ 0.001). A mean fall of 33.72 mmHg and 19.10mm Hg was observed in systolic and diastolic BP respectively which was statistically highly significant (P⬍0.001). The JNC-7 goal of blood pressure ⬍130/80 was achieved in 79.05% patients. At the end of the therapy 20.8% patients achieved normoalbuminuria. CONCLUSION: The fixed dose combination of Losartan and Ramipril showed good to excellent efficacy response in 98.10% patients and achieved a target blood pressure of 130/80 mm Hg in 79.05% patients and 98.41% patients reported good to excellent tolerability. The combination reduced the urinary albumin excretion in majority of the patients with microalbuminuria and proteinuria. CLINICAL IMPLICATIONS: Better control of blood pressure and reduces microalbuminuria. DISCLOSURE: D.R. Pawar, None.

molecules cannot be administered without a solvent in vivo. PEG can be employed to dissolve compounds to make them water soluble and usable. However, the effect of PEG on cardiovascular system has not been studied. The goal of this study is to test the effect of PEG on cardiovascular system in rat models. METHODS: All the experiments have been performed on two groups of male S-D rats weighing 250-300 g. The control group (10 rats) were subjected to intraperitonealy (IP) with 0.5 ml of 5% D/W in normal saline and the second group (6 rats) with PEG 400, 2 ml/Kg Ip, twice a day for one week. After 4 week under general anesthesia, a 1.4 French ultra miniature Pressure/Volume catheter was placed in left ventricle via right carotid artery to measure comprehensive hemodynamic changes. The data was acquired with Aria-1 Conductance System and analyzed with PVAN pressure-volume analysis software. RESULTS: All the systolic and diastolic parameters were similar in both groups except peripheral arterial elastance (Ea) which was decreased in PEG group. There were no significant differences in maximum (dp/ dtmax), and minimum (dp/dtmin) development of pressure stroke work, cardiac out put, ejection fraction, Vmax (maximum LV volume during cardiac cycle), Vmin (minimum LV volume during cardiac cycle), end systolic volume (Ves), end diastolic volume, dv/ dtmax, dv/dtmin and the peripheral arterial elastance (Ea). CONCLUSION: We have demonstrated that PEG as a solvent, decreases arterial elastance in rat models in comparison to placebo. Therefore PEG as a solvent should be used cautiously in cardiovascular research. CLINICAL IMPLICATIONS: PEG may effect Arterial Elastance and should be used causiously in cardiovascular reasearch.

HR/ min

Vmax

Vmin

Pmax

SV

EF%

CO EA micl/ SW mmhg/ minmmhg*micl micl

dp/dt max mmhg/ sec

dv/dt max micl/ sec

CONTROL

259.72

18.68

6.71

137.82

11.97

65.24

3085.13

1292.7

12.31

8087.83 324.98

PEG

261.51

21.83

7.97

131.28

13.86

64.88

3570.76

1407.5

8.77

9042.86 367.77

P Value

0.91

0.28

0.49

0.30

0.26

0.93

0.19

0.59

0.01

0.89

0.41

DISCLOSURE: S. Samsam Shariat, None. LONG-TERM EFFECTS OF DOMICILIARY BILEVEL NONINVASIVE POSITIVE PRESSURE VENTILATION (NPPV) ON SLEEP APNEA, CARDIAC FUNCTION AND SYMPATHETIC NERVOUS ACTIVITY IN STABLE CONGESTIVE HEART FAILURE Hitoshi Koito, MD*; Keiko Kohno, MD; Katsuya Maruyama, MD; Satoshi Morita, MD; Hiroshi Yutaka, MD; Kansai Medical Univerity, Otokoyama Hospital, Yawata, Kyoto, Japan

PURPOSE: PEG (Poly Ethylene Glycol) is a solvent and used in a wide range of biomedical applications including use in research as a precipitating agent for proteins and other macromolecules. Many fatty acid based

PURPOSE: The purpose of this study is to assess the effects of long-term domiciliary bilevel noninvasive positive presurre ventilation (NPPV) on sleep apnea (AP), cardiac function and sympathetic nervous activity in stable congestive heart failure (CHF). METHODS: The subjects were 6 patients with CHF (5 dilated cardiomyopathy and 1 old myocardial infarction) who completed 1 year of domiciliary NPPV, and divided into central SA (central apnea index (CAI)ⱖ8615;3 cases) and obstructive SA (CAI ⬍8315). These patients were examined with SpO2, chest and abdominal wall motion, nasal air flow sensor and electrocardiographic monitoring system (TEIJIN, Morpheus C) and urinary noradrenaline level during sleep under room air and NPPV before (Control;C) and after 1 month (1M), 4 month (4M) and 1 year (1Y) of domiciliary NPPV. Next morning mood index (NMI), chest rentgenogram, Doppler-echocardiography, respiratory function, serum noradrenaline and Epworth sleepiness scale (ESS) were also evaluated before and after 1M, 4M and 1Y of NPPV. RESULTS: Apnea hypopnea index (AHI) improved from 23/h (C;Air) to 9 (C;NPPV), 9 (1M;NPPV), 10 (4M;NPPV) and 10 (1Y;NPPV), and obstructive SA contributed to this. CAI improved from 11 (C;Air) to 2 (C;NPPV), 2(1M;NPPV), 3 (4M;NPPV) and 1 (1Y;NPPV), although CAI of 1M;Air, 4M;Air or 1Y;Air did not show significant change, and central SA contributed. Left ventricular (LV) systolic dimension decreased from 50mm (C) to 46 (1M), 43 (4M) and 43 (1Y), and obstructive SA

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STUDY OF CARDIOVASCULAR AND ITS HEMODYNAMIC EFFECTS OF PEG (POLYETHYLENE GLYCOL) IN RAT MODEL Mohammad R. Movahed, MD; Seyed Ahmad Samsam Shariat, M.D.*; Mehrnoosh Hashemzadeh, Ph.D.; University of California, Irvine, Irvine, CA

Wednesday, October 27, 2004 Cardiovascular Diseases - Therapeutic Options, continued contributed. LV ejection fraction and % fractional shortening increased from 42, 21 (C) to 51, 28 (1M), 53, 29 (4M), and 56, 32 (1Y), respectively. Right ventricular systolic pressure decreased from 43mmHg (C) to 35 (1M), 33 (4M) and 35 (1Y), and central SA contributed. Serum noradrenaline had decreased tendency in 1M and 1Y. CONCLUSION: Long-term domiciliary bilevel NPPV improved SA, cardiac function and sympathetic nervous activity in patients with stable CHF. CLINICAL IMPLICATIONS: Long-term domiciliary bilevel NPPV may be the useful complementary therapy to improve SA, cardiac function and sympathetic nervous activity in patients with stable CHF. DISCLOSURE: H. Koito, None.

EFFECTS OF ASSISTED VENTILATION ON BRAIN NATRIURETIC PEPTIDE LEVELS IN ELDERLY HEART FAILURE PATIENTS WITH CHEYNE-STOKES RESPIRATION Yi M. Yuan, MD*; West China Hospital of Sichuan University, Chengdu, Peoples Republic of China

“ADEQUATE”“ RATE CONTROL IN ATRIAL FIBRILLATION Kimberly Parks, DO; Jerry Jones, MPH; Joseph E. Parrillo, MD; Umaima Fatima, MBBS*; Toby R. Engel, MD; Cooper University Hospital, Camden, NJ PURPOSE: In atrial fibrillation (AF) conventional practice is to stringently control ventricular rate. However, the effect of rate control on exercise performance is not clearly established and stringent control may in fact worsen quality of life (QOL). We examined whether stringent control of the ventricular response to AF in fact had an adverse effect on exercise performance and QOL. METHODS: Exercise performance was measured by a 6-minute walk test and QOL by a questionnaire, before and after decreasing control of ventricular response by beta blockers, calcium channel blockers and digoxin in various combinations. RESULTS: Eight patients with chronic AF were all being treated with multiple drugs to rigorously control their ventricular rate, reflecting the practice in our referred population, not our study design. Their ages were 60-80 years; six were male. Seven had hypertension, two diabetes, and two coronary heart disease. None had symptoms of heart failure on treatment and 6 of 8 have normal left ventricular ejection fractions. Mean left atrial diameter was 4.7cm ⫹ 0.54 SD. Upon discontinuation of one or more drugs, average exercise heart rate increased from 84.3 bpm ⫹ 12 SD to 106.5 ⫹ 13, p ⬍ 0.002. Every subject walked further in 6 minutes (1,428 feet ⫹ 438 to 1797 ⫹ 535, p⬍0.002), and QOL improved in all but one (47.8 ⫹ 13 to 61.4 ⫹ 7, p ⬍ 0.005). The increased distance walked correlated with the improved QOL (r ⫽ 0.81). We intended a crossover design; however, all but one of our patients refused to resume their entry medications. In that patient, stricter control lead to a decrease in distance walked and worsened QOL. CONCLUSION: Adequate control of AF was achieved with fewer medications when “adequacy” was defined by exercise performance and QOL. CLINICAL IMPLICATIONS: Guidelines for control of rate in AF require further study with a crossover design but careful control may be inadequate control. DISCLOSURE: U. Fatima, None.

QUANTIFICATION OF OROGASTRICALLY ADMINISTERED ASPIRIN Stephen P. Wood, MS*; Boston MedFlight, Boston, MA

INTRAVENOUS PROCAINAMIDE FACILITATES VENTRICULAR ARRHYTHMIA INDUCTION IN BRUGADA SYNDROME Craig A. McPherson, MD*; Fadi Alsous, MD; Eteri Byazrova, MD; Bridgeport Hospital/Yale University, Bridgeport, CT

PURPOSE: To determine the practicality of administering 325 mg (4 tablets, 81 mg/tablet) of crushed aspirin tablets via an 18 French orogastric tube. METHODS: Tablets were crushed with a mortar and pestle device, and then solubilized in 60 mL of tap water. The suspension was then drawn up in a 60 mL catheter tip syringe and flushed through an 18 French orogastric tube into a retrieval container for analysis. A standard curve of several concentrations of aspirin was obtained using commercially prepared laboratory acetylsalicylic acid with a spectrophotometer. 5 mL aliquots of the orogastric dose were refluxed with 1 M NaOH. This solution was diluted with distilled water and complexed with 0.02 M FeCL3 solution. This final solution was evaluated spectrophotometrically at a wavelength of 530 nm. Data was plotted on a Beer’s plot and moles of acetylsalicyclic acid were converted to a quantitative value based on data from the standard curve.

PURPOSE: Brugada Syndrome is an entity in which people with no structural heart disease suffer ventricular tachycardia (VT) and sudden death. Its hallmark is an abnormal electrocardiogram (ECG) consisting of an atypical pattern of right bundle branch block (RBBB) with an unusual morphology of ST-segment elevation in leads V1 to V3. These alterations may be transitory and are often unveiled by antiarrhythmic drugs that block the sodium channel such as procainamide (PA). Recent studies have suggested that those patients with syncope or inducible VT in the baseline state at electrophysiology study (EPS) should receive an implantable cardioverter defibrillator (ICD) to improve their survival. We recently cared for 2 men whose ECG tracings demonstrated typical Brugada changes after PA infusion. Though no VT was induced in either at baseline, it was provoked in both after PA was infused. METHODS: The 2 patients underwent routine history and physical, ECG, echocardiogram, cardiac catheterization and EPS. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Cheyne-Stokes respiration with central sleep apnea (CSRCSA) has been detected in as many as 50% of patients with chronic congestive heart failure(CHF). The presence of CSR-CSA in a patient with CHF confers a worse prognosis. Unfortunately,there are few data on treating CSR-CSA in patients with CHF. The plasma concentration of several neurohormones has been shown to be independent markers of left ventricular ejection fraction(LVEF) and mortality in patients with heart failure.Our study was to compare the effects of assisted ventilation(Autoset CS, ResMed, Australia) on clinical outcomes and plasma BNP concentrations in elderly patients with heart failure and CSR-CSA. METHODS: 25 consecutive patients with stable heart failure were underwent overnight polysomnographic study, echocardiographic evaluation and 6 minute walk test before and after treatment. In addition to standard therapy,patients with CSR-CSA(n⫽16) were treated by Autoset CS for 4 weeks. Plasma BNP concentrations were measured by radioimmunoassay. RESULTS: Plasma BNP levels were significantly greater in patients with CSR-CSA than in patients without CSR-CSA[458.6⫾228.6ng/ L(n⫽16) vs 245.4⫾212.4ng/L(n⫽9), p⬍0.01]. Plasma BNP levels were negatively correlated with LVEF(r⫽-0.78, p⬍0.01) and 6 minute walk distance(r⫽-0.58, p⬍0.05). There was positive correlation between BNP and central apnea-hypopnea index(AHI, r⫽0.64, p⬍0.05) in patients with CSR-CSA. Autoset CS treatment was associated with decrease of plasma BNP levels(458.6⫾228.6ng/L to 245.4⫾181.4ng/L, p⬍0.05) and improvement of central AHI(31.5⫾9.6 per hour to 10.1⫾7.6 per hour,p⬍0.001), LVEF(0.29⫾0.18 to 0.38⫾0.22, p⬍0.05) and exercise capacity(220⫾114 meters to 332⫾121 meters, p⬍0.01). CONCLUSION: CSR-CSA is also common in elderly heart failure patients.Autoset CS is effective in treating CSR-CSA in heart failure patients according to clinical and neurohormonal changes. CLINICAL IMPLICATIONS: CSR-CSA should be a target for current heart failure treatment strategies.BNP plasma levels could reflect the level of therapeutic success in patients with heart failure. DISCLOSURE: Y.M. Yuan, None.

RESULTS: Five trials of this procedure were performed. The milligram values of the dosing regimens ranged from 54 - 110 mg. The mean value of a single dose of orogastrically administered aspirin was 78.2 mg. CONCLUSION: The standard practice of crushing aspirin tablets with a mortar and pestle, solubilizing in 60 mL of water and administering this suspension via an orogastric tube does not deliver an optimal dose of this drug. This study quantifies the dose of aspirin administered by this method, and reveals that approximately 24 % of the actual dose is actually delivered. CLINICAL IMPLICATIONS: Considering the importance of aspirin dosing in acute coronary syndromes, orogastric administration may not be an adequate method of delivering an appropriate dose. Alternative methods of administration, such as rectal administration, should be considered an alternative to orogastric dosing. DISCLOSURE: S.P. Wood, None.

Wednesday, October 27, 2004 Cardiovascular Diseases - Therapeutic Options, continued RESULTS: Patient 1 was a 51 year-old Korean man with atypical chest pain but no syncope or dizziness. Two of his 16 sibs had died (at ages 32 and 54). Patient 2 was a 38 year old Dominican man with atypical chest pain, 1 possible episode of syncope 3 months earlier and an episode of palpitations and dizziness while dancing 2 nights before admission. His mother and maternal grandmother had died between age 50 and 55. The physical exam, echocardiogram and cardiac cath data were normal in both men. At baseline their ECG demonstrated atypical RBBB and “saddleback” type ST-segment elevation in V1-2; no VT ⬎ 5 beats was induced. After PA, ST-segment elevation became more prominent and “coved” in appearance and ventricular fibrillation was induced in both. CONCLUSION: Procainamide may unveil heightened VT risk in Brugada patients in whom no arrhythmia is inducible at baseline EPS. CLINICAL IMPLICATIONS: Until further data become known, we recommend ICD implantation in patients with the Brugada ECG pattern and VT that is inducible in the baseline state or after intrravenous procainamide. DISCLOSURE: C.A. McPherson, None.

PRE-TREATMENT WITH PROPRANOLOL IMPROVES THE OUTCOMES OF CPR Gianluca A. Cammarata, MD*; Shijie Sun, MD; Lei Huang, MD; Wanchun Tang, MD; Max H. Weil, MD; ICCM, Palm Springs, CA PURPOSE: During cardiac arrest, global myocardial ischemia accounts for post resuscitation myocardial dysfunction. Based on earlier studies by Ditchey et al (J Am Coll Cardiol 1994) and by Tang et al. (Circulation 1995) we investigated the effects of non specific beta-adrenergic blockade on the outcomes of cardiopulmonary resuscitation (CPR) in an established rat model of cardiac arrest. METHODS: Ten Sprague-Dawley rats were randomized to receive either propranolol (1mg/kg) or saline placebo at 15 minutes prior to inducing ventricular fibrillation (VF). VF was untreated for 8 minutes. CPR, including chest compression and mechanical ventilation, was started at 8 minutes and defibrillation was attempted after 6 minutes of CPR. RESULTS: All animals were successfully resuscitated. Post resuscitation myocardial function, as measured by the rate of left ventricular pressure development at 40 mmHg (dP/dt40), was significantly better after pretreatment with propranolol in comparison with placebo. The number of post resuscitation ectopic ventricular beats was also significantly reduced and, importantly, the duration of survival was significantly increased (Table). CONCLUSION: Non-specific beta-adrenergic receptor blocking agent does not decrease the success of resuscitation but reduces both the severity of post-resuscitation myocardial dysfunction and improves survival of animals resuscitated after prolonged cardiac arrest. CLINICAL IMPLICATIONS: Use of beta-adrenergic bloking agent during cardiopulmonary resuscitation.

Table: Duration of survival, dP/dt40 (mmHg/sec) and ventricular premature beats (VPB) after resuscitation.

Treatment

dP/dt40 120 min, PR

dP/dt40 240

Number of VPB

Duration of survival

Propranolol

5760⫾540**

5450⫾570**

55⫾28*

62⫾10**

Control

4870⫾160

4510⫾390

92⫾33

20⫾17

PR ⫽ post resuscitation. **p⬍0.01 *p⫽0.05 vs Control DISCLOSURE: G.A. Cammarata, None.

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CHALLENGING THE RATIONALE OF THREE SEQUENTIAL SHOCKS FOR DEFIBRILLATION Gianluca A. Cammarata, MD*; Tommaso Pellis, MD; Carlos J. Castillo, MSEE; Wanchun Tang, MD; Shijie Sun, MD; Max H. Weil, MD; ICCM, Palm Springs, CA PURPOSE: The current guidelines of cardiopulmonary resuscitation (CPR) recommend that defibrillation may be attempted with up to three sequential shocks when ventricular fibrillation is identified. However, we hypothesized that the additional time required for repetitive rhythm analyses and recharging of the capacitor of 20 seconds or more prior to the delivery of the second and then the third shock in each sequence and the consequences of more prolonged interruptions of chest compression may compromise the success of defibrillation. METHODS: In 101 pigs ventricular fibrillation (VF) was electrically induced and untreated for between 4 and 7 minutes. After one minute of CPR, including precordial compression and ventilation, up to three sequential shocks were delivered. All animals were successfully resuscitated. For purposes of the present study we analyzed the success of the first, second, or third shock of the sequence. RESULTS: After the first shock 71% of the animals were restored to spontaneous circulation, 18% after the second shock, and only 11% after the third shock. Importantly, successful defibrillation was closely related to a threshold level of 15 mmHg of coronary perfusion pressure (CPP) and 16 mmHg of end-tidal CO2 (Table). The present study therefore indicates that it is the first shock in each sequence that is associated with the highest CPP and the greatest likelihood of successful defibrillation. The data support the earlier reports of Falk et al. (1988) and Paradis et al. (1990). CONCLUSION: The present study supports the use of a single electrical shock, especially when threshold levels of CPP or ETCO2 are achieved during precordial compression, rather than a sequence of three shocks. CLINICAL IMPLICATIONS: In ventricular defibrillation settings, deliver only one shock in lieu of three between chest compression increase the likelihood of successful defibrillation.

Table Sequential 1st 2nd 3rd

Resuscitated Animals

CPP

PETCO2

72 18 11

19⫾7**† 15⫾6 10⫾6†

16⫾6*† 12⫾2 11⫾2

†p⬍ .05 vs 2nd; **p⬍ .01 vs 3rd; *p⬍.05 vs 3rd. DISCLOSURE: G.A. Cammarata, None.

Cardiovascular Surgery Updates 12:30 PM - 2:00 PM SYSTEMATIC OFF-PUMP CORONARY ARTERY BYPASS: RISK FACTOR FOR ON-PUMP CONVERSION Hitoshi Hirose, MD*; Atsushi Amano, MD; Ruzheng Li; Juntendo University Hospital, Tokyo, Japan PURPOSE: We assessed the feasibility of systematic off-pump coronary artery bypass (OPCAB) and identified the risk factors for on-pump conversion. METHODS: Between 07/01/2002 and 12/31/2003, OPCAB was attempted for all patients who required isolated coronary artery bypass grafting (CABG) in our institution. The perioperative results of patients were prospectively entered structured database and the results were analyzed to identify the risk of requirement of cardiopulmonary bypass. RESULTS: OPCAB was performed in all but 4 patients, giving OPCAB success rate of 98.3% (229/233). The reason for cardiopulmonary bypass was hemodynamic instability occurred during the reoperative surgery in 3 (3/14, 21.4%), and cardiogenic shock developed after induction of general Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Cardiovascular Surgery Updates, continued anesthesia in 1 (1/1, 100%). OPCAB success rate was 99.5% (218/219) in primary CABG and 78.6% (11/14) in reoperative CABG, p⬍0.001. The risk factor for on-pump conversion was reoperation (relative risk 11.6, 95% confident level 5.7-619.1). Mean number of distal anastomosis by OPCAB was 3.7 ⫾ 1.2, and complete revascularization rate was 92.1% (211/229). There was one hospital death (0.4%, 1/233) due to perioperative myocardial infarction. Other postoperative complications included stroke in 2, mediastinitis in 2, respiratory failure in 2, postoperative bleeding in 1, and ventricular tachycardia in 1. During a mean follow-up period of 1.0 ⫾ 0.4 years, two patients developed angina, which were treated with catheter intervention; otherwise, no death, or other cardiac events were observed. CONCLUSION: Systematic OPCAB feasible except for the patients who are undergoing reoperative surgery or the patients who are experiencing on-going cardiogenic shock. Systematic OPCAB provided successful complete revascularization and its short term results were acceptable. CLINICAL IMPLICATIONS: Systematic OPCAB provided successful complete revascularization and its short term results were acceptable. DISCLOSURE: H. Hirose, None.

PURPOSE: Transmyocardial revascularization (TMR) was used as a sole therapy treatment for patients with severe angina not amenable to CABG and PCI. Several clinical trials have demonstrated significant angina relief at 12 months and beyond. Our single center results in patients who had TMR with a Holmium:YAG laser were previously reported and demonstrated significant angina improvement at 12 months. This longitudinal follow-up evaluated mid-term (3-year) mortality and angina status in those patients who received TMR. METHODS: From July 1999 to August 2002, thirty-nine (39) limitedoption patients underwent TMR via left anterior thoracotomy. Baseline characteristics included ejection fraction (mean 50), age (mean 67), previous CABG and/or PTCA [93%(36/39)], hypertension [90% (35/39)], triple-vessel disease [90%(35/39)]. Mean follow-up was 3.1⫹1.2 years (range 0.1 to 4 years). Canadian Cardiovascular Society Angina Scores (CCSAS) were determined in all consenting patients. RESULTS: Mean angina class was 3.1 at baseline and 1.2 at mean of three years, demonstrating significant angina relief (p⬍0.0001). Angina improvement (⬎2 class CCSAS reduction) was 78% (21/27) at 3 years. No patients required additional revascularization procedures (e.g. CABG, PCI and/or redo TMR) subsequent to their TMR therapy. At a mean of 3 years, the overall mortality was 13% (5/39). CONCLUSION: The significant angina relief that had been observed 12 months following sole therapy TMR in limited-option patients was sustained for three years. TMR data seen here, and in other reports, supports the application of TMR as an alternative revascularization strategy in this challenging patient population. CLINICAL IMPLICATIONS: TMR provides significant long term angina relief in patients who suffered end stage angina. It improves patient’s quality of life. DISCLOSURE: M. Alzeerah, None. DONOR TROPONIN-T LEVELS IN HEART TRANSPLANTATION: 7-YEAR FOLLOW-UP STUDY Palaniswamy Vijay, PhD*; Thomas G. Sharp, MD; Aly Darraca, RN; Yousuf Mahomed, MD; Mark W. Turrentine, MD; Jackie O’Donnell, MD; John W. Brown, MD; Indiana University School of Medicine, Indianapolis, IN PURPOSE: The donor heart must to be of high quality with less myocardial damage and highly viable cells at implant. In this study we report the intermediate term outcomes of patients who received hearts from donors stratified by serum levels of troponin-T (Tn-T, ng/ml) as an index of myocardial damage preoperatively. METHODS: Cardiac transplant recipients were divided into groups based on donor blood Tn-T levels ( I: 0.48 ⫾0.1, n⫽7; II: 3.84⫾0.6, n⫽11; III: 6.78⫾0.8, n⫽4). Rejections were identified in endomyocardial biopsies done every 2-3 months for 1 year after the surgery and yearly thereafter. Data regarding intermediate outcomes and hospital encounters of the recipients were obtained from medical records.

Group I II III

Mean # Biopsies(⫾SD)

Negative

1A/B

2

3

19⫾5 16⫾3 23⫾2

60% 51% 39%

40% 49% 38%

13%

10%

DISCLOSURE: P. Vijay, None. OFF-PUMP CORONARY ARTERY BYPASS REDUCES MORTALITY AND MORBIDITY IN A COMMUNITY HOSPITAL SETTING Christopher T. Strzalka, MD*; James Donnelly, BA; Dennis M. Michalak, MD; Michael D. Butler, MD; Jay Williams; Joseph R. McClellan, MD; Hamot Heart Institute, Erie, PA PURPOSE: Although off-pump coronary artery bypass (OPCAB) may result in improved clinical outcomes, there has been limited clinical adoption of this technique in the US. Further comparison of OPCAB with conventional on-pump coronary artery bypass (CABG) is needed to define and enhance ideal patient selection, especially as applied in routine clinical practice. METHODS: Comparative data was collected and analyzed on 2,471 consecutive patients (933 OPCAB, 1538 CABG) who underwent isolated coronary artery bypass between January 1, 2000 and December 31, 2003, at a single community hospital. The vast majority of OPCAB procedures were performed by a single surgeon (CS) who does OPCAB almost exclusively. Patient selection for OPCAB was based on individual surgeon preference. RESULTS: OPCAB and CABG patients were similar in age, gender, LV function, presence of left main coronary artery disease and most co-morbid conditions. CABG patients had a greater average number of grafts performed. Overall 4-year surgical mortality was 1.2%. OPCAB mortality was 0.6% versus 1.5% for CABG (Relative Risk (RR) 0.43, 95% Confidence Interval (CI) 0.17-1.05). There was less post-op respiratory failure with OPCAB (OPCAB 2.9% vs CABG 3.8%; RR 0.75, CI 0.48-1.18) in spite of the higher incidence of preop COPD. OPCAB patients also had lower rates of post-op sternal wound infection (OPCAB 1.0% vs CABG 1.8%; RR 0.52, CI 0.25-1.12), acute renal failure (OPCAB 0.4% vs CABG 1.0%; RR 0.41, CI 0.14-1.22), return to OR (OPCAB 1.3% vs CABG 1.9%; RR 0.68, CI 0.35-1.33), post-op stroke (OPCAB 1.2% vs CABG 1.5%; RR 0.78, CI 0.39-1.61), and post-op MI (OPCAB 0.3% vs CABG 0.7%; RR 0.49, CI 0.14-1.79). CONCLUSION: Although overall outcomes for CABG were excellent, OPCAB applied in a community hospital setting resulted in a substantial reduction in surgical mortality and morbidity. Patient selection bias may have influenced the outcomes, however our results affirm the value of OPCAB in routine clinical practice. CLINICAL IMPLICATIONS: The learning-curve for OPCAB is steep, and surgeon experience must be factored into any comparative trial conducted in the future. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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TRANSMYOCARDIAL REVASCULARIZATION IMPROVES THREE-YEAR OUTCOMES IN A SINGLE CENTER FOLLOW-UP STUDY Masoud Alzeerah, MD*; Northwest, Amrillo, TX

RESULTS: The majority of hearts (90%) came from donors with head trauma. Recipients underwent orthotopic heart transplantation for idiopathic dilated or ischemic cardiomyopathy. At a mean interval of 32.7⫾8.4 days post-transplantation, group I had 0, group II had 4.72 ⫾1 Grade 1, and group III had 4⫾2 rejections of Grade 3A. At the time of their most recent follow-up (mean 6.2 ⫾1.2 years), the rejection episodes were given in the table. Rejection episodes of Grade 3 necessitated increased doses of immunosuppressant therapy that was associated with reduced bone density. At last follow up, the LVEF and RV dimensions are normal in all recipients and do not significantly differ between the groups. The serum creatinine levels averaged 1.4⫾0.8. One patient died 4 years after transplantation due to cardiomegaly with mild biventricular hypertrophy and dilatation. All other patients exhibit normal cardiac function. CONCLUSION: The quality of donor hearts as measured by Tn-T levels predicts the frequency and severity of rejection episodes following transplantation. This does not appear to affect long-term cardiac function, but treatment for rejection episodes may affect bone density and thus quality of life. CLINICAL IMPLICATIONS: The assessment of donor heart before transplantation is critical and the condition of myocardium relates to future rejection episodes.

Wednesday, October 27, 2004 Cardiovascular Surgery Updates, continued Variables

Opcab

Percent

Cabg

Percent

Number Age Woman Mortality Obesity Pul Htn COPD EF⬍ 40% CHF Renal Dis Redo Left Main # of Grafts Lad Disease Circ Disease RCA Disease

933 66 313 6 92 41 211 292 32 61 29 196 3.0 854 670 738

37%

1538 65 453 23 183 37 193 443 41 46 77 340 3.9 1429 1284 1340

62%

34% 0.6% 10% 4% 23% 31% 3% 6% 3% 21% 92% 72% 79%

29% 1.5% 12% 2% 13% 29% 3% 3% 5% 22% 93% 83% 87%

DISCLOSURE: C.T. Strzalka, None.

PATIENT RISK-PROFILE, OUTCOME, COSTS AND PREDICTORS OF ICU READMISSION FOLLOWING ELECTIVE CABG Joseph Alex, OHP*; Rajesh Shah, FRCS; Alex R. Cale, FRCS; Steven C. Griffin, FRCS; Michael E. Cowen, FRCS; Sean Bennett, FRCA; Levent Guvendik, FRCS; Castle Hill Hospital, Hull, United Kingdom PURPOSE: Analyse risk-profile, outcome, costs and identify predictors of ICU readmission after elective coronary artery bypass grafting. METHODS: Prospectively entered data of 3120 consecutive CABG patients was analysed using Chi-square, t-test and multivariate logistic regression analysis. Group-A (n-118, readmission to ICU), Group-B (n-3002, routine single ICU admission). Respiratory failure, haemodynamic instability, acute renal failure and re-exploration were the main reasons for readmission. RESULTS: Preoperatively, Parsonnet (16 vs 7, p-0.0001), Euroscore (6 vs 3, p-0.0001), age (70 vs 64, p-0.0001), BMI (27 vs 28, p-0.03), COAD (21% vs 18%, p-0.001), PVD (21% vs 10%, p-0.001), renal dysfunction (6% vs 2%, p-0.003), unstable-angina (39% vs 8%, p-0.0001), CCF (38% vs 19%, p-0.0001), poor LV function (17% vs 4%, p-0.0001), inotropic support (4% vs 1%, p-0.001) cardiopulmonary bypass (74min vs 62min, p-0.0001) and ischemia (44min vs 34min, p-0.0001) times were higher in group-A. The gender-ratio, smoking, diabetes, hypertension, CVA, MI and coronary disease severity were comparable. Postoperatively, inotrope ⫹ IABP (73% vs 12%, p-0.0001), arrhythmia (73% vs 28%, p-0.0001), MI (12% vs 1%, p-0.0001), re-exploration (26% vs 3%, p-0.0001), blood loss (830mls vs 641mls, p-0.001), transfusion (799mls vs 235mls, p-0.0001), CVA (8% vs 1%, p-0.0001), renal dysfunction (42% vs 4%, p-0.0001), wound infection (12% vs 5%, p-0.002), sternal dehiscence (14% vs 1%, 0.0001), multisystem failure (11% vs 0, p-0.0001) and mortality (32% vs 1%, p-0.0001) were higher in group-A.Longer ICU (183hrs vs 30hrs, p-0.0001), HDU (9days vs 2days, p-0.0001) and ward stay (9days vs 5 days, p-0.0001) meant that the cost of care per patient in group-A was four times greater than group-B (£18,380 vs £4,335). CONCLUSION: Despite a four-fold increase in cost, the mortality rate of patients readmitted to ICU is 23 times higher than routine patients. Ischaemia time ⬎ 80 min, Parsonnet ⬎ 10, Euroscore ⬎ 9, sternal dehiscence, ventricular arrhythmias and postoperative renal dysfunction are predictors of readmission. CLINICAL IMPLICATIONS: Longer HDU care for high-risk patients based on predictors could be a cost-effective way to reduce mortality and readmission rate.

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Table – I. Predictors of ICU readmission in our analysis. Predictors

p-value

Odds ratio

95% confidence interval

X-clamp time ⬎ 80 min Parsonnet score ⬎ 10 Euroscore ⬎ 9 Sternal dehiscence VF / VT Postoperative renal failure

0.0001

4.1

2 –8.4

0.0001

4.7

2.4–9.2

0.0001 0.0001

29.6 9.7

10 –87.2 2.8–32.9

0.0001 0.0001

39.8 18.6

13.6–116.4 5 –69.5

DISCLOSURE: J. Alex, None. OFF-PUMP BYPASS SURGERY IN PATIENTS WITH LEFT VENTRICULAR DYSFUNCTION (LVD) Tahir Tak, MD, PhD; Zahir Rashid, MD*; Martha Linn, PA-C; Marshfield Clinic, Marshfield, WI PURPOSE: Approximately 30% of coronary artery bypass surgeries are done off-pump in the United States. Recent studies show some benefits of off-pump coronary artery bypass (OPCAB) surgery. This benefit is more significant in a selected group of patients. Our experience has shown that all patients benefit from OPCAB. In this study we reviewed all patients with LVD (ejection fraction less than or equal to 40%) who underwent OPCAB and compared them to patients who underwent conventional coronary artery bypass (CCAB). METHODS: Data from our prospective computerized database were collected and analyzed in a retrospective manner between 2000 and 2002. Patients with left ventricular ejection fraction less than or equal to 40% were included. Chi square test was used for categorical variables to evaluate the significance of results. For continuous variables the Wilcoxon Rank Sum Test was performed. RESULTS: A total of 103 patients with LVD (ejection fraction less than or equal to 40%) underwent OPCAB as opposed to 193 CCAB. Overall morality (⬍1% vs. 7%) and morbility were lower in OPCAB compared to CCAB. Length of hospital stay in OPCAB was 6.68 vs. 9.82 days in CCAB (p⫽0.0012). Blood transfusion rate was higher in CCAB patients compared to OPCAB (p⫽0.010). Six patients in the CCAB group required re-exploration for operative hemorrhage compared to 1 in OPCAB (p⫽0.0254). OPCAB patients also had a lower incidence of postoperative respiratory failure (p⫽0.001) and renal failure requiring dialysis (p⫽0.07). CONCLUSION: OPCAB is a safe technique with comparable morbidity or mortality compared to CCAB. In patients with LVD, the advantage of OPCAB over CCAB is more obvious. Prospective randomized studies in a larger series of patients are needed to support our findings. CLINICAL IMPLICATIONS: OPCAB is associated with fewer complications and results in decreased morbidity and mortality in patients with LVD. It may be the procedure of choice in such patients. DISCLOSURE: Z. Rashid, None. OPEN CARDIAC SURGERY IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES Shyama Bala, MD*; Mikhail Vaynblat, MD; Ajay Dhadwal, MD; Joseph Cunningham, MD; Maimonides Medical Center, Brooklyn, NY PURPOSE: Hematological malignancies are disorders characterized by malignant proliferation of immunologically incompetent leukocytes. There has been limited assessment of post-operative outcomes after open cardiac surgery in this patient population. Our study retrospectively reviewed outcomes after open cardiac procedures in these patients. METHODS: Twenty nine patients (ages 50-88 years, 24 men, 5 women) with hematological maliagnancies (11 chronic myelogenous leukemia (CML), 8 chronic lymphocytic leukemia (CLL), 7 with nonAbstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Cardiovascular Surgery Updates, continued CHARACTERIZATION OF PREMATURE ATRIAL CONTRACTION ACTIVITY PRIOR TO THE ONSET OF POSTOPERATIVE ATRIAL FIBRILLATION IN CARDIAC SURGERY PATIENTS C. A. Bashour, MD*; Mirela Visinescu, MS; Bala Gopakumaran, PhD; Oussama Wazni, MD; Frank Carangio; Jean-Pierre Yared, MD; Norman Starr, MD; The Cleveland Clinic Foundation, Cleveland, OH PURPOSE: The purpose of this study is to characterize conducted premature atrial contractions (PACs) that occur prior to the onset of postoperative atrial fibrillation (PAF) as an indicator of high probability of developing PAF. METHODS: A computer algorithm was developed to detect conducted PACs. To validate the algorithm, signals were randomly selected from collected ECG data. A staff cardiologist (OW) manually annotated conducted PACs. The 2-channel PAC detection algorithm was applied to the same set of signals to compare it to manual detection. The algorithm detected PACs with 91(⫾9)% accuracy. Twenty-four patients who underwent cardiac surgey and developed PAF were identified. The PAC detection algorithm was applied to analyze PAC patterns in these patients. RESULTS: Of the 24 patients who developed PAF, 21(87.5%)had PACs prior to the onset of PAF. These patients showed either a pattern of sustained uniform PAC activity (fig.1) or spontaneous bursts of high PAC activity interspaced with relatively quiet periods of PAC activity (fig. 2). CONCLUSION: In this study, PACs were identified and characterized in patients who developed PAF. There were two patterns of PAC activity prior to the onset of PAF. Either pattern, or both in combination, might be an antecedent pattern that indicates a high probability of new-onset PAF. CLINICAL IMPLICATIONS: If characterisic PAC patterns are shown to reliably predict PAF, pharmacologic interventions with agents

METABOLIC SYNDROME AND POSTOPERATIVE COMPLICATIONS IN CARDIOTHORACIC AND VASCULAR SURGICAL AND PERCUTANEOUS INTERVENTIONS Krishnaswami Vijayaraghavan, MBBS*; Michelle Jeffries, MS; Mara Windsor, BS; Anne Yost, BS; Bridget Stiegler, BS; Ned Williams, BS; Arizona Heart Institute, Phoenix, AZ PURPOSE: Metabolic syndrome (M.S.) constitutes a cluster of risk factors for cardiovascular disease such as hypertriglyceridemia, hypertension, diabetes, central obesity and low high density lipoprotein levels. Any three of the above risk factors qualifies to be classified as M.S. Many patients undergoing cardiovascular surgical and percutaneous interventions may not have been diagnosed and treated adequately for this syndrome so as to prevent perioperative morbidity. The prevalence of M.S and postoperative complications has not been described adequately in literature. METHODS: All patients undergoing cardiovascular and thoracic surgery and percutaneous interventions at a specialty hospital over a 12 month period between June 2001 and June 2002 were included in the study. Data was collected on demographics, risk factors, lab data and diagnostics preoperatively and type of intervention and postoperative complications. Patients were classified as having metabolic syndrome with at least 3 or 4 or 5 risk factors. Analysis was performed using SPSS version 12.0. RESULTS: Of the 312 patients, 68.6% were males and 31.4% females. M.S. was prevalent in 54.4% of patients with 33.3% having 3 risk factors, 14.4% having 4 risk factors and 6.7% having all 5 risk factors. Most frequent interventions were Percutaneous coronary interventions (27%), Endoluminal graft of aorta (16%), peripheral arterial interventions (15%), coronary artery bypass surgery (14%), abdominal aneurysm repair (11%), carotid endartectomy (10%) and femoral popliteal bypass surgery (5%). Most common postoperative complications include renal dysfunction (20%), blood transfusion requirement (17%), pleuropericardial effusion (12%), atrial fibrillation (7.4%), congestive heart failure (2%) and stroke (2%). Overall prevalence of complications was 42%. CONCLUSION: 1. Prevalence of metabolic syndrome is high in patients admitted to hospital for cardiothoracic and vascular surgical or percutaneous interventions. 2. Prevalence of postoperative complications is high in this high risk interventional procedure. CLINICAL IMPLICATIONS: An opportunity exists to identify patients with metabolic syndrome preoperatively in cardiothoracic and vascular interventions (both surgical and percutaneously) and implement preventative therapeutic strategies to decrease postoperative morbidity and mortality. DISCLOSURE: K. Vijayaraghavan, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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Hodgkin’s lymphoma (NHL), 2 Hodgkin’s lymphoma (HL) and 1 multiple myeloma) underwent open cardiac surgery (21 coronary artery bypass grafting (CABG), 2 aortic valve replacement (AVR), 2 CABG and AVR, 2 CABG, AVR and mitral valve replacement (MVR) and 1 pericardiectomy) in our institution between January 2000 and March 2004. The mean age was 71 ⫾ 2.5 years. The mean ejection fraction was 39.75%. Sixteen patients underwent CABG and cardiopulmonary bypass (CPB) performed using standard techniques of cannulation, moderate hypothermia and antegrade/retrograde cardioplegia. The rest underwent CABG without CPB (off pump). RESULTS: Hospital mortality occurred in two (6.9%) patients. Morbidity occurred in eight (26.6%) patients. Four (13.8%) had respiratory failure requiring prolonged mechanical ventilation, two patients developed renal failure, one had stroke and one developed sepsis in the immediate post operative period. There were no sternal wound infections. The average length of hospital stay was 11.72 days (3-74) days and the average length of post operative intensive care unit (ICU) stay was 6.68 days (1-68 days). CONCLUSION: The hospital mortality, morbidity and post-operative ICU and hospital stay in patients with hematological malignancies undergoing open cardiac surgery is highter than the general population. Respiratory failure, renal failure, sepsis and stroke are among the major causes for the prolonged post-operative stay and mortality. CLINICAL IMPLICATIONS: Open cardiac procedures performed in patients with hematological malignancies carry an increased risk of post-operative complications, mortality and prolonged hospital stay. These findings call for caution during patient selection. DISCLOSURE: S. Bala, None.

Wednesday, October 27, 2004 Cardiovascular Surgery Updates, continued used to treat PAF could be initiated when the characterisitc PAC pattern is first detected, and be continued during the highest PAF risk period (postoperative days 1 - 5) to decrease the incidence of this morbid postoperative complication. The clinical objective is that if the onset of PAF can be reliably predicted, PAF might be preventable in certain cases. DISCLOSURE: C.A. Bashour, None.

Mycobacterial Disease 12:30 PM - 2:00 PM TUBERCULOSIS IN HEALTH CARE WORKERS AT A GENERAL HOSPITAL IN TIJUANA, MEXICO Rafael Laniado-Laborin, MD*; Noemi Cabrales-Vargas, MD; Hospital General de Tijuana, Tijuana, Mexico PURPOSE: Tuberculosis (TB) is a potential occupational hazard for health care workers. This is especially true if basic infection control measures are not enforced. Our objective was to determine the rate of TB among health care workers at the Tijuana General Hospital during a five year period. METHODS: Retrospective study including all the cases of TB diagnosed among personnel of the hospital during the period of 1 January 1998 and 31 December 2003. The hospital is a 140-bed facility, that admits 77.6 ⫹- 12.2 new TB cases per year. Diagnosis was based on culture isolation of Mycobacterium tuberculosis. RESULTS: The mean number of employees per year at the hospital during that 5-year period was 819 ⫹- 21.7. Eighteen new cases of TB were diagnosed among them, for an overall rate of 439.5 per 100,000; this was 10.9 times higher than the rate for the general population of the city. The rate for physicians was 860.2 per 100,000, 365.8 per 100,000 for nurses, and 1,846.1 per 100,000 for physicians in training. This last group had a higher risk of TB than physicians (2.14, CI95% 1.3, 35.6) and nurses (5.04, CI95% 3.1, 83.3). The isolated strain was drug resistant in three cases (16.6% of the cases), one of them multidrug resistant (isoniazid, rifampin and pirazinamide). CONCLUSION: TB rate for the health workers at the Tijuana General Hospital is extremely high in comparison with that of the general population; this risk includes the transmission of drug resistant strains. CLINICAL IMPLICATIONS: Even in developing countries many of the most common factors contributing to tuberculosis transmission can be eliminated with simple and inexpensive control measures. The implementation of basic control measures is an urgent priority to reduce this occupational hazard at our institution. DISCLOSURE: R. Laniado-Laborin, None. SUCCESS OF TREATMENT OF INTERRUPTION OF PULMONARY TUBERCULOSIS (PTB) IS INVERSELY PROPORTIONATE TO THE DURATION OF INTERRUPTION & DIRECTLY PROPORTIONATE TO THE NUMBER OF DRUGS IN THE REGIMEN M. Ishaq, MD; SMI Khan, MD*; Al-Junaid Hospital, Nowshera, Pakistan PURPOSE: Treatment interruption of tuberculosis, resulting from lack of drug supply,improper drugs regimen, ATD duration may result in the emergence of drugs resistant tuberculosis(MDR), a simple ignorance of patients/health care providers may result in this tragic incidence. METHODS: In the Pulmonology department of Al-Junaid Hospital,Jan.2002-Dec.2003, 300 newly diagnosed patients with PTBwere registered,120 (40%)were AFB smear-positive. No evidence of MDR TB of registered patients( including male/female,18-65 years age, mean age 41 years). were documented by subsequent culture and susceptibility testing. Successful treatment outcomes were documented for 67 (56%) smearpositive patients, the remaining 53(44%) patients with poor outcomes, therapy failed in 12 (23%),30(57%) defaulted while 11(20%) died. In the later 3 died in the first month, 2 with in 2nd & 6 in the 3rd month of treatment. Treatment interruption of 2-8 weeks had been observed in 35 patients with 10 (29%), interrupted treatment, during the intensive phase(1-2weeks), 14 (40%) interrupted during the continuation phase (2-4 weeks), while 11(31%) during both phases of treatment(4-8weeks). The mean duration of interruption was on an average being 3 weeks, cough

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fever & anemia being the harbinger of interrupted ATD. Of 40 patients having successfully completed ATD, 24(60%) had 9 months, 14(35%)had 10 months & the rest of 2(5%) had completed 11 months of scheduled ATD. RESULTS: The incidence of MDR had been significantly higher amongst individuals with frequent interruptions & lack of supervised ATD therapy. CONCLUSION: Therapeutic interruptions even of shorter durations are of :utmost importance as strict patient’s adherence consequently leads to a successful therapeutic outcome. CLINICAL IMPLICATIONS: Chemotherapeutic interruption had been more amongst patients from remote regions, those with poor compliance even on repeated notification for ATD, also those with discontinuation of ATD on symptomatic relief with false impression of cure of infection. DISCLOSURE: S. Khan, None.

RESULTS OF SPUTUM SMEAR EXAMINATION FOR DIAGNOSIS OF PULMONARY TUBERCULOSIS UNDER PROGRAM CONDITIONS Jai Kishan, MBBS*; Govt. Medical College, Patiala, India PURPOSE: World Health Organization and Revised National Tuberculosis Control Program (RNTCP) of India recommends 3 sputum smear examinations(Day-1:1st spot,Day-2:Early morning specimen ⫹2nd spot) for diagnosis of pulmonary tuberculosis in patients having cough of 3 weeks or more.To evaluate the performance of RNTCP for diagnostic activities,a study to find out any gap between recommended guidelines and actual performance under program conditions need to be carried out. METHODS: A retrospective study of 3916 patients attending TB & Chest Hospital Patiala who were advised sputum smear examination was undertaken.A note was made of gender,number of sputum specimens examined and result of sputum examination. Findings were analyzed. RESULTS: Out of 3916 chest symptomatics,2221(56.71%) were males and 1695(43.28%) were females.Out of these 3916 patients,1354(34.5%) patients did not undergo requisite specimen examinations. 685(50.59%), 657(48.52%) and 22(1.62%) patients missed one, two and three specimens examinations respectively. Sputum examination on Day-1 was positive in 256(88.58%) males and 145(43.67%) females out of a total 289 males and 332 females respectively. CONCLUSION: One out of three patients did not undergo 3 requisite smear examinations. Although more females (19.58%) were having sputum positive than males (13.01%) but on Day-1, more number of males (88.58%) as compared to females (43.67%) were positive. Females may be feeling more comfortable at home for producing sputum for smear examination. Single day sputum smear examination cannot be recommended because only 401(64.57%) patients out of a total of 621 sputum positive patients were positive on Day-1. CLINICAL IMPLICATIONS: Since 34.5% patients didnot undergo 3 requisite sputum smear examinations, a foolproof methodology need to be implemented to trace the patients who miss the requisite number of smear examinations. All patients especially females should be told the importance of examination of 3 specimens. Patients should be demonstrated the correct technique of producing sputum specimen. Sputum specimen should be collected under supervision. A separate enclosure can be useful for producing sputum specimen to avoid hesitancy in front of onlookers. DISCLOSURE: J. Kishan, None.

A STUDY OF SOCIO -ECONOMIC IMPACT OF TUBERCULOSIS ON PATIENTS AND THEIR FAMILY Nirmal Chand, MD, FCCP*; Tejbir Singh, MD; J. S. Khalsa, MBBS; Vishal Verma, MBBS; Jorawar S. Rathore, MBBS; Medical College, Amritsar, India PURPOSE: To quantify the socio-economic impact of tuberculosis on patients and their families from the costs incurred by patients in rural and urban areas.. METHODS: An detailed interview based upon the prepared questionnaire was taken to collect socio-economic demographic characteristics, employment, income particulars, expenditure on illness and effects on children from newly detected sputum-positive pulmonary tuberculosis patients. The direct and indirect costs including money spent on diagnosis, Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Mycobacterial Disease, continued drugs, investigations, travel and loss of wages. Total costs were projected for the entire 6 months of treatment. RESULTS: The study population consisted of 200 patients (reporting at Chest & T.B. Hospital, Amritsar), 80 of whom were females. Mean direct cost was Rs. 1824/-, indirect Rs. 4129/- and total cost was Rs. 5953/-. The mean number of work days lost was 88 and mean debts totaled Rs. 2214/-. Both rural and urban female patients faced rejection by their families (8%). Twelve percent of schoolchildren discontinued their studies, an additional 7% took up employment to support their family. CONCLUSION: The total costs, and particularly indirect costs due to TB, were relatively high. The average period of loss of wages was 3 months. Care giving activities of female patients decreased significantly, and a 12% of schoolchildren discontinued their studies. CLINICAL IMPLICATIONS: These studies may be useful in eradicating social stigmas like rejection of tubercular patients in the society .Health education may help students to continue their studies in the school. DISCLOSURE: N. Chand, None.

PURPOSE: Diagnosis of pulmonary tuberculosis can be made with certainty only if the presence of mycobacteria is demonstrated in culture or smear microscopy of sputum. The present study was undertaken to compare various techniques for demonstration of mycobacteria (AFB) in smears, prepared by different techniques from sputum of patients suspected to be suffering from pulmonary tuberculosis. Results of culture for mycobacteria were taken as gold standard. METHODS: Early morning 100 samples of sputum from as many patients suspected to be suffering from pulmonary tuberculosis, on the basis of history, examination and chest radiographs were collected in sterile containers. The samples were mixed well on vortex mixer. Direct smears for Ziehl-Neelsen stain, cold stain and fluorescent stain were prepared. Part of sample was processed for concentration smear by petroff’s method and culture on L-J medium. Another portion of the sample was put to concentration by floatation method (Krawsnov and Lawrence, 1969). Smears prepared by petroff’s and floatation method were also stained by Z-N stain. RESULTS: As depicted in table I, floatation method proved to be the most reliable in demonstrating the presence of acid fast bacilli in sputum samples. CONCLUSION: Concentration by floatation method gives significantly better results as compared to direct smear (p⬍0.001). The next best was concentration smear by petroff’s method followed by fluorescent stained smears. CLINICAL IMPLICATIONS: Use of floatation method needs to be popularized as this method detects significantly more number of active pulmonary tuberculosis cases and also does not require any specialized equipment , electricity or skilled manpower as is the case with fluorescent microscopy or petroff’s concentration method.

Table I: Showing sensitivity, specificity and predictive value (Pv) of positivity of various methods. Direct Cold Fluorescent Concentration Floatation smear Stain stain smear method Sensitivity Specificity Efficiency Pv of positivity

57.4 97.8 76.0 96.8

51.8 100.0 74.0 100.0

62.9 93.5 77.0 91.9

DISCLOSURE: M.S. Parhar, None.

70.4 95.6 82.0 95.0

82.5 95.6 90.0 95.8

PURPOSE: A sizable population of multi drug resistant tuberculosis [MDR-TB] patients exists in India. Revised National Tuberculosis [TB] Control Program using DOTS caters all kind of TB but the MDR. The management of MDR-TB despite being challenging, difficult, and expensive carry poor prognosis. WHO recommends that such patients be managed by experts at specialized MDR centers. So as to have a clear insight about outcome of patients being treated at our MDR-TB center, we retrospectively analyzed their records. METHODS: We evaluated 60 patients registered at our center, [01.01.1999 -11.02.02]. The diagnosis was confirmed by culture and sensitivity depicting resistance to a minimum of isoniazid [H] plus rifampicin[R]. After base line liver and renal functions and having counseled patients and their families on anticipated problems, standard WHO regimens for MDR-TB were started on domiciliary basis. Patients were followed fortnightly during intensive phase [IP] and monthly during maintenance phase [MP] for general condition, adverse effects etc. Sputum smear and culture was done monthly during IP and quarterly there after. Chest X-Ray was done initially, on completion of IP and of MP. Compliance was assessed by pill counting and checking empty wrappers. RESULTS: Among 60 patients of 15 -60 years of age, male to female ratio was 2:1 and majority belonged to lower economic strata. All were HIV negative, 58 had pulmonary and 4 extra pulmonary TB. Most had taken 3-5years of prior chemotherapy. Fifty patients revealed resistance to 2-3 drugs [H, R, Streptomycin], resistance to more drugs was low and uncommon to reserve drugs. Sputum converted in 70% cases within 2- 8 months of chemotherapy, 18.3% had treatment failure, 21.6% defaulted and 11.6% died. CONCLUSION: Overall cure rate under unsupervised chemotherapy at MDR-TB centre was 66.6%, however, default rate [21.6%], mortality rate [11.6%], and failure rate [18.3%] was high. Drug toxicity occurred in 20% cases. CLINICAL IMPLICATIONS: The cure rate under unsupervised chemotherapy is quite favorable; however, it can possibly be further improved if treatment is given under direct observation. DISCLOSURE: A.K. Janmeja, None.

HEALTH RELATED QUALITY OF LIFE(HRQL) SCORING IN TUBERCULOSIS Jorawar Singh, MBBS*; Nirmal C. Kajal, MD; Mohinder Singh, PhD; Vishal Verma, MBBS; Medical College, Amritsar, India PURPOSE: To evaluate the impairment of health related quality of life in tuberculosis patients during treatment at 0 week, 4 week & 8 week by HRQL questionnaire. METHODS: 100 patients (15 years & older) put on treatment under RNTCP on DOTS categories at chest & TB Hospital Amritsar were included. All patients were subjected to pretested questionnaire used by Dhingra & Rajpal 2003. Questionnaire was based on symptoms (score I), Physiological, Psychological & social interaction of the patients (score II). Patients were asked to evaluate their symptoms on a scale of 1-3. RESULTS: : Data was analyzed after grouping the patients as DOT categories I, II, & III, in relation to site of disease (Pulmonary of extrapulmonary), sex and sputum status. It was observed that there was perceptible increase in the HRQL score at 4 week & 8 week in all categories of the patients as shown in table I. It was also noticed that increase in HRQL score in case of patients, who did not convert sputum negative at end of intensive phase, was low as compared to those who turned sputum negative. CONCLUSION: HRQL score is useful in quantifying the overall health of the patients as perceived by him/her. This is evident from the results of the study. The HRQL scoring increased as the patients improved with treatment. Betterment was observed in all the areas i.e. psychological, physiological as well as social interaction. Improvement was observed in both the males & females patients with pulmonary or extrapulmonary disease. HRQL questionnaire did discriminate among patients not showing improvement as indicated by their sputum positivity for AFB even after 8 weeks of treatment. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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COMPARATIVE STUDY OF VARIOUS METHODS FOR DETECTING MYCOBACTERIA IN SPUTUM FROM PULMONARY TUBERCULOSIS PATIENTS Mohinder S. Parhar, PhD*; N. C. Kajal, MD; Sandeep Gupta, MD; Deepak Aggarwal, MBBS; Medical College, Amritsar, India

EFFICACY AND SAFETY OF UNSUPERVISED CHEMOTHERAPY AT A MULTI DRUG RESISTANT TUBERCULOSIS CENTER IN INDIA Ashok K. Janmeja, MD*; Government Medical College, Chandigarh, India

Wednesday, October 27, 2004 Mycobacterial Disease, continued CLINICAL IMPLICATIONS: HRQL scoring in TB is useful as it provide hard data quantifying the health of the patient as perceived by the patients. However it has to be used with caution in individual patients and may not be taken as a substitute for observation made regarding clinical improvement.

DOTS Categories I II III

O week

4 week

8 week

22.92 ⫾2.23 22.04 ⫾ 4.92 22.61 ⫾ 15.7

28.10 ⫾1.38 26.5 ⫾ 5.73 28.57 ⫾ 1.77

33.10 ⫾2.85 31.80 ⫾ 7.10 34.07 ⫾ 1.71

DISCLOSURE: J. Singh, None.

MYCOBACTERIUM BOVIS INFECTIONS IN A NEW YORK CITY HOSPITAL: A CASE SERIES Rakesh V. Alva, MD; Christina M. Coyle, MD; Alpana Chandra, MD*; Albert Einstein College of Medicine, Bronx, NY PURPOSE: Mycobacterium bovis (M. bovis) is implicated in 0.1-1.4% of cases of tuberculosis in industrialized countries. This study describes the prevalence and manifestations of M. bovis infections in a Bronx hospital. METHODS: Microbiology records were reviewed from 1/98 until 2/04 to identify patients with culture isolates of M. bovis. RESULTS: Of 78 patients with tuberculosis in a 6-year period, 10 patients (1.3%) were identified with M. bovis infections. The mean age of the patients was 36⫾22 (range 4-76). Seven patients were male and 9 were immigrants. Patients immigrated 4.5⫾4 years before their illness. A child 4 years of age, who was born in the US, without any travel history, was exposed as an infant to visitors from Mexico who were coughing. One of 8 patients tested HIV positive. In addition, a woman was diagnosed during the third trimester of her pregnancy. Extrapulmonary involvement occurred in 7 patients. The following sites were affected: cervical lymphadenitis (1), salivary gland enlargement (2), genital (1), CNS(1), peritoneal (1) and pelvic abscess with osteomyelitis (1). Of these patients, only 2 had abnormal chest x-rays. There were 3 patients with isolated pulmonary involvement. Four patients had isolates resistant to pyrazinamide. All 10 patients were successfully treated with chemotherapy. CONCLUSION: The prevalence for M. bovis of 1.3% at our hospital may be due the large immigrant population. Extrapulmonary manifestations were common and patients were not likely to have comorbidities. Clinical disease was indistinguishable from M. tuberculosis. These patients probably have reactivated M. bovis, which was acquired in endemic countries. The case of the child without a travel history may be suggestive of human-to-human transmission. CLINICAL IMPLICATIONS: Clinicians should suspect M. bovis in patients who are from endemic regions,younger, immunocompetent and present with extrapulmonary granulomatous disease. Continued surveillance for this organism is important given intrinsic resistance to PZA in many isolates. DISCLOSURE: A. Chandra, None.

radiographic, microbiologic and physiologic studies, as well as treatment information and clinical response. RESULTS: Forty-nine patients were studied. The median age was 75 (interquartile range 62-78) years and 32 were female (65%). Twenty-one (43%) patients had predominantly middle lobe and lingular involvement. Eighteen (37%) patients were treated for at least 3 months with a multi-drug, macrolide-containing regimen (17, 14, 6 patients treated with fluoroquinolone, ethambutol and rifampin, respectively). Symptoms primarily drove the decision to treat, but retrospective analysis showed that 14/18 (78%) met diagnostic criteria. No patient discontinued therapy due to intolerance. After a median of 13 months of treatment, symptoms improved in 13/18 (72%) and sputum conversion occurred in 3/18 subjects (17%). Subjects with middle lobe and lingular involvement were treated less often than those with other imaging patterns (27% vs. 59%, p⫽0.04), and tended to respond better to treatment (88% vs. 60% clinical response, p⫽0.20). Nineteen patients had baseline and follow-up pulmonary function tests (PFTs) at a median follow-up of 28 (IQR 18-33) months. Agreement between symptoms and PFT change was poor. CONCLUSION: Pulmonary MAC patients with middle lobe and lingular involvement were less commonly treated and had a tendency toward better response. Antimicrobial therapy with a macrolide-based, predominantly non-rifamycin containing regimen was very well tolerated, and resulted in clinical but not microbiologic improvement in most patients. In this cohort, we were unable to demonstrate agreement between PFT and symptom changes. CLINICAL IMPLICATIONS: In patients with pulmonary MAC, middle lobe and lingular involvement represents milder disease and may predict better treatment response. Macrolide-based treatment improves symptoms, but the role of PFTs in disease monitoring is unclear. DISCLOSURE: S.R. Pendharkar, None.

SIGNIFICANT DIFFERENCE OF CLINICAL MANIFESTATIONS BETWEEN SMEAR NEGATIVE AND SMEAR POSITIVE PULMONARY TUBERCULOSIS Thomas C. Tsao, MD*; Ming-Long Chung, MD; Po-Yi Yang, MD; Wen-Ko Chiou, PhD; Buddhist Tzu Chi General Hospital, Hualien, Taiwan ROC

PURPOSE: To assess the management and outcomes of patients with non-HIV associated pulmonary Mycobacterium avium complex (MAC). METHODS: We performed a retrospective cohort study of patients referred to a tertiary care institution with pulmonary MAC isolates who were assessed by one of the investigators between January 1, 2001 and March 20, 2004. We collected data regarding demographic, clinical,

PURPOSE: Pulmonary tuberculosis (TB) with a positive smear signifies a larger bacterial population in TB lesions whereas several negative smears suggest a smaller bacterial load. The latter should have milder clinical symptoms and signs. METHODS: To confirm above hypothesis, we retrospectively reviewed the clinical records and chest radiographs of total 1,199 patients with positive sputum cultures in an University Hospital at Taiwan. RESULTS: In the 1,199 sputum-culture-positive pulmonary TB patients, 442 (36.9%) of them were smear-negative (SN) and 757 (63.1%) were smear-positive (SP). The mean age was significantly higher in SN (54.1 ⫾ 18.1) than in SP patients (51.4 ⫾ 17.2). The SN patients had less clinical symptoms of cough (84.2 %vs. 92.0 %), fever (50.0 % vs. 57.7 %) and body weight loss (62.5 % vs. 70.7 %). There were significantly more SP patients than SN patients with anemia (68.5 % vs. 61.5 %). In drug sensitivity tests, there was no difference of drug resistance between two groups for INH, RIF, EMB and KM, but SN patients had significantly more drug resistance for SM (17.9 % vs. 13.2 %). There were significantly more SN patients whose TB lesion involved within one lobe 38.7 % vs. 25.4 %), on the contrary, there were significantly more SP patients whose TB lesions involved three or more lobes (51.2 % vs. 37.9 %). The SN patients were more frequently than the SP patients with underlying diseases (54.1% vs. 45.0%). The former was significantly composed of more cancer patients. The mortality rate was significantly higher in SN patients compared to SP patients (12.7 % vs. 9.0 %). CONCLUSION: The SN patients were significantly older and with less clinical symptoms e.g., cough, fever, and body weigh loss. However the SN patients were significantly more common with underlying diseases such as cancer and which might account for the higher mortality rate. CLINICAL IMPLICATIONS: Patients with SN pulmonary TB usually have less clinical symptoms/signs but higher mortality. The physician should pay more attention to take care of them. DISCLOSURE: T.C. Tsao, None.

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MANAGEMENT AND OUTCOMES OF PULMONARY MYCOBACTERIUM AVIUM COMPLEX AT AN ACADEMIC CENTRE Charles K. Chan, MD, FCCP; Michael A. Hutcheon, MD; Theodore K. Marras, MD; Sachin R. Pendharkar, MD*; University of Toronto, Toronto, ON, Canada

Wednesday, October 27, 2004 Mycobacterial Disease, continued PREVALENCE AND EVOLUTION OF ANEMIA IN PATIENTS WITH TUBERCULOSIS Sei Won Lee, MD*; Deog Kyeom Kim, MD; Dong Seok Ko, MD; Chul-Gyu Yoo, MD; Sung Koo Han, MD; Young-Soo Shim, MD; Jae-Joon Yim, MD; Young Whan Kim, MD; Seoul National University Hospital, Seoul, South Korea

Table1. Distribution of Hemoglobin Sex Male Hemoglobin (g/dl)

⬃7.0 7.1⬃8.0 8.1⬃9.0 9.1⬃10.0 10.1⬃11.0 11.1⬃12.0 12.1⬃12.9 13⬃

Total

Female

Total

0 3 3 26 45 83 130 123 413

0 3 10 41 71 121 189 462 897

0 0 7 15 26 38 59 339 484

Table2. Risk Factors of Anemia Proportion of anemia Sex

Male: 28% Age; ⬍65 vs ⬎65 ⬍65: 28% Pulmonary vs Pulm: Extrapulmonary 32% TB

Female: 37% ⬎65: 49% Extra: 35%

Odds ratio (95% C.I.)

Significance (p value)

1.112 - 1.98

0.007

1.805-3.539

0.001

0.866-1.686

0.266

DOES HIV INFECTION CHANGES CLINICAL PICTURE OF DRUG RESISTANCE PULMONARY TUBERCULOSIS PATIENTS? AN INDIAN SCENARIO Govind N. Srivastava, MD*; Banaras Hindu University, Varanasi, India PURPOSE: There are some clinical features, which suggest emergence of drug resistance in patients who are on anti TB treatment and suspected by the persistence of symptoms. When these patients have co-infection with HIV, does there presentation differ? METHODS: 352 pulmonary TB cases were included in this study, whose sputum smear for AFB & culture were positive for M tuberculosis. All were having resistant to one or more than one anti TB drugs. 310 patients were HIV sero-negative while 42 were HIV sero-positive. Their clinical symptoms and sign were studied. The duration of illness was also noted. A study of their clinical presentation was analyzed among HIV sero-positive & negative group. RESULTS: Among 310 HIV sero-negative pulmonary TB cases, the symptoms were cough with/without expectoration (69.5%) followed by fever (65.9%), weight loss (63.04%) anorexia(60.80 %), breathlessness (47.4%) chest pain (45.36%), haemoptysis (16.5%), extra pulmonary involvement (9.27%) and lymph node enlargement (6.8%). The duration of illness was more then 2 Yr. in 78.32% cases. Among 42 HIV sero-positive cases, fever was in (82.75%) followed by cough (75.86%), weight loss (72.42%),anorexia (65.17%) breathlessness (55.17%), chest pain (41.37%), haemoptysis (13.95%), extra pulmonary involvement (11.2%) and lymph node enlargement was in 8.4% cases. The duration of illness was short and majority (62.8%) cases were within 2 years. CONCLUSION: The clinical presentation was same in both groups. Though extra pulmonary involvement was higher in HIV sero-positive group, but statistically insignificant. There were no distinctive clinical manifestation among drug resistance. HIV Sero-positive or negative group. The progression of disease was more rapid among the HIV positive patients. CLINICAL IMPLICATIONS: Studies from western world shows the extra pulmonary involvement is more in HIV infected cases than pulmonaryinvolvement. But in our study (INDIA) the high pulmonary involvement is because of high prevalence of pulmonary tuberculosis, may be due to re-activation of disease when they get infected with HIV, not like as in Western Countries, were tuberculosis is an opportunistic infection in HIV positive patients. DISCLOSURE: G.N. Srivastava, None.

THE HOSPITAL ADMISSION FOR TB AND THE RELATED DRG CLASSIFICATION SYSTEM Ciro Rampulla, MD*; Anna Maria Moretti, MD; Carlo Sturani, MD; Walter Arossa, MD; Franco Falcone, MD; Alfredo Potena, MD; Licia Ballerin, MD; Giovanna Magni, MD; Carlo Buniolo; Associazione Italiana Pneumologi Ospedalieri, Pavia, Italy PURPOSE: To split DRGs 79-80 hospitalizations into two populations that differ for mean length of stay (LOS): patients with tuberculosis (TB) and patients with respiratory infection and inflammations other than TB (NTB) in principal diagnosis. METHODS: Data are from PneumoSTAR project database, developed in Italy since 1999 by A.I.P.O (Associazione Italiana Pneumologi Ospedalieri) and QUBIsoft (236,000 discharge forms, 90 Italian Respiratory Units). We used data from 120,000 discharge forms, relative to years 2001-2002-2003. RESULTS: In 2001, DRG79 (n⫽1040, 2.7% of all DRGs) counted 336 TB (32.3%) and LOS⫽15.8 days; 704 NTB (67.7%) and LOS⫽16.9 : (LOS p⫽0.33) DRG80 (n⫽646, 1.7%) counted 326 TB (50.5%) and LOS⫽19.4; 320 NTB (49.5%) and LOS⫽12.9: (p⬍0.01). In TB, LOS is different between DRGs 79-80 (p⫽0.02); in NTB, the same but in the opposite way (p⬍0.01). In 2002, DRG79 (n⫽982, 2.9%) counted 349 TB (35.5%) and LOS⫽17.2; 633 NTB (64.5%) and LOS⫽ 5.3: (p⫽0.1). DRG80 (n⫽499, 1.5%) counted 253 TB(50.7%) and LOS⫽15.4; 246 NTB(49.3%) and LOS⫽2.7: (p⫽0.019). In NTB, LOS is different between the two DRGs (p⬍0.01); it isn’t so in TB (p⫽0.18). In 2003, CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Anemia is well-known hematologic abnormality in patients with pulmonary tuberculosis (TB). However, the prevalence of anemia varied in each study and the evolution of anemia with short course anti-TB chemotherapy has been not known yet. The aim of this study was to elucidate the prevalence, risk factors, and progression of anemia during the treatment in patients with TB. METHODS: 1063 patients who took anti-tuberculosis medication with diagnosis of TB from June 1st, 2001 to May 31st, 2002 in Seoul National University Hospital, Seoul, South Korea were enrolled. We retrospectively reviewed their medical records including the levels of hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration through the treatment period. Anemia was defined as hemoglobin concentration less than 13g/dL in men and 12g/dL in women. RESULTS: Among 1063 patients with TB, 166 patients were excluded because they had other causes of anemia other than TB. Among remaining 897 patients, 293(32.7%) patients had anemia initially. Anemia was usually mild, no man had hemoglobin concentration less than 8.0g/dL and no woman less than 7.0g/dL. Normocytic and normochromic anemia was most common and identified in 211 (72%) of patients with anemia. Microcytic and hypochromic anemia was next common (26 patients, 9%). Female sex (p⫽0.007, OR⫽1.11-1.98) and old age (p⬍0.001, OR⫽1.813.54) were associated with the presence of anemia while type of tuberculosis was not related with risk factor of anemia (p⫽0.266, OR⫽0.871.67). In 180 (61.4%) patients anemia was resolved and the mean of period from initiation of treatment to resolution of anemia is 118.8 (5-321) days. CONCLUSION: Mild anemia is common hematologic complication of TB and usually normocytic and normochromic pattern. The risk factors for presence of anemia were female sex and old age. In 60% of patients, anemia was resolved with anti-TB treatment. CLINICAL IMPLICATIONS: Anemia associated with TB usually has benign course, so we can observe it with treatment of TB. If anemia is

severe (Hb⬍8.0g/dl for men, Hb⬍7.0 for women), we should consider cause of anemia other than TB. DISCLOSURE: S. Lee, None.

Wednesday, October 27, 2004 Mycobacterial Disease, continued

DRG79 (n⫽710, 2.7%) counted 189 TB (26.6%) and LOS⫽15.8; 521 NTB (73.4%) and LOS⫽15.9: (p⫽0.96). DRG80 (n⫽339,1.3%) counted 135 TB (39.8%) and LOS⫽15.5; 204 NTB (60.2%) and LOS⫽12.3: (p⫽0.02). In NTB, LOS is different between the two DRGs (p⬍0.01); it isn’t so in TB (p⫽0.87). CONCLUSION: In 2001-2002-2003 both DRGs 79-80 produced by TB, hospital admission is decreased. In DRG80, TB cases are less than in DRG79: lower comorbidity can be explained by the younger age in TB patients (55.9 years) versus NTB patients (65.3 years). CLINICAL IMPLICATIONS: In DRG79, TB and NTB don’t differ in term of LOS, while this difference can be observed in DRG80. Moreover, TB LOS is not different in DRGs 79-80: it may means that in TB, the pathology itself determines LOS, and not the comorbidity. On the contrary, comorbidity has an important role on LOS in presence of respiratory infection and inflammations other than TB. DISCLOSURE: C. Rampulla, None.

LONG TERM TREATMENT OUTCOME IN MULTI DRUG RESISTANT TUBERCULOSIS(MDR-TB) Rajendra Prasad, MD*; K.G. Medical University, Lucknow, India PURPOSE: Multidrug resistant tuberculosis (MDR-TB) is an increasing worldwide problem which is notoriously difficult to treat and has greater risk of relapse. Our study analyzes the longterm treatment outcome with second line drugs in patients with MDR-TB. METHODS: A descriptive analyses of 39 consecutive patients with MDR-TB attending the department of Tuberculosis and Chest Diseases, King George Medical University, Lucknow, India between june 1998 to april 2002 with followup till april 2004. All patients were admitted for an average duration of 64 (15-136) days and received an individually tailored regimen essentially based on previous treatment history, chosen from Kanamycin, PAS, Ethionamide, Cycloserine, Flouroquinolone,Clofazimine. Kanamycin was used only for an average period of 4.2(2.5-6) months till sputum smear conversion, rest of the drugs continued for an average period of 20(18-25) months. Cure was defined when sputum culture was negative at the end of 2 year treatment. RESULTS: All the patients had resistance to atleast isoniazid and rifampicin with resistance to mean no of 4 drugs. Average duration of pretreatment chemotherapy was 26.9 months. All the patients were sero-negative for HIV. Out of 39 patients enrolled, 31 completed the treatment as planned. 2 patients died during the treatment and 6 patients abandoned it or lost to follow up. Out of 31 who had completed the treatment, 28 were declared cured. Considering the best scenario (excluding the lost and expired patients) cure rate was 90%(28/31) and in worst scenario (considering the lost and expired patients as failure) cure rate was 71%(28/39). Out of 28 cured patients, 21 patients came for follow-up for mean duration of 16 (range:3-48) months. 3 out of 21 (14%) patients showed relapse. Significant side effect was experienced in 8(19%) patients. CONCLUSION: MDR TB can be cured successfully and requires much effort from both the patients and health care workers. CLINICAL IMPLICATIONS: Adequate combination of drugs for an adequate duration under supervision can cure MDR-TB. DISCLOSURE: R. Prasad, None.

from April 1994 to March 2004. The diversity of pleural involvement, the underlying disorders, the causative pathogens, the treatments and the prognosis were analyzed. RESULTS: Eight patients (6 males and 2 females) were enrolled in the study. The mean age was 66.8 years old. Four had pleuritis associated with pneumothorax, two had pleuritis without pneumothorax and the other two had pyothorax associated with bronchopleural fistula. On the review of the chest radiographies, cavitary lesions were found in all pneumothorax patients. The rupture of the cavity was confirmed in three pneumothorax cases by chest CT. As the co-morbit conditions, all the patients were non-HIV, but three had underlying disorders: one patient was under steroid therapy for rapidly progressive glomerulonephritis, the other was after was after total gastrectomy, and the last one was receiving warfarin for chronic pulmonary thromboembolism. As causative pathogens, M. avium was isolated from four cases, M. intracellulare from two, M. kansasii and M. xenopi from each one, respectively. Chest drainage was required in six cases and surgery was performed in five. Two cases of pleuritis alone caused by M. avium or M. kansasii were medically treated without chest drainage and had good clinical courses. The prognosis was relatively good and all the patients survived except for one who was complicated with respiratory failure and undergone mechanical ventilation. CONCLUSION: Pleuritis was the most common form of pleural involvement of NTM infection, and M. avium was the most common pathogen. Cavitary lesions were found in all the patients who were associated with pneumothorax, suggesting the responsibility of such cavitary lesions in the pathogenesis of pneumothorax. CLINICAL IMPLICATIONS: Early surgical intervention is essential for successful treatment for NTM infection complicated with pneumothorax. DISCLOSURE: M. Kawabata, None.

PREVALENCE OF PULMONARY TUBERCULOSIS AMONG FORMER MINEWORKERS IN TRANSKEI, SOUTH AFRICA Banwari L. Meel, MD, FCCP*; University of Transkei, Umtata, South Africa

PURPOSE: To clarify the clinical features of pleural involvement in nontuberculous Mycobacteria (NTM) infection. METHODS: We retrospectively reviewed the medical records of NTM cases with pleural involvement who were admitted to our hospital

PURPOSE: It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis.1 In 1996 the World health Organization (WHO) estimated that South Africa had one of the highest TB incidence rates in the world. 2 Historical neglect of the TB epidemic, a fragmented health service due to the apartheid system, and poor management of TB have left a legacy characterized by high incidence rates of TB, especially in Transkei. Therefore, the purpose of this study is to determine the prevalence of current or past pulmonary tuberculosis (PTB), measure the distribution of PTB in different age and service categories and to establish the association between tuberculosis and silicosis. METHODS: Three hundred former mineworkers’ chest X-rays were selected randomly, and sent for reading by an independent Radiologist, between 1997 and 1999. RESULTS: Sixty-four percent (64.2%) former mineworkers were found to be suffering from PTB with or without silicosis: 35.8% PTB without silicosis, and 28.4% PTB with silicosis. PTB recorded high (62%) in the middle age groups (36 to 55 years) and those, who were exposed to dust from 6 to 20 years (72%). The association between PTB and silicosis has been established and found to be about 5-times (OR⫽5.08) higher in the former mineworkers who had silicosis. The p value found to be ⬍0.01 suggestive of that these results did not occurred by chance. Chi-square (27.30) is also confirming the validity of the study. CONCLUSION: The prevalence of PTB is 64.2% among former mineworkers. It is 62% among middle age-groups (36 to 55). PTB and silicosis have strong association (OR⫽5.08). CLINICAL IMPLICATIONS: It will help to clinicians, epidemiologists and health policy makers in understanding of the problem PTB in this region. DISCLOSURE: B.L. Meel, None.

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CLINICAL CHARACTERISTICS OF PLEURAL INVOLVEMENT IN NONTUBERCULOUS MYCOBACTERIOSIS Masateru Kawabata, MD*; Susumu Sakamoto, MD; Kazuma Kishi, MD; Eiyasu Tsuboi, MD, FCCP; Koji Narui, MD; Sakae Homma, MD, FCCP; Kunihiko Yoshimura, MD, FCCP; Toranomon Hospital, Tokyo, Japan

Wednesday, October 27, 2004 COPD Therapies: Antibiotics, Steroids, Bronchodilators, and Immune Modulators 12:30 PM - 2:00 PM ABSENCE OF ELECTROCARDIOGRAPHIC FINDINGS WITH DAILY TIOTROPIUM IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Steven Kesten, MD*; Cara Cassino, MD, FCCP; Craig Conoscenti, MD, FCCP; Boehringer-Ingelheim, Ridgefield, CT

Mean changes in heart rate (HR) from baseline (beats/min) HR (beats/min) ECG pre-dose ECG post-dose 24-hour Holter

Tiotropium 8 wks 12 wks

Placebo 8 wks 12 wks

0.87 -1.73 0.26

1.06 -0.11 0.73

-0.35 -2.09 0.2

1.55 0.65 0.55

Mean changes in heart rate (HR) from baseline (beats/min) DISCLOSURE: S. Kesten, Boehringer-Ingelheim CLINICAL EFFICACY OF 23-VALENT PNEUMOCOCCAL CAPSULAR POLYSACHARIDE VACCINE IN COPD PATIENTS Jesu´ s Mun˜ oz, MD; Inmaculada Alfageme, MD; Nuria Reyes, MD*; Mercedes Merino, MD; Jose Perez-Ronchel, MD; Jorge Lima, MD; HU Valme, Seville, Spain PURPOSE: The aim was to evaluate the clinical efficacy of 23-valent PCPV among COPD immunocompetent patients by use of a populationbased intervention in our health-area (South Area of Seville). METHODS: A randomized, controlled trial, in which COPD patients (FEV1⬍/⫽65%) were randomized to receive or not, PCPV. 600 patients were incorporated; 4 were missing during follow-up. 596 patients (mean age: 65.8⫾9.7 years) were finally included: 298 with PCPV and 298 without PCPV. End-point was pneumococcal pneumonia and pneumonia of any etiology. Pneumonia was diagnosed when the patient had symptoms of a lower respiratory tract infection and evidence of a new infiltrate

SWITCHING TREATMENT FROM IPRATROPIUM TO TIOTROPIUM IMPROVES SHORT-TERM CLINICAL OUTCOMES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Steven Kesten, MD, FCCP*; Walter G. Vincken, MD, PhD; Jan A. van Noord, MD, PhD; Piet J. Cornelissen, PhD; Boehringer Ingelheim, Ridgefield, CT PURPOSE: Tiotropium 18 mcg daily has proven superior to ipratropium bromide 36 mcg qid for multiple outcomes in trials of up to one year duration. However, it is assumed that short-term negative fluctuations in clinical status do not occur during the period immediately following the switch from ipratropium to tiotropioum. The purpose of this post-hoc analysis was to investigate potential changes in clinical status when treatment was switched from ipratropium to tiotropium in patients with COPD. METHODS: From previously reported one-year clinical trials (tiotropium vs. ipratropium), we conducted a post-hoc analysis of all patients receiving ipratropium prior to randomization. At randomization, these patients either continued with blinded ipratropium or were switched to blinded tiotropium. We compared the outcomes over the first 4 weeks on variables that would be indicative of clinical improvement or deterioration. Variables included the percent of patients with a mean weekly change in AM PEFR of ⱖ5% or ⱖ10%, or a mean weekly change in albuterol use of ⱖ1 puff/day, and the mean weekly percent of patients who had an exacerbation of COPD. The outcomes were defined by the relative risk (RR) (i.e., % in tiotropium group divided by % in ipratropium group). RESULTS: There were 332 patients from the entire cohort (n⫽535) who were receiving ipratropium prior to randomization. The mean age of the cohort was 65 years; 85% were men. Mean baseline FEV1 was 1.14 L (41% predicted). The RR for increases or decreases in AM PEFR and albuterol use are displayed in the table below. The cumulative RR of an exacerbation of COPD over weeks 1, 2, 3 and 4 were 1.32, 0.86, 0.69 and 0.74, respectively. CONCLUSION: In this post-hoc analysis, patients switched to tiotropium from ipratropium were more likely to have improvements in these short-term clinical outcomes than if they had remained on ipratropium. CLINICAL IMPLICATIONS: Conversion to tiotropium can be accomplished with the reasonable expectation of a prompt improvement in the clinical outcomes of COPD. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Although uncommon, increases in heart rate may be associated with inhaled anticholinergics. Tiotropium, an inhaled anticholinergic, provides 24-hour efficacy with once-daily dosing. While peak plasma levels occur within 5 minutes, steady state occurs following several weeks of treatment. We sought to examine electrocardiographic findings of tiotropium in COPD patients following acute and chronic dosing. METHODS: A 12-week, randomized, double-blind, placebo-controlled, parallel-group study was performed in COPD patients. ECGs (pre-dose and 5 minutes post-dose) and 24-hour Holter monitoring were performed at baseline and following 8 and 12 weeks of tiotropium 18 mcg once daily or placebo delivered via the HandiHaler®. Efficacy measures (spirometry, prn albuterol use, global COPD ratings, EQ5D) were included to demonstrate that the study population exhibited the characteristic improvements observed in previous tiotropium studies. RESULTS: 196 patients were randomized: mean age 65 years; 58% male; mean FEV1 1.022 L. Mean changes in heart rate (HR) from baseline (beats/min) were similar between groups (table below). There were no differences in percent of patients developing abnormalities in rhythms or conduction. Frequency of premature beats, and mean and maximal changes in PR, QRS, QT, QTcB and QTcF were similar between groups. No patients developed new onset QT or QTc ⬎500 msec; there were no differences in percent of patients developing new QT prolongation ⬍30 msec, 30-60 msec or ⬎60 msec. Cardiac adverse events were observed in 1 tiotropium and 4 placebo patients. At 12 weeks, improvements with tiotropium over placebo in morning pre and post-dose FEV1 were 184 and 265 mL respectively (p⬍0.001); prn use of albuterol was reduced by 25% (p⬍0.05). Global ratings of COPD by physicians and patients, and EQ5D visual analogue scale were improved with tiotropium (p⬍0.05). CONCLUSION: Tiotropium was not associated with electrocardiographic evidence of changes in heart rate, rhythm, QT intervals and conduction. Tiotropium provided spirometric and symptomatic benefits to patients with COPD. CLINICAL IMPLICATIONS: Tiotropium 18 mcg daily has a favorable therapeutic profile in patients with COPD.

on a chest radiograph. Pneumococcal pneumonia was considered by isolation of Streptococcus pneumoniae in blood, pleural fluid or bronchial samples. No intervention was made in the regular clinic or hospital care given to the patients by their physicians. All patients were followed for development of radiologically confirmed pneumonia, during a median period of 30 months (range 3-36 months). Conventional Statistical Analyses and Kaplan-Meier survival curves were performed with SPSS for windows (ver 11.5). RESULTS: Forty-one episodes of pneumonia were observed among patients who received pneumococcal vaccine and 42 episodes among those who did not. Nineteen of these 83 pneumonias were of known to be caused by agents different from streptococcus pneumoniae or with negative pneumococcal urinary antigen test; there were 64 pneumonic episodes caused by S pneumoniae or unknown germen: 30 (10.07%) among vaccinated-patients and 34 (11.4%) among non-vaccinated-patients. There were only four episodes of documented pneumococcal pneumonia and all of them were found among non-vaccinated patients (1.34%, Fisher test, p⫽0.062). Kaplan-Meier curves were slightly better for vaccinated patients although without statistical significance (p⫽0.3, Log Rank test). CONCLUSION: We do not find statistical differences in the incidence of pneumococcal and unknown etiology pneumonias between immunocompetent COPD patients with or without PCPV. CLINICAL IMPLICATIONS: Although we failed to prove statistical results, we recommend the use of PCPV in COPD patients due to we do not find pneumococcal pneumonia among vaccinated patients. DISCLOSURE: N. Reyes, SEPAR and SAS

Wednesday, October 27, 2004 COPD Therapies: Antibiotics, Steroids, Bronchodilators, and Immune Modulators, continued Albuterol (puffs/day)

AM PEFR

Increase Decrease Increase Decrease Increase Decrease ⱖ5% ⱖ5% ⱖ10% ⱖ10% ⱖ1 ⱖ1 Week Week Week Week

1 2 3 4

1.60 1.90 1.78 1.77

0.63 0.50 0.46 0.38

1.52 1.76 1.95 1.64

0.42 0.61 0.26 0.40

1.00 0.72 0.63 0.83

1.17 1.31 1.41 1.38

DISCLOSURE: S. Kesten, Boehringer Ingelheim

BACTERIOLOGIC ERADICATION OF HAEMOPHILUS INFLUENZAE IN PATIENTS WITH ACUTE BACTERIAL EXACERBATIONS OF CHRONIC BRONCHITIS: A COMPARISON OF MOXIFLOXACIN TO MACROLIDE AGENTS Michael Niederman, MD*; Antonio Anzueto, MD; Sanjay Sethi, MD; Shurjeel Choudhri, MD; Amar Kureishi, MD; Daniel Haverstock, MS; Renee Perroncel, BS; Winthrop University Hospital, Mineola, NY PURPOSE: H. influenzae is the most common pathogen associated with acute bacterial exacerbations of chronic bronchitis (ABECB). With increasing H. influenzae resistance to macrolides new treatment options are needed. METHODS: Data were pooled from four double-blind, multicenter, randomized trials comparing moxifloxacin (400mg QD x 5-10d) to macrolides (azithromycin 500mg/250mg QD x 5d, or clarithromycin 500mg BID x 5-10d) in the treatment of ABECB. Clinical and bacteriologic success rates for the efficacy-valid population were recorded at the test-of-cure (TOC) visit (7-37 days post-therapy). RESULTS: Of 910 microbiologically valid patients, 292 (32%) patients had infection with H. influenzae. The treatment groups were balanced based on demographic/baseline medical characteristics (62% male, mean age 55 yr, 58% current smokers, 29% past smokers, 61% ⬍⬍26⬎2 ABECB previous year). Comparative bacteriologic eradication and clinical success rates for moxifloxacin and macrolide agents are provided below. Moxifloxacin had consistently higher bacteriologic eradication rates than the macrolides in both patients with ⬍⬍26⬎2 or ⬎2 exacerbations in the previous year. CONCLUSION: For patients with ABECB due to H. influenzae, moxifloxacin consistently provided superior bacteriologic eradication rates than macrolide therapy. CLINICAL IMPLICATIONS: The superior bacteriologic eradication rates provided by moxifloxacin in the treatment of H. influenzae-associated ABECB may reduce the risk of antibiotic resistant mutants and prolong the infection-free interval in these patients.

Drug Comparison

Clinical Success

Moxifloxacin vs. 90% (128/ Macrolides 143) 85% (Clarithromycin⫹(127/149) Azithromycin) Moxifloxacin vs. 89% (72/ Clarithromycin 81) 88% (74/84) Moxifloxacin vs. 90% (56/ Azithromycin 62) 82% (53/65)

P-value*

P⫽0.278

93% (133/ 143) 73% (109/149)

P⫽0.001

90% (73/ 81) 64% (54/84) 97% (60/ 62) 85% (55/65)

P⫽0.001

P⫽0.156

* chi-squared tests DISCLOSURE: M. Niederman, Bayer

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Denis E. O’Donnell, MD*; Francois Maltais, MD; Peter Frith, MD; Anne Marie Southcott, MD; Steven Kesten, MD, FCCP; Alan Hamilton, PhD; Queens University, Kingston, ON, Canada PURPOSE: Both breathing discomfort and leg discomfort contribute to perceived symptom limitation in many COPD patients during incremental cycle ergometry (IE); perceived symptom limitation during constant work rate cycle ergometry (CWRE) has not been evaluated. In a double-blind, placebo-controlled study evaluating the effects of tiotropium on exercise tolerance in patients with COPD, we compared perceived symptom limitation during IE and CWRE, and evaluated the effects of tiotropium on perceived symptom limitation during CWRE. METHODS: 248 COPD patients performed IE and CWRE at screening, and CWRE after 6 weeks of treatment. Patients rated breathing discomfort and leg discomfort (Borg scale) at the point of symptom limitation and reported the perceived symptom limitation using a simple questionnaire (Hamilton et al CHEST 1996;110:1255). RESULTS: The table below shows the percentage of patients who perceived symptom limitation as breathing discomfort alone (BD), a combination of breathing and leg discomfort (BD / LD), leg discomfort alone (LD), neither breathing nor leg discomfort (None). There was a significant shift in perceived symptom limitation following treatment with tiotropium, with a reduction in the proportion of patients with BD alone as the perceived symptom limitation and an increase in the proportion of patients with LD alone as the perceived symptom limitation (p⬍0.01). At the point of symptom limitation, breathing discomfort was greater than leg discomfort at baseline (adjusted mean: 7 vs. 6.3 Borg units) and with placebo (7 vs. 6.5 Borg units), but breathing discomfort was less than leg discomfort with tiotropium (6.3 vs. 6.5 Borg units). CONCLUSION: As a result of tiotropium-induced reductions in exertional dyspnea, patients are more likely to report that leg discomfort contributes to symptom limitation during exercise. CLINICAL IMPLICATIONS: In the assessment of disability in patients with COPD, consideration should be given to the relative role of breathing discomfort and leg discomfort to symptom limitation.

Screening

Number of patients BD BD / LD LD None

Day 42 CWRE

IE

CWRE

Tiotropium

248

248

131

50.8% 33.1% 16.1% 0%

40.3% 43.5% 14.5% 1.6%

27.5%* 41.2% 29.8%* 1.5%

Placebo 117 41.9% 38.5% 18.0% 1.7%

* p⬍0.01 vs. placebo, Chi-square test

Bacteriologic P-value* Eradication

P⫽0.873

PERCEIVED LOCUS OF SYMPTOM LIMITATION DURING CONSTANT WORK RATE CYCLE ERGOMETRY IN COPD PATIENTS TREATED WITH TIOTROPIUM

P⫽0.019

DISCLOSURE: D.E. O’Donnell, Boehringer Ingelheim and Pfizer THE EFFICACY OF 5-DAY GEMIFLOXACIN ONCE DAILY FOR THE TREATMENT OF ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS (AECB) Glenn S. Tillotson, MS; Douglass Campbell, MD*; Gerry San Pedro, MD; Lionel Mandell, MD; University of Mississippi School of Medicine, Jackson, MS PURPOSE: To provide an overview of the efficacy of gemifloxacin once daily for the treatment of acute exacerbations of chronic bronchitis (AECB). METHODS: Three controlled studies (Studies 068, 070 and 069) and one open-label study (Study 061) were conducted to demonstrate the efficacy of gemifloxacin in the treatment of AECB. RESULTS: In the two principal clinical studies (Studies 068 and 070), the clinical and bacteriologic efficacy of gemifloxacin when administered for 5 days was at least as good as that of clarithromycin 500mg twice daily for 7 days Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 COPD Therapies: Antibiotics, Steroids, Bronchodilators, and Immune Modulators, continued and amoxicillin clavulanate 500mg/125mg tid for 7 days. In one supportive clinical study (Study 069), the clinical and bacteriologic efficacy of gemifloxacin when administered for 5 days was at least as good as that of trovafloxacin 200mg od for 5 days At the test of cure visit, the eradication rates of key AECB pathogens for the combined gemifloxacin treatment group from the principal and supportive clinical studies (Per Protocol population) were: H. influenzae (45/49, 91.8%), including beta-lactamase producing strains, M. catarrhalis (29/30, 96.7%), S. pneumoniae (15/20, 75.0%), including penicillin-resistant and macrolide-resistant strains, H. parainfluenzae (16/18, 88.9%), and S. aureus (5/7, 71.4%).In the open-label study (Study 061), high clinical and bacteriologic success rates were demonstrated with gemifloxacin 320 mg od administered for 7 days. CONCLUSION: These data support the use of gemifloxacin at a dose of 320mg for 5 days to treat AECB due to H. influenzae (including beta-lactamase producing strains), M. catarrhalis, S. pneumoniae (including penicillin-resistant and macrolide-resistant strains), H. parainfluenzae and S. aureus. CLINICAL IMPLICATIONS: Gemifloxacin represents a useful addition to the therapeutic options available to treat AECB. DISCLOSURE: D. Campbell, None.

PURPOSE: To demonstrate that five days of treatment with gemifloxacin is at least as effective as seven days of treatment with levofloxacin in adult patients with acute exacerbation of chronic bronchitis (AECB). METHODS: A total of 360 adults (⬎40yrs of age) with AECB were randomly assigned gemifloxacin 320 mg once daily for 5 days or levofloxacin 500 mg once daily for 7 days in a randomized, double-blind, double dummy, multicenter, parallel group study. RESULTS: In total, 335/360 patients completed the study (93.1%). Seven patients receiving gemifloxacin withdrew from the study compared to 18 patients receiving levofloxacin; this difference was statistically significant (Fisher’s Exact Test: p⫽0.02). In the ITT (intent-to-treat) population, the clinical success rate at follow-up (Day 14-21) was 85.2% (155/182) with gemifloxacin and 78.1% (139/178) with levofloxacin. Clinical success rate in the per-protocol (PP) population was 88.2% (134/152) with gemifloxacin and 85.1% (126/148) with levofloxacin. At long-term follow-up (Day 28-35), the clinical success rates in the PP population were 83.7% (123/147) with gemifloxacin and 78.4% (109/139) with levofloxacin. The difference in success rates was 5.26% (95% CI: -3.83, 14.34). In the ITT population, clinical success rate at long-term follow-up was 80.8% with gemifloxacin and 70.8% with levofloxacin. The 95% CI for the treatment difference (1.18, 18.78) shows statistical superiority of gemifloxacin over levofloxacin for clinical efficacy at longterm follow-up in the ITT population. CONCLUSION: The clinical efficacy of gemifloxacin 320mg once daily for five days in AECB was at least as good as levofloxacin 500mg once daily for seven days. Fewer withdrawals and superior clinical efficacy at long term follow-up were also seen with gemifloxacin. CLINICAL IMPLICATIONS: Gemifloxacin represents an excellent therapeutic option for the treatment of AECB. DISCLOSURE: G.S. Tillotson, Oscient Pharmaceuticals

ROLE OF 7-DAY AND 14-DAY COURSES OF ORAL PREDNISOLONE TREATMENT IN ACUTE EXACERBATION OF COPD Mostafizur Rahman, MBBS, FRCP*; Mostafizur Rahman, MBBS, FRCP*; S.M. Abdullah A. Mamun, MBBS, MD; M.D.A. Haque, MBBS, MCPS; NIDCH, Dhaka, Bangladesh PURPOSE: The purpose of this study was to compare the efficacy of 7-day and 14-day courses of oral prednisolone treatment in patients with acute exacerbation of COPD with FEV1⬍50% predicted. METHODS: It was a prospective randomized, single blind study in a tertiary care center, the study patients were included and randomized into

PILOT STUDY OF ANTI-IGE ANTIBODY IN THE TREATMENT OF SEVERE OBSTRUCTIVE PULMONARY DISEASE Clifford G. Risk, MD*; John L. Ohman, MD; Marlborough Medical Center, Marlborough, MA PURPOSE: Patients with asthma mediated by the allergen-IgE pathway may show a clinical benefit from treatment with hybridized antibody to IgE (omalizumab). Some patients with severe obstructive disease may also have a comorbid asthmatic component mediated by IgE antibody; we asked whether this patient group might also benefit from omalizumab. METHODS: We screened 250 patients in a pulmonary practice who carried a diagnosis of either asthma or chronic bronchitis. Twelve patients were identified who had clinically severe obstructive disease, primary or heavy secondary cigarette exposure, positive skin tests to one or more relevant allergens and an IgE of ⬎30IU/ml. The endpoints of the study were reduction in the number of acute exacerbations resulting in hospitalizations or in outpatient visits, reduction in inhaler usage, and improvements in dyspnea and in cough severity. Each patient served as his own control. The baseline period was the 12 month period prior to the first omalizumab injection. The treatment period began 1 month after the initial injection. RESULTS: The optimal FEV1 at baseline was ⬍ 60% predicted in 9 of the 12 patients (range 30% to 60%). Reversibility with bronchodilators (improvement ⬎ 20%) was present in just 2 of the 12. Eight patients have received omalizumab for 3 to 8 months (median 7.0 months), and their results are reported. (Four patients have received ⬍ 2 months of treatment). The total number of hospitalizations in the 8 patients decreased from 7 pretreatment to zero with treatment. Outpatient exacerbations decreased from 14 pretreatment to 1 with treatment. Inhalant usage decreased from 6.8 to 5.2/day/patient. Dyspnea improved in 6 patients. Of 4 patients with difficulty expectorating thick mucous, 3 improved. CONCLUSION: Preliminary observations suggest that omalizumab might be effective in treating patients with severe obstructive disease with evidence of IgE directed against relevant allergens. CLINICAL IMPLICATIONS: Patients with severe obstructive disease should be screened for an IgE-mediated allergic component and may benefit from treatment with omalizumab. DISCLOSURE: C.G. Risk, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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5 DAYS ORAL GEMIFLOXACIN COMPARED TO 7 DAYS ORAL LEVOFLOXACIN IN THE TREATMENT OF ACUTE EXACERBATION OF CHRONIC BRONCHITIS Glenn S. Tillotson, MS*; Ashok Fulambarker, MD; Oscient Pharmaceuticals, Waltham, MA

two groups: 7-day group received oral prednisolone 30 mg./day for 7 days, and 14-day group was administered the same dosage of oral prednisolone for 14 days. There was no significant difference between the groups for age, smoking pack years, symptoms of COPD in years, no. of previous exacerbations, blood eosinophilia, baseline FEV1,and FVC levels. One patient from 7-day group developed pneumothorax and one from 14-day group died of acute Myocardial Infarction. RESULTS: Both groups showed significant improvements of FEV1 and FVC on D-1, D-3, D-5, D-7, D-10 and Day-14 from the baseline (7-day group, p ⫽ 0.0001, 0.0001, 0.008, 0.009, 0.008, 0.011and 14-day group, p ⫽ 0.000, 0.000, 0.000, 0.000, 0.000, 0.000.) and the improvement of FVC is also significant in both the groups, but there was no significant difference of improvement between the two groups on day-7 and day-14 (p ⫽ 0.100, 0.079). There was also significant improvement of symptom score from baseline on day-7 and day-14, but no significant difference of improvement between two groups. CONCLUSION: In acute exacerbation of COPD there is no difference between 7-day and 14-day courses of treatment with oral prednisolone. The peak of FEV1 and FVC in 7-day group on day-10 where corticosteroid was already stopped on day-7, (peak in 14-day group was on day-7) might be due to some other factor/factors responsible which would be cleared by further study. CLINICAL IMPLICATIONS: There was no difference between 7-day and 14-day courses of prednisolone treatment, so, 7-day might be the shortest effective course of steroid treatment in Acute exacerbation of COPD to avoid the burden of cost and side effects. DISCLOSURE: M. Rahman, None.

Wednesday, October 27, 2004 COPD Therapies: Antibiotics, Steroids, Bronchodilators, and Immune Modulators, continued THE EFFECT OF INFLIXIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Hester van der Vaart, MD*; Gerard H. Koe¨ ter, PhD; Henk F. Kauffman, PhD; Dirkje S. Postma, PhD; Nick H. ten Hacken, PhD; University Hospital Groningen, Groningen, the Netherlands PURPOSE: Chronic obstructive pulmonary disease (COPD) is a smoking related inflammatory lung disease. Tumor necrosis factor-alpha is thought to play an important role in the induction and maintenance of this inflammation. No effective anti-inflammatory agents are currently available to reduce airway inflammation in COPD. Aim: To evaluate the anti-inflammatory effect of the anti-TNF drug infliximab in patients with mild COPD. METHODS: 22 current smokers with COPD (GOLD stage I/II) participated: 18 males, mean (SD) age 56 (6) years, packyears 58 (38), postbronchodilator FEV1 86 (12) % predicted. Baseline characteristics were similar in both groups. Design: an exploratory double-blind, placebocontrolled randomised trial. 14 patients received three infusions of infliximab (5 mg/kg) at week 0, 2 and 6. Sputum samples, Control of COPD Questionnaire (CCQ), exhaled Nitric Oxide and FEV1 were evaluated at day 1 (baseline) and 2, week 2, 6 and 8. Bronchial hyperresponsiveness to Adenosine 5’-Monophosphate (AMP) was measured at baseline and week 9. RESULTS: Outcome variables (table 1) did not change significantly after treatment with infliximab compared to placebo. Exhaled Nitric Oxide increased significantly at day 2, week 6 and 8 in patients receiving infliximab versus controls. Sputum neutrophils decreased significantly after infliximab in patients with ⬎ 44 (median) packyears on day 2 from baseline [median (ranges) 71 (56-78) % to 53 (31-72) %], whereas in the placebo group no significant changes were observed [63 (57-71) to 61 (58-66) %]. No serious adverse events were reported within 9 weeks. CONCLUSION: Our exploratory study, which was not powered, did not show a short-term effect of infliximab on respiratory symptoms as assessed by CCQ, FEV1 and sputum cell count in patients with mild COPD. CLINICAL IMPLICATIONS: Before definite conclusions can be drawn as to the effectiveness of anti-TNF treatment in COPD, additional studies are needed with more severe COPD patients, larger groups and a longer follow-up.

Table 1. Values are presented as medians (ranges) infliximab

CCQ

FEV1 % predicted

Sputum neutrophils (%)

LOG2 PC20 AMP

Week 8

Baseline

Week 9

68(5777)

57(5082)

2.6 (1.36.5)

2.7 (-1.44.4)

67(4980)

66(1892)

2.4 (0.16.5)

2.2 (-0.26.5)

Baseline

Week 8

Baseline

Week 8 Baseline

No

1.2 (0.72.2)

1.1 (0.72.3)

77(53101)

79(57101)

Yes

1.1 (0.42.1)

1.1 (0.31.7)

78(5496)

77(4693)

DISCLOSURE: H. van der Vaart, None.

COPD Outcomes 12:30 PM - 2:00 PM PREDICTIVE FACTORS OF HOSPITAL READMISSIONS AND MORTALITY FOR ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE Zhenying Cao*; Philip Eng; Tze Pin Ng; Wan Cheng Tan; Kian Chung Ong; National University of Singapore, Singapore PURPOSE: To ascertain 6-month post-discharge rates of hospital readmissions and mortality and evaluate factors predicted of re-hospital-

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izations and mortality in patients with acute exacerbation of COPD (AECOPD). METHODS: We conducted a prospective cohort study of 155 patients with moderate to severe COPD who were admitted for acute exacerbations to two large general hospitals, and determined hospital readmissions and mortality for AECOPD during a 6-month follow up period. Information on potential risk factors, including socio-demographic characteristics, clinical and functional status, patient care, and quality of life (St George quality of life, SGQOL) was collected during hospitalization. RESULTS: During the 6-month post-discharge period, 76 patients (49%) had at least one hospital readmissions, and 21 (13.5%) patients died. Multivariate analysis revealed that hospital readmissions were predicted by previous frequent readmissions (OR⫽ 5.12; 95% CI: 2.52 to10.42) and FEV1⬍45% predicted (OR⫽ 2.16; 95% CI: 1.07 to 4.39); worse Symptoms Score of SGQOL was shown to be a significant predictor of readmissions in univariate analysis but not multivariate analysis. Mortality was significantly predicted by previous frequent readmissions (OR⫽ 5.13; 95% CI: 1.51 to17.37), older age (OR⫽ 4.43; 95% CI: 1.27 to15.46), FEV1⬍45% predicted (OR⫽ 3.28; 95% CI: 1.00 to 10.72), and poor patient compliance (OR⫽ 3.47; 95% CI: 1.03 to 11.65). Univariate analysis also showed that mortality was significantly predicted by lower BMI and psychiatric disorder, but they were not significant predictors in multivariate analyses. CONCLUSION: Readmission and mortality for COPD exacerbation were predicted by disease severity, psychosocial and health care factors. CLINICAL IMPLICATIONS: Modifications of these factors are potential methods for the decrease of mortality and hospital readmission in patients with acute exacerbations of COPD. DISCLOSURE: C. Zhenying, Gerontological Research Programme, NUS

EFFECT OF EXACERBATIONS OF COPD (AE)ON THE MULTIDIMENSIONAL BODY MASS INDEX (B), AIRFLOW OBSTRUCTION (O), DYSPNEA (D) AND EXERCISE CAPACITY (E), BODE INDEX Claudia G. Cote, MD*; Bartolome R. Celli, MD; Bay Pines VA Medical Center, Bay Pines, FL PURPOSE: Lung function (FEV1), and dyspnea are known to worsen during AE of COPD. AE are associated with decreased health related quality of life and with increased mortality. The multidimensional BODE index predicts mortality in COPD patients. The effect of acute exacerbations in disease severity of COPD as measured by BODE, is not known. METHODS: We prospectively evaluated 51 patients with COPD (98% male), mean age 67 ⫾ 8 years (range 48 to 85). At baseline we measured: FEV1%, modified medical research dyspnea scale (MMRC), 6 minute walking distance (6MWD) and BMI to establish a BODE score (possible range 0-10). These measurements were repeated in 27 patients during an AE (exacerbator group) and compared to 24 patients who did not exacerbate (non exacerbator group). Measurements were repeated after 6 months in both groups. RESULTS: As shown in figure 1, the BODE score worsened 48% from baseline and recovered to 78% of the original value at 6 months. These significant changes (p⬍0.001 by ANOVA) were due to lesser changes in the individual components FEV1%, MMRC, and 6MWD without changes in BMI. CONCLUSION: The simple BODE index captures the impact of exacerbations in patients with COPD. The lack of return to the baseline value at 6 months in AE compared to non-exacerbators indicates the contribution of AE to further progression of disease. CLINICAL IMPLICATIONS: The multidimensional BODE index can accurately reflect the changes resulting from the clinical evolution of COPD. Exacerbations result in significant changes in BODE which fail to return to normal after the episode resolves. Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 COPD Outcomes, continued

DISCLOSURE: C.G. Cote, None.

PURPOSE: To measure the quality of life (QOL) in patients with acute exacerbation of COPD (AECOPD) and the frequency of potential risk factors, and to evaluate the association of risk factors with poor QOL in patients with AECOPD. METHODS: A prospective cohort study of 132 patients with moderate to severe COPD admitted for acute exacerbations to two large general hospitals were studied. The St George QOL (SGQOL) scale at 6-month post discharge and hospital readmissions during the 6-month follow up period were determined. Socio-demographic, clinical and patient care characteristics, including depression and spirometry were ascertained in the stable state before discharge and at one-month post discharge. RESULTS: There was a high prevalence of current or ex-heavy smokers, depression and consumption of psychotropic drugs, and low prevalence of care giver support, pulmonary rehabilitation and vaccination. At 6-month post-discharge, the mean scores for the different domains were 53.7 for Symptoms; 63.7 for Activity; 31.4 for Impact; and the mean of overall Total scores was 44.8. Multiple regression analysis showed that worse Symptoms Score of SGQOL was predicted by readmissions (ⱖ1) during the 6-month follow up period (p⬍0.001), use of psychotropic drugs (p⬍0.01), severe dyspnea (degree of dyspnea ⱖ3) (p⬍0.01) and previous frequent hospital readmissions (ⱖ2) (p⬍0.01). Worse Activity Score was significantly predicted by previous frequent readmissions (p⬍0.001), older age (⬎70 yrs) (p⬍0.01) and lower FEV1% (⬍45%) (p⬍0.01). Worse Impact Score was significantly predicted by psychiatric disorder (HADⱖ8) (p⬍0.001) and previous frequent readmissions (p⬍0.01). Worse Total Score of SGQOL was predicted by psychiatric disorder (HADⱖ8) (p⬍0.001), previous frequent readmissions (p⬍0.01), and readmissions during the 6-month follow up period (p⬍0.05). CONCLUSION: Poor QOL in patients with COPD exacerbation was predicted by disease severity, psychosocial and health care factors. CLINICAL IMPLICATIONS: Modifications of these factors are potential methods for the improvement of QOL in patients with acute exacerbations of COPD. DISCLOSURE: C. Zhenying, National University of Singapore THE BODY-MASS INDEX, AIRFLOW OBSTRUCTION, DYSPNEA, AND EXERCISE CAPACITY INDEX IN PREDICTING HOSPITALIZATION FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE Wai F. Chong, BN, MBA*; Kian Chung Ong, MBBS; Cindy Soh, BSc; Seow Pek Tan; Arul Earnest, MSc; Bee Hoon Heng, MPH; Jason Cheah, MPH; National Healthcare Group, Singapore, Singapore PURPOSE: The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index, a multidimensional grading system, is better than the forced expiratory volume in one second (FEV1) at predicting the risk of death among patients with chronic obstructive pulmonary disease (COPD). We hypothesised that the BODE index would also better predict other outcomes such as hospitalisation for exacerbation of COPD in these patients.

SEXUAL DYSFUNCTION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: IS THE SEVERITY OF ERECTILE DYSFUNCTION RELATED TO THE FORCED EXPIRATORY VOLUME IN ONE SECOND (FEV1) AND CARBON MONOXIDE DIFFUSION (DLCO)? Peter Spiro, MD, FCCP; Vinette E. Coelho-D’Costa, MBBS; Samuel K. Dartey-Hayford, MBChB*; Harlem Hospital Center/Columbia University, New York, NY PURPOSE: Erectile dysfunction (ED) affects the sexual health and quality of life of individuals with chronic diseases. The risk factors are diabetes mellitus, heart disease, hypertension and chronic obstructive pulmonary disease (COPD). Medications used in these conditions (except COPD) also affect erectile function. We attempted to examine the sexual satisfaction in African American males with COPD and to determine whether there is a relationship between the degree of ED and pulmonary function. METHODS: A Sexual Health Inventory for men (SHIM) questionnaire was administered to male COPD patients attending the Harlem hospital chest clinic over one month. Each patient’s SHIM score was calculated, their medical records reviewed for other comorbidities and medication history; and their Pulmonary Function Tests analyzed, particularly the FEV1 and the DLCO. Correlation coefficient was used to determine a relationship between the severity of ED and the FEV1 and/or the DLCO. RESULTS: A total of 23 patients were classified into two groups: Group A(COPD only) had 10 patients whilst Group B(COPD with other co-morbidities) had 13 patients. Mean age was 60.8 years in Group A and 59.7 years in Group B. The mean SHIM scores were 10 and 13 for Groups A and B respectively. Patients in Group B were taking various antihypertensive agent(s) either singly or in combination. The comorbidities included hypertension, coronary artery disease, heart failure and atrial fibrillation. The correlation coefficients between the SHIM score versus the FEV1 and SHIM score versus the DLCO were 0.52 and 0.57 respectively overall; 0.60 and 0.87 respectively in Group A. CONCLUSION: ED is common among patients with chronic diseases including COPD. There was no appreciable correlation between the SHIM score and the FEV1 or DLCO overall. However in patients with only COPD, there was a strong correlation between the SHIM score and the DLCO suggesting that the degree of the ED is related to the severity of the DLCO derangement. CLINICAL IMPLICATIONS: All patients with COPD and reduced DLCO should be screened for ED and treatment options offered. DISCLOSURE: S.K. Dartey-Hayford, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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POOR QUALITY OF LIFE IN PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND THEIR PREDICTIVE FACTORS Zhenying Cao*; Wan Cheng Tan; Philip Eng; Tze Pin Ng; Kian Chung Ong; National University of Singapore, Singapore

METHODS: We prospectively evaluated the variables and computed the point values of the BODE index in a cohort of 95 patients with COPD. Using Poisson regression analysis, we analysed the ability of the BODE index to predict the risk of hospital admission for exacerbation of COPD over a six-month period in these patients. RESULTS: There were 35 patients who required at least one hospital admission. Patients with higher BODE scores were at higher risk of hospitalisation. A significant effect of BODE score on the number of hospital admissions (coefficient ⫽ 0.18; 95 percent confidence interval, 0.08 to 0.27; P⬍0.001) was found. In comparison, there was also a significant but smaller effect of the FEV1 percent predicted on the number of hospital admissions (coefficient ⫽ -0.02; 95 percent confidence interval, -0.04 to -0.004; P⫽0.015). There was no significant effect of the BODE score or the FEV1 percent predicted on the total number of days in the hospital. CONCLUSION: The BODE index is better than the FEV1 at predicting the risk of hospitalisation for exacerbation among patients with COPD. CLINICAL IMPLICATIONS: A multidimensional grading system like the BODE index should be used in preference to a physiological variable such as the FEV1 to better categorise and predict outcomes of patients with COPD. DISCLOSURE: W.F. Chong, None.

Wednesday, October 27, 2004 COPD Outcomes, continued HYPERPOLARIZED 3HELIUM MAGNETIC RESONANCE IMAGING IN PATIENTS UNDERGOING SURGERY FOR EMPHYSEMA Barbara A. Lutey, MD*; Stephen S. Lefrak, MD; David S. Gierada, MD; Dimitry A. Yoblonskiy, PhD; Jason Woods, PhD; Joel D. Cooper, MD; Mark S. Conradii, PhD; Washington University School of Medicine, St. Louis, MO PURPOSE: Using inhaled hyperpolarized 3Helium (3He) and diffusion-weighted magnetic resonance (MR) imaging, anatomically correlated maps of the Apparent Diffusion Coefficient (ADC) of 3He gas, an indirect measurement of the degree of restriction placed upon random motion of 3He atoms within the lung, can be produced. ADC values thus reflect the size of the airspaces, and are greater in emphysema. (D.A. Yablonskiy et al, PNAS 99(5): 2002 pp 3111-3116.). We used ADC measurements as a noninvasive means to explore the effects of surgery for emphysema on airspace structure at the microscopic level, and thus elucidate the anatomical alterations underlying postoperative subjective and physiologic changes. METHODS: Six patients undergoing surgical therapy for treatment of severe emphysema were scanned pre- and post-operatively. The resulting mean ADCs were analyzed in the context of traditional assessment tools such as dyspnea indexes and pulmonary function tests. RESULTS: The results for the six patients are shown in the following table. CONCLUSION: Surgery for emphysema produced little change in mean ADC, suggesting that peripheral airspace size remains stable after resection of emphysematous lung tissue. Postoperative subjective and physiologic changes were unrelated to an effect of surgery on airspace size as measureable by this techniques. Pre- and postoperative changes in antomical distribution of ADC may correlate more closely with outcome. CLINICAL IMPLICATIONS: Surgical intervention in meticulously selected patients with emphysmea improves dyspnea and physiological parmaters including 6 minute walk distance. Since these improvements are not correlated with a mean change in peripheral airspace size, it may imply that these changes do not reflect a change in the underlying structural abnormality in the lung.

Patient

Intervention

Pre/Post Mean ADC (Cm2/sec)

Pre/Post FeV1 (Liters)

Pre/Post RV/TLC

Pre/Post 6Minute Walk (Feet)

Dyspnea Index Scores

1

Bil LVRS

.48/.48

.96/2.10

73%/49%

1325/1675

Improved

2

Bil LVRS

.60/.56

.54/1.04

80%/57%

1350/1650

Improved

3

Bil LVRS

.50/.43

.54/1.05

78%/43%

1125/1650

Improved

4

Left BULL

.47/.48

.88/1.23

75%/55%

1350/1710

Improved

5

Left BULL

.40/.44

.99/1.51

70%/54%

800/995

Improved

6

Left BULL

.42/.35

2.42/2.67

56%/39%

1800/1500

Improved

(LVRS⫽Lung Volume Reduction Surgery, BULL⫽Bullectomy) DISCLOSURE: B.A. Lutey, None. NURSE-LED CARE COORDINATION REDUCES HOSPITAL UTILISATION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Gary M. Russell, MBBS, FCCP*; Janice Osteraas, RN; Bendigo Health Care Group, Bendigo, Australia PURPOSE: To assess the effectiveness of a Nurse-led care coordination program in reducing hospital utilisation, in patients with chronic obstructive pulmonary disease (COPD). METHODS: We examined hospital admissions in a cohort of patients admitted to our acute hospital facility with a primary diagnosis of COPD, and who were referred for inclusion in our Nurse-led care coordination program (Program Cohort). We compared the number of admissions in the 12 months before and after referral, and also examined admission rates of a cohort of like patients, who had not been referred to the program (Standard Care Cohort). Essential elements of this program

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were: 1) practice redesign across the continuum of care to align practice with current guidelines; 2) capacity-building, by education of involved health professionals and patients, and by enhancement of rehabilitation and self support programs; 3) self-management monitoring by a dedicated nurse practitioner, and 4) coordination of additional service provision by the same nurse practitioner. RESULTS: The Program Cohort (n⫽78) had 164 admissions preprogram, compared to 9 post-program. Standard Care Cohort (n⫽65) had 124 and 59 admissions respectively during the same time frame. Admissions were reduced to a significantly greater degree in the Program Cohort (Pearson’s X 2⫽42.073, df⫽1, P⬍0.001). CONCLUSION: Participation in a Nurse-led care coordination program was associated with a signficant reduction in hospital demand for the ensuing 12 months. CLINICAL IMPLICATIONS: This study supports the introduction of a Nurse-led care coordination program in reducing hospital demand for patients with COPD. DISCLOSURE: G.M. Russell, None.

PREDICTORS OF NEED OF MECHANICAL VENTILATION AND REINTUBATION IN PATIENTS WITH ACUTE RESPIRATORY FAILURE SECONDARY TO COPD Gopi C. Khilnani, MD, FCCP*; Amit Banga, MD; All India Institute of Medical Sciences, New Delhi, India PURPOSE: To determine the predictors of need of mechanical ventilation (MV) and reintubation, after a planned extubation, in patients with acute respiratory failure (ARF) secondary to COPD (COPD-ARF). METHODS: Eighty-two patients with COPD-ARF, admitted to ICU, were included. Clinical profile and laboratory abnormalities at the time of admission to ICU including APACHE II score were recorded. Study group was split on the basis of need of MV and parameters were compared between the two groups. In the MV group, number of weaning trials with the mode of weaning was recorded. PaCO2 levels at initiation of weaning, extubation and rise in 12 hrs after extubation were recorded and compared along with the parameters at baseline, in the patients who required reintubation with those who did not. RESULTS: Independent predictors of need of MV were pH⬍7.26 (OR,95%CI: 4.9, 1.1-21.3; p⫽0.03) and serum albumin⬍3.5 g/dL (OR, 95%CI: 6.3, 1.4-27.7; p⫽0.01). Weaning trials, given in 45 patients (T-piece:n⫽31, 68.9%; reducing SIMV breaths:n⫽14, 17.2%), lead to a planned extubation. Reintubation was required in eight patients (17.8%). PaCO2 rise 12 hours after extubation (OR, 95%CI: 1.25,1.0-1.5; p⫽0.01) and high APACHE II score (OR, 95%CI: 1.33,1.0-1.7; p⫽0.03) were independent predictors of need of reintubation. A cut-off level of 7.2 mmHg for CO2 rise had sensitivity and specificity of 100% and 84% respectively whereas cut-off of 11.5 for APACHE II score had sensitivity of 87.5 % and specificity of 62.2%. Reintubation was associated with increased ICU stay (16 days & 9 days, p⫽0.017) and mortality (75% vs 23%, p⫽0.002). CONCLUSION: Presence of pH⬍7.26 and serum albumin⬍3.5 g/dL are independent predictors of need of MVin patients with COPD-ARF. Reintubation rates are significant in these patients. High APACHE II score at baseline and a rising PaCO2 levels after extubation independently predict need of reintubation. CLINICAL IMPLICATIONS: COPD patients with acidemia and hypoalbuminemia are most likely to require MV. A high APACHE II score at admission and a sharply rising PaCO2 after extubation should alert the physician to the need to reintubation. DISCLOSURE: G.C. Khilnani, None.

PREDICTORS OF OUTCOME AND LENGTH OF STAY IN PATIENTS WITH COPD EXACERBATION Satyendra Sharma, MBBS; Michael Gupta, MD*; University of Manitoba, Winnipeg, MB, Canada PURPOSE: Natural history of COPD is characterized by intermittent COPD exacerbations. COPD exacerbations often require hospitalization, are associated with significant morbidity and mortality, and contribute to the rising cost of care for these patients. Studies have shown that more than 13% of hospitalizations are from COPD exacerbations. Knowledge of patient characteristics and their role in causation and outcome in COPD exacerbation is crucial. Our study analyzed multiple variables to deterAbstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 COPD Outcomes, continued

Lung Transplantation 12:30 PM - 2:00 PM THE MICROEXTRACTION OF RNA FROM ARCHIVAL CARDIAC ALLOGRAFTS EMBEDDED IN PARAFFIN Kenneth Groshart, MD; Qing Zhang; Michael Quasney, MD; Amrita Dosanjh, MD*; Brian Bledsoe, MS; University of Tennessee, Memphis, TN PURPOSE: One of the difficulties encountered in studying rejection in patients is the availability of tissue. The goal of our study was to isolate RNA from archival allograft tissue, and to demonstrate that it is of suitable quality for further molecular experimentation. METHODS: Thirty-seven allograft archival samples were obtained from 18 patients (13 cardiac/5 renal transplant patients), based on a three year retrospective search of our University teaching hospitals tissue banks. RNA was extracted from the paraffin blocks and amplified by reversetranscription-polymerase chain reaction (RT-PCR). Grade 3A and higher and non-rejection samples were tested. In addition, normal mouse liver tissue was isolated for comparison. Negative control samples were also included. Thirty-two cardiac biopsy samples were analyzed. Patient ages ranged from 15-67 years with a mean of 49.2 ⫾ 15.1 SD. The average age of the blocks used was 2.0 years ⫾ 1.29 SD (range from 13 days to 3.5 years in age). Renal allograft samples were also obtained for comparison, since renal biopsy tissue samples tend to be larger than endomyocardial samples. RESULTS: Pathology slides were assigned histologic grades using the International Society for Heart and Lung Transplantation (ISHLT) 7 scale, and then compared to the original report after unblinding. All specimens had the same grade as the original pathology report. RT-PCR amplification of 18s RNA, 324 bp target sequence, revealed readily detectable bands. Our study showed a higher than expected yield from 31 samples studied, based on semi-quantitative RT-PCR analysis. Only one block, three years old, did not yield detectable RNA secondary to presumed degradation. CONCLUSION: We conclude that RNA from archived allograft tissue can be used for further experiments. The use of this tissue offers distinct advantages when correlating gene expression with clinical outcome and therapeutic response. Formalin-fixed, paraffin-embedded tissue represents widely available clinical material for retrospective patient studies.

CLINICAL IMPLICATIONS: These tissues are an invaluable resource for the elucidation of rejection mechanisms, and exploration of differentially expressed genes as novel therapeutic targets or prognostic indicators. DISCLOSURE: A. Dosanjh, None.

ETA-1 AS A STAGING MARKER IN CONSTRICTIVE BRONCHIOLITIS OBLITERANS Jennifer A. Svetlecic, MD*; Betty Herndon, PhD; Agostino Molteni, MD, PhD; University of Missouri-Kansas City, Kansas City, MO PURPOSE: Long term survival of lung transplantation is compromised by bronchiolitis obliterans (CBO). Other methods of inducing CBO, such as extended toxicant inhalation, produce histopathologic patterns seen with lung transplant CBO. Research has failed to discriminate early cellular markers that lead to CBO, which would provide clinical clues to disease progression. Our laboratory has produced both toxicant and transplant CBO models in the rat demonstrating small bronchiolar fibrosis preceded by peribronchiolar inflammation. We examined Eta-1 (Osteopontin) in these models, assessing this cytokine signal in order to identify the cellular correlate of the basic pathophysiologic mechanisms involved. Eta-1, a cytokine secreted by activated T lymphocytes, is reported to recruit and activate pulmonary macrophages, and could be an important mediator in CBO. METHODS: Rat models of inbred-mismatch tracheal transplant CBO were tested by whole lung BAL at 7 and 42 days. Toxicant-induced CBO (papaverine) was instituted in oubred SD rats by osmotic intratracheal pump delivery. Whole lung BAL was performed at 7 and 28 days. BAL from an intratracheal ARDS model was measured as control. Rat Eta-1 was measured by ELISA. RESULTS: Eta-1 was significantly elevated in toxicant-induced CBO at 7 days (p⬍0.02 ANOVA), with little chronic reactivity. Transplantinduced CBO exhibited no upregulation of Eta-1 in BAL at 7 or 42 days. The ARDS model demonstrated off-scale high Eta-1 at 7 and 14 days, disappearing by day 28, when chronic fibrosis begins. CONCLUSION: Early differences in BAL Eta-1 in the two CBO models suggest pathway differences to a similar final endpoint. Eta-1 has been reported in delayed-type immune responses early and in autoimmunity late. It appears to be neutrophil independent, but IL-12 related. These data suggest that a unique set of cell-mediated inflammatory cells and cytokines participate in early toxicant-induced CBO. Eta-1 could be useful in predicting CBO development. CLINICAL IMPLICATIONS: Markers of specific pathways to bronchial damage could be of immense importance to the early diagnosis of toxicant CBO. Further investigation continues to elucidate early immunologic markers of transplant induced CBO. DISCLOSURE: J.A. Svetlecic, None.

LINEZOLID USE IN LUNG TRANSPLANT RECIPIENTS WITH STAPHYLOCOCCUS AUREUS BRONCHO-PULMONARY INFECTION Maria M. Crespo, MD*; University of Pittsburgh, Pittsburgh, PA PURPOSE: Response rates determined by clearance of S. aureus from follow-up surveillance BAL. METHODS: From March 2002 to October 2003, thirteen lung transplant recipients (8 bilateral, 4 single, 1 bilateral lobar) (7 cystic fibrosis, 3 interstitial lung disease, 3 emphysema) received linezolid treatment (mean 816 ⫾ 1068 days post-transplant) for S. aureus (10 methicillin-resistant, 3 methicillin-susceptible), isolated from bronchoalveolar lavage (BAL). Response rates were determined by clearance of S. aureus from follow-up surveillance BAL. RESULTS: Resolution of infection occurred in 7/13 patients (54%) within 36.3 ⫾ 29.8 days of treatment. Lung function measured by FEV1 improved from pre-treatment values of 1.69L ⫾ 0.65 to 1.83L ⫾ 0.64. Of the three patients having biopsy-proven pneumonia or acute bronchitis, all had complete histologic amelioration. Of the patients that had persistent S. aureus colonization, 5/6 (83%) had chronic airways disease, including bronchiectasis and/or fibrotic airway strictures. Linezolid was tolerated well and did not cause thrombocytopenia or liver function test abnormalities. CONCLUSION: Linezolid appears to be effective for S. aureus broncho-pulmonary infections after lung transplantation. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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mine their effect on length of stay and outcome in patients hospitalized to the non ICU settings. METHODS: Our study is a retrospective analysis of admissions for COPD exacerbations at two tertiary care hospitals in Winnipeg, Canada. The preliminary results include 45 consecutive admissions. Multiple variables for each admission were recorded. These included outpatient therapy, previous admissions, laboratory results, pre-admission pulmonary function tests, sputum cultures, and antibiotic use. Statistical analysis was carried out to determine if these variables had a significant effect on length of stay or outcome. RESULTS: The majority of admissions were for female patients (63.4%). Average age was approximately 69.9 years. A significant proportion of patients had no co-morbid conditions (82.9%). Absolute mean outpatient FEV1 was 0.89L/sec. Average length of stay was 10 days. Neither the use of home oxygen (p⫽0.6836) nor the use of inhaled corticosteroids (p⫽0.5565) was found to correlate with patient outcome. Outpatient FEV1 or the sputum culture positivity did not predict patient outcome. The only variable that achieved significance for predicting outcome was antibiotic use. Patients who received antibiotic of any type, were more likely to be discharged home (p⫽.0263). None of the variables affected length of hospital stay. CONCLUSION: Outcome of patients admitted for COPD exacerbation in non ICU setting is excellent as only 1 out of 45 consecutive patients died. FEV1, other comorbidities and treatment modalities did not affect the outcome. CLINICAL IMPLICATIONS: Patients with COPD exacerbation consume significant resources but have a much lower mortality. Further efforts should be directed at earlier discharge planning and shortening length of stay in these patients. DISCLOSURE: M. Gupta, None.

Wednesday, October 27, 2004 Lung Transplantation, continued CLINICAL IMPLICATIONS: Due to availability in oral formulation, linezolid may offer a significant advantage compared to intravenous antibiotic preparations. Inhalational delivery of linezolid should be explored for patients with chronic airways disease who fail systemic therapy. DISCLOSURE: M.M. Crespo, None.

CRITICAL PATHWAY AND STRATEGIES TO IMPROVE LUNG TRANSPLANT OUTCOME Karen Pelletiere, RN; Wickii T. Vigneswaran, MBBS*; Sangeeta Bhorade, MD; Edward Garrity, MD; Sachin H. Shah, MD; Loyola University Medical Center, Maywood, IL PURPOSE: Lung transplant is an effective treatment for end-stage lung disease in selected patients. Management strategies following transplantation remain variable within and between institutions. We have recently applied critical pathways to guide the care of our patients undergoing lung transplantation. Herein, we review the outcomes of patients who underwent isolated lung transplantation following the application of these critical pathways. METHODS: We retrospectively reviewed the outcomes of 117 consecutive patients who underwent isolated lung transplantation between January 2000 and December 2003. A single postoperative critical pathway was developed between the specialties of Thoracic Surgery, Pulmonary Medicine, and Critical Care Nursing and employed during the preoperative and postoperative care of patients undergoing lung transplantation. Demographic and outcome data were compiled and analyzed. RESULTS: During the study period, 62 and 55 patients underwent bilateral and single lung transplantation, respectively. The indication for transplantation was obstructive airway disease (n⫽43), pulmonary fibrosis (n⫽30), cystic fibrosis (n⫽20), sarcoidosis (n⫽8), pulmonary hypertension (n⫽5), bronchiolitis obliterans (n⫽5), lymphangioleimyomatosis (n⫽3), bronchiectasis (n⫽2), and scleroderma (n⫽1). Hospital length of stay was 8.6 days and hospital mortality was 5.98%. CONCLUSION: Fast track strategies and the development of institutional, multidisciplinary critical pathways result in lower length of stay, morbidity, and mortality. Our results over the study period compare favorably with both national averages and historical outcomes at our institution. CLINICAL IMPLICATIONS: In the current era of cost containment, shortened hospital length of stay is critically important. ‘Fast tracking’ following lung transplantation is feasible and reduces morbidity and mortality. Implementation of critical pathways requires multidisciplinary input to achieve consensus in patient care. DISCLOSURE: W.T. Vigneswaran, None.

flaps, and one underwent subsequent omental transfer. Two LL patients required decortication for empyema. Most patients with PSP could be managed without further surgical intervention. Donor-recipient size mismatch was not significantly different between PSP and non-PSP patients (p⫽0.81). CONCLUSION: The incidence of PSP in LL recipients is similar to that reported in the literature on cadaveric transplant recipients (Ferrer et al. J Heart Lung Transplant. 2003 Nov;22(11):1217-25). Most PSPs can be managed non-operatively, although early aggressive intervention for large air leaks and judicious chest-tube management are essential for a good outcome. CLINICAL IMPLICATIONS: The relatively small lobe in the contaminated chest cavity of LL recipients in general, and CF patients in particular, does not predispose to development of empyema despite immunosuppression. DISCLOSURE: L.M. Backhus, None.

SPECTRUM OF MYCOBATERIAL ISOLATES IN SOLID ORGAN RECIPIENTS Vincent G. Valentine, MD; Denise M. Fuchs, RN; Wanda H. Eppling, MT; Leonardo Seoane, MD; David E. Taylor, MD; Fady G. Jamous, MD*; Tulane University, New Orleans, LA PURPOSE: Few reports exist regarding prevalence and morbidity of mycobacterial disease in solid organ recipients (SOR). We describe the mycobacterial isolates from 1995 to 2003 in all SORs from our institution. METHODS: A review of all mycobacterial cultures from 1995-2003 was done. The prevalence was determined among the individual kidney, heart, liver, and lung transplant recipients from the database. A case was defined as a patient with at least one isolate of a single mycobacterial species from any source in one year. Patients with the same organism isolated repeatedly in different nonconsecutive years were counted as new cases. RESULTS: Of 781 mycobacterial isolates, 691 cases were found of which 62(7.9%) isolates were identified in 51 (7.4%) of the SOR. The majority of the cases in the SOR (78%) had isolates cultured from the respiratory tract (n⫽ 40). All cases in lung recipients were identified from the airways or pleural space. The following mycobacterial species were isolated: M avium (n⫽23), M abscessus (n⫽14), M chelonei (n⫽7), M gordonae (n⫽2), and M kansasii (n⫽2) with one case of M xenopi, and M marinum. The only case of infection due to Mycobacteria tuberculosis occurred in a kidney recipient, seven years after living-related transplantation. While M avium was the most common species isolated (45%) in SOR, half of the M abscessus cases were seen in the lung transplant recipients in 2002 and 2003. The table below represents the proportions of cases according to the transplanted organ. CONCLUSION: While mycobacterial infection continues to be an uncommon complication in organ transplantation, up to 7.9% of cases in a transplant center originate from organ recipients. The highest proportion of mycobacterial isolates (10.4%) is recovered from the lung recipients which is nearly 10 times greater than kidney or liver recipients.

PLEURAL SPACE PROBLEMS FOLLOWING LIVING LOBAR TRANSPLANTATION Leah M. Backhus, MD*; Eric M. Sievers, MD; Robert D. Bart, MD; Felicia A. Schenkel, RN; Robbin G. Cohen, MD; Mark L. Barr, MD; John J. Nigro, MD; Vaughn A. Starnes, MD; Ross M. Bremner, MD; Keck School of Medicine, University of Southern California, Los Angeles, CA

Cases/ Proportion of all Solid institutional Distribution in Solid Organ cases Organ Recipients Recipients

PURPOSE: We reviewed our experience with adult living lobar lung transplants (LL) to assess whether size and shape mismatch of donor organ to recipient predisposes to the development of pleural space problems (PSP). METHODS: Eighty-seven LL were performed on 84 adult recipients from 1993 through 2003. Seventy-six patients had cystic fibrosis (CF). Charts were examined for PSP defined as air leak or bronchopleural fistula for ⬎7 days, pneumothorax, loculated pleural effusions, or empyema. RESULTS: The overall incidence of PSP was 32%. The most common PSP was air leak/bronchopleural fistula accounting for 29% of PSPs. The second most common PSP was pleural effusion (24%). Empyema was uncommon (10% of PSP) in our series of patients despite the large contingent of cystic fibrosis patients. In 4 patients, CT-guided drainage was used for loculated effusions following chest-tube removal. Five LL patients required surgery for persistent air-leak; three required muscle

Liver (n⫽ 675) Heart (n⫽ 634) Cadaveric Kidney (n⫽ 666) Living Related Kidney (n⫽ 264) Lung (n⫽ 192)

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0.8%

12%

0.9% (n⫽ 6) 2.5% (n⫽ 16) 0.9% (n⫽ 6)

2.3%

31%

0.9%

12%

0.4%

6%

1.1% (n⫽ 3)

2.9%

39%

10.4% (n⫽ 20)

Wednesday, October 27, 2004 Lung Transplantation, continued CLINICAL IMPLICATIONS: M abscessus is becoming a more common pathogen in lung recipients than previously reported and may represent a future threat to lung transplantation. DISCLOSURE: F.G. Jamous, None. THE EFFECTS OF ALVEOLAR MACROPHAGE SECRETORY PRODUCTS ON ALVEOLAR EPITHELIAL CELLS EXPOSED TO HYPOXIA AND REOXYGENATION Alexander S. Farivar, MD*; Steven M. Woolley, MRCS; Brendan Patterson-Mackinnon, BS; Michael S. Mulligan, MD; University of Washington, Seattle, WA

OFF PUMP BILATERAL SEQUENTIAL LUNG TRANSPLANTATION THROUGH MEDIAN STERNOTOMY Arun K. Singhal, MD, PhD*; Ann Marie Kuzma, MSN; Valentino Piacentino III, PhD; Carol Fisher, BA; Mahender Macha, MD; James McClurken, MD; Francis Cordova, MD; Satoshi Furukawa, MD; Temple University School of Medicine, Philadelphia, PA PURPOSE: The two standard surgical approaches for bilateral sequential lung transplantation, the “clamshell” incision and two separate anteriolateral thoracotomies, are both associated with significant postoperative pain. This pain is often responsible for decreased respiratory effort, delayed ambulation, and poor pulmonary toilet. Clinical studies suggest that a median sternotomy approach for lung surgery significantly reduces post-operative pain. Utilizing cardiac stabilization devices to eliminate the need for cardiopulmonary bypass, we assessed the safety, efficacy, and pain associated with this procedure. METHODS: Sixteen bilateral sequential lung transplants were performed via bilateral thoracotomy (BT, n⫽6) and median sternotomy (MS, n⫽10) between January 1999 and December 2003. Retrospective review of patient charts compared demographics, medical histories, surgical outcomes, and subjective pain scores. RESULTS: Demographics were not significantly different between groups except for age (BT: 59.3⫾6.0 vs MS: 49.4⫾7.0, p⬍0.01; mean⫾SD). Three patients who had prior lung volume reduction surgery

Respiratory Infections: Microbiology and Treatment 12:30 PM - 2:00 PM INDICATORS OF POTENTIALLY DRUG RESISTANT BACTERIA IN SEVERE NURSING HOME ACQUIRED PNEUMONIA Ali A. El Solh, MD, MPH*; Celestino Pietrantoni, MD; Abid Bhat, MD; Milapchand Bhora, MD; Eileen Berbary, RN; University at Buffalo, Buffalo, NY PURPOSE: Knowledge of the determinant factors responsible for the presence of antimicrobial-resistant pathogens in severe nursing home acquired pneumonia (NHAP) is deemed essential for antibiotic selection. METHODS: During a 36-month period, all cases of institutionalized patients with confirmed severe pneumonia by protected bronchoalveolar lavage (ⱖ103 CFU/ml) were analyzed. A classification tree was developed with a sensitivity of 100% by binary recursive partitioning to predict those patients who are unlikely to have DRP related pneumonia. RESULTS: Of the 88 patients who satisfied the inclusion criteria, 17 had at least one drug-resistant pathogen (DRP) recovered from the lower respiratory tract. The predictor variables were Activity of Daily Living score and prior use of antibiotics. Prospective application of the model in 47 patients over 24 month yielded a sensitivity of 100% (95% CI 71.3%-100%) and 69.4% specificity (95% CI 51.9%-83.6%). CONCLUSION: The use of the tree may provide a more rational basis for selecting initial therapy for severe NHAP. CLINICAL IMPLICATIONS: the classification tree can be used as a guideline for health care providers in clinical decision making that optimizes the use of antimicrobial therapy and minimizes the emergence of drug resistant bacteria in intensive care settings.

DISCLOSURE: A.A. El Solh, None.


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PURPOSE: Lung ischemia reperfusion injury (LIRI) is a morbid complication following thoracic organ transplantation. The alveolar macrophage (AM) orchestrates early reperfusion events ultimately resulting in florid lung injury via an early proinflammatory burst of TNF and IL-1 which primes surrounding cells such as type 2 pneumocytes (T2P). These studies characterized the effects of AM secretory products on T2P undergoing hypoxia and reoxygenation (H&R). METHODS: Primary cultures of AM underwent 2 hrs hypoxia (FIO2 0.5%) followed by up to 4 hrs reoxygenation. AM experimental media was harvested and used for pretreatment of T2P. T2P were pretreated with either unstimulated macrophage media (negative control), or media from macrophages undergoing 2 hrs hypoxia and 15 minutes (HR15) of reoxygenation, or 2 hrs hypoxia and 4 hrs (HR4) reoxygenation. T2P were subsequently exposed to 2 hrs hypoxia and up to 4 hrs reoxygenation. Media was again harvested to quantitate T2P chemokine secretion by ELISA, while EMSA assessed transcription factor transactivation. RESULTS: ELISAs demonstrated that CINC (p⬍0.05) and MCP-1 (p⬍0.05) secretion, but not MIP-1, was significantly increased after 2 hrs hypoxia and 4 hrs reoxygenation in isolated T2P. There was a synergistic increase in expression of CINC and MCP-1 after treatment of T2P with HR15 (p⬍0.05) and HR4 (p⬍0.05) macrophage media compared with negative controls. MIP-1, which was not dramatically secreted from isolated T2P, was significantly increased after AM media pretreatment. NFkB transactivation in T2P was increased in the HR15 and HR4 pretreated groups. CONCLUSION: These studies demonstrated that secretion of the potent chemokines CINC and MCP-1 is increased in T2P undergoing H&R, and that this expression is synergistically augmented after pretreatment with AM media undergoing previous H&R. Interestingly, MIP-1 secretion from the T2P was significant only after treatment with HR AM media (at levels above that present in isolated AM media). The AM primes alveolar epithelial cells, augmenting their eventual response to oxidative stress. CLINICAL IMPLICATIONS: Nebulized anti-inflammatory strategies targeting AM in thoracic organ donors (during organ procurement) may have dramatic protective effects against LIRI. DISCLOSURE: A.S. Farivar, None.

were done via BT. One of 10 transplants performed with MS required intraoperative conversion to cardiopulmonary bypass. Ischemic times (BT: 376⫾69 min vs MS: 378⫾84 min, p⬎0.05), time to extubation (BT: 4.0 days vs MS: 3.0 days, p⬎0.05; median) and 30 day mortality (BT: 17% vs MS: 0%, p⫽0.38; Fisher exact test) were similar between groups. All transplant surgeons (AKS, MM, JM, SF) utilized both approaches and subjectively felt that the MS afforded satisfactory operative field and rapid control of the pulmonary hilum. Compared to the BT group, severity of pain on postoperative days 1-14 was significantly less in the MS group (p⬍0.05, Chi square). CONCLUSION: Off pump bilateral sequential lung transplantation can be performed via median sternotomy using cardiac stabilization devices. Ischemic time, time to extubation, and 30 day mortality were equivalent in both groups. Postoperatively, patients had significantly less pain in the median sternotomy group relative to the bilateral thoracotomy group. CLINICAL IMPLICATIONS: The observed decrease in postoperative pain with median sternotomy should enhance recovery and reduce complications such as pneumonia. Furthermore, this approach provides optimal exposure in the event cardiopulmonary bypass is required. DISCLOSURE: A.K. Singhal, None.

Wednesday, October 27, 2004 Respiratory Infections: Microbiology and Treatment, continued CLINICAL EVALUATION OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC BRONCHITIS TREATED EMPERICALLY WITH TELITHROMYCIN Abdalla Abu Hussein, MBBS*; Abdel-Rehim Ads, MD; Manal ElHamamsy, MD; Tanta Int’l Cardiothoracic Vascular Center, Tanta, Egypt PURPOSE: Acute exacerbation of chronic bronchitis (AECB) is characterized by increase in cough and worsening of dyspnoea due to, in some cases, bacterial infection. There is always a need to develop first line antimicrobial agents that cover major respiratory pathogens, with low potential to select for resistance, favorable safety and efficacy profiles, and convenient dosing regimen. Objective: To evaluate the outcome of treating AECB patients empirically with Telithromycing 800 mg once daily for 5 days. METHODS: Design: Open, prospective. Patients: Male and females aged 18-65 years, identified with AECB, who have not had antibiotics within 14 days before enrollment. Methods: Test of cure (TOC) was defined as disappearance of signs and symptoms of AECB with no requirement for further treatment with antibiotics. Adverse events, including abnormal laboratory values, were monitored, recorded and analyzed. RESULTS: Two hundred and fifty three patients were enrolled. After 5 days of treatment, the clinical outcome was 85% cure in the per-protocol (PP) patients and 80% in intent-to-treat (ITT) analysis. The cure rates increased after 10 days of treatment to 98% and 90% in the PP and ITT analysis respectively. The main adverse event was gastric upset. Nonetheless, all adverse events were of mild to moderate intensity and were easily alleviated with symptomatic intervention. CONCLUSION: The empiric treatment with Telithromycin for AECB patients appears to be safe and efficacious. CLINICAL IMPLICATIONS: The results of this work support those found elsewhere in the literature and the FDA results on Telithromycin in the AECB indication. DISCLOSURE: A. Abu Hussein, None.

THE CLINICAL EFFECT OF 4 DAYS OF EMPIRICAL ANTIBIOTIC TREATMENT EAT IN PATIENTS CLASS III WITH COMMUNITY ACQUIRED PNEUMONIA: THE MORELIA EXPERIENCE E. A. Maldonado-Ortiz, MD*; Michael S. Niederman, MD; Julia Ramirez-Hernandez, Nurse; Cecilia Guerrero, MD; Ruben Solorio, MD; Marcela Garcia-Villa, MD; Beatriz Galvan, MD; Reyna Pin˜ on, MD; Hospital de la Mujer, Morelia, Mexico PURPOSE: Duration of EAT in hospitalized patients p with community acquired pneumonia CAP is not defined and the rule is 7 to 10 days d. The potential risk of toxicity, resistance and cost could be an effect of non always justified prolonged antibiotics abs administration. Our objective is to evaluate the clinical impact of EAT during 4 d and the role of Clinical Pulmonary Infection score CPIS. METHODS: Consecutive hospitalized p with CAP admitted to 3 hospitals were included. Epidemiological and clinical/bacteriological data were recorded. EAT was administred ⬍ 3 hours h period after CAP diagnosis based on The Grupo Multicentrico Michoacano para el Control de las Infecciones Respiratorias GOMMICHIR local guidelines (Quinolones⫹Macrolides, Cephalosporines⫹Macrolides or Ertapenem⫹Macrolides ). EAT success or failure were evaluated at 72h and 28d. The CPIS value at admission and after 72 h was compared between p received EAT 4 vs ⬎ 5 d. RESULTS: 62p were included, 98.3% were female, age 66.5⫹20, (17-99 yrs). 60p, (96.7%) had comorbidities and risk factors. 24/62p (38.7%) received previous abs. EAT success was present in 44/62p, (71%) but defervescence was evident and EAT stoped at 4 d in 40/44p, (90.9%) without readmission at 28th d. The length of exposure to abs was 4 d vs 11.9⫹6.8 ( 6-34 d) p⫽0.000 in ⬍ 4 and ⬎ treatment group respectively. CPI score decrease in EAT success p from 7.17 to 3.6 (p⫽0.000) and increase respectively in prolonged treatment group from 7.9 to 10.7 (p⫽0.000). The CPIS fall in responders at 72 h Fever and tracheal secretions are the most rapidly resonded components. CONCLUSION: In the Morelia experience, 4 d of combined EAT based on our local CAP guidelines is enougt to resolve CAP without readmission at 28th d. The evolution of CPIS at 72 h from admission is the “ golden tool ” to define EAT success in Class III CAP population.

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CLINICAL IMPLICATIONS: The short course of combined EAT in hospitalized patients could reduce potential toxicity and prolonged unnecesary antibiotic administration.

Clinical Pulmonary Infection Score evolution

CPIS Temperature ⬎ to 39°C Blood leukocites ⬍ 4000 or ⬎ 11.000 Tracheal secretions ( purulent tracheal secretions)) Oxygenation: Pao2/ Fio2 ⬎ to 240 and no ARDS Pulmonary radiograph Localizad infiltrates Progression of pulmonary infiltrate. Radiographic progresio´ n (alter CHF anda ARDS excluded) Culture of tracheal secretions Pathogenic bacteria cultured in moderate or heavy quantity

Responders at admission 32 p, 80%

Responders 72 hours

Non Responders at admission

Non Responders 72 hours

3p, 7.5% 15p, 68.1% NA 14p, 63.6%

14p, 63.6% 17p, 77.2%

39p,97.5%

NA

20p, 90.9%

18p, 81.8%

29p, 72.5%

1p, 2.5% 14p, 63.6%

15p, 68.1%

39p, 97.5.%

NA

21p, 95.4%

1p, 4.5%

NA

NA

1p, 4.5% 17p, 77.2%

NA

22p, 55%

1p, 4.5% 22p, 100%

23p, 57.5%

DISCLOSURE: E.A. Maldonado-Ortiz, None.

SEQUENTIAL HYSTOLOGICAL AND BACTERIOLOGICAL CHANGE ON LUNGS FROM 6 TO 72 HOURS OF MECHANICAL VENTILATION IN HEALTHY PIGS E. A. Maldonado-Ortiz, MD*; Marcela Lopez, Nurse; Julia Ramirez, Nurse; Camerino Moreno, MD; Hector Herrera, MD; Pulmonary and Respiratory Care Department, Hospital de la Mu, Morelia, Mexico PURPOSE: Mechanical Ventilation MV and orotracheal intubation are consider the major risk factor to develop Ventilator associated Pneumonia VAP. Our objective is to compare H and bacteriological B findings on healthy lungs during 6 to 72h of MV. METHODS: MV protocol was conducted in HP during 6, 12, 18, 24, 48 and 72 h. In vivo/post mortem respiratory samples were obtained to H and B evaluation. RESULTS: All animal under MV⬍ 24 h, showed different grade of tissue inflammation and neutrophiles aggregation, but pneumonia was absent. B growth from lung cultures was considerated colonization. HP ventilated ⬎ 24h had a different grade of HB change suggested of pneumonia from severe acute inflammatory infiltrate, localized-confluent consolidation zones, and on basal zones an abcessed areas was observed. H and B correlation of pneumonia was identified in cultures with Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Respiratory Infections: Microbiology and Treatment, continued moderate to heavy concentration of E. Coli, Streptococcus sp and Staphylococcus coag. Negative. CONCLUSION: The Morelia Experience data show that develop of VAP is strongly associated to the length of MV (late phase ⬎24h vs early phase ⬍24h) Future clinical research in animals are mandatory to define this information in order to evaluate the possible benefict in humans. CLINICAL IMPLICATIONS: To consider the possibility to decrease the exposure period of MV and/or use others alternatives as non invasive MV or rescue extubation when possible. DISCLOSURE: E.A. Maldonado-Ortiz, None. SHORT-COURSE GEMIFLOXACIN THERAPY IS EFFECTIVE AGAINST STREPTOCOCCUS PNEUMONIAE IN A MURINE MODEL OF PNEUMONIA Darrin J. Bast, PhD*; Xueynn Chen, BS; Ryan Goren, BSc; Mei Yue, MD; Carla L. Duncan, BSc; Linda Dresser, PharmD; Lionel A. Mandell, MD; Donald E. Low, MD; Joyce C. de Azavedo, PhD; Toronto Centre for Antimicrobial Research & Evaluation, Toronto, ON, Canada

A MULTICENTER, OPEN-LABEL, RANDOMIZED STUDY COMPARING GATIFLOXACIN VS CLARITHROMYCIN AND CEFTRIAXONE FOR TREATMENT OF COMMUNITYACQUIRED PNEUMONIA Nathan C. Dean, MD*; Matthew Wikler, MD; Paul Sperry, MStat; Mary Suchyta, DO; Carol Hadlock, RN; Sandy Yeates, RN; Intermountain Health Care, Salt Lake City, UT PURPOSE: We studied differences in symptom course and process of care between pneumonia patients treated with gatifloxacin vs clarithromycin with ceftriaxone added for patients having 3 or more risk factors. METHODS: We measured time to return to usual activities, pneumonia specific symptom scores, and SF12 over 7 interviews ending 42 days. We used an open label, randomized design to determine if the different antibiotics changed likelihood of hospitalization. The study sites were the LDS hospital Emergency Department and 4 urgent care centers in Salt Lake City, and the Emergency Department and 3 rural outpatient clinics in Sanpete Valley, Utah. RESULTS: We enrolled 266 patients over age 18 with radiographically confirmed pneumonia between September 2000 and June 2003. Mean

SAFETY AND EFFICACY OF GEMIFLOXACIN COMPARED TO HIGH DOSE AMOXICILLIN/CLAVULANATE FOR THE TREATMENT OF COMMUNITY-ACQUIRED PNEUMONIA (CAP) OF SUSPECTED PNEUMOCOCCAL ORIGIN Glenn S. Tillotson, MS; Thomas File, MD*; Lionel Mandell, MD; Northeastern Ohio Universities College of Medicine, Rootstown, OH PURPOSE: To compare the safety and efficacy of gemifloxacin to high dose amoxicillin/clavulanate (amox/clav) for the treatment of CAP of suspected pneumococcal origin (based on clinical characteristics including gram stain findings of sputum). METHODS: Randomized, multicenter, double-blind, double-dummy study. 324 patients with CAP received oral gemifloxacin 320mg once daily for 7 days or oral amox/clav 1g/125mg 3 times daily for 10 days. Outcome measures were clinical, bacteriological, and radiological responses at the end of therapy (EOT; Day 12-14) and follow-up (FU; Day 24-30). RESULTS: In 228 Per Protocol (PP) patients, clinical resolution at FU was 88.7% for gemifloxacin and 87.6% for amox/clav [95% CI -7.3,9.5]. Clinical resolution at EOT was 95.3% for gemifloxacin vs. 90.1% for amox/clav.[ 95%CI, -1.2, 11.7] Bacteriologic responses for PP patients at EOT were 96.3% for 7-day gemifloxacin and 91.8% for the amox/clav group [95%CI, -4.7, 13.6], and at FU were 87.2% for gemifloxacin and 89.1% for the amox/clav group [95%CI -15.0, 11.2]. Gemifloxacin eradicated 95.7% (22/23) and amox/clav eradicated 100% (21/21) of Streptococcus pneumoniae including penicillin- and macrolide-resistant strains. Radiological responses at EOT were 89.1% for gemifloxacin and 87.6% for amox/clav. The most frequently reported drug-related events were in the gemifloxacin group, diarrhea (6.0%) and rash (3.0%) and in the amox/clav group, diarrhea (11.1%) and fungal infection, vaginitis and vomiting (each 2.0%). There were statistically fewer withdrawals due to lack of therapeutic effect in the gemifloxacin group (2/33; 6%) vs the amox/clav cohort (9/33; 27%), (95% CI -8.8;0.6; p⫽0.03). CONCLUSION: Gemifloxacin 320 mg once daily for 7 days was clinically, bacteriologically, and radiologically as effective as 10 days of amox/clav 1g/125mg 3 times daily for the treatment of suspected pneumococcal CAP. CLINICAL IMPLICATIONS: Gemifloxacin represents a valuable addition to the therapeutic options to treat CAP. DISCLOSURE: T. File, None. AN OVERVIEW OF THE EFFICACY OF GEMIFLOXACIN FOR THE TREATMENT OF COMMUNITY-ACQUIRED PNEUMONIA (CAP) Glenn S. Tillotson, MS; Lionel Mandell, MD; Brian Carlin, MD*; Alleghany General Hospital, Pittsburgh, PA PURPOSE: To assess the efficacy of once daily gemifloxacin in the treatment of CAP. METHODS: Six clinical studies were conducted with adult patients suffering from CAP. Gemifloxacin (320mg qd 7 or14 days) was compared to amoxicillin/clavulanate (1g/125mg tid 10 days), cefuroxime/clarithromycin (500mg/500mg bid 7 or14 days), trovafloxacin (200mg qd 7 or14 days) and IV ceftriaxone/oral cefuroxime (2g qd/500mg bid 1-7 days ⫹ 1-13 CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Inappropriate use of antibiotics like fluoroquinolones (FQ) has led to rising rates of resistance among clinical isolates of Streptococcus pneumoniae (SPN). Short-course FQ therapy using the most potent agent in the class has been advocated for treatment of community-acquired pneumonia on the basis that rapid bacterial eradication likely minimizes resistance. In an effort to address this issue, we investigated FQ treatment of pneumococcal pneumonia in mice comparing 2-day (d) versus 5d treatment with gemifloxacin (GEM), which has the highest in vitro activity against SPN. METHODS: Thirty Swiss Webster mice were inoculated endotracheally with 5-log10 cfu of a SPN serotype 3 strain, fully susceptible in vitro to levofloxacin (MIC 1 mg/L)and GEM (MIC 0.03 mg/L). The surface temperature (ST) of a mouse has been previously shown to predict pulmonary bacterial load & histologic changes indicative of the severity of pneumonia. ST at 24 h was used to assess disease severity & stratify the mice prior to drug treatment (moderately ill: ⱖ 32°C; severely ill: ⬍32°C). GEM was administered subcutaneously OD (50 mg/kg) at 24-h postinfection to 10 mice each for 2d and 5d and taking into account numbers of moderately & severely ill mice in each group. An additional 10 mice were left untreated & served as our positive control. Viable counts for whole-lung homogenate (limit of detection of ⬍ 1.7 log10 cfu) was determined for all mice. This experiment was done twice. RESULTS: GEM was exceptionally effective in the complete eradication of SPN from all mice, independent of disease severity prior to treatment & the length of treatment. By comparison, untreated mice had a mean bacterial count of 8.4 ⫹ 0.4 log10 at their time of death, which generally preceded the time point for euthanasia (median time to death 65h). CONCLUSION: GEM completely eradicates SPN in mouse lung whether it is 2d or 5d course therapy. CLINICAL IMPLICATIONS: Short-course therapy with GEM may be effective in the treatment of pneumococcal pneumonia in patients independent of disease severity. DISCLOSURE: D.J. Bast, None.

age was 53.7 ⫾ 19.6 years, 54% were female. Mean number of pneumonia risk factors was 1.5 ⫾1.5 and was similar in both groups. 64% of patients were class 1 by PSI, 22% class 2, 9% class 3, and 5% class 4. 91% of patients completed at least 5 of the 7 symptom interviews, and 88% completed the last interview at 42 days post-enrollment. 64% of patients randomized to clarithromycin received at least one dose of ceftriaxone. We found no significant difference between groups in time to return to usual activities, pneumonia specific symptom scores, and SF12. Of individual symptoms examined, only bad taste differed between the 2 groups, more common in clarithromycin patients. Hospital admission rate was not statistically different. Cost of therapy was less for gatifloxacin monotherapy, US$ 100 versus 257. CONCLUSION: Gatifloxacin monotherapy is equivalent to clarithromycin ⫾ceftriaxone for treatment of pneumonia in symptom resolution and admission rate. Liberal use of combination therapy in the clarithromycin group may have masked outcome differences. CLINICAL IMPLICATIONS: While the two drug regimens produce similar clinical outcomes, gatifloxacin monotherapy is less expensive. DISCLOSURE: N.C. Dean, This study was funded by a grant from Bristol Myer

Wednesday, October 27, 2004 Respiratory Infections: Microbiology and Treatment, continued days). Outcome measures were clinical, bacteriological, and radiological responses at follow-up. RESULTS: Clinical resolution was 90.5% for the combined gemifloxacin group compared with 91.1% for the combined comparators. Bacteriological response rates were 88.9% for gemifloxacin and 88.7% for the combined comparator group. Radiological response rates were between 87.9% and 94.0% for gemifloxacin and between 87.6% and 94.2% for the comparators. Gemifloxacin achieved 100% (12/12) eradication of penicillin-resistant S. pneumoniae (MIC ⱖ2ug/mL ) and was similarly effective in patients with macrolide-resistant S. pneumoniae. 14/16 (87.5%) patients with erythromycin-resistant S. pneumoniae and 19/22 (86.4%) patients with clarithromycin-resistant S. pneumoniae achieved clinical and bacteriological success at follow-up. Gemifloxacin was effective against CAP due to multi-drug resistant S. pneumoniae (MDRSP), i.e., S. pneumoniae resistant to 2 or more of the following: penicillin, second generation cephalosporins, macrolides, tetracyclines and TMP/SMX. Of 22 patients with MDRSP treated for 7 days, 19 (86.5%) achieved clinical and bacteriological success at follow-up. Of the pathogens isolated from these patients, 11 were penicillin-resistant, 19 macrolide-resistant, 16 TMP-SMX-resistant, 16 tetracycline-resistant and 14 resistant to a second generation cephalosporin. CONCLUSION: Gemifloxacin 320 mg once daily for 7 days was found to be at least as effective clinically, bacteriologically and radiologically as the comparator regimens for the treatment of CAP. CLINICAL IMPLICATIONS: Gemifloxacin offers an effective new option in the treatment of CAP. DISCLOSURE: B. Carlin, None. SAFETY AND TOLERABILITY OF GEMIFLOXACIN: A REVIEW OF CLINICAL TRIAL DATA Glenn S. Tillotson, MS; Lionel Mandell, MD*; Paul Iannini, MD; Thomas File, MD; Gary Patou, MD; McMaster University, Hamilton, ON, Canada PURPOSE: Gemifloxacin is a newly approved fluoroquinolone for the treatment of respiratory tract infections. Tolerability data from 20 clinical trials was reviewed to assess the safety profile of gemifloxacin. METHODS: A meta-analysis of 20 Phase II and III clinical studies was conducted to determine the frequency of adverse events (AEs), serious adverse events (SAEs) and withdrawals from the study as compared to levofloxacin, trovafloxacin, ciprofloxacin, ceftriaxone, cefuroxime, clarithromycin, or amox/clav). RESULTS: 6775 patients were treated with gemifloxacin and 5248 with comparator agents. The overall incidence of AEs with gemifloxacin and comparators was similar (44.7% gemifloxacin; 47.5% comparators). The most common drug-related AEs were diarrhea, rash, and nausea for the gemifloxacin group (3.6%, 2.8% and 2.7%, respectively) and were diarrhea, nausea, and headache for the comparator group (4.6%, 3.2% and 1.5%, respectively). Patients with at least one SAE were identified among 3.6% of gemifloxacin-treated and 4.3% of comparator-treated patients. The most common SAEs were pneumonia (gemifloxacin 0.3%; comparators 0.5%) and chronic obstructive airway disease (gemifloxacin 0.2%; comparators 0.3%). Withdrawals due to drug-related AEs occurred in 2.2% of gemifloxacin-treated and 2.1% of comparator-treated patients. The most common reasons for withdrawal among the gemifloxacin-treated patients were rash (0.9%), nausea (0.3%), and diarrhea (0.3%). The most common reasons for withdrawal among the comparator-treated patients were diarrhea (0.5%), and nausea, rash, and vomiting (all 0.3%). CONCLUSION: In these studies, gemifloxacin 320 mg once daily was shown to be as safe and well tolerated as other commonly prescribed antibiotics. Mild rash was more common in gemifloxacin treated patients and diarrhea was more common with comparators. CLINICAL IMPLICATIONS: Gemifloxacin represents a safe and effective addition to the current treatment options for lower respiratory tract infections. DISCLOSURE: L. Mandell, None. A NEW CLINICAL SIGN IN INVASIVE PULMONARY ASPERGILLOSIS: LOCALIZED KNEE LEVIDO RETICULARIS? Patrick Evrard, MD; Isabelle Michaux, MD; Manu Gonzalez, MD; Etienne Installe´ , MD; Pierre A. Bulpa, MD, FCCP*; Cliniques Universitaires de Mont-Godinne, Yvoir, Belgium PURPOSE: Despite treatment, mortality rate remains high in patients (pts) suffering from invasive pulmonary aspergillosis (IPA). Early diagno-

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sis is crucial to improve survival. Even with extensive diagnostic procedure, definitive diagnosis is still difficult and often made at autopsy. Some clinical signs, such as fever, hemoptysis or pleural pain, may rapidly suggest IPA but they are non specific or rare. Recently, we observed the appearance of localized knee levido reticularis in pts with pulmonary infiltrates suspected to have IPA. Consequently, we reviewed the presence of localized knee levido reticularis in such pts. METHODS: In our ICU, between 01/2000 and 03/2004, IPA (proven [positive tissue biopsies and/or autopsy] or highly probable [repeated positive cultures for Aspergillus with consistent clinical and radiological findings]) was diagnosed in 15 pts. During the ICU stay, the occurrence of localized knee levido reticularis was investigated in every pt. RESULTS: There were 11 males and 4 females, with a mean age of 58 years (range: 34-80), and 12 were immunocompromised (hematological malignancy: 3; lung transplant recipient: 4; prolonged steroid therapy: 5). All pts had pulmonary infiltrates compatible with IPA. IPA was proven in 14 and highly probable in 1 pt. Localized knee levido reticularis was encountered in 8 pts (53%), none developed hypotension or received vasopressors, and only one presented fever. At that time, no bacteria could be isolated except in one pt. This clinical sign seemed not related to antifungal therapy (No treatment: 3; Amphotericin B: 1; Abelcet: 2; Caspofungin: 1 and Itraconazole: 1). Localized knee levido reticularis was seen a mean of 3 days (range: 4 hours-9) and 14 days (range: 2-41) before the administration of vasopressors or death, respectively. Only two pts survived and none showed localized knee levido reticularis. CONCLUSION: In pts at risk for IPA and with pulmonary infiltrates, invasive pulmonary aspergillosis should be suspected when localized knee levido reticularis was present without any hypotension or vasopressors administration. CLINICAL IMPLICATIONS: Localized knee levido reticularis may suggest and be related to the severity of IPA. DISCLOSURE: P.A. Bulpa, None. LEVOFLOXACIN 750MG DAILY FOR 5 DAYS FOR COMMUNITY ACQUIRED PNEUMONIA: OUTCOMES IN THE ELDERLY Andrew F. Shorr, MD, MPH*; Neringa Zadeikis, MD, MBA; Mohammed M. Khashab, BS; Alan M. Tennenberg, MD, MPH; E W. Ely, MD, MPH; Walter Reed Army Medical Center, Washington, DC PURPOSE: Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality in the elderly. Nonetheless, little is known about the impact of specific antibiotic regimens on outcomes in this cohort. METHODS: We conducted a subgroup analysis of elderly patients (defined as age ⬎ 65 years) from a multicenter, double-blind study of CAP. In this trial, patients were randomized to treatment with either levofloxacin (L) 750 mg daily for 5 days or to L 500mg daily for 10 days. Clinical success (cure or improvement) served as the primary endpoint. Mortality assessed between days 28-31 and microbiologic eradication rates represented secondary endpoints. We also extracted data regarding safety and adverse events. RESULTS: The original trial included 528 patients (both outpatients and inpatients) of which 172 (32.6%) were 65 years or older. The most frequently isolated pathogens were M. pneumoniae (n⫽19), S. pneumoniae (n⫽16), and H. influenzae (n⫽13). Individuals receiving the 750mg regimen were slightly younger than those treated with 500mg (73.1 years vs. 75.0 years, p⫽0.03) but were otherwise comparable (% male: 53.8% vs. 57.6%, p⫽NS; median Pneumonia Severity Index class: III in both groups). Outcomes are shown in the table. Both regimens were well tolerated in the elderly with few serious adverse events: 11.3% for 750 mg vs. 16.7% for 500mg (p⫽0.31). CONCLUSION: In this subgroup analysis of elderly patients with CAP, treatment with 750mg L for five days performed as well as 500mg for 10 days. Both regimens were well tolerated.

Clinical Success: Clinically Evaluable Patients Micro-Eradication: Microbiologically Evaluable Patients Mortality

750mg

500mg

P

88.5%

92.2%

0.49

90.3%

87.5%

0.77

5.0%

4.4%

0.86


Wednesday, October 27, 2004 Respiratory Infections: Microbiology and Treatment, continued CLINICAL IMPLICATIONS: Levofloxacin 750mg daily for 5 days is a safe and effective alternative for CAP in the elderly. DISCLOSURE: A.F. Shorr, OMP

MULTIDRUG-RESISTANT STREPTOCOCCUS PNEUMONIAE (MDRSP) IN U.S. ADULT PATIENTS: A 2003 LOCAL PERSPECTIVE Renee Blosser, MS; Mark E. Jones, PhD*; Robert K. Flamm, PhD; Glenn S. Tillotson, PhD; David A. Styers, BS; Ronald N. Master, MS; Daniel F. Sahm, PhD; Focus Technologies, Inc., Herndon, VA

THORACOSCOPIC TREATMENT OF BRONCHIECTASIS SECONDARY TO RESISTANT ORGANISMS Gary K. Lovelady, MD, MPH; John R. Roberts, MD, MBA*; The Surgical Clinic; Centennial Hospital; Baptist Hospital, Nashville, TN PURPOSE: Increasingly effective antibiotics have diminished the need for surgical therapy for bronchiectasis. However, drug resistant strains have lessened the impact of antibiotics. Further, rural patients may present with more advanced disease, either because of increased allergen exposure or lesser medical availability. We evaluated our experience with thoracoscopic surgical therapy for bronchiectasis in a predominantly rural community. METHODS: Patients with radiologic evidence of bronchiectasis, recurrent pneumonia, and antibiotic resistant organisms underwent thoracoscopic resection. Data were analyzed for typical demographic features, type of surgery and length of stay, and need for subsequent hospitalization. Patients were considered to have died from surgery if they died during the hospitalization for the surgery, or within 90 days of surgery. RESULTS: Eighteen patients (27-77 years of age), underwent nineteen resections. Three patients had FEV1% ⬍ 35% predicted–the average was 60%. Nine underwent segmentectomy and eight lobectomy (one patient underwent two lobectomies). Eleven (58%) underwent thoracoscopic resection. The length of stay was 7.2 days. No patients required intubation nor ICU stay. There was no mortality. While two patients required long-term antibiotics after surgery to clear bronchitis, only one patient (with severe emphysema) required inpatient admission.

PULMONARY BLASTOMYCOSIS: A RETROSPECTIVE CASE SERIES David M. Hiestand, MD*; Eric Bensadoun, MD; University of Kentucky, Lexington, KY PURPOSE: We undertook a retrospective study to describe the clinical, radiographic, diagnostic, and therapeutic features of pulmonary blastomycosis in an area endemic for this disease. METHODS: Mycology data from the University of Kentucky and VA Medical Center were queried for all positive Blastomysosis dermatidis cultures from pulmonary sources from 1992-2003. Medical records were obtained for further analysis of demographic data, clinical findings, treatment, and outcomes. This study was approved by the Institutional Review Board. RESULTS: The study population consisted of 35 patients with culture proven pulmonary blastomycosis, of which 12 were immunocompromised. The average age at the time of diagnosis was 56 years (range: 23-86 years). All but one patient was symptomatic at the time of presentation. The most common presenting symptoms were: cough (79%), dyspnea (51%), fever (43%), and weight loss (43%). The mean duration of symptoms prior to presentation was 52 days (range: 3-180 days). The most common radiographic abnormalities were air space disease (57%) and single or multiple mass/nodule (28%). The patients had the following diagnostic tests: sputum (66%), serology (63%), bronchoscopy (74%), transthoracic needle aspiration (14%), and open lung biopsy (6%). The yield from these tests was: sputum (48%), serology (27%), bronchoscopy (85%), needle aspiration (66%), and open lung biopsy (100%). Patients were treated with amphotericin B alone (19%), an azole alone (58%), or a combination of these drugs (23%). In this series the mortality rate was 27% and 89% of the deaths occurred in the immunocompromised group. CONCLUSION: Pulmonary blastomycosis often presents with subacute or chronic symptoms. Radiographic findings are non-specific, however, the presence of nodules or masses should raise suspicions. Sputum studies and serology are unreliable and more invasive tests such as bronchoscopy are usually required to make the diagnosis. While most patients respond well to therapy, immunocompromised patients have a very high mortality rate. CLINICAL IMPLICATIONS: A high index of suspicion for pulmonary blastomycosis is required in endemic areas, particularly in immunocompromised patients. Invasive testing is usually necessary to make the diagnosis. DISCLOSURE: D.M. Hiestand, None. DISTINCT IMMUNE RESPONSES IN TLR2, TLR4 OR MYD88 DEFICIENT MICE FOLLOWING PSEUDOMONAS AERUGINOSA LUNG INFECTION Tong-Jun Lin, DrPh*; Melanie Power, BSc; Elana Maydanski, BSc; Jean S. Marshall, PhD; IWK Health Center, Dalhousie University, Halifax, NS, Canada PURPOSE: Pseudomonas aeruginosa is a cause of serious lung infection in cystic fibrosis patients. The receptors on the host cells responsible for the recognition of this bacterium are unclear. Toll-like receptors (TLR) induce distinct patterns of host responses through MyD88dependent and/or –independent pathways depending upon the nature of the pathogen. Our study examines the specific contribution of TLR2, TLR4 and a TLR adaptor protein MyD88 in the host defense against P. aeruginosa lung infection. METHODS: TLR2-deficient mice, TLR4 mutant mice and MyD88deficient mice were challenged intranasally with cystic fibrosis-associated P. aeruginosa (strain 8821). After 4, 8 or 24 h infection, bronchoalveolar lavage fluids and lung tissues were collected for the examination of bacterial clearance and airway inflammation. Neutrophil recruitment was determined by myeloperoxidase assay and histological examination of the CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Respiratory infections caused by MDRSP are an important global issue facing physicians, the response to which has been the development and approval of some antimicrobials (e.g., gemifloxacin [GEM]) for the treatment of MDRSP. Monitoring local changes in the prevalence of MDRSP and in the efficacy of new agents on a continual basis is therefore important. We examined the current prevalence of MDRSP in the U.S. in adults geographically and by patient age. METHODS: TSN Database-USA (2003 only) was used to evaluate the current prevalence of MDRSP in 9 geographic regions of the U.S. (Atlanta, Baltimore/DC, Carolinas, Central Florida, Chicago, Dallas, Los Angeles, Ohio, South Florida). The prevalence of MDRSP from these regions combined was also analyzed according to patient age (18-44 y, 45-65 y, ⬎65 y). MDR was defined as resistance (R) to ⱖ2 among PEN, erythromycin (ERY), and trimethoprim-sulfamethoxazole (SXT). In addition, we selected 30 MDRSP strains to evaluate the in vitro activities of respiratory fluoroquinolones (GEM, gatifloxacin [GAT], moxifloxacin [MXF], and levofloxacin [LFX]). RESULTS: Overall, 19.2% of the SP collected were MDR; R to PEN, ERY, and SXT was the most common MDR phenotype. By region, MDR was lowest in Los Angeles (9.1%) and highest in South Florida (32.2%); MDR was ⬎20% in Baltimore/DC, Central Florida, and Dallas. According to patient age, MDR was lowest among SP collected from patients 18-44 y (10.4%), compared with patients 45-65 y (19.6%) and ⬎65 y (24.2%). R to PEN, ERY, and SXT was the most common MDR phenotype encountered in all patient age groups. For the 30 MDRSP centrally tested, the fluoroquinolone MIC ranges were as follows: 0.0080.03 mg/L (GEM), 0.12-0.25 mg/L (GAT), 0.06-0.25 mg/L (MXF), 0.5-1 mg/L (LFX). CONCLUSION: MDRSP in adults is an important issue faced in both the hospital and community settings and shows an increased prevalence with an increase in patient age. CLINICAL IMPLICATIONS: GEM was the most active fluoroquinolone tested against MDRSP and should continue to be monitored as it is introduced into clinical use. DISCLOSURE: M.E. Jones, None.

CONCLUSION: Improved antibiotics have decreased the incidence of bronchiectasis and other chronic airway infections. However, surgical therapy for bronchiectasis is still necessary for patients with resistant infections. This surgery can often be done thoracoscopically, with little risk, and decreases the need for inpatient hospitalization. CLINICAL IMPLICATIONS: Patients with recurrent bronchitis and evidence of brconchiectasis should be considered for thoracoscopic resection. DISCLOSURE: J.R. Roberts, None.

Wednesday, October 27, 2004 Respiratory Infections: Microbiology and Treatment, continued lung. TNF, IL-1 and MIP-2 in the BALF and lung homogenates were determined by ELISA. TLR2 and TLR4 expression in the lung was examined by real-time RT-PCR. RESULTS: Both TLR2-deficient mice and TLR4 mutant mice showed partial inhibition of neutrophil recruitment into the lung and production of TNF, IL-1 and MIP-2, compared to wild-type mice. Strikingly, MyD88 mice showed near complete inhibition of neutrophil infiltration and production of TNF, IL-1 and MIP2, and an impaired clearance of P. aeruginosa from the lung. Interestingly, P. aeruginosa-infection stimulated TLR2 but not TLR4 expression in the lung. CONCLUSION: TLR-MyD88 pathway plays an essential role in the development of host response to P. aeruginosa lung infection. TLR2 and TLR4 are involved in this process. However, additional TLRs or interactions between TLR2 and TLR4 are important for the full development of host defense against this bacterium. The increase of TLR2 expression in the lung suggests that the role for TLR2 may increase as the infection progresses. CLINICAL IMPLICATIONS: Targeting TLRs and their adaptor molecule MyD88 for the development of vaccine or for the regulation of immune response may serve as an additional approach for the management of P. aeruginosa lung infection. DISCLOSURE: T. Lin, None.

Lung Cancer 12:30 PM - 2:00 PM ESTIMATING THE STANDARD MORTALITY RATIO FOR LUNG CANCER DUE TO THE CONFOUNDING EFFECTS OF SMOKING Robert M. Ross, MD*; Baylor College of Medicine, Houston, TX PURPOSE: The Standard Mortality Ratio (SMR) is frequently used to assess the risk of lung cancer associated with exposure to various substances. However, it is virtually impossible to adequately control for THE major confounder, smoking. This abstract presents a mathematical formula and table that determine what the SMR would be, based solely on differences in smoking-related factors between a study group and the general population. METHODS: Figure #1 presents the equation. In order to accurately determine the smoking-related SMR, the prevalence of ever-smokers and their relative-risk, for both the study group and the general population, must be known. This is not possible. However, presently approximately 50% of men are ever-smokers and their relative-risk for lung cancer is about 15 times that of non-smokers. The percentage and relative-risk are decreasing. Different study groups have ever-smoker prevalences up to about 80% and relative-risks up to about 20. From these ranges for the 4 variables, estimates can made and the smoking-related SMR obtained from table #1. RESULTS: To use table #1, first choose the sub-column that most closely reflects the relationship between the ever-smoking-relative-risks for the study group and the general population (for example, relationship B). The smoking-related SMR is then found at the intersection of the row showing the prevalence of ever-smokers in the general population and the column indicating the absolute percent increase in ever-smokers in the study group compared to the general population. Small differences can cause a significant increase in the SMR. However, this is not due to the substance being studied.

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Table # 1 Standard Mortality Ratios (SMR) for lung cancer solely due to smoking for study groups that have more ever-smokers than the general population. Values displayed are for examples of different prevalences of ever-smokers and different relative-risks associated with ever-smoking between the study group and the general population. For example, if a study group has an ever-smoking prevalence of 60% and those people have an average relativerisk which is 15-fold that of non-smokers while the general population has an ever-smoking prevalence of 40% and their relative-risk is 10-fold, the smoking-related SMR would be 2.04 (a). Relative-Risk-of-Death from Lung Cancer for Ever-Smokers compared to Non-Smokers for a Study Group compared to the General Population Relationship A Relationship B Study Group Study Group 15-fold General 20-fold General Population 15- Population 15fold fold Prevalence of EverSmokers in the General Population

Relationship C Study Group 15fold General Population 10fold

Relationship D Study Group 20-fold General Population 10fold

60% 1.15 1.30 1.45 1.52 1.72 1.93 1.69 1.91

2.13 2.23 2.53 2.83

50% 1.18 1.35 1.53 1.55 1.79 2.03 1.71 1.96

2.22 2.25 2.60 2.95

40% 1.21 1.42 1.64 1.59 1.88 2.17 1.74 2.04(a) 2.35 2.28 2.70 3.11 30% 1.27 1.54 1.81 1.65 2.02 2.38 1.78 2.16

2.54 2.32 2.84 3.35

20% 1.37 1.74 2.11 1.76 2.26 2.76 1.86 2.36

2.86 2.39 3.07 3.75

10% 20% 30% 10% 20% 30% 10% 20%

30% 10% 20% 30%

Absolute Increase in Prevalence of Ever-Smokers in a study Group compared to the General Population CONCLUSION: A study group that has more ever-smokers, who on average have more smoke exposure or have other factors that increase their risk of death from lung cancer will have an increased SMR. Further, the SMR increase is magnified as the prevalence and relative-risk associated with ever-smoking decreases in the general population. CLINICAL IMPLICATIONS: Elevated SMR’s are generally inadequate as the sole criteria to determine if exposure to a substance increases the risk of lung cancer. DISCLOSURE: R.M. Ross, None. HEALTH-RELATED QUALITY OF LIFE IN INDIAN PATIENTS WITH LUNG CANCER: CORRELATION WITH CLINICAL PARAMETERS Anant Mohan, MD*; Randeep Guleria, DM; Ashutosh Pathak, MBBS; Chinmoyee Das, MBBS; Hemraj Pal, MD; Rajesh Sharma, MD; All India Institute of Medical Sciences, New Delhi, India PURPOSE: Lung cancer is usually diagnosed at an advanced stage and survival has not improved inspite of several therapeutic advancements. Since most patients depend on palliative care, it is imperative to evaluate and maintain a satisfactory quality of life in them. Several questionnaires, mostly in western languages, have been used for this purpose. However, Indian data on this aspect is sparse. METHODS: A 26-item WHO-Quality of Life – Bref questionnaire in Hindi was used to assess the quality of life in lung cancer patients. This questionnaire comprises four domains-Physical, Psychological, Social and Environmental. RESULTS: A total of 76 patients were evaluated. 66 (86.8%) were males, had a mean age of 55.36 years; presented with cough (82.9%), dyspnea (72.4%), chest pain (65.8%), and haemoptysis (43.4%). Eight patients (10.5%) had superior venacaval obstruction. The mean duration of symptoms was 5.9 months. 89.5% had Non-Small Cell Cancer (NSCLC). The mean pack-years was 23.7. Most patients had Karnofsky Performance Scale (KPS) of 70 (52.6%).There was no significant correlation of any quality of life domain with age, sex, duration of symptoms, extent of smoking, cough, dyspnea, chest pain, hemoptysis or hemoglobin. The environmental domain correlated significantly with the serum albumin (p⬍0.016). The physical domain scores of patients with KPS of 80% correlated significantly with those having KPS of Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Lung Cancer, continued 70% and 60% (p ⬍ 0.001 and p ⬍ 0.003 respectively). The psychological domain scores of patients with KPS 80% correlated significantly with those having KPS 70% (p ⬍ 0.005). CONCLUSION: Environmental factors influence nutritional status such as albumin levels. The Karnofsky Performance Scale is an important marker of assessing quality of life. It is a simple numerical tool that reliably predicts deteriorating quality of life, particularly the physical and psychological aspects. CLINICAL IMPLICATIONS: Quality of life in lung cancer is not affected by age, sex, presence of symptoms and their duration or extent of smoking. Karnofsky Performance Scale is a useful surrogate marker of quality of life in these patients. DISCLOSURE: A. Mohan, None. RISK FACTORS ASSOCIATED WITH LYMPH NODE METASTATSIS IN BRONCHOGENIC LUNG CANCER: A SEER (SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS) STUDY Arnold M. Schwartz, MD, PhD*; Donald E. Henson, MD; Matthew Tuck, BS; George Washington University Medical Center, Washington, DC

Clinical and Radiographic Presentations Dyspnea Cough Hemoptysis Weight Loss Chest pain Non-resolving Pneumonia Bronchorrgea Fever Solitary Nodule/Mass Air bronchogram Multiple nodules Pneumonic consolidation Diffuse interstitial infiltrate Cavitary Mass Atelectasis Pleurale effusion

Percent 30% 27.5% 12.5% 12.5% 5% 5% 2.5% 2.5% 65% 32.5% 22.5% 12.5% 5% 7.5% 2.5% 2.5%

EIGHT-YEAR EXPERIENCE WITH BRONCHIOLOALVEOLAR CARCINOMA Raed A. Hamed, MBBS*; Damanpaul Sondhi, MBBS; Gonzalo Gianella, MD; Michael Lippmann, MD; Albert Einstein Medical Center, Philadelphia, PA PURPOSE: Bronchioloalveolar carcinoma (BAC) has nonspecific clinical and roentgenographic presentations. We reviewed clinical manifestations, radiographic presentations, staging, treatments and survival of BAC. METHODS: The records of forty patients (pts.) diagnosed with BAC from January 1995 to June 2003 were reviewed for demographic data, smoking history, symptoms, radiographic presentations, diagnosis, staging, treatment and survival. RESULTS: The mean age was 67.5 years, 62.5% were females. 75% were smokers. 45%were asymptomatic.(Table1 Summarizes clinical and radiographic presentations). Preoperative staging showed: 30% stage I , 5% Stage II, 20% stage III and 42.5%stage IV. One pt. was lost to follow up before staging and treatment was initiated. 52.5% were

DISCLOSURE: R.A. Hamed, None.


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PURPOSE: Bronchogenic carcinoma may present as an intraparenchymal tumor (T1). Recurrence increases and overall survival decreases with the presence of bronchial/hilar lymph node metastases (N1). This study investigates epidemiologic data and tumor characteristics, derivable from the SEER data set, in order to identify factors that predict early aggressive behavior. METHODS: The SEER Registry was investigated analyzing the incidence of lung cancer cases from 1973 - 2001, which were AJCC T1 lung cancers. The incidences of these tumors were analyzed according to nodal status, N0 and N1, and a risk (odds) ratio of T1N1/T1N0 was generated as a surrogate indicator of relative cancer aggressiveness. Lung cancers that were equal to or greater than T2, N2, and M1 were excluded. RESULTS: The overall risk odds ratio, T1N1/T1N0, for all non-small cell carcinomas is 0.13, significantly less than for small cell undifferentiated carcinoma. The ratio increases with size of the tumor; respectively 0.09 and 0.15 for tumors less than 2 cm., and those between 2 and 3 cm. Similarly, increasing the histologic grade of adenocarcinoma from well differentiated to moderately differentiated to poorly differentiated increases the risk ratio from 0.07 to 0.15 to 0.20, respectively. As expected, the risk ratio for adenocarcinoma markedly exceeds that for bronchioloalveolar carcinoma. Interestingly, the risk ratio for African American (Blacks) is higher than that for Whites. CONCLUSION: The odds risk ratio, T1N1/T1N0, represents a parameter indicating metastatic potential. Classical features of tumor size and grade are associated with increasing risk ratios. Epidemiologic data, such as racial/ethnic background and gender are also predictive of risk ratio differences. CLINICAL IMPLICATIONS: The risk ratio, T1N1/T1N0, indicates the relative risk of a T1 tumor to metastasize to N1 nodes and represents a marker of relative tumor aggressiveness. Patient stratification may be performed using the risk ratio even in the absence of supporting imaging data for dissemination. DISCLOSURE: A.M. Schwartz, None.

treated surgically (stage I, II&IIIA), 50% underwent lobectomy, one patient had pneumonectomy. The 7 pts with stage IIIA received postoperative radiation (3 pts.) and postoperative radiation and chemotherapy(4 pts), the one pt with stage IIIB received radiation. The 17 pts with stage IV received chemotherapy (6 pts.), radiation (6 pts.), and both chemotherapy and radiation(5 pts). The overall one and two-year survival was 70%&47% respectively (median survival was 22 months). The one and two-year survival for stage I&II was 100%&84% respectively, it was 54%&26% for stage III&IV. The median survival for stage III&IV was 13 months. The overall one, two and three-year survival in pts whom tumor was completely resected was 86%, 64%&47% respectively (median survival was 32 months) it was 43%, 18%&9% respectively for pts who received palliative treatment (median survival was 5 months). The one and two-year survival were higher in asymptomatic than in symptomatic pts (94%&75% vs. 50%&23% respectively), and were higher in females than in males (78%&60% vs. 57%&12% respectively).(Figure1 shows Kaplan-Maier survival curve for pts with stage 1&II vs. III&IV). CONCLUSION: The majority of patients have significant smoking history. females represented the majority of our patients. Most patients presented with a solitary mass. Bronchorrhea and air- bronchogram are specific for BAC.The staging, treatment and prognosis of BAC are similar to those with NSCLC. CLINICAL IMPLICATIONS: BAC has nonspecific clinical and radiographic presentations.

Wednesday, October 27, 2004 Lung Cancer, continued UTILITY OF CT-GUIDED TRANSTHORACIC NEEDLE BIOPSY (TNB) IN THE DIAGNOSIS OF HILAR AND MEDIASTINAL MASSES IN PATIENTS WITH NON-SMALL-CELL LUNG CANCER (NSCLC) Jeffrey S. Klein, MD; Erin McQuaide, MD*; FAHC, Burlington, VT PURPOSE: To determine the accuracy and complication rate of CT-TNB for hilar or mediastinal masses or enlarged lymph nodes on CT in patients with NSCLC. METHODS: We retrospectively obtained a list of patients for whom TNB was performed over the period 1996-2004 to sample a hilar or mediastinal mass, or enlarged hilar or mediastinal lymph nodes (short axis ⬎ 10 mm) in patients with a primary lung lesion representing NSCLC. Those patients with suspected sarcoidosis or those with proven small cell carcinoma or a history of an extrathoracic malignancy who underwent TNB to detect nodal metastases from malignancies other than non-small cell lung cancer were excluded. We sought to determine the size and distribution of enlarged mediastinal and hilar lymph nodes or masses as seen on chest CT. The diagnostic yield and complication rate, in particular pneumothorax, bleeding, and chest tube insertion rate, were determined from a procedural database. The final pathologic diagnosis and TNM staging classification resulting from the biopsy was obtained from the pathology report. RESULTS: There were 21 patients who underwent CT-guided biopsy of a mediastinal or hilar lesion with NSCLC. The distribution of lesions were: right paratracheal (6), hilar (8), prevascular/anterior mediastinal (4), subcarinal (2) and aortopulmonary window (1). An extra-visceral pleural approach utilizing existing parasternal or paravertebral tissue, pleural fluid, or iatrogenically-created pneumothorax was possible in 15 of 21 patients (71%). There were 20 patients proven to have mediastinal or nodal disease and one patient proven surgically to be node negative: all were correctly diagnosed by CT-guided TNB (accuracy ⫽ 100%). In all but two patients, the results of the biopsy precluded attempts at surgical resection. Three patients (14%) developed a pneumothorax, with 2 (10%) requiring catheter drainage. CONCLUSION: CT-guided TNB is an accurate and safe technique in selected patients for nodal staging of NSCLC. CLINICAL IMPLICATIONS: This minimally-invasive technique can guide clinicians confronted with abnormal CT scans or positron emission tomography studies for hilar and mediastinal nodes to more accurate select surgical candidates with NSCLC. DISCLOSURE: E. McQuaide, None.

CONCLUSION: Quality of life in lung cancer patients is directly related to their respiratory status, especially the presence of dyspnea and chest pain. VAS, 6MWT and SBC reliably assess a patient’s physical, psychological and social aspects of quality of life. Spirometry is not very useful in quality of life measurements. CLINICAL IMPLICATIONS: Efforts to ameliorate chest pain and dyspnea in lung cancer patients may significantly improve the quality of life in lung cancer.

Demographic Profile and Mean Domain Scores Number of patients: 90 Mean age (years): 55.5 Males/females: 77/13 Mean duration of symptoms (months): 7.23 Mean pack-years: 23.2 Non-small cell cancer: 80 Small-cell cancer

Cough

: 72

Dyspnea Chest pain Hemoptysis

: 65 : 61 : 39

Mean Scores: Domain I

: 10.69

: 10 Domain III Domain IV

Domain II 11.39 : 13.2 :11.42

DISCLOSURE: A. Mohan, None.

RESECTABILITY OF LUNG CANCER IN THE UNIVERSITY HOSPITAL IN PRAGUE, CZECH REPUBLIC Miloslav Marel, MD*; Zdenek Skacel, MD; Irena Spasova, MD; Martina Vichova, MD; Pavel Pafko, MD; Jan Schutzner, MD; Ronald Pospisil, MD; Department of Pulmonary Medicine, 1st Medical Faculty of Cha, Prague, Czech Republic

PURPOSE: Most patients with lung cancer are already inoperable at diagnosis. Of these, several are unable to tolerate chemotherapy and are managed palliatively. We looked for any correlation between respiratory symptoms and pulmonary functions on morbidity and quality of life. METHODS: A 26-item WHO-Quality of Life – Bref questionnaire in Hindi was used to assess the quality of life. This questionnaire comprises four domains-Physical, Psychological, Social and Environmental. Domain scores were correlated with forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow rate, forced expiratory flow, mean inspiratory and expiratory pressures as well as dyspnea indices including visual analogue scale (VAS), six-minute walk test (6MWT), single breath count (SBC) and breath holding time (BHT). RESULTS: There was no significant correlation of any domain with cough, dyspnea, or hemoptysis. Chest pain correlated significantly with the physical domain (p⫽ 0.40). Among pulmonary functions, only forced vital capacity correlated with the social domain (p⫽0.01). The physical and psychological domains correlated with VAS and 6MWT (p⫽ 0.000, 0.000, 0.007 and 0.001 respectively). Psychological and social domains correlated with SBC (p⫽0.002 and 0.036 respectively).

PURPOSE: Lung cancer is the most frequent killing malignant tumor in men and the second in women in the Czech Republic. Early stages I and II are diagnosed in less than 20%, only l2% of patient (pts) are sent to surgery and 5-year survival is only 6%. The aim of our study was to describe results of diagnosis and therapy in lung cancer pts during the period l998-2003 in the Pulmonary and Surgical Departments of University Hospital in Prague Motol. METHODS: To asses changes in diagnostic procedures and therapy results we compared two subgroups of pts. The group A was created by pts from l998-2000, the group B involved pts from 2001-2003. 1024 pts with lung cancer were prospectively followed. 415 pts created the Group A and 609 the Group B. Men to women ratio was 2:1. RESULTS: Adenocarcinoma was confirmed in 24% in the Group A and in 30% in the Group B. 24% of the Group A and 31% of the Group B were diagnosed in early stages. 275 pts of the whole group of 1024 pts (27%) were sent to surgery. 55% and 60% of lobectomy were done in Group A and B, respectively. Neoadjuvant chemotherapy was applicated in 8% of pts in the Group A and in 17% of pts in the Group B. The concordance between cTNM and pTNM balanced around 55%, cTNM was underestimated in 30%, overestimated in 15% in both groups. CONCLUSION: We conclude that the percentage of adenocarcinoma, the number of early stages diagnosed and the number of resected pts increased during the two followed period. The neoadjuvant chemotherapy was more frequently used and more parenchyma sparing resection was carried on in the period 2000-2003. CLINICAL IMPLICATIONS: Our figures are comparable with the results of other centers in EU or US. To increase the number of resecable pts we advocate for development of new methods of lung cancer screening, for example low-dose CT, in the frame of international clinical studies. DISCLOSURE: M. Marel, None.

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RELATIONSHIP BETWEEN HEALTH-RELATED QUALITY OF LIFE AND PULMONARY FUNCTIONS IN INDIAN PATIENTS WITH LUNG CANCER Anant Mohan, MD*; Randeep Guleria, DM; Ashutosh Pathak, MBBS; Hemraj Pal, MD; Chinmoyee Das, MBBS; Rajesh Sharma, MD; All India Institute of Medical Sciences, New Delhi, India

Wednesday, October 27, 2004 Lung Cancer, continued

CT FLUOROSCOPY-GUIDED PERCTANEOUS NEEDLE BIOPSY OF PULMONARY LESIONS: CORRELATION BETWEEN CT IMAGES AND HISTOLOGICAL APPEARANCE Hitomi Awaya, MD*; Sakae Nagaoka, MD; Masahiro Tanabe, MD; Tsuneo Matsumoto, MD; Yamaguchi University School of Medicine, Ube, Japan

GLOBAL INITIATIVE ON OBSTRUCTIVE LUNG DISEASES (GOLD) CLASSIFICATION OF COPD AND INCIDENT LUNG CANCER: FINDINGS FROM A COHORT STUDY David M. Mannino, MD*; Dennis Doherty, MD; A S. Buist, MD; Fernando Holguin, MD; University of Kentucky, Lexington, KY PURPOSE: To determine whether the GOLD classification criteria predict incident cases of lung cancer in a cohort of subjects followed for up to 11 years. METHODS: We analyzed data from 15,759 adult participants, aged 43-66 years at baseline, in the Atherosclerosis Risk in Communities (ARIC) study. All baseline and follow-up data were available for 15,432 (97.9%) of the initial participants. We excluded 851 subjects (5.4%) who stated they had a cancer diagnosis at the baseline evaluation, resulting in 14,581 subjects in our final cohort. We classified subjects using the GOLD criteria for COPD, and added a “restricted” category (FEV1/FVC ⬎ 70% and FVC ⬍ 80% predicted). Our endpoint of interest was either the first hospitalization that listed a lung cancer diagnosis (ICD-9 code 162) or a

Disease GOLD 3/4 GOLD 2 GOLD 1 GOLD 0 Restricted Normal Total

n

Lung Ca Rate/ Lung Person 1000 Person % Cancer Years years Hazard Ratio

177 1.1

16

1366

11.7

11.9(6.3,22.5)

886 5.7 38 7631 2141 13.9 54 19078 2399 15.5 23 21600 1091 7.1 13 9605 7887 51.1 26 72397 14581 170 131677

5.0 2.8 1.1 1.4 0.4 1.3

6.1(3.6,10.2) 3.5(2.2,5.8) 2.2(1.3,3.9) 2.6(1.3,5.1) 1.0

Cardiothoracic Surgery - Therapeutic Options 12:30 PM - 2:00 PM CARDIAC SURGERY WITHOUT CHEST TUBES AND PLEUROVACS: A NEW STANDARD OF CARE Walter J. Ehrman, MD; Nancy A. Pike, NP; Steven R. Gundry, MD*; The International Heart & Lung Institute, Palm Springs, CA PURPOSE: Chest tubes are the “Gold Standard” for drainage following cardiac surgery, but are large, uncomfortable, and painful. They require a PleurovacR which is cumbersome. Flexible, 19F drains with ridges (BlakeR), connected to 50cc grenade bulbs fitted with “Heimlich” one-way valves could provide effective and comfortable drainage following cardiac operations, but there is fear that these drains cannot handle potential bleeding. METHODS: 146 consecutive adult pts undergoing cardiac surgery from the inception of a new cardiac surgery program had two 19F BlakeR drains (Ethicon, Summerville, NJ) placed; one in the left pleural space when a LIMA was harvested, and the other wrapped around the heart. Valve cases had both drains placed in the pericardium. Double IMA’s had 3 drains, one in each pleural space. All drains exited the midline and were connected to 50cc bulbs. Drain tubing was stripped routinely. Drains were removed when drainage was ⬍100cc/12 hrs. Pts were assessed for cardiac tamponade, take-back for bleeding, pleural effusions, and perceived comfort. RESULTS: There were no early or late episodes of tamponade. There were no early or late returns to the OR for bleeding. There were no pleural effusions requiring drainage. Pts were ambulatory immediately post-op with their drains clipped to their robes. Redo pts rated BlakeR drains superior in comfort and ease of removal over their previous chest tubes. CONCLUSION: BlakeR drains meet and/or exceed all criteria for mediastinal and pleural drainage following cardiac surgery, result in superior pt comfort and mobility, and should be considered standard of care. CLINICAL IMPLICATIONS: Chest tubes and their removal remain one of the most painful parts of cardiothoracic surgery. Blake drains provide equal or better drainage ability but also offer superior comfort. DISCLOSURE: S.R. Gundry, None. EARLY SURGICAL MANAGEMENT OF CONGENITAL AORTIC ARCH COMPLEX ANOMALIES Jung M. Yu, MD; Tsung P. Tsai, MD, PhD*; Fong L. Chen, MD; Yin T. Liu, MD; Yi L. Wu, MD; Jen A. Wang; Shu M. Kuo, MD; Zen C. Weng, MD; Chung-Shan Medical University Hospital, Taichung, Taiwan ROC PURPOSE: Anomalies of the aortic arch complex (vascular rings) occur in multiple forms, often forming rings that cause tracheal obstruction and respiratory distress. The symptoms are usually non-specific but are potentially lethal. Echocardiography with a barium swallow or 3-D computerized tomography is feasible and accurate in the early diagnosis of CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: The relationship between the location of the biopsy needle and the nodule can be retrospectively confirmed by the video in the computed tomographic fluoroscopy (CTF)-guided percutaneous needle biopsy. Our purposes of this study are to clarify the diagnostic ability of CTF guided needle biopsy of pulmonary lesions, and to evaluate the usefulness of comparing CT video images with pathologic findings. METHODS: From July 1996 to June 2003, 118 patients (80 men and 38 women; mean age, 66.6 years; age range 23 to 90 years) underwent CTF-guided percutaneous needle biopsy of pulmonary lesions using an18G core needle. 30 patients in 118 patients had the operation enforced. The rate of complication and the diagnostic ability of the biopsy were evaluated. The improvement of diagnosis by the comparing between the pathologic features and images in lung biopsy was evaluated. RESULTS: Pneumothorax and hemosputum occurred in 24.9% and 3.3%, respectively. The diagnostic ability of CTF-guides percutaneous needle biopsy for malignant disease was sensibility 90%, specificity 100%, and accuracy 95%. For the information only on the histopathological findings of CTF, there were 25% of definite diagnostic impossible examples such as fibrotic change and necrosis. Fibrotic change included focal fibrosis, organizing pneumonia, the central fibrosis of adencarcinoma, and so on. The diagnosable cases increased 10% by examining the histopathological findings with reference to the CTF image at the time of puncture. CONCLUSION: CTF-guided percutaneous needle biopsy of pulmonary lesions is a safe technique. By leaving image data, evaluation of the biopsy of which portion of a pulmonary lesion was carried out was attained, and it was considered to be near by exact diagnosis. CLINICAL IMPLICATIONS: The information CT images in CTFguided perctaneous needle biopsy is an important role to make an accurate pathologic diagnosis. DISCLOSURE: H. Awaya, None.

death listing lung cancer. We used Cox proportional hazard models to determine the risk of impaired lung function on incident lung cancer, after adjusting for age, race, sex and smoking status. RESULTS: 170 (1.2%) of subjects developed lung cancer by the end of 1997. The rate of lung cancer development ranged from 0.4 per 1000 person years among normal subjects to 11.7 /1000 among subjects with GOLD 3 or 4 COPD (Table). After adjusting for covariates, all GOLD categories, along with the restricted category, predicted a higher risk of incident lung cancer (Table). CONCLUSION: The GOLD classification system of COPD predicts incident lung cancer in this cohort of middle-aged Americans followed for up to 11 years. CLINICAL IMPLICATIONS: Pulmonary function testing may be useful in the clinical evaluation of patients risk for the subsequent development of lung cancer. DISCLOSURE: D.M. Mannino, None.

Wednesday, October 27, 2004 Cardiothoracic Surgery - Therapeutic Options, continued congenital aortic arch complex anomalies. Early management to relieve the tracheobronchael compression to prevent mental retardation is mandatory. METHODS: Though the integrated school-based health screening survey of the prevalence of congenital and acquired heart disease in 92,884 native born school children at Taichung Country, Taiwan (from June 1, 2002 to August 31, 2003), 55 patients of undiagnosed vascular ring were found by portable echocardiographic examination with Agilent opti-Go echocardiography among the children with mental retardation. After the diagnosis of a vascular ring, patients underwent spiral CT scan with 3-D reconstruction to evaluate the severity of airway compression. In compression to clinical symptoms if any and the severity of tracheobroncheal compression, 35 out of 55 patients with a vascular ring underwent surgical correction. RESULTS: Thrity-five patients(20 males and 15 females; age ranged from 2 months to 45 years with mean of 9.98 years) underwent surgical correction of a vascular ring. No mortality resulted. Minor complications (3 chylothorax, 1 minor stridor, 2 with minimal shortness of breathing) were found during the follow-up (mean of 5.2 months). CONCLUSION: Early diagnosis through health screening programs and early management of the congenital aortic arch complex anomalies will reduce the preoperative and postoperative morbidity and eliminate potential respiratory sudden death in these patients. CLINICAL IMPLICATIONS: School children with suspected mental retardation associated with respiratory distress should undergo health screening with echocardiography. Early surgical management in patients with vascular rings to prevent t he deterioration of symptoms or sudden death is mandatory. DISCLOSURE: T.P. Tsai, None.

myocardial damage 6h post-Aorta declamping, as showed by significant lower plasma cTnI concentrations. CLINICAL IMPLICATIONS: Therapeutic value of dexamethasone is evident postoperatively for the myocardium and it is of no importance in preventing ischemia/reperfusion injuries in kidneys, intestine and liver.

PROPHYLACTIC USE OF DEXAMETHASONE IN CARDIOPULMONARY BYPASS Leon P. Aarts, MD, PhD; Piet W. Boonstra, MD, PhD; Gerhard Rakhorst, DVM, PhD; Aurora M. Morariu, MD*; Wim G. Rietman, MD; Berthus G. Loef, MD; Anne H. Epema, MD, PhD; Wim van Oeveren, PhD; BME, Faculty of Medicine Groningen, Groningen, the Netherlands PURPOSE: Bioincompatibility of the extracorporeal circuit is a triggerfactor for the systemic inflammatory response in patients undergoing on-pump CABG. Blood contact with synthetic surfaces leads to activation of complement, neutrophils and subsequent cytokine expression. Corticosteroids were recommended to inhibit the activation of inflammation and reduce the reperfusion injuries. The present study aims to document the effect of prophylactic dexamethasone on myocardial, renal, intestinal, and hepatic injury associated with CPB. METHODS: 20 patients scheduled for first-time CABG were prospectively, double-blind randomized in two groups receiving either dexamethasone (1mg/kg before anesthesia induction and 0.5mg/kg after 8 hours) or placebo. Inflammatory reaction was documented with plasma interleukins IL6,IL8,IL10. Organ-damage was assessed by measuring specific markers: troponinI (cTnIѠmyocardial damage), urine N-acetyl-␤-D-glucosaminidase (NAGѠkidney damage), urine intestinal-type fatty acid binding protein (IFABPѠintestinal damage), plasma a´ -glutathione Stransferase (alphaGSTѠliver damage). RESULTS: Significant lower values of IL6,8 and higher IL10 were measured as main effect of dexamethasone (Mann-Whitney p⬍0.001). cTnI peaked at 6h post-Ao declamping with significant higher concentrations in placebo-group (Mann-Whitney p⫽0.009).There was no main effect for dexamethasone on overall plasma cTnI concentration. Urine NAG peaked at 2hICU with no main effect for dexamethasone on overall urine NAG concentration (F⫽0.297,p⫽0.592) Urine IFABP: maximum difference with the base line was reached at 2hICU(Wilcoxon p⬍0.001); There was no main effect for dexamethasone (F⫽0.262,p⫽0.615). Significant independent predictors for IFABP and NAG at 2hICU were serum glucose at end-CPB (IFABP:R2⫽0.31,Sig.⫽0.015; NAG: R2⫽0.33,Sig.⫽0.008 ) and pump-perfusion time(IFABP: R2⫽0.23,Sig.⫽0.031; NAG:R2⫽0.25,Sig.⫽0.02). Plasma alpha-GSTpeaked at end-CPB with no significant difference between groups at any time-point. CONCLUSION: Transient, subclinical myocardial, renal, intestinal and hepatic injury was detectable even following uncomplicated CPB in low-risk patients.Prophylactic dexamethasone, even if active in inhibiting the inflammatory response, seemed to be ineffective in preventing abdominal organ-damage. Patients receiving dexamethasone had lower

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DISCLOSURE: A.M. Morariu, None.

OPEN CARDIAC MASSAGE FOLLOWING CORONARY ARTERY BYPASS SURGERY Janne P. Karhunen, MD; Eero I. Sihvo, MD; Raili T. Suojaranta-Ylinen, MD; Antti Vento, MD; Paula K. Maasilta, MD; Ulla-Stina Salminen, MD*; Helsinki University Hospital, Dept of Surgery, Helsinki, Finland PURPOSE: Cardiopulmonary resuscitation after cardiac surgery has an incidence of 2%-3%. Signs of inadequate tissue perfusion, myocardial ischemia, and increased need for inotropic and mechanical support were predictive for postoperative hemodynamic collapse in our previous studies. Now we focused on complications related to this event and factors predictive for survival. METHODS: A total of 8807 patients underwent isolated CABG between 1988 and 1999. Unrelated to pericardial bleeding or tamponation, 76 (0.9%) faced sudden hemodynamic collapse resulting in open cardiac massage during the immediate postoperative course. Of these, 41 (54%) survived. We statistically compared survivors and non-survivors. Additional comparison was performed between all 76 patients facing hemodynamic collapse and 76 preoperatively matched controls. RESULTS: In patients facing open cardiac massage, the rate of cardiac (85%/20%, p⬍0.0001), neurological (22%/4%, p⫽0.001), pulmonary (54%/5%, p⬍0.0001), and renal (15%/0%, p⫽0.001) complications was more frequent than in matched controls. Infections were more common (39%/5%, p⫽0.0001), additional surgery was more often required (41%/ 4%, p⬍0.0001), and both ICU stay (p⬍0.0001) and total hospital stay (p⬍0.01) were longer. Cardiopulmonary bypass time was longer (p⬍0.01) in non-survivors than in patients surviving open cardiac massage. Surprisengly, arterial grafts (internal thoracic and/or radial artery) were more Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Cardiothoracic Surgery - Therapeutic Options, continued frequently (p⬍0.05) used in survivors. Long-term survival turned out to be equal in open cardiac massage survivors and matched controls. CONCLUSION: Sudden hemodynamic collapse resulting in need of open cardiac massage is fatal in almost one half of patients and leads in frequent complications and prolonged ICU and hospital stay. Despite the higher rate of complications, patients who survive this event reach excellent long-term result, which may at least partly be due to the frequent use of arterial grafts with well-known good long-term patency. CLINICAL IMPLICATIONS: This study shows, that although the mortality rate of sudden hemodynamic collapse resulting in open cardiac massage and the rate of related complications is high, patients surviving reach a long term result comparable to that of patients undergoing CABG with uneventful postoperative course. DISCLOSURE: U. Salminen, None. CARDIAC WORKING CONDITIONS CAN BE OPTIMIZED BY SYNCHRONIZED PULSATILE EXTRACORPOREAL LIFE SUPPORT Koen Reesink, MS; Loes Sauren, BS*; Andre Dekker, PhD; Theo van der Nagel; Ervin Severdija; Cecile Soemers, MD; Gijs Geskes, MD; Erik van der Veen, PhD; Jos Maessen, MD, PhD; Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands

RISK FACTORS FOR RESPIRATORY FAILURE AND LONGTERM SURVIVAL FOLLOWING CORONARY ARTERY BYPASS GRAFTING Ioannis K. Toumpoulis, MD*; Constantine E. Anagnostopoulos, MD; Robert C. Ashton, MD; Cliff P. Connery, MD; Joseph J. DeRose, MD; Daniel G. Swistel, MD; Columbia University College of Physicians and Surgeons, New York, NY PURPOSE: Respiratory failure (RF) following coronary artery bypass grafting (CABG) has been linked to increased early morbidity and mortality. We sought to determine risk factors for RF and to compare early and long-term outcome. METHODS: We studied 3760 consecutive patients who underwent CABG between 1992 and 2002. Patients without RF were compared with those who developed RF postoperatively (intubation and ventilation for a period of 72 hours or more). Long-term survival data (mean follow-up 5.2 years) were obtained from the National Death Index. Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots. The propensity for RF was determined by logistic regression analysis and each patient with RF was then matched with 5 patients without RF. RESULTS: One hundred and sixty-two patients (4.3%) developed RF. The independent predictors for RF were increased age, low ejection fraction, shock, congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, smoking and other major complications: stroke, deep sternal wound infection, sepsis, bleeding, renal failure and gastrointestinal complications. After adjustment for all pre-, intra- and post-operative factors the adjusted hazard ratio of long-term mortality for patients with RF was 2.07 (95% confidence interval 1.562.75; P⬍0.001). One hundred and eighteen patients with RF were matched with 590 patients without RF using propensity scores identical to within 1%. Early outcome of matched groups is shown in table and

Variable EuroSCORE Length of stay (days) 30-day mortality, n (%) In-hospital mortality, n (%) Intraoperative stroke, n (%) Stroke over 24 hours, n (%) Postoperative myocardial infarction, n (%) Deep sternal wound infection, n (%) Bleeding/reoperation, n (%) Gastrointestinal complications, n (%) Renal failure/dialysis, n (%) Sepsis/endocarditis, n (%)

Without RF (n⫽590)

With RF (n⫽118)

P value

8.0⫾3.9 12.8⫾15.4 39(6.6) 35(5.9)

8.1⫾3.6 28.2⫾31.2 20(16.9) 25(21.2)

0.857 ⬍0.001 0.001 ⬍0.001

36(6.1)

7(5.9)

0.999

17(2.9)

4(3.4)

0.766

4(0.7)

1(0.8)

0.999

10(1.7)

5(4.2)

0.088

40(6.8)

9(7.6)

0.694

26(4.4)

4(3.4)

0.804

14(2.4)

4(3.4)

0.521

13(2.2)

3(2.5)

0.739


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PURPOSE: To investigate the potential of synchronization of pulsatile extracorporeal life support (p-ECLS). METHODS: Five calves (60⫾21 kg) were instrumented and subjected to partial femoro-femoral veno-arterial ECMO. Heart rate was synchronized to pump-ejection by a custom made pacemaker system. The cardiac-to-pump ejection delay was varied in 50 ms steps along the cardiac cycle. Data analysis focused on cardiac workload and peripheral perfusion. RESULTS: Based on LV afterload (PLVpeak) three markers were identified in each animal: Maximum increase (I), mean (II), and maximum decrease (III) of afterload (see Figure 1 and 2). The Table shows that systolic arrival of the p-ECLS pulse increased LV afterload (I). Elevated LV afterload is associated with an increase in PVA (oxygen consumption) and a decreased ventricular efficiency (EW/PVA). The diastolic coronary flow fraction during diastolic arrival (III) is about twice as high as during systolic arrival. Among the subjects the fraction of total peripheral flow delivered by the LV varied substantially (Table). Figure 1 and 2 show the delay dependency of multiple hemodynamic variables in two distinct cases of LV contribution. The balance between peripheral (and coronary)

perfusion and cardiac workload can be improved by avoiding systolic pulse arrival (Figure 1 and 2). CONCLUSION: During partial pulsatile ECLS ventricular efficiency can be improved upto 30 percent by avoidance of systolic impairment. Synchronization is more effective in subjects with a small left ventricular contribution to total peripheral flow. CLINICAL IMPLICATIONS: Well-adjusted pulsatile extracorporeal life support may be more versatile than asynchronous or continuous systems in facilitating recovery of cardiac function. DISCLOSURE: L. Sauren, None.

Wednesday, October 27, 2004 Cardiothoracic Surgery - Therapeutic Options, continued CLINICAL IMPLICATIONS: Therefore it is a possible solution for a more efficient use of existing IC-capacity. DISCLOSURE: G.M. Van, None.

SUPRA-CORONARY AORTIC VALVE IN A PIG MODEL WITH SEVERE AORTIC INSUFFICIENCY Michael Michel, MD*; Jerry W. Pratt, MD; Keesler Medical Center, Keesler AFB, MS

Kaplan-Meier curves are shown in figure. Freedom from all-cause mortality at 5 years was 70.1⫾2.0% in patients without RF versus 51.7⫾5.1% in patients with RF (P⬍0.0001). CONCLUSION: We identified preoperative and postoperative risk factors for RF following CABG. Patients with RF had significantly higher early and late mortality when compared with patients without RF. CLINICAL IMPLICATIONS: RF had increased incidence in CABG patients with impaired cardiac or pulmonary function, increased age and major postoperative complications; its effect on patient survival extends far beyond the 30-day and in-hospital mortality time periods. These data suggest the need for a more frequent follow-up among patients with RF. DISCLOSURE: I.K. Toumpoulis, None.

THE NEED FOR MORE EFFICIENT USE OF EXISTING INTENSIVE CARE CAPACITY: IS SHORT STAY IC FOR CABGPATIENTS THE SOLUTION? Ghislaine M. Van, MS*; Hans Severens, Professor; John Heijmans, doctor; Paul Roekaerts, doctor; Gemma Voss, PhD; Jos Maessen, doctor; University Hospital of Maastricht, Maastricht, the Netherlands PURPOSE: Due to an increase of high-risk cardio-surgical patients, budget constrains,improvements in anesthetic and cardio-thoracic procedures their is a need to re-evaluate the existing IC capacity. A randomised controlled clinical equivalence trial was conducted to evaluate the safety and cost-effectiveness of Short Stay Intensive Care (SSIC) for CABGpatients. METHODS: For this, 600 patients were included to undergo either SSIC (⬍ 8 hours, n⫽300) or a traditional IC-treatment (TICT)⬎16 hours, n⫽300). The primary endpoints were IC re-admissions and total hospital stay. The secondary endpoints were mortality, morbidity, Quality of Life (QoL) and total hospital costs. QoL was measured using the EuroQoL and expressed in Quality Adjusted Life Months (QALMs). The follow-up of the study was until one month after surgery. Incremental Cost-Effectiveness Ratio (ICER) was calculated of cost/QALMs. Bootstrap analysis were performed to quantify the uncertainty around the base case ICER. In addition to this, sensitivity analyses on costs were performed to explore the robustness of the findings. RESULTS: No significant differences in IC re-admissions between SSIC (n⫽8) and TICT (n⫽4) were found (p-value⫽.241). The total hospital stay (p-value⫽.807), 30 day-mortality (p-value⫽.317), morbidity and QALMs (95%CI: -0,004, 0,0003) were also not significantly different between the two groups. 165 (55%) patients in the SSIC-group were transferred from IC to Medium Care within 8 hours. The total hospital costs were significantly lower in the SSIC (€5.441) compared to the TICT-group (€4.625) (95% CI: € -1581, €-174). These cost savings were largely due to fewer hours of IC stay (SSICmean⫽19.7 and TICT mean⫽31.0) and fewer laboratory procedures. The ICER is (Cost/ QALM) €-815/-0.00211⫽385.773, indicating that SSIC leads to cost savings without relevant efficacy loss. After analysing the uncertainty and performing sensitivity analysis this result still held and was proven to be very robust. CONCLUSION: Compared to TICT, SSIC is safe, lowers IC hours and the total hospital costs.

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PURPOSE: Transcatheter placement of aortic valves is a therapeutic option currently under investigation. This study evaluates the placement of an aortic valve in the supra-coronary position in pigs with severe aortic insufficiency. METHODS: Fifteen pigs were randomized to 3 equal groups: supracoronary aortic valve (experimental) vs. control vs. off pump control. The off pump control group was not placed on cardiopulmonary bypass (CPB) and was used to control for the possible effect of CPB. Median sternotomy with isolation of the right coronary artery was performed in all 3 groups. The experimental and control groups were placed on CPB and the aorta was cross clamped and transected. In the experimental group, all leaflets of the aortic valve were excised, and a mechanical valve was placed in the supra-coronary position. In both groups the aorta was re-anastomosed and the animals were weaned from CPB. All surviving animals were monitored for 4 hours and administered escalating doses of dobutamine while hemodynamic, laboratory, and coronary flow data were recorded. RESULTS: All 5 animals in the experimental group died upon discontinuation of CPB. All animals were age and weight matched. All pre-operative and pre-CPB hemodynamic, laboratory values, and coronary flow characteristics were not significantly different among the 3 groups. None of the hemodynamic values or coronary flow characteristics were significantly different between the control and the off pump control groups throughout the 4 hour monitoring period. The significant differences during the 4 hour monitoring period in laboratory values between the control and off pump control groups include creatine kinase (CK), CK–MB fraction, troponin-I, and aspartate aminotransferase (AST); all p values ⬍0.05. CONCLUSION: Aortic valve replacement in the supra-coronary position is fatal in pigs with severe aortic insufficiency. Based on the hemodynamic and coronary flow data, CPB does not appear to be a factor in this conclusion. CLINICAL IMPLICATIONS: Advances in aortic valve replacement are being continually investigated. This data suggests supra-coronary placement of an aortic valve is not a feasible alternative in severe aortic insufficiency. DISCLOSURE: M. Michel, None.

VALUE OF OFF-PUMP CORONARY ARTERY BYPASS (OPCAB) SURGERY IN ELDERLY PATIENTS Tahir Tak, MD, PhD*; Martha Linn, PA-C; Zahir Rashid, MD; Marshfield Clinic, Marshfield, WI PURPOSE: Advancement in technology and operative techniques has resulted in increased interest in OPCAB procedures. This, along with publicized possible side effects of cardiopulmonary bypass, raises the question, does OPCAB surgery improve the outcome over conventional coronary artery bypass (CCAB) surgery? We compared the preoperative risk profile and overall outcome of patients who underwent OPCAB in our institution to those who underwent CCAB during the same period. METHODS: Data from our prospective computerized database were collected and analyzed in a retrospective manner between 2000 and 2002. Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Cardiothoracic Surgery - Therapeutic Options, continued

DISCLOSURE: M.A. Vaz, None.

Respiratory Infections: Evaluation and Outcomes 12:30 PM - 2:00 PM ACUTE EFFECT OF INTERMITTENT POSITIVE PRESSURE BREATHING (IPPB) AND POSITIVE EXPIRATORY END PRESSURE (PEEP) IN POSTOPERATIVE CORONARY ARTERY BYPASS SURGERY Francisco S. Vargas, MD, FCCP; Marcelo A. Vaz, MD*; Maria I. Feltrim; Daniela G. Mont’Alverne; Pulmonary Division - Heart Institute (InCor) University of Sao Paulo, Brazil PURPOSE: To analyze the impact of positive pressure on acute postoperative recovery after Coronary Artery Bypass Surgery (CABG). METHODS: 60 patients who underwent elective CABG, were randomized into 3 groups. Control group was submitted to breathing exercises and early walking. The IPPB⫹PEEP group was submitted to the same exercises described for the control group, in addition to IPPB (25 cmH2O-10 breaths/minute over a ten minute period and in association with PEEP at 10 cmH2O). The IPPB group was submitted to the same procedure of the second group excluding the PEEP. The parameters evaluated were forced vital capacity (FVC), Pulse oximetry (SaO2), Pain score (visual analogue scale) and Chest Radiography (atelectasis and pleural effusion). All these data had been collected in preoperative and from the first to the sixth postoperative day. Atelectasis was graded using a 0 to 4 scale (0⫽no atelectasis; 4⫽lobar atelectasis). Pleural effusion was graded using a 0-3 scale (0⫽no pleural effusion; 3⫽effusion occupying more than two intercostal spaces). RESULTS: The results were expressed as mean ⫾standard errors(em). In all groups FVC and SaO2 decreased more than 50% (p⬍0,05), in the first postoperative day, improving with time. In the 6th day, the FVC in the IPPB⫹PEEP group was higher than the other two groups. Pain score started over score 3 (all groups) and declined progressively through the 6th day, when it become “No pain”. Pleural effusion was seen in higher scores in control groups (40%)(p⬍0,001), than in IPPB group(10%), or IPPB⫹PEEP group(0%). Atelectasis were seen in higher scores in control groups (25%)(p⬍0,039), than in IPPB group(5%), or IPPB⫹PEEP group(0%). CONCLUSION: We conclude that CABG decreases Pulmonary function in volume and gas exchange. This impairment recovers during the first days after the surgery. CLINICAL IMPLICATIONS: The combined use of IPPB and PEEP improves pulmonary volume as well atelectasis and pleural effusion after Coronary Artery Bypass Surgery.

INDICATORS OF LATE READMISSIONS OF ELDERLY PATIENTS WITH PNEUMONIA Michael Gough, BSc; Ali A. El Solh, MD, MPH*; Thomas Brewer, DO; Mifue Okada, MD; Omar Bashir, MBBS; University at Buffalo, Buffalo, NY PURPOSE: To identify modifiable risk factors of late unplanned readmissions for elderly with pneumonia. METHODS: Three university affiliated tertiary care hospitals A case control study was performed in three University affiliated tertiary care centers. Two hundred four case-control pairs were identified. Case patients referred to all patients readmitted with pneumonia 30 days to one year after discharge. Control subjects were matched for age, admission date, and residence prior to admission. RESULTS: Median time to readmission was 123 days (IQR, 65-238 days). Readmission was not associated with increased severity or length of hospital stay. In a Cox proportional hazards regression model, swallowing dysfunction (HR, 2.15; 95% CI 1.46-2.97), current smoking (HR, 2.04; 95% CI 1.48-2.82), the use of tranquilizers (HR, 1.5; 95% CI 1.02-2.22), and lower activity of daily living (HR, 1.06; 95% CI 1.02-1.10) were independently associated with readmission for pneumonia. The receipt of angiotensin converting enzyme inhibitors (HR, 0.46; 95% CI 0.27-0.78) and prior pneumococcal vaccination (HR, 0.59; 95% CI 0.42-0.82) had a protective effect. CONCLUSION: Routine evaluation of swallowing dysfunction and use of pharmacologic agents to improve the cough reflex deserve further evaluation in multicentered controlled trials. CLINICAL IMPLICATIONS: While there are limited effective measures to improve functional status, preventive strategies that include smoking cessation and pneumococcal vaccination should be actively pursued. DISCLOSURE: A.A. El Solh, None.


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A subgroup analysis of patients ⬎70 years was done. Chi square test was used for categorical variables to evaluate the significance of results. For continuous variables, Wilcoxon Rank Sum Test was performed. RESULTS: A total of 364 patients underwent OPCAB as opposed to 866 CCAB. The overall mortality (1% vs. 3%) and morbidity (15% vs. 25%) were lower in OPCAB patients compared to CCAB, although it did not reach statistical significance, probably due to smaller numbers of study patients. Length of hospital stay in OCPAB was 6 days vs. 7 days in CCAB patients (p⫽0.0012). Twenty-nine patients from the CCAB group required re-exploration for postoperative hemorrhage compared to 1 in OPCAB (p⫽0.0254). OPCAB patients had a lower incidence of postoperative respiratory failure (p⫽0.002). There were 181 patients aged 70 years or older in the OPCAB group compared to 383 patients in the CCAB group. For patients ⬎70 years the hospital mortality (p⫽0.010), blood transfusion rate (p⫽0.0003), postoperative respiratory failure (p⫽0.007), postoperative renal failure requiring dialysis and hospital stay (p⬍0.001) were significantly less for OPCAB patients. CONCLUSION: OPCAB is a safe technique with comparable morbidity or mortality compared to CCAB. In our experience OPCAB shows a trend towards lower postoperative complication rate and mortality. This improved outcome is also seen in elderly patients (⬎70 years). CLINICAL IMPLICATIONS: OPCAB may be associated with fewer complications and results in decreased morbidity and mortality. Prospective randomized studies in a larger series of patients are needed to support our findings. DISCLOSURE: T. Tak, None.

Wednesday, October 27, 2004 Respiratory Infections: Evaluation and Outcomes, continued CLINICAL AND PRACTICAL EXPERIENCES BETWEEN LATIN AMERICAN INTENSIVE CARE UNITS IN VENTILATOR ASSOCIATED PNEUMONIA APPROACH: INTERAMERICAN CONSENSUS CONFERENCE ABOUT NOSOCOMIAL AND VENTILATOR ASSOCIATED PNEUMONIA REPORT Abel Maldonado-Ortiz (1), MD*; Michael S. Niederman (2), MD; Flavio Nacul (3), MD; Justino Regalado (4), MD; Stenio Cevallos (5), MD; Francisco Arancibia (6), MD; Mario Luppi (6), MD; Fernando Veliz (7), MD; Miguel Chung (5), MD; Julio Osorio (8), MD; Aurelio Rodriguez, MD; Federico Corona, MD; EAT LATINOAMERICA Study; Hospital de la Mujer, Morelia (1), Mexico PURPOSE: Sustantial differences exist between Intensive Care Units ICUS in developing countries concerning epidemiology EP, diagnosis DX, antibiotics abs, TX, and resources in the approach of ventilator associated pneumonia VAP. Despite the effort from International Int conferences, the real knowleadge about clinical/practical CP routines in VAP at Latinamerica (LA-ICUS) is limited. The objective was to evaluate VAP information about the CP experience in LA-ICUS. METHODS: 35 questions Q about VAP was designed to collect data in person and electronically from LA-ICUS practitioners. The 1st/2nd phase started at the 1st Interamerican Consensus Conference about VAP in Morelia, Me´ xico, Int LA meeting in Brazil ( May 2003), Int conference in Orlando (Nov. 2003) and the 3rd phase through e-mail correspondence. Q was classified in EP, risk factors RF, DX, etiology ET, TX, prevention PV and research RS.. Data was processed (1) and reviewed by an International guest Chairman from Mineola, NY. RESULTS: Seven LA countries were enrolled. EP: 58.3% of peers recongnized differences in selected critically ill patients (p) with VAP; RF: endotracheal tube (66.7%), along with MV (41.7%); DX: Respiratory samples (Invasive, 50% and non invasive 16.7%; ET: ICU flora were defined (58.3%), qualitative 58.3% vs quantitative 41.7%; TX: by ICU team (75%) and infectious disease consultants (25%), Guidelines were followed for EAT ( Int 50%, regional 16.7%, local 16.7%). Cost (83.3%) defined combination EAT (83.3%) againts Gram negative bacilli (100%). Carbapenems are the first line of choice(50%). EAT success is evaluated (clinically 83% vs bacteriologically 8.33%), and adjusted by MIC (always 33.3%, sometimes 16.7%, and with EAT failure 25.%); PV: semirrecumbent position (83.3%), selective descontamination (8.3%), sub glotic aspiration (8.3%); RS: LA multicentric studies are mandatory to optimize VAP approach (100%). CONCLUSION: Despite the limitation of this study, to our knowleadge this is the most recent effort to evaluate CP VAP experience in LA ICUS. CLINICAL IMPLICATIONS: Large Multicenter LA data base is necessary to optimize and recommend future LA guidelines and/or to consider including special chapter in International guidelines. DISCLOSURE: A. Maldonado-Ortiz (1), None.

THE IMPACT OF A VENTILATOR ASSOCIATED PNEUMONIA PROTOCOL (VAP) ON HEALTH CARE UTILIZATION Shahid Yakoob, MBBS*; Khalid Malik, MD, FCCP; Noreen Tompkins, PharmD; Omer Bajwa, MD; Marvin Balaan, MD, FCCP; Brian Carlin, MD, FCCP; Peter Kaplan, MD, FCCP; Bryan Veynovich, DO, FCCP; Allegheny General Hospital, Pittsburgh, PA

Available medical records on patients categorized as having VAP based on infection control criteria. RESULTS: Median age was 73 years (range, 46-77 years) in the pre-protocol vs.58 years (range, 29-86 years) post-protocol group, respectively. Median ventilator days were 30 (range, 5-98) vs. 32 (range, 9-137), P⫽ 0.63). Median ICU length of stay (28 days, range, 5-105 ) vs. 29 (range, 10-137) days, P⫽ 0.52). Median hospital length of stay (30 days, range, 5-105) vs. 39 (range, 10-137) days, P⫽ 0.51). No difference in overall mortality ( P⫽ 0.337, OR 1.94 ( 0.29-13.8), RR 1.33 (0.65-2.73) or attributable mortality ( P⫽0.346, OR 3.3 (0.22-109.9), RR 1.9 ( 0.37-9.76) were noted. CONCLUSION: The implementation of a VAP protocol did not impact healthcare utilization in our institution. Further evaluation is needed to determine severity of illness and other confounding variables that may attribute to health care utilization. CLINICAL IMPLICATIONS: Further studies are needed to assess underlying factors which account for health care utilization. DISCLOSURE: S. Yakoob, None.

PULMONARY FUNCTION IN SURVIVORS OF SEVERE ACUTE RESPIRATORY SYNDROME (SARS) Veronica L. Chan, MBChB*; Judy Y. Lam, MBBS; Wah-Shing Leung, MBChB; Alsa W. Lin, RN; Chung-Ming Chu, FCCP; United Christian Hospital, Kowloon, Hong Kong PRC PURPOSE: Severe acute respiratory syndrome (SARS) is a newly recognized viral pneumonia caused by a novel coronavirus (SARS-CoV). It can cause diffuse alveolar damage and respiratory failure in the acute stage. It is unknown whether there is permanent impairment of pulmonary function. We aim to study whether SARS survivors have any persistent pulmonary function impairment. METHODS: This is a prospective study of the pulmonary functions in SARS survivors. Pulmonary function tests including spirometry, diffusion capacity for carbon monoxide (DLCO) and static lung volumes were performed at 6 and 9 months after discharge for SARS. Impaired pulmonary function was defined by FVC ⬍ 80% predicted, FEV1 ⬍ 80% predicted, FEV1/FVC ⬍ 70% or DLCO ⬍ 70% predicted. RESULTS: Sixty-three patients (22 male, 41 female, mean age 39.0 ⫾ 11.9 years) who survived SARS during the epidemic in March 2003 were studied. At 6 months after discharge, 19 (30.2%) had impaired pulmonary function as defined above: 14 patients (22.2%) had mild impairment, 4 patients (6.4%) had moderate impairment and 1 patient (1.6%) had severe impairment. By 9 months, there were significant improvement in FVC (p⫽0.002), FEV1 (p⫽0.009) and DLCO (p⬍0.001); most patients (95.2%) had no respiratory impairment. Only 3 patients (4.7%) had mild impairment, and none had more severe impairment. CONCLUSION: A significant proportion of SARS survivors had impaired pulmonary functions 6 months after discharge. However, most of them showed further improvement in follow up. No patient had moderate or severe respiratory impairment at 9 months after SARS. CLINICAL IMPLICATIONS: Regular follow up of lung function is important in SARS survivors. Information from this study is important for the disability assessment in health care workers who contracted SARS at work. DISCLOSURE: V.L. Chan, None.

PURPOSE: VAP is the most common acquired infection in mechanically ventilated patients. It occurs more than 48 hours after intubation with a 2-10 times higher mortality risk. There is no gold standard for diagnosis and therapy is usually empiric. A number of studies have demonstrated the appropriateness of the initial antibiotic regimen as a vital factor in determining outcome. Therefore, the correct choice of the empiric regimen is crucial. A VAP protocol was introduced at our institution in October 2001 which included cefepime and gentamicin as the empiric antibiotics of choice (alternative: cefepime and levofloxacin in patients with acute renal failure). METHODS: Institutional Review Board approval was obtained. A retrospective chart review was conducted in medical and coronary intensive care unit patients before and after implementation of the VAP protocol (pre-protocol group, n⫽10 patients vs. post-protocol group, n⫽15). The pre-protocol study period was January/March 2001 vs. post-protocol study period was January/ March 2002. Inclusion criteria:

THE CHARACTERISTICS AND USEFULNESS OF STREPTOCOCCUS PNEUMONIAE URINARY ANTIGEN TEST IN EVALUATING PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA Masayuki Nakayama, MD*; Takefumi Saito, MD; Takio Takaku, MD; Kouzou Morimoto, MD; Yoshiko Kaneko, MD; Takahide Kodama, MD; Koichi Watanabe, MD; Kenji Hayashihara, MD; National Hospital Organization Ibarakihigashi National Hospital, Ibaraki, Japan

858S


PURPOSE: Streptococcus pneumoniae (S. pneumoniae) urinary antigen test has been reported to be simple and quick method to perform, and have high sensitivity and specificity. But in clinical examination, because of complicated background, such as pneumonia complicated with other pathogens, clinical usefulness of this test has not been proven yet. The purpose of this study is to clarify its characteristics and usefulness in clinical situation.

Wednesday, October 27, 2004 Respiratory Infections: Evaluation and Outcomes, continued

SHOULD ALL THE BACTEREMIC PNEUMOCOCCAL PNEUMONIA PATIENTS BE CONSIDERED SEVERE COMMUNITYACQUIRED PNEUMONIA? Marcos I. Restrepo, MD, MSc*; Eric M. Mortensen, MD, MSc; Namal Waratunge, MD; Jacqueline A. Pugh, MD; Antonio Anzueto, MD; University of Texas Health Science Center, San Antonio, TX PURPOSE: Community-acquired pneumonia (CAP) is the leading infectious cause of death in the United States. The most common pathogen isolated from CAP patients is Streptococcus pneumoniae. Previous studies considered bacteremic pneumococcal CAP as severe CAP. The primary aim of this study was to examine if patients hospitalized with bacteremic pneumococcal (BP) CAP should be considered to have severe CAP. METHODS: A retrospective, observational study was conducted at a two tertiary teaching hospitals. Eligible patients were admitted with a diagnosis of CAP and positive blood culture for pneumococcus between 1/1/1999 and 12/31/2001. All patients had a chest x-ray consistent with CAP, and had a discharge ICD-9 diagnosis of pneumonia. Patients were excluded if they were “comfort measures only” or transferred from another acute care hospital. Patients were stratified between severe and non-severe CAP according to Pneumonia Severity Index (PSI) class V, revisited American Thoracic Society (rATS) criteria, British Thoracic Society (CURB and CURB-65 rules), or if they had severe sepsis or septic shock. RESULTS: One hundred and eight patients met inclusion criteria. 71% were male, and 35% were admitted to the intensive care unit (ICU). 22% of the patients with BP-CAP were intubated and 22% received vasopressors. By severity of illness classification BP-CAP patients were PSI classes I-III in 50 (46%) of the cases, class IV in 35 (32%), and class V in 24 (22%). In addition, severe BP-CAP by CURB was defined in 44%, CURB-65 in 49%, rATS in 33%, severe sepsis 48% and septic shock in 31%, respectively. In-hospital mortality occured in 0% of the patients in PSI classes I-III, 23% in PSI IV, and in 37% in PSI V, respectively. CONCLUSION: Bacteremic patients with pneumococcal CAP should not be considered as severe CAP, and appropriate therapy should be empirically started to improve clinical outcomes. CLINICAL IMPLICATIONS: Further study is needed to determine whether patients with pneumococcal pneumonia could be treated differently as those with CAP. DISCLOSURE: M.I. Restrepo, None.

DEVELOPMENT AND EVALUATION OF A CLINICAL MANAGEMENT GUIDELINE FOR SUSPECTED HOSPITAL-ACQUIRED PNEUMONIA IN INTENSIVE CARE UNIT PATIENTS Jill M. Westlund, BS; Olavo Fernandes, PharmD*; Gary Wong, BScPhm; Monique Pitre, BScPhm; Muhammad Mamdani, PharmD, MPH; John Granton, MD; University Health Network, Toronto, ON, Canada PURPOSE: Hospital-acquired pneumonia (HAP) results in considerable morbidity and mortality in critically ill patients and is difficult to distinguish from non-infectious conditions with similar signs and symptoms. Liberal use of antibiotics increases antibiotic resistance and superinfection and is costly. We hypothesized that a systematic approach to HAP management will promote appropriate use of antibiotics and improve patient outcomes. METHODS: Overall Study Design: Prospective, before-and-after assessment. To detect a clinically significant difference in duration of antibiotic therapy of three days, we targeted a sample size of 160 patients. This study was approved by the Research Ethics Board. Phase I: Observation of current practice. Inclusion criteria: MSICU patients hospitalized for ⬎48 hours and a reasonable suspicion of new HAP. Exclusion criteria: Colonized lung transplant or already receiving treatment for HAP. We collected demographics, previous antibiotic use, risk factors, duration of therapy, length of stay, sequential clinical pulmonary infection scores (CPIS), antibiotics prescribed, and pathogens cultured. Phase II: Development of management guideline. We reviewed relevant literature and studies and consulted experts in respiratory, infectious disease, and ICU medicine as well as nursing and allied health clinicians. Data from Phase I was used to optimize the guideline. Phase III: Implementation of guideline (in progress) Phase IV: Evaluation of guideline (autumn 2004). RESULTS: Phase I: Of patients treated, empiric therapy was prescribed in 85.5% and therapy was adequate in 75% of cases. The mean duration of therapy was 8.3 ⫾ 4.8 days. Development of a second HAP and respiratory superinfection occurred in 12.5% and 7.5% of patients respectively. Initial CPIS scores of ⬎ 6 occurred in 23% of patients. Phase II: A guideline was designed which included a tool for decision-making regarding antibiotic therapy (the CPIS), guidelines for selection of empiric antibiotics and structured reassessment. CONCLUSION: A hospital-specific HAP management guideline can be developed using a multi-disciplinary approach. Site-specific observations can be used to optimize the guideline. CLINICAL IMPLICATIONS: Ongoing HAPI study will evaluate the impact of the management guideline on antibiotic usage and patient outcomes.

DISCLOSURE: O. Fernandes, None.


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METHODS: S. pneumoniae urinary antigen test was performed to 111 patients suspicious of Community-Acquired Pneumonia (CAP), who had admitted to our hospital. We retrospectively compared clinical characteristics and data between antigen positive and negative group of patients with CAP. RESULTS: S. pneumoniae urinary antigen tests were positive for 15 patients among 80 ones with CAP (sensitivity 18.8%), and negative for 30 patients among 31 ones without CAP (specificity 96.8%). Positive and negative predictive value rate in diagnosing CAP was 93.8%, and 31.6%. As one of characteristics of positive group in CAP patients, they showed a tendency to be less complicated with other pulmonary diseases than CAP. In CAP patients antibiotics had been given before the test, positive rate was 29.4% (5 of 17 patients), and in CAP ones without antibiotics before the test, positive rate was 15.9% (10 of 63 patients). The blood test showed that the levels of C-reactive protein (CRP) and total protein (TP) were significantly higher and lower respectively in positive group than in negative group (p⫽0.02, p⫽0.04). Severity of CAP was significantly higher in positive group than in negative group (p⬍0.05), but there was no significant difference in mortality between two groups. CONCLUSION: S. pneumoniae urinary antigen test is likely to be less influenced by antibiotic treatment and moreover, is suggestive of severity of CAP. This test is very useful both in detecting the pathogen of CAP and in evaluating the severity of CAP. CLINICAL IMPLICATIONS: This test is available not only for establishing the early diagnosis of CAP but also for predicting the prognosis of CAP. DISCLOSURE: M. Nakayama, None.

Wednesday, October 27, 2004 Respiratory Infections: Evaluation and Outcomes, continued ANTIBIOTIC CHOICES FOR PULMONARY RESECTIONS– GRAM-NEGATIVE PROPHYLAXIS DECREASES PULMONARY COMPLICATIONS BUT INCREASES WOUND INFECTIONS John R. Roberts, MD, MBA*; The Surgical Clinic: Centennial Medical Center; Baptist Hospital, Nashville, TN PURPOSE: Prophylaxis for pulmonary surgery has, almost by default, been those antibiotics typically used for cardiac surgery, which cover primarily gram-positive organisms. We report a study in which we performed a historical comparison of the complications between two groups of patients–those receiving preoperative gram-positive coverage and those receiving preoperative gram-negative coverage. METHODS: All patients undergoing lung resection were eligible for comparison. Data collected were age, stage of tumor, incidence of atelectasis or mucous plugging requiring bronchoscopy, wound infection, life-threatening complications, and death. Patients undergoing surgery between September 1997 and November 2000 received cefazolin and those undergoing surgery between December 1, 2000 and August 2003 received cefipime. Cefipime was chosen because it covers the most common Pseudomonas grown in our hospitals. Means were compared using student’s t test and proportions with chi-square. p less than 0.05 was accepted as significant. RESULTS: Four hundred sixty-seven patients underwent lung resection in the five year period. Two hundred twenty-three received cefazolin while two hundred forty received cefipime. No differences in age, reintubation rate, life-threatening complications, nor mortality rate were found. Significant differences in the incidence of pulmonary complications (measured by the need for urgent bronchoscopies) were found that favored cefipime. However, seven patients receiving cefipime developed chest wall infections with MRSA. Only one such minor infection was found in patients receiving cefazolin. These differences were highly significant. CONCLUSION: Gram-negative prophylaxis in pulmonary resections decreases the incidence of pulmonary complications in patients undergoing lung resection. However, those patients with chest wall resections are prone to develop methicillin resistant mesh infections, and should be covered with gram-positive coverage. CLINICAL IMPLICATIONS: Preoperative gram-negative antibiotic coverage decreases perioperative pulmonary complications in patients undergoing lung resection. AGE (years)

Broncho-

Reintuba-

Wound Infections

Mortality

Gram-Positive Antibiotics

62.5 ⫾ 13.2

15.6%

5.83%

0.5%

2.2%

Gram-Negative Antibiotics

58.8 ⫾ 14.5

4.7%

4.8%

7.8%

3.3%

0.128

0.0220

0.864

0.0000254

0.456

p-Value

DISCLOSURE: J.R. Roberts, None.

Critical Care Outcome 12:30 PM - 2:00 PM ADULT EXTRACORPOREAL MEMBRANE OXYGENATION SUPPORT IN MORIBUND SEPSIS MAY IMPROVE OUTCOMES Rolando Berger, MD; William Douglas, MD; Michael Zgoda, MD*; University of Kentucky Medical Center, Lexington, KY PURPOSE: To examine, by retrospective analysis, the use and outcome of extracorporeal life support in adults with severe respiratory failure and moribund sepsis. METHODS: Measurements included ventilatory support parameters and systemic PaO2/FiO2 ratio before extracorporeal life support (ECLS), time on ECLS, number of ventilator days, number of intensive care unit

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days, number of hospital days, associated extracorporeal membrane oxygenation (ECMO) complications, transfusion need, and survival. RESULTS: Eight patients between 22 and 45 years of age with severe respiratory failure and moribund sepsis were selected for ECLS as a salvage maneuver. Each patient was objectively in extremis and pending emminent demise as evidenced by multiorgan failure, refractory hypotension,refractory hypoxia, and the inability to provide adequate oxygen delivery. If the patient had no absolute contraindications, such as acute brain hemorrhage, then venoarterial or venovenous ECLS was employed. All patients required continuous venovenous hemodialysis prior to ECLS. Prior to initiating ECLS all patients were on the ventilator for at least 12 hours with oxygen saturations of ⬍80% despite FiO2 at 1.0,and PEEP ⬎19cm water. Multiple pressors were needed to barely maintain a mean arterial pressure ⬎55mmHg. Low tidal volume and high frequency techniques were applied in all patients before ECLS and very low tidal volumes of 3cc/Kg were utilized during ECLS. Two of the 8 failed prone positioning maneuvers prior to ECLS. Six patients survived to decanulation. Two patients expired within 12 hours of starting ECLS. Six are alive, with follow-up times ranging from 1 to 7 yrs. CONCLUSION: ECLS may be a life-sustaining supportive therapy that enables a reasonable increase in survivability in a relatively young population who otherwise would have a 100% mortality. CLINICAL IMPLICATIONS: ECLS, usually reserved for infants and occasionally adults with lung limitted disease, could potentially have an increased survivability when employed to those with multiorgan failure from moribund sepsis. Unfortunately, because of high expense and the limited number of facilities experienced in adult ECLS, a prospective randomized trial is not likely to take place. DISCLOSURE: M. Zgoda, None.

VOLUME LOAD AND NATRIURETIC PEPTIDES IN SEPTIC MODEL Kanetaka Maeshiro, MD; Akihiro Hayashi, MD; Kazuo Shirouzu, MD; Shinzo Takamori, MD, FCCP*; Keisuke Miwa, MD, FCCP; Hiroharu Mifune, PhD; Kurume University, Kurume, Japan PURPOSE: Patients with sepsis undergo acute alterations in the volume and composition of fluid in the intracellular and extracellular spaces. Natriuretic peptides are vasodilator hormones involved in the regulation of blood pressure and volume homeostasis. To elucidate the functional responses of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP), those peptides levels were measured in the plasma and lung tissue in septic rats with volume load. METHODS: Wister rats were anesthetized with ketamine hydrochloride and were intraperitonealy administered 1 ␮g/kg of lipopolysaccharide (LPS). Three hrs after the LPS administration, normal saline was intravenously infused at 0, 2, 4, and 6 ml/kg/hr for 3 hrs. The samples of blood and lung tissue were taken, and the concentration of ANP and CNP in those were studied by radioimmunoassay. Statistical analyses were performed by Mann-Whitney U test and Kruskal-Wallis test. RESULTS: Plasma ANP level 3 hrs after the LPS administration increased significantly to 10 times comparing to that of control. By volume load at 2 and 6 ml/kg/hr, plasma ANP levels increased significantly. Lung ANP level 3 hrs after the LPS administration also increased significantly to 2.5 times comparing to that of control. Plasma CNP levels decreased significantly after the LPS administration. By volume load at 2 and 6 ml/kg/hr, plasma CNP levels decreased significantly. Lung CNP decreased significantly after the LPS administration, and showed no significant change by volume load. CONCLUSION: ANP and CNP were strongly influenced by LPS administration. Plasma ANP was increased and plasma CNP was decreased by volume load, whereas lung ANP and CNP did not significantly change by volume load in this septic model.. CLINICAL IMPLICATIONS: Plasma ANP and CNP are quickly responsive to volume load in septic state. DISCLOSURE: S. Takamori, None.


Wednesday, October 27, 2004 Critical Care Outcome, continued CHANGES OF LUNG ATRIAL NATRIURETIC PEPTIDE RECEPTORS BY NEUTRAL ENDOPEPTIDASE INHIBITOR IN RAT SEPTIC MODEL Kanetaka Maeshiro, MD*; Shinzo Takamori, MD, FCCP; Keisuke Miwa, MD, FCCP; Mari Fukunaga, MD; Hisashi Nakamura, MD; Akihiro Hayashi, MD; Junichi Honda, MD; Hiroharu Mifune, PhD; Kazuo Shirouzu, MD; Department of Surgery, Kurume University, School of Medicine, Kurume, Japan

ADRENAL INSUFFICIENCY IN SEPTIC SHOCK: ARE WE LOOKING HARD ENOUGH? Nasser M. Elsouri, MD*; Vasantharama Arepally, MD; Mamon M. Tahhan, MD; Jorge A. Guzman, MD; Joseph J. Bander, MD; Harper University Hospital, Wayne State University, Detroit, MI PURPOSE: Impairment of the normal corticosteroid response during critical illness can be multifactorial. The frequency of adrenal insufficiency (AI) in patients with septic shock is variable and the incidence varies depending on the underlying clinical condition. Recent data suggests that the majority of patients with septic shock should be worked up for AI. We conducted this retrospective study to assess how frequently physicians suspected AI amongst this cohort and to identify the circumstances that lead them to do so, if any. METHODS: The records of patients admitted to the MICU requiring vasopressors were reviewed and those meeting criteria for septic shock were analyzed. AI was confirmed with a random serum cortisol level ⬍ 15 mcg/dl or with a random cortisol level between 15-34 mcg/dl and an increase in response to cosyntropin-stimulation test (250 mcg) ⬍ 9 mcg/dl. RESULTS: Ninety two patients were included in the study. Mean (⫾ SD) age was 59 ⫾ 18 years. APACHE II, SOFA, and SAPS II scores were 27.6 ⫾ 8.5, 11.6 ⫾ 3.8, and 60.2 ⫾ 21.5, respectively. Overall mortality was 51%. AI was suspected in 44 patients (48%) and confirmed in 25 (57%). Maximal doses of vasopressors were comparable between groups but more patients in whom AI was suspected were on phenylephrine and/or vasopressin and more were treated with activated protein C (aPC) (P ⬍ 0.05). Patients in whom AI was suspected were in shock for 3.1 ⫾ 7.4 days before work up was initiated. CONCLUSION: In spite of evidence of increased incidence of AI in septic shock, this condition was suspected only in about half of our patients. No reliable indicators leading to AI work up could be identified other than increased number of vasopressors needed and the use of aPC.

Adrenal insufficiency

APACHE II

SOFA

MICU Na⫹ (mmol/ K⫹ (mmolL) LOS (d) L)

Survival (%)

26.3 ⫾ 7.9

11.3 ⫾ 3.5

11.2 ⫾ 138.0 ⫾ 5.1 4.5 ⫾ 1.3 12.4

50

Not Suspected 28.8 ⫾ 8.9

11.8 ⫾ 4.1

8.4 ⫾ 8.2

44

Suspected

137.7 ⫾ 6.1 4.5 ⫾ 0.9

DISCLOSURE: N.M. Elsouri, None.

ADJUVANT THERAPY OF MEDIASTINITIS WITH IGM-ENRICHED IMMUNOGLOBULINS (ATMI) – A MULTICENTER, RANDOMIZED CONTROLLED TRIAL Gu¨ nter Marggraf, MD*; Rolf Lefering, PhD; Matthias Thielmann, MD; Wilhelm Struff, MD; Edmund Neugebauer, MD; Heinz Jakob, MD; The ATMI Study Group; Department of Thoracic and Cardiovascular Surgery, West-Germ, Essen, Germany PURPOSE: Mediastinitis is a rare but severe complication in patients after open heart surgery with cardiopulmonary bypass (CPB). The adjuvant application of IgM-enriched immunoglobulins (Pentaglobin®) was assumed to improve patients outcome and to reduce postoperative complications and infections. METHODS: In a prospective, placebo-controlled, double-blind randomized multicenter phase-III study, 125 patients were enrolled between 01/1999 and 04/2002 with postoperative mediastinitis after median sternotomy with CPB and reoperation for wound infection with at least 2 symptoms of systemic inflammation. Pentaglobin® or placebo was administered before wound revision and subsequently as a continuous infusion (5mg/kgBW/d for 5 days IV). Primary endpoint was the sum of daily therapeutic intervention scoring system points for 28 days (cumulative TISS-28). Secondary endpoints were ICU stay, change of MOF score and duration of wound infection. RESULTS: One hundred and twenty-five patients were included, 64 received Pentaglobin®, and 61 placebo. Basic data were comparable. Efficacy analysis showed that the median cumulative TISS-28 was lower in the Pentaglobin group by 61 points (189 vs. 250 points, respectively) which on average corresponds to 2 days less of ICU. This difference was not significant (P⫽0.08; U-test, one-sided). Mean duration of intensive care (7.9⫾9.1 vs. 9.1⫾10.1 days), duration of wound infection (10.4⫾9.7 vs. 12.1⫾10.9 days) and the MOF score (14⫾35 vs. 17⫾37) were reduced as well in the Pentaglobin group. Adverse events were distributed equally. In each group 6 patients (10%) died. CONCLUSION: The data demonstrate a clear tendency in favor IgM-enriched immunoglobulins as compared to placebo, although a statistical significance was missed. DISCLOSURE: G. Marggraf, None.

INFECTIOUS DISEASES IN A NEWLY OPENED MEDICAL INTENSIVE CARE UNIT Yun S. Kim, MD*; Min Ki Lee, MD; Doo Soo Cheon, MD; Jin Hoon Cho, MD; Soon Kew Park, MD; Pusan National University Hospital, Busan, South Korea PURPOSE: Severe infection is a common reason for intensive care and contributes to increased morbidity and mortality. The aim of this study was to identify clinical differences in patients with bacteremia between newly opened medical intensive care unit(MICU) and longstanding CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Atrial natriuretic peptide (ANP) has been shown to play a crucial role in the regulation of hemodynamics, natriuresis, and vasorelaxation. ANP has physiological receptor (NPR-A) and clearance receptor (NPR-C). ANP is increased in septic state. Thiorphan, one of the neutral endopeptidase (NEP) inhibitors, inactivate ANP, but its physiological role remains unclear. The purpose of this study is to characterize the changes in lung ANP receptor expression by thiorphan administration in septic model. METHODS: Wistar male rats were anesthetized with ketamine hydrochloride and were divided into three groups as to Group A, control group (n⫽5); Group B, LPS administration group (n⫽5); and Group C, lippopolysaccharide (LPS)⫹thiorphan administration group (n⫽5). LPS of 1 ug/kg was intraperitonealy administered in Group B. One hour after the LPS administration, thiorphan was infused with 3.5 mg/kg for 30 min in Group C. The blood and lung tissue were taken in each group at 2 and 4 hrs after the LPS administration. The concentration of ANP was measured by radioimmunoassay, and NPR-A and NPR-C mRNA expression were measured by quantitative PCR. Statistical analyses were performed by ANOVA. RESULTS: In Group B, plasma ANP concentration at 4 hrs significantly increased compared to those of the other groups (p⬍0.05). Lung ANP concentration at 4 hrs significantly increased comparing to those of the other groups (p⬍0.05). The NPR-A mRNA expression at 2 hrs in Group B was significantly higher than the those of the other groups (p⬍0.05). NPR-C mRNA expression at 4 hrs in Group C was significantly higher than those of the other groups (p⬍0.05). CONCLUSION: Four hrs after the LPS administration, plasma and lung ANP increased significantly, and thiorphan increased NPR-C mRNA expression significantly. CLINICAL IMPLICATIONS: Thiorphan facilitates the exhaust serum ANP via lung NPR-C mRNA elevation in the septic state. DISCLOSURE: K. Maeshiro, None.

CLINICAL IMPLICATIONS: AI occurs frequently in patients with septic shock but clinicians under diagnose this condition. Adoption of clinical algorithms incorporating cortisol testing early on the course of septic shock can avoid delays in diagnosis and improve outcomes.

Wednesday, October 27, 2004 Critical Care Outcome, continued medico-surgical ICU(MSICU) patients and to evaluate the consequence of ICU or community-acquired infection on morbidity and mortality. METHODS: A total of 61 patients(MICU 37, MSICU 24) with bacteremia admitted for more than 48hr to the MICU or MSICU at Pusan Natinal University Hospital from 1 March 2002 to 18 August 2003 were retrospectively evaluated. Medical records were reviewed to obtain the clinical and bacteriologic informations. RESULTS: The mean age of the patients with bacteremia of MICU(60.8 ⫾ 13.5 yr) was greater than that of MSICU(55.2 ⫾ 18.3 yr)(p ⬍ 0.05), and the average day of hospital and ICU stay was shorter in MICU patients than MSICU patients(p ⬍ 0.05). The prevalence of community-acquired infections was significantly higher in MICU patients than in MSICU patients(MICU 18.8%, MSICU 5.0%)(p ⬍ 0.01) whereas MSICU patients showed higher prevalence of hopital-acquired infection than MICU patients(MICU 84.4%, MSICU 95%)(p ⬍ 0.05). The common primary sites of infection were catheter-related infection, pneumonia and urinary tract infection(UTI). The most common pathogenic organisms in MICU and MSICU were methicillin-resistant staphylococcus aureus(MRSA) and Acinetobacter baumanii, respectively. A significant proportion of bacteremia was originated from candida spicies(MICU 10.8%, MSICU 12.5%). The most relevant independent factors associated with mortality rate were bacteremia due to vancomycin-resistant enterococci(VRE) or extended spectrum ␤-lactamase(ESBL) producing bacteria and candidemia. Also, the mortality rate of ICU patients was associted with previous use of antibiotics or immunosuppressive, primary focus of infection and hospital days. CONCLUSION: These findings are useful for empirical treatment of ICU patients and for implementation of strict infection control policy in our hospital. CLINICAL IMPLICATIONS: These results may help in reducing high mortality rate of ICU patients. DISCLOSURE: Y.S. Kim, None.

Site of Infection A

B

C

D

E

Blood stream infection only Blood stream infection with other infections Vascular access infection only Vascular access infection w/other infection Blood stream (BS) or vascular access (VA) infection BS or VA along with other infections Urinary tract infection only Urinary tract infection with other infection Chest infections only Chest infections with other infections

OD group

NOD group

P value

5/33 10/41

1/24 3/28

NS NS

1/33

0/24

NS

2/41

0/28

NS

6/33

1/24

NS

5/41

3/28

NS

11/33 16/41

5/24 7/28

NS NS

7/33 10/41

15/24 18/28

⬍0.003 0.001

DISCLOSURE: S. Patel, None.

INITIAL EXPERIENCE WITH A NEW SYSTEM FOR THE CONTROL AND CONTAINMENT OF FECAL OUTPUT FOR THE PROTECTION OF PATIENTS IN A LARGE BURN CENTER Jane L. Echols, RN; Bruce C. Friedman, MD*; Robert F. Mullins, MD; Joseph M. Still, MD; Research Consortium, Inc, Doctors Hospital, Augusta, GA ACUTE ORGAN DYSFUNCTION AND INFECTION IN PATIENTS ADMITTED TO THE INTENSIVE CARE UNIT Sangita A. Christian, MD; Christa Schorr, RN, BSN; R. P. Dellinger, MD; David Gerber, DO; Samiran Patel, MD*; Cooper University Hospital, Camden, NJ PURPOSE: To determine the association between site of infection and acute organ dysfunction at the time of admission in ICU patients. METHODS: Using the PROJECT IMPACT (PI) database, 69 medical patients with infection on ICU admission from July 2003 to February 2004 were identified. All were admitted to the ICU from the emergency department or were transferred from another ED. Patients were divided into two groups: a)acute organ dysfunction (by predetermined criteria)on admission (OD, N⫽41) and b)no acute organ dysfunction on admission(NOD, N⫽28). The presence of organ dysfunction was examined relative to site of infection (PI criteria) for patients with sinle sites of infection (33 OD, 24 NOD) and for all patients with infection (patients with both single and multiple sites of infection) (41 OD, 28 NOD)using the Fisher’s exact test. RESULTS: 41/69 (59%) patients admitted to the ICU with infection had organ dysfunction at the time of admission. No sites of infection, alone or in combination, were associated with a greater incidence of organ dysfunction at admission. Chest infection was present in a significantly greater percentage of patients without vs with OD (Table). This was not explained by acuity as APACHE II(SD) was similar for patients with chest infection alone with and without(OD): 17.6 (5.07) vs 20.4 (12.01); chest infection alone without OD vs all patients with OD: (17.6 (5.07) vs 20.29 (7.79); and all chest infection vs all other patients regardless of OD status: 17.46 (5.71) vs 19.24 (8.05). CONCLUSION: Organ dysfunction in infected patients is common at the time of admission to the ICU, but site of infection does not correlate with the presence of dysfunction. The presence of chest infection appears to be associated with a lower likelihood of organ dysfunction at time of admission. CLINICAL IMPLICATIONS: Early identification of organ dysfunction in patients admitted to the ICU may impact upon treatment and outcome and should be pursued in patients with infection at the time of admission regardless of site.

PURPOSE: The ability to contain and divert stool or GI waste in the burn population has certainly been a challenge. The control and containment of fecal output has proven not only to be challenging, but costly with respect to utilization of supplies and staff. These patients are at risk for skin and wound contamination with breakdown and are repeatedly exposed to an environment that may be contaminated with pathogens from the fecal stream. After several attempts to control soilage and protect patients using products either poorly designed or off-label, our burn center was forced to use more conventional methods of stool management, such as rectal bags, chux pads, expensive burn pads, and/or multiple bed/dressing changes. These measures provided inadequate protection from frequent stool contact with the patient. METHODS: Patients with severe burns involving perineal/rectal area, loss of bowel control, pre-grafting(burns or wounds), immobility related to condition/sedation, patients threatening need for colostomy had a Zassi Bowel Management System inserted. Data regarding infection, patient/ staff satisfaction, safety, and cost effectiveness were evaluated. RESULTS: 297 patients with the BMS and 208 patients without the BMS were evaluated. Infection from enteric pathogens were dramatically decreased in urine, blood, and skin and soft issue in the patients with the Zassi BMS. No complications noted, 140 catheters used, great staff/ patient satisfaction. CONCLUSION: Zassi BMS has proven to be a safe and effective catheter to contain/divert stool. Staff satisfaction with BMS catheter: time as well as cost savings. No patient related complications. Decrease in infection rates: UTI’s, Skin and soft tissue, and blood stream. CLINICAL IMPLICATIONS: As a large burn center,with over 900 admissions per year, the BMS has proven advantages for our patient population. Some noted advantages include, improved patient comfort as well as dignity, improved skin care/prevention ofbreakdown, cost savings related to supplies and human resources, and decreased rate of infections related to foley, central line, or wound contamination. DISCLOSURE: B.C. Friedman, None.

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Wednesday, October 27, 2004 Critical Care Outcome, continued THE PHARMACOKINETICS OF DROTRECOGIN ALFA (ACTIVATED) IN SEVERE SEPSIS PATIENTS WEIGHING >135 KG Rebecca L. Qualy, MS; Howard Levy, MD, PhD*; David S. Small, PhD; Darell E. Heiselman, DO; Jay S. Steingrub, MD; Christelle Darstein, MS; Ellen Mongan, MD; Richard R. Riker, MD; Eli Lilly and Company, Indianapolis, IN

N Mean weight (kg) [range] Mean BMI [range] DrotAA steady-state concentration (ng/ mL) [interquartile range] DrotAA half-life (minutes) [interquartile range]

ⱕ135 kg

⬎135 kg

32 93 [59-133] 33 [22-59] 60.2 [48.172.4]

20 158 [137227] 59 [41-75] 65.5 [49.981.0]

19.1 [15.323.0]

16.7 [12.221.1]

DISCLOSURE: H. Levy, Eli Lilly and Company

PURPOSE: Our prior research (Crit Care Med, 2003; 31,12:126-453) demonstrated that survival from severe sepsis improved significantly when therapy was initiated earlier. We designed a multidisciplinary Sepsis Pathway to focus resuscitation on Early Goal Directed Therapy. To help establish a control for the Sepsis Pathway, we chose to review the time intervals from the inclusion criteria to resuscitation milestones for Early Goal Directed Therapy (EGDT) (N Engl J Med 2001; 345:1368-1377). METHODS: We retrospectively studied patients from 2001-2003 with severe sepsis who received therapy with a Swan-Ganz™ catheter. The five EGDT resuscitation milestones were time in hours to 1) antibiotics, 2) CVP 3 8mmHg, 3) MAP 3 65, 4) ScvO2 or SmvO2 3 70%, and, 5) patient transfer to ICU bed. All time values had a resolution of 15 minutes and were truncated at the first 24 hours. Range, mean and standard deviation were computed by MS Excel. RESULTS: Twenty patients charts were reviewed. The demographic data was 10 (50 %) male, 10(50 %) female. The average age was 60 years. Mortality at 28 days was 9 out of 20 (45 %). CONCLUSION: All milestones are delayed in the treatment of severe sepsis prior to the implementation of EGDT. CLINICAL IMPLICATIONS: Our new designed and implemented Sepsis Pathway is expected to significantly reduce the time of all milestones. We are presently gathering the milestone data prospectively with patients receiving either the PreSep™ or Swan-Ganz™ catheter.

Sepsis Treatment Data: Initial 24 hours

P-value P⫽⬍0.001 Patient # P⫽⬍0.001 P⫽0.5995

P⫽0.3960

Time to ABX

1 1.75 2 1.00 3 3.00 4 10.00 5 3.25 6 3.50 7 3.25 8 5.00 9 13.50 10 2.00 11 15.00 12 1.00 13 1.00 14 4.00 15 6.75 16 9.00 17 0.75 18 10.00 19 17.00 20 1.00 hr, range 1 -13.5 hr, mean 5.59 hr, SD 5.10

Time to CVP 10.25 N/A 14.00 1.00 N/A 24.00 24.00 N/A N/A 24.00 N/A 3.00 N/A N/A N/A 24.00 N/A 24.00 1.00 4.00 1 -24 13.93 10.36

Time to Time to Time EDMAP SvO2 ⬎ICU 0.50 10.25 6.25 5.00 N/A 1.00 4.00 20.00 N/A 25.00 24.00 9.00 6.00 N/A 10.25 10.25 24.00 4.75 8.25 24.00 8.75 4.00 N/A 2.00 3.50 N/A 2.50 5.75 N/A 8.25 11.00 N/A 7.00 3.00 6.00 N/A 1.00 N/A N/A 1.00 24.00 5.50 1.00 N/A 3.00 1.00 24.00 2.50 1.00 0.50 2.25 1.00 24.00 2.00 1.00 N/A 1.00 1.00 8.50 0.50 1 - 0.5 -24 0.5 -10.25 10.25 4.71 17.20 3.89 5.76 9.02 3.20

DISCLOSURE: A. Verceles, Edwards Lifesciences LLC


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PURPOSE: The FDA approved Drotrecogin alfa (activated) [DrotAA] for the reduction of mortality in adult patients with severe sepsis [sepsis with acute organ dysfunction] and a high risk of death (e.g. APACHE II score ⱖ25). In PROWESS, a Phase III clinical trial, limited supplies of DrotAA necessitated excluding patients whose actual body weight was ⬎135 kg. The primary objective of this open label, Phase 4 trial was to compare the exposure to DrotAA in severe sepsis patients at high risk of death who weighed ⬎135 kg to those who weighed ⬍⬍26⬎135 kg. A secondary purpose was to quantify the elimination half-life of DrotAA in severe sepsis patients. METHODS: PROWESS inclusion/exclusion criteria were used, except patients ⬎135 kg were also enrolled. Blood samples were taken for DrotAA steady state concentration analysis once each day and for elimination half-life analysis at 0, 15, 30, 45, 60, 90, and 120 minutes after terminating the infusion. DrotAA activity was assayed at a central laboratory. Weight-normalized clearance of DrotAA was calculated and values for patients weighing ⬍⬍26⬎135 kg were compared with those ⬎135 kg. RESULTS: Patient weight range was 59 kg – 227 kg. Of 52 patients enrolled, 32 weighed ⬍⬍26⬎135 kg, 12 weighed 136-159 kg, and 8 weighed ⬎160 kg. CONCLUSION: There is no statistically significant difference in steady-state concentrations or elimination half-life of DrotAA in patients ⬍⬍26⬎135 kg and ⬎135 kg. CLINICAL IMPLICATIONS: Dosing of DrotAA should be based on actual body weight.

A SEPSIS PATHWAY DESIGNED USING EARLY GOAL DIRECTED THERAPY: “THE NEED FOR SPEED” Avelino Verceles, MD*; Paul Birnbaum, MD; R. M. Schwarcz, MD; Roman Krol, MD; Khaleeq Ghulam, MD; ICU Nurses; The ED Nurses; Sang L. Wong, BS; Han C. Ryoo, PhD; Leonard Samuels, MD; Herbert Patrick, MD, MSEE; Navasuma Havaligi, MD; Praveen Mannam, MD; Soma Jyothula, MD; Drexel University College of Medicine, Division of Pulmonary, Philadelphia, PA

Wednesday, October 27, 2004 Critical Care Outcome, continued EARLY ANTITHROMBIN (AT) ADMINISTRATION IMPROVES OUTCOMES IN PATIENTS WITH SEVERE SEPSIS: A SUBSTUDY OF THE KYBERSEPT TRIAL Alain A. Eid, MD*; Gary Kinasewitz, MD; Pulmonary Associates, Colorado Springs, CO PURPOSE: A major challenge of the KyberSept study was the “window” created to ensure enrollment of patients with severe sepsis within 6h after onset. Although the intention was to enroll patients early in their disease, the design of the study protocol made it possible to enroll patients who were in severe sepsis for longer than six hours. At our center, to ensure early enrollment, patients were evaluated for the study only if their ICU stay was less than 48 hours. METHODS: Enrollment criteria of the KyberSept protocol were used. Patients with severe sepsis (3 of the 4 SIRS criteria and organ failure present within a 6 hours window) were randomized to AT infusion (6000 U bolus and 250 U/h for 96 consecutive hours)(n⫽40) or placebo (n⫽41). The majority of our patients were enrolled early after the onset of sepsis (80% within 24 hours and 93% within 48 hours of ICU admission). Prophylactic low-dose heparin was administered to 90% of the patients. Fisher’s exact test was used to test binary data and student t-test was used to analyze continuous data. RESULTS: There were no differences in demographics or APACHEII score values between groups. Baseline AT levels were not significantly different between groups (69%⫾18 for placebo and 65%⫾26, p⫽0.45). Fifteen of forty patients (38%) in the AT group died versus 21 of 41 (52%) in the placebo group (Absolute mortality reduction: 14% and relative reduction: 27%, Odds Ratio 0.57 with 95% CI 0.23-1.38). Total number of organ failures was significantly reduced in patients receiving AT on days 10 through 28. Six patients had significant bleeding in the AT group versus one patient in the placebo group (p⫽0.057). Other side effects were similar in both groups. CONCLUSION: Administration of AT to patients with severe sepsis early after onset of their disease resulted in an absolute mortality reduction of 14%. The administration of heparin in prophylactic dosage did not diminish the benefit of AT. CLINICAL IMPLICATIONS: AT appears to reduce mortality in severe sepsis. DISCLOSURE: A.A. Eid, None.

ORTHOGONAL POLARIZATION SPECTRAL (OPS) IMAGING DEMONSTRATES MICROVASCULAR IMPAIRMENT IN A PORCINE MODEL OF SEPSIS Alexander J. Mathew, MD; Felicitas Ross, BA; Jasmeet Bajaj, MD; S. B. Waheed, MD; E. Kassas, MD; P. Jasty, MD; Roy D. Goldfarb, PhD; R. P. Dellinger, MD; Joseph E. Parrillo, MD; Steven M. Hollenberg, MD; Massimiliano Guglielmi, MD*; RWJMS, Camden, NJ PURPOSE: Microvascular alteration is a key physiological feature of sepsis and a determinant of multiple organ failure. OPS imaging allows non-invasive visualization of microvascular network of mucosal surfaces. We used OPS to assess microcirculation impairment in our porcine model of septic shock. METHODS: Sublingual microvascular flow and density were investigated in 6 pigs (26.5⫾3.6kg), by OPS imaging. Basal data were collected in healthy animals, before surgery for implantation of hemodynamic monitoring probes. After recovery, an E. coli laden fibrin clot was implanted intraperitoneally. OPS data were acquired for 6 hours following implant or until animals died. In survivors data were then acquired every 24 hours. At each time 2-4 sequences were captured for off-line analysis. Microvascular flow was graded semi-quantitatively by independent observer as 0:no-flow, 1:intermittent or sluggish, 2:continuous slow-moving and 3:brisk continuous. Density for perfused vessels (DPV) ⬍20mm was assessed as number of vessels intersecting a grid superimposed on the analyzed field. Data are expressed as mean⫾SD. Two-way ANOVA and Pearson Correlation were used as statistical tests. RESULTS: 3 animals expired prior to 6 hours, 3 survived over 24 hours. Microvascular Flow Score (MFS) was 2.62⫾0.41 for basal and 1.22⫾0.48 for sepsis (p⫽0.0002, 53.4% decrease). MFS improved markedly in animals that survived, to 2.11⫾0.20. Concomitantly DPV decreased from 14.12⫾1.93 to 12.35⫾2.09 vessels/mm (12.5% reduction), and increased subsequently to 14.37⫾1.32 vessels/mm. No correlation

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was found between cardiac output (CO) and either MFS or DPV (p⫽0.12 and p⫽0.13 respectively). CONCLUSION: OPS provides a reliable method to investigate microvascular impairment. We demonstrated deterioration of microvascular flow and DPV from the onset of sepsis and showed recovery in survivors. The poor correlation between CO and MFS or DPV may suggest that microvascular abnormalities persist despite normalization of systemic hemodynamic parameters (“cryptic shock”). CLINICAL IMPLICATIONS: OPS may have clinical utility to quantify microvascular perturbation in sepsis and to evaluate its time course. DISCLOSURE: M. Guglielmi, None.

COMPARISON OF PROGRESS SEVERE SEPSIS REGISTRY PATIENTS TO INDEPTH INTEGRATED SEVERE SEPSIS CLINICAL TRIAL DATABASE PLACEBO PATIENTS Richard Beale, MD*; Konrad Reinhart, MD; Eliezer Silva, MD; Geoffrey Dobb, MD; Samiha Sarwat, MS; Rekha Garg, MD; Jean-Louis Vincent, MD, PhD; Guy’s St. Thomas’ Hospital, London, England PURPOSE: PROGRESS, an international web-based severe sepsis registry, was created to provide a representative, contemporary description of severe sepsis worldwide. We compare baseline characteristics of over 4000 severe sepsis patients enrolled to date in PROGRESS with characteristics of placebo patients from the severe sepsis combined clinical trial database, INDEPTH. METHODS: PROGRESS is a prospective, observational registry. Participating ICUs enroll patients who have severe sepsis (suspected or proven infection and ⱖ1 acute sepsis-induced organ dysfunction). All data handling is by secure website and all patient data are de-identified. An independent advisory committee with professional society representation governs PROGRESS. PROGRESS software development and website maintenance was funded by Eli Lilly. INDEPTH placebo patients are from 4 severe sepsis clinical trials conducted in 13 countries. All of the INDEPTH trials had similar entry criteria and were conducted by the same sponsor (Eli Lilly). Exclusion criteria differed in the INDEPTH trials and PROGRESS has no exclusion criteria. RESULTS: As of April 1, 2004, PROGRESS has enrolled 4387 severe sepsis patients in 32 countries. Baseline characteristics of PROGRESS patients are compared with those of INDEPTH placebo patients in the table. CONCLUSION: Many of the disease severity measures examined indicate the “real-life” patients enrolled in PROGRESS are more severe at baseline. Absence of exclusion criteria in PROGRESS may lead to enrollment of more severe patients. Further comparisons must take into account these and other differences, such as possible country variations. CLINICAL IMPLICATIONS: Differences in baseline disease severity between clinical trial patients and clinical practice patients may potentially influence outcomes observed with new therapies.

INDEPTH Combined Severe PROGRESS Sepsis Clinical Severe Trial Database Sepsis Placebo Patients Registry N⫽1231 N⫽4387 Age, mean ⫾ SD Male, % Caucasian, % APACHE II, mean ⫾ SD Multiple organ dysfunction (%) Mechanical ventilation (%) Vasopressors (%) Cardiovascular organ dysfunction (%) Respiratory organ dysfunction (%) Lung as site of infection (%)

60.3⫾16.5 57.6 79.4 24.6⫾7.8 78.0 78.3 64.1 73.2

59.1⫾18.8 59.4 52.6 22.2⫾8.2 87.7 83.5 79.5 74.3

77.5 52.1

82.3 46.6

DISCLOSURE: R. Beale, I have served as a consultant to Eli Lilly & Co.


Wednesday, October 27, 2004 Critical Care Outcome, continued ASSOCIATION OF TROPONIN I CONCENTRATIONS WITH OUTCOMES IN SEPSIS Praveen Mannam, MD*; Veena S. Devarakonda, MD; Eric T. Wittbrodt, PharmD; Michael Sherman, MD; Siva K. Ramachandran, MD; Drexel University College of Medicine, Philadelphia, PA

CLINICAL USE OF DROTRECOGIN ALFA (ACTIVATED): PATIENTS TREATED IN THE XEUS STUDY DIFFER FROM HIGH RISK PROWESS PATIENTS Tim Rickert; Steingrub Jay, MD*; Cheatham Michael, MD; Safcsak Karen, RN; Lipsett Pamela, MD; Mark Effron, MD; Walter LindeZwirble, PhD; Michael Zeckel, MD; Baystate Medical Center, Springfield, MA PURPOSE: Experience from clinical practice may differ from randomized trials both in patient (pt) selection and outcomes. Xigris Evaluation in the United States (XEUS) is a prospective observational study of drotrecogin alfa (activated) (DrotAA) use in clinical practice. This report compares patients treated in clinical practice (XEUS) with those enrolled in a randomized clinical trial (PROWESS). METHODS: Between April 2003 and March 2004, data were prospectively collected from a convenience sample of patients receiving DrotAA at 61 acute care hospitals in the United States. Collected data included demographics, organ dysfunction, organ support, and outcomes. Pts were followed until hospital discharge or up to 28 inpatient days whichever came first (HD-28). Since DrotAA is indicated for reduction in mortality in adult severe sepsis (SS) patients at high risk of death, the XEUS population was compared to PROWESS patients at high risk of death (APACHE II ⱖ 25) who received placebo (HRP) and those who received DrotAA (HRX). RESULTS: 484 records were available for review. The mean APACHE II score was 28.4; however, since only 36.2% of XEUS patients had these scores recorded, no analyses using APACHE scores were performed. XEUS pts were younger, had more baseline (BL) multiorgan failure (⬎ 1 organ dysfunction), and more vasopressor use compared to HRP and HRX (Table). The HD-28 mortality was 36.8% for XEUS, 41.9% for HRP, and 29.5% for HRX. CONCLUSION: XEUS pts appeared to be younger, but were more severely ill (number of dysfunctional organs and vasopressor use) than HRP and HRX. The higher mortality rate in XEUS compared to HRX may reflect more advanced SS in XEUS. CLINICAL IMPLICATIONS: SS is a progressive disease with mortality closely related to the number of dysfunctional organs. The greater frequency of vasopressor use and multiorgan failure in the XEUS population suggests either more rapid disease progression or later patient identification than was seen in PROWESS.

Table-Summary of Troponin I in Sepsis Study

Group 1a n⫽13

Mean⫾ SD Median

Group 2b n⫽11

Mean⫾ SD Median p value

a

Age (y)

Troponin I (ng/ml)

ICU Stay (Days)

62.3⫾14.5 63

0.22⫾0.27 0.10

5.3⫾5.7 4

Ventilator Pressordays daysc

APACHE II Score

28-day Mortality

1.5⫾2.8 0

1⫾1.8 13.54⫾4.54 0 13

1/13(7.69%)

63⫾19.4 12.81⫾22.76 16.3⫾17.4 12.4⫾11.4 67 4.8 10 10

8⫾9.8 20.64⫾6.84 6 20

5/11(45.45%)

0.7943

⬍0.0001

0.082

0.0016

0.0235

0.0108

DISCLOSURE: S. Jay, None.

p⬍0.04

Group 1: Troponin I⬍1 ng/ml CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Troponin I is a sensitive test used for the diagnosis of acute coronary syndromes. Sepsis is a leading cause of death in intensive care units (ICU), characterized by diffuse end organ damage including myocardial dysfunction. The clinical significance of elevated troponin I concentrations in sepsis is not clearly understood. We retrospectively examined the association of troponin I concentration with selected outcomes in patients who were diagnosed with sepsis. METHODS: The medical records of 24 patients admitted with documented troponin I concentrations within 10 days after onset of sepsis were reviewed. Patients with acute coronary syndrome, cardiac surgery, pulmonary embolus, or cerebrovascular accident were excluded. Continuous data were compared using Mann-Whitney U test. Correlation of selected outcomes was calculated using the Spearman rank correlation test. Mortality was compared using Kaplan-Meier analysis with log rank test. RESULTS: Mean age was similar between groups of patients with normal troponin I (⬍1ng/ml, n⫽13, group 1) and elevated troponin I (⬎1ng/ml, n⫽11, group 2). Patients in group 2 were more ill (mean APACHE II score 20.6 vs. 13.5, p⫽0.01), required increased use of pressors (pressor-days 9.9 vs. 1, p⫽0.006), and experienced longer duration of mechanical ventilation (12 vs. 2 days, p⫽0.002). Mortality was significantly higher in group 2 (45.4% vs. 7.7%, log rank test ⫽ 4.218, p⬍0.04). The degree of elevation of troponin I concentrations correlated with APACHE II scores (r⫽ 0.66; 95% CI, 0.34-0.84, p⫽0.0004). Patients in group 2 experienced a statistically nonsignificant trend toward longer ICU stay (16.3 vs. 5.3 days, p⫽0.082). CONCLUSION: Elevated troponin I concentrations are associated with greater severity of illness, increased 28-day mortality, and longer duration of mechanical ventilation and vasopressor use in patients with sepsis. CLINICAL IMPLICATIONS: The presence of elevated troponin I is a function of both the severity of sepsis and also the extent of myocardial injury, both of which contribute to poorer outcomes in such patients.

Troponin I concentration may serve as a useful marker in identifying patients with sepsis at increased risk of mortality. DISCLOSURE: P. Mannam, None.

Wednesday, October 27, 2004 Smoking Cessation and Tobacco Control 12:30 PM - 2:00 PM POPULATION PREVALENCE OF RESPIRATORY SYMPTOMS IN BIDI AND CIGARETTE SMOKERS IN INDIA Surinder K. Jindal, MD*; V. K. Vijayan, MD; George D’Souza, MD; S. K. Katiyar, MD; Postgraduate Institute of Medical Education & Research, Chandigarh, India PURPOSE: Bidi, a product of cottage industry, is the most prevalent form of tobacco smoked in India. A bidi contains crude tobacco wrapped in a dry Tendu leaf (Dyospyros melonaxylon). Health effects of bidi may therefore be different from those of cigarettes. METHODS: Smoking habits and respiratory symptoms were analyzed from the data collected as a part of a large multi-centric population survey conducted in/around four cities in India for studying the prevalence of asthma. RESULTS: Preliminary analyses of data from 55,641 adult subjects (28363 men and 27278 women) revealed 16.4% prevalence of self reported smoking (30% men and 2.3% women). Amongst smokers 67.6% smoked bidis, 27.6% smoked cigarettes and 4.7% smoked hooka (traditional water pipe). Prevalence of common respiratory symptoms was higher in smokers than in non-smokers and in bidi than cigarette smokers. Multiple logistic regression modeling revealed higher OR’s for bidi smoking vis-a`-vis cigarette smoking (Table 1). CONCLUSION: Bidi smoking highly prevalent in India and is associated with a high risk of respiratory symptoms that is even greater than cigarette or hooka smoking. CLINICAL IMPLICATIONS: Tobacco cessation should be targeted at bidi smoking as much as cigarettes.

Table 1: Prevalence of respiratory symptoms in relation to different smoking habits % Prevalence of the symptom

Logistic Regression analysis with non- smokers as reference category Cigarettes

Symptom

Bidi

Hooka OR* 95%CI OR*

Hooka

95%CI

OR* 95%CI

1.78

1.5-2.1

1.49

1.77

1.6-2.0

1.39

1.0-1.9

1.8-2.7

2.94

2.6-3.4

2.14

1.5-3.0

2.55

2.1-3.0

2.81

2.4-3.2

2.39

1.7-3.4

2.19

1.8-2.7

2.62

2.3-3.0

2.12

1.5-3.0

1.91

1.5-2.4

2.94

2.5-3.4

2.46

1.7-3.6

NS

Cigarettes

Bidi

Wheezing

2.5

4.9

5.4

7.9

1.75

1.4-2.1

Dyspnoea on exertion

5.0

8.5

9.9

14.4

1.72

1.4-2.0

Cough at night

2.5

6.4

8.9

10.7

2.22

Cough in morning

2.2

6.7

8.3

11.2

Phlegm in morning

2.0

6.1

7.9

10.0

Phlegm in morning ⬎3 months/year

1.6

4.3

6.8

9.3

1.0-2.2

*OR adjusted for age, sex, socio-economic status, atopy and family history of asthma. (NS ⫽ non-smokers) DISCLOSURE: S.K. Jindal, None.

telephone contacts the first week of the therapy and then every 2 weeks for 3 months treatment, while the result has been recorded. Clinical visits were scheduled after 2 weeks, 2nd, 6th, and 12th month of treatment. RESULTS: 179 (73%) individuals completed the medical treatment. The treatment has been interrupted by 27 (11.1%) individuals due to unserious side effects (Xerostomia, insomnia, anxiety, nausea) and by 39 (15.9%) due to unwillingness. 66 individuals from 179 (37%) interrupted smoking after 2 months, 59 (33%) after 3 months and 52 (29%) after 6 months treatment. Among 123 who received only advisory support, interrupted smoking 19 (15.5%) after 2 months, 16 (13%) after 3 months and 15 (12.2%) after 6 months treatment. CONCLUSION: Treatment with bupropion SR in combination with counseling resulted in significantly higher long-term rates of smoking cessation than use only advisory support. We observed a moderate to high percentence of side effects, which are unserious and temporary. CLINICAL IMPLICATIONS: Smoking cessation is associated with clear health benefits and therefore should always be a major health care goal. Behavioral and pharmacologic methods help patients stop smoking. DISCLOSURE: E.G. Karabatsos, None.

A SMOKING CESSATION PROGRAM DELIVERED BY STUDENT NURSES Peter R. Smith, MD*; M. Rafferty, MA, MPH, RN; D. Grasso, MSN, RN; J. Mackin, EdD, RN; K. Downie; J. Edwards; K. Kusterbeck; S. Matthews; K. Garrett-Szymanski, RRT; M. Bergman, MD; P. Meade, RN; Long Island College Hospital, Brooklyn, NY PURPOSE: Inpatient smoking cessation programs (ISCPs) are frequently more effective in achieving sustained (12 months) abstinence than ambulatory programs. Time constraints may impact the ability of hospital staff to provide the necessary counseling. In 1996 the US Department of Health and Human Services (DHHS) recommended that hospitals develop ISCPs and that clinicians (MDs, RNs etc) learn cessation techniques. We developed an adjunct to our ISCP utilizing student nurses (SNs). To our knowledge, this has not been previously reported. METHODS: 61 senior SNs were trained in smoking cessation (SC) based on the 1996 DHHS guideline (AHCPR No. 96-0692). This 1 hour training was reinforced through written materials and exam questions. Beginning in 2/04, teams of two SNs each spent a half-day providing SC counseling to an average caseload of 4 patients (Pts). Sessions lasted about 15 minutes. SNs suggested that Pts ask their physicians about pharmacotherapy to assist SC. The intervention was documented in the medical record, and reported to the Pt’s RN. SNs completed a data sheet for tracking abstinence after discharge. Pts agreeing to continued contact were telephoned on a monthly basis. RESULTS: Over 10 weeks SNs visited 104 Pts. SNs reported a high degree of satisfaction with the program. Results of the program are shown in the Table. CONCLUSION: SNs can effectively deliver SC interventions to hospitalized patients. Although the data are preliminary, the cessation rates achieved may be consistent with reported ISCPs.

Results of SN Smoking Cessation Interviews with Hospitalized Patients BUPROPION FOR THE TREATMENT OF NICOTINE DEPENDENCE Michalis G. Patentalakis, MD; Emmanuil Kastanakis, MD; Maria Dimitriadou; Moshakis Moshos, MD; Elias G. Karabatsos, MD*; Antony E. Kopanakis, MD; Naxos Hospital, Naxos, Greece

Accepted written materials Accepted counseling

90/ 104

(90%)

83/ 104 77/ 104 20/ 104 71/77

(80%)

27/71 8/27

(38%) (30%

PURPOSE: The aim of the study was to estimate the smoking cessation success rates of bupropion sustained release (SR) as medical treatment given daily for 8 weeks. METHODS: 368 individuals with mean age the 46 years (range 22 to 66 years), who smoked 10 or more cigarettes per day, had high nicotine dependence and without clinical depression, participated in this study, which took place in the special medical center of smoking cessation of a hospital in Greece. A total of 245 participants received bupropion SR 150 mg daily for 1 week and then 300 mg daily for 7 weeks (total duration of medication 8 weeks) in combination with counseling. The rest 123 were treated with advisory support. The target quitting date was one week after the beginning of treatment. Brief counseling has been provided by

Committed to SC attempt Received anti-smoking Rx Provided home phone no. Contacted post disch. Abstinence 1 mo. post disch.

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(74%) (19%) (92%)

Wednesday, October 27, 2004 Smoking Cessation and Tobacco Control, continued CLINICAL IMPLICATIONS: SNs could be a key component of ISCPs. The required skills are easily integrated into the SN curriculum, and the program provides valuable experience in patient education. DISCLOSURE: P.R. Smith, None.

THE SUCCESSFUL OUTCOME OF THE ROLE OF THE MASS MEDIA & SCHOOL PROGRAM IN THE PREVENTION OF SMOKING AMONGST ADOLESCENT HIGH SCHOOL BOYS M. Ishaq, MD*; S.M.I. Khan, MD; Al-Junaid Hospital, Nowshera, Pakistan

Type of Category

Smoking frequency /week

Cate-A

10-12

Reason for smoking

Smoking incitation by peers / OR parents

To appear as elders/weak performance at study, Impressed from Industry sponsored sports.do..

Both

Socioeconomic status, Poor*2

Study performance in class/school

Poorhigh*3

Current smokers

Activity

Cigarettes/ day

Former smokers

Cigarettes/ day

Physicians

7.7%

5.5(SD 5)

15.3%

5.5(SD 7)

Faculty

4.5%

11 (SD3.5)

35.8%

12.5(SD 9)

Nurses

17.1%

12.5(SD 6)

28.6%

6 (SD4.5)

Health technicians

29.0%

11 (SD 7)

17.9%

5.5(SD4.5)

Other health professionals

20.9%

8.5(SD4.5)

10.4%

3 (SD1.5)

Office workers

28.9%

13 (SD 8)

13.2%

8.5(SD 7)

DISCLOSURE: D. Chiesa, None.

Critical Care Outcomes 12:30 PM - 2:00 PM

Cate-B

8-10

..do..

Both

Poor-high middle class*3

Improving with quitting

Cate-C

9-11

..do..

Mostly parents

Poor-high middle class*3

Significantly improving with quitting

*aExisting smoking population *1one/ or both smoking parents(one smoking parent/or other user of smokeless tobacco).*2. combined annual income equal/or less than the standard for poor living in the under developed countries.*3 Income as(*2. )/lavish income for living standards in the underdeveloped countries.

DISCLOSURE: M. Ishaq, None.

PURPOSE: Smoking remains the main cause of preventable deaths worldwide. Healthcare staff plays an important role in educating public about health hazards of tobacco and in advising people to quit smoking. The aim of our study was to determine the prevalence of tobacco smoking among professionals of Hospital de Clıńicas de Porto Alegre. METHODS: Cross-sectional survey among hospital employees, using a self-administered questionnaire, with questions about demographics, place of work, activities, smoking habits and attitudes towards smoking. RESULTS: The questionnaire was fulfilled by 1.019 employees (24.0% out of 4.245). Physicians were 27.5%, faculty 6.7%, nurses 3.5%, healthcare technicians 19.6%, other healthcare professionals 6,7% and office workers 35.7%. Age ranged from 18 to 70 years, mean 35.8 years (SD 9.7) and 59.9% were female. Prevalence of current smokers was 21.6% and former smokers was 20.8%. All smokers started to smoke before the age of 18 years (16.1 ⫾ 6.3) and 86.6% wanted to quit smoking. Asked about advising patients to quit smoking, 70.0% answered always, 24.8% sometimes and 7.1% never. Former smokers started to smoke at the mean age of 17.4 years (SD 3.6) and smoked in average 5 pack-years. CONCLUSION: The prevalence of cigarette smoking among health professionals of Hospital de Clıńicas de Porto Alegre is lower than that observed in the general population of Brazil (30%). CLINICAL IMPLICATIONS: Smoking is still a problem among healthcare professionals. Because they are behavior models for patients they should be discouraged to smoke.

NOSOCOMIAL INFECTIONS IN A RESPIRATORY INTENSIVE CARE UNIT: AN INDIAN EXPERIENCE Dheeraj Gupta, MD*; Ritesh Aggarwal, MD; Surinder K. Jindal, MD; Postgraduate Institute of Medical Education & Research, Chandigarh, India PURPOSE: There is a paucity of data on nosocomial infections from India. We determined prevalence, pattern, risk factors and outcome of infections acquired in patients admitted to our Respiratory Intensive Care Unit (RICU). METHODS: Data on RICU-acquired infection were collected prospectively over a 15-month period. The presence of risk factors such as the endotracheal intubation, surgical drains, invasive lines, renal failure, diabetes mellitus, malignancy and immunosuppressive therapy were evaluated in patients who developed infections using univariate and multivariate logistic regression analyses. The effect of infection on RICU stay was studied using survival analysis and log-rank test.


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PURPOSE: Since smoking commence in adolescence the idea is to curb it at this age before it could advance into a much dreadful stage. METHODS: In the ongoing project the cessation role of school health & mass media prevention campaign towards adolescent boys, at the raised risk of smoking. A group of students(N⫽ 2000), ages 15-19 years were surveyed yearly for 5 years period at baseline from three institutions i.e,Category A(Cat-A)(n⫽660,with 29%smoking rate*a, (the control group from a distant region of the district) not involved in either school program/media exposure,Cate-.B(N⫽755,25%smoking rate) exposed to school program only Cate-.C(n⫽585),smoking rate27% exposed to both school program & media campaign(incitation for quitting,cessation advises/persuasion media messages).The assessment of smoking tendency had been made from the questionnaire(In the table) delivered to all the three institutions(with consent from school authorities/parents & keeping all the data confidential). RESULTS: Logistic Regression with Odds Ratios for Tripartite Schools revealed significant findings at the end of final term examination, Cat-. A, on an average(OA)further 5%rise in the smoking tendency (OR ⫽1.05, p ⬍ .05 ),Cate-B.(OA)3%reduction in smoking pool(OR⫽.97, p ⬍ .001),Cate-C,(OA)5%reduction(OR⫽.95,p⬍.001). This outcome reflected the fact that effective media campaigning supported by school health program& follow up interventions towards the growing age group could reduce the smoking habits resulting in the later on reduction in morbidity/mortality outcomes. CONCLUSION: In the industry’s strategy cigarette promotional activities are mainly diverted towards adolescent/young adults “the age group to follow industry sponsored activities with enthusiasm”. CLINICAL IMPLICATIONS: Media campaign& school health program complement each other in tobacco control program. MIM khan et.al.alj.h.nsr.nwfp pk.

SMOKING PREVALENCE AMONG HEALTH PROFESSIONALS Daniela Chiesa, MD*; Marli M. Knorst, MD; Andre´ Franciscatto; Candice Krumel; Kelin M. Mezzomo; Hospital de Clıńicas de Porto Alegre / UFRGS, Sao Leopoldo, Brazil

Wednesday, October 27, 2004 Critical Care Outcomes, continued RESULTS: Of the 217 patients enrolled, 201 were included in the final analyses. Seventy-seven (38.5 %) patients developed one or the other infection. The most frequently acquired ICU infection was pneumonia (23%). The other infections were clinical sepsis (10.5%), bacteremia (7.5%), urinary tract infection (1.5%), catheter related bloodstream infection (1%) and Clostridium difficile colitis (1%). Positive cultures were obtained in 40 (51.9%) patients. The commonly identified organisms included the Acinetobacter species (34.8%), Pseudomonas aeruginosa (23.9%), and Escherichia coli (15.2%). Length of stay in RICU (OR ⫽ 1.22), renal failure (OR ⫽ 3.15) and presence of invasive intra-vascular lines (OR ⫽ 3.6) were the more significant risk factors for RICU-acquired infection. Increasing APACHE II scores (OR 1.11; 95% CI: 1.05-1.18) and presence of endotracheal tube (OR 4.11; 95%CI: 1.07-15.87) or invasive lines (OR 3.44; 95%CI: 1.03-11.5) contributed significantly to mortality; infection was not a significant factor (OR⫽1.88; 95%CI: 0.85-4.98). Median stay in patients with infection (13 days) was longer than in those without infection (4 days). CONCLUSION: Infections acquired during hospitalization prolonged ICU stay but had no effect on ICU survival. CLINICAL IMPLICATIONS: Identification of risk factors for and causative microorganisms of infections in RICU can help in formulating appropriate management and preventive strategies. DISCLOSURE: D. Gupta, None. PATIENT DEMOGRAPHICS AT FLEET HOSPITAL EIGHT INTENSIVE CARE UNIT Gregory Hoeksema, MD; William L. Boyan, MD*; Bremerton Naval Hospital, Bremerton, WA PURPOSE: US Navy fleet hospitals can be deployed to any global location to support combat operations. In February of 2003, Fleet Hospital Eight was deployed to Rota, Spain to support operation Enduring Freedom/Operation Iraqi Freedom. The Fleet Hospital cared for Americans evacuated from more forward deployed military medical facilities in Afghanistan, Iraq, Kuwait and ships at sea. METHODS: Throughout the deployment the authors collected patient demographic data for all admissions to the intensive care unit, ICU. After returning to the United States, these data were reviewed and analyzed. RESULTS: 153 patients were admitted to the intensive care unit. Average length of stay was slightly longer than three days. The patients were overwhelmingly male. Most were between 21 and 35 years of age with a mean age of 32 years. Patients served in all branches of military service, but most were from the army. Officers were treated in the ICU, but most patients were enlisted. The majority of patients were admitted to the medical service and chest pain was the most common diagnosis. A significant number of patients had ischemic heart disease confirmed by cardiac enzymes or exercise stress testing, but the majority of chest pain patients were returned to duty in Iraq or Kuwait. Trauma was the second most common diagnosis. Extremity trauma was the most frequent type, but polytrauma was nearly as common. In addition to critical care, the ICU functioned as a post anesthesia care unit and short stay unit for procedures under conscious sedation. 362 such procedures and recoveries were performed. CONCLUSION: Fleet hospital intensive care units function to evaluate and treat a variety of critical illnesses for a wide variety of patients. CLINICAL IMPLICATIONS: Planning for future Fleet Hospital Deployments will consider these demographics. DISCLOSURE: W.L. Boyan, None.

survival outcomes in patients with ventilator-dependent respiratory failure. METHODS: We retrospectively studied 206 patients with ventilator-dependent respiratory failure admitted to a long-term acute care facility for weaning. Patients were divided into the following groups based on their BMI: Underweight (BMI⬍20); Normal (BMI 20-25); Overweight (BMI 25-30); Obese (BMI 30-40) and Morbidly Obese (BMI ⬎40).The following data was abstracted: age, sex, BMI, weaning outcome (successful wean defined as being off ventilator⬎7 days) and survival outcome (alive or expired at discharge). Relation between BMI-subgroups and outcomes was determined by Chi-square test. Effect of BMI ⬎20 and BMI ⬍20 on outcomes was also determined. p⬍0.05 was statistically significant. RESULTS: Of 206 patients, 52% were females and 48% males with a mean age of 66⫾16 years. Sixty-eight percent weaned; 72% survived. Twenty percent were underweight; 30% normal; 22% overweight; 20% obese; 8% morbidly obese. Weaning and survival outcomes of these patient-subgroups are shown in Table 1. Weaning and survival outcomes of patients with BMI⬍20 and ⬎20 are shown in Table 2. CONCLUSION: Comparison between the five BMI-subgroups showed no significant difference in weaning and survival outcomes. However, patients with BMI ⬍20 had a worse survival outcome, but no difference in weaning outcome, than those with BMI ⬎20. CLINICAL IMPLICATIONS: Obesity doesnot affect weaning or survival outcomes in patients with ventilator-dependent respiratory failure. BMI ⬍20 can serve as a prognosticator for less favorable survival outcome (but NOT a less favorable weaning outcome) in these patients.

Body Mass Index (kg/sq m) Outcome Weaned Failed Survived Expired

⬍20

20-25

25-30

30-40

⬎40

p

26/39 13/39 20/ 39** 17/39

41/63 22/63 42/63***

29/47 18/47 35/47*

31/40 9/40 31/40*

12/17 5/17 14/17

⬎0.05 ⬎0.05

18/63

11/47

8/40

3/17

* ⫽ Number of patients transferred to acute facility.

Outcome Weaned Failed Survived Expired

BMI⬍ 20 (n⫽39)

BMI⬎ 20 (n⫽167)

26 13 20* 17

113 54 122** 40

p ⬎0.05 0.009

*⫽2 patients transferred to acute facility. DISCLOSURE: D. Datta, None. PULMONARY FUNCTION AND EXERCISE CAPACITY IN SURVIVORS OF SEVERE ACUTE RESPIRATORY SYNDROME Kian C. Ong, MBBS*; Alan W. Ng, MBBS; Lawrence S. Lee, MBBS; Gregory Kaw, MBBS; Seow Khee Kwek, MBBS; Melvin K. Leow, MBBS; Arul Earnest, MSc; Tan Tock Seng Hospital, Singapore, Singapore

PURPOSE: Obesity has been cited in literature to result in variable survival outcomes in critically ill patients. Studies have shown low body mass index (BMI) to be associated with increased mortality in these patients. Effect of BMI on weaning outcomes has received little attention. Obesity can result in increased work of breathing by decreasing thoracoabdominal compliance and causing an abnormal diaphragmatic position. This could result in difficulty in weaning from ventilatory support. The objective of this study was to determine the effect of BMI on weaning and

PURPOSE: Severe Acute Respiratory Syndrome (SARS) is an acute respiratory illness caused by infection with a new coronavirus. The sequelae of SARS coronavirus infection remain undefined. The aim of this study is to investigate the pulmonary function and exercise capacity in a group of survivors of SARS. METHODS: At 3 months after hospital discharge, 46 survivors of SARS underwent the following evaluation: spirometry, static lung volumes, carbon monoxide transfer factor (TL,CO). Forty-four of these patients underwent cardiopulmonary exercise testing. RESULTS: No abnormalities were detected in the pulmonary function tests in 23 (50%) of the patients. Abnormalities of FVC, FEV1, FEV1/ FVC and diffusing capacity for carbon monoxide (DLCO) were detected in 7 (15%), 12 (26%), 1 (2%), and 18 (39%) patients respectively. All these abnormalities were mild except in 1 case, who had moderate impairment

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THE EFFECT OF BODY MASS INDEX ON SURVIVAL AND WEANING OUTCOMES IN PATIENTS WITH VENTILATORDEPENDENT RESPIRATORY FAILURE Debapriya Datta, MD*; Paul Scalise, MD, FCCP; Manchester Hospital, Manchester, CT

Wednesday, October 27, 2004 Critical Care Outcomes, continued of DLCO. In 18 patients (41%), the maximum aerobic capacity ( O2max) was below the lower limit of the normal range. Breathing reserve was low in 4 patients and significant oxygen desaturation was detected in 4 patients. Comparison of the measured exercise capacity with resting pulmonary function tests showed many cases of discordance in impairment. CONCLUSION: Pulmonary function defects were detected in half of the recovered SARS patients at 3 months after hospital discharge but the impairment was mild in almost all cases. Many patients had reduced exercise capacity that cannot be accounted for by impairment in pulmonary function. CLINICAL IMPLICATIONS: Further studies for the evaluation of extra-pulmonary causes of morbidity in recovered SARS patients are required. The finding of reduced ability to exercise without significant impaired lung function impairment in most patients in this study suggests that emphasis on physical and psychosocial rehabilitation after their acute illness is likely to contribute to improved management of these patients. DISCLOSURE: K.C. Ong, A*STAR Biomedical Research Council

PURPOSE: Survivors of critical illness experience decrease quality of life due to physical limitations. It is assumed patients are too fragile to tolerate vigorous activity in an early phase of their illness incurring unavoidable immobilization. We postulate early activity is achievable and can be performed safely. METHODS: We recorded all activity over 150 days from June through December 2003 in our Respiratory ICU. Activity was defined as dangle (sit without back support), chair (sit with back support) and ambulation (walk in the hallway). We defined 6 activity-related complications; fall to knees, tube removal, systolic BP⬎200, systolic BP⬍90, desaturation⬍80%, and extubation. RESULTS: (Mean ⫾ SD): The patient population was defined as critically ill (APACHE II 17 ⫾ 5), elderly (age 62 ⫾ 15 years), with a prolonged ICU stay (16 ⫾ 12 days). Sixty-nine percent of patients had ARDS, COPD, pneumonia, or sepsis. During the study period, there were a total of 1,449 activity events in 119 patients. Activity type was broken down into the following: 17% Dangle, 31% Chair, and 52% Ambulation. During activity, 41% of patients had an endotrachial tube, 11% had a tracheostomy tube, and 48% were not intubated. Oxygen concentrations prior to activity were ⬍40% oxygen in 27% , 40% oxygen in 51%, 50% oxygen in 14%, and ⬎ 60% oxygen in 8% of patients respectively. A total of 14 activity complications (⬍1%) were recorded. Complications included; 5 falls to knees (without injury), 1 feeding tube removal, 1 Systolic BP⬎200, 4 Systolic BP⬍90, 3 desaturation ⬍80%, and no extubations. CONCLUSION: Activity is safe in respiratory failure patients early in their critical illness, including intubated patients on mechanical ventilation. Activity complications were infrequent (⬍1%), and did not lead to injury or prolonged deterioration. Our study is limited by the lack of blinding and randomization. CLINICAL IMPLICATIONS: Early activity is achievable and can be performed safely in mechanically ventilated patients. Therefore, the complications that occur from prolonged immobilization may be preventable. DISCLOSURE: V.J. Spuhler, None. HEMOPTYSIS IN THE INTENSIVE CARE UNIT: ETIOLOGY AND OUTCOME IN A SERIES OF 115 PATIENTS Jens M. Walz, MD*; Ciaran J. McNamee, MD; Alan A. Conlan, MD; University of Massachusetts Medical Center, Worcester, MA PURPOSE: Hemoptysis can be differentiated into mild or massive and the etiology may vary depending on the patient population studied. We conducted a retrospective analysis on the etiology of hemoptysis and the outcomes of patients with hemoptysis while receiving mechanical ventilation in the Intensive Care Unit (ICU). METHODS: We identified 115 patients diagnosed with hemoptysis during their ICU-stay (combined Medical/Surgical) at the University of Alberta Hospital between the years 1990 to 1995. Hemoptysis was characterized by site (local or diffuse) and by amount - minor (⬍400

EFFECTIVENESS OF A DEDICATED NON-INVASIVE VENTILATION UNIT IN A GENERAL HOSPITAL Kian C. Ong, MBBS*; Yee Mun Choo, BSc; Wai Fung Chong, BN, MBA; Seow Pek Tan; Cindy Soh, BSc; Tan Tock Seng Hospital, Singapore, Singapore PURPOSE: The use of non-invasive ventilation (NIV) for acute respiratory failure outside the intensive care unit (ICU) is common in some hospitals. This study aims to evaluate the outcomes of episodes of acute respiratory failure (ARF) treated by NIV in a dedicated “sub-ICU” unit in comparison to the treatment of such cases in general wards (GW) of the hospital. METHODS: We assessed the severity of disease and the rates of NIV success of 121 patients with ARF treated in the non-invasive ventilation unit (NIVU) and compared these with 46 historical controls treated in the GW. The NIVU is a 4-bedded unit with a 1:4 nurse:patient ratio largely devoted to NIV treatment of ARF, that was opened in 2001 in response to increasing frequency of NIV treatment in GW due to unavailability of intensive care beds. GW nurses with minimal previous training in NIV flexibly staffed the NIVU and were supported by respiratory therapists. RESULTS: The commonest causes of ARF treated in the NIVU were decompensated COPD (67.5%), obesity-hypoventilation syndrome (6.7%), bronchiectasis (5.8%), and pneumonia (9.2%). There was no significant difference between the mean baseline pH among cases treated in NIVU and controls (7.27 vs 7.27; P⫽0.811). However, the mean baseline PaCO2 was significantly higher in NIVU cases than controls (86.4mmHg vs 68.3mmHg respectively; P⫽0.028). The rate of NIV success in the NIVU was significantly higher than controls (82.9% vs 52.2% respectively; P⬍0.001). There were 21 cases of deaths (17.4%) in the NIVU compared to 19 (41.3%) among the controls (P⫽0.002). CONCLUSION: Outside the ICU, the rate of success with NIV treatment of ARF in a dedicated unit can be significantly higher compared to isolated cases treated in general wards. CLINICAL IMPLICATIONS: With the increasing practice of NIV outside the ICU in some hospitals, consideration should be made to concentrate medical, nursing and equipment resources in a dedicated unit as this may lead to significant improvement in outcomes with minimal additional expenditure. DISCLOSURE: K.C. Ong, None.


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EARLY ACTIVITY IS SAFE IN RESPIRATORY FAILURE PATIENTS George E. Thomsen, MD; Louise Bezdjian, RN, BSN; Vicki J. Spuhler, RN, MS*; Polly Bailey, RN, APRN, C; Kristy Veale, RN, BSN; Intermountain Health Care, Salt Lake City, UT

ml/24h) or massive (⬎400 ml/24h). Outcome was analyzed with respect to medical (including bronchus balloons and bronchial artery embolization) or surgical management (rigid bronchoscopy and thoracotomy). A comparison between groups was done using students t-test; identification of factors associated with mortality was performed using a logistic regression model. The null hypothesis was rejected for p⬍0.05. RESULTS: Overall mortality was 24% in patients admitted with hemoptysis (n⫽42) compared to 36% in patients who developed the condition while in the ICU (n⫽73). Massive hemoptysis was more frequent in the first group (63% vs. 24%, p⬍ 0.01). Mortality was 45% for patients with diffuse hemoptysis and 20.3% for those with localized bleeding (p⬍ 0.01). The most common factors associated with hemoptysis were hematological abnormalities (58%), sepsis (56%) and congestive heart failure (CHF) (24%). Thrombocytopenia is the only independent risk factor associated with mortality in our study. Surgical treatment of hemoptysis was performed in 32 patients (mortality 32%) whereas the rest received medical therapy (mortality 33%). There was a trend towards lower mortality in those patients suffering from massive hemoptysis who were treated with a surgical intervention (p⫽0.058). CONCLUSION: Mortality is significantly higher in ICU patients who suffer from diffuse hemoptysis compared to those who have localized bleeding. Localized hemoptysis is more likely to be amenable to surgical treatment. CLINICAL IMPLICATIONS: Our study suggests that for ICU patients suffering from massive but localized hemoptysis, surgical intervention has a better outcome than medical management. DISCLOSURE: J.M. Walz, None.

Wednesday, October 27, 2004 Critical Care Outcomes, continued POST-ICU MECHANICAL VENTILATION: FUNCTIONAL STATUS BEFORE AND AFTER PROLONGED MECHANICAL VENTILATION David J. Scheinhorn, MD*; Meg Hassenpflug, MS, RD; David C. Chao, MD; Chris Palma, MPH; Barlow Respiratory Hospital and Research Center, Los Angeles, CA PURPOSE: To compare pre-morbid functional status to that at admission, discharge, and 12-months post-admission, for patients transferred to Barlow Respiratory Hospital (BRH), a long term acute care hospital (LTAC), for weaning from prolonged mechanical ventilation (PMV). METHODS: Data were collected as part of an observational multicenter study with a 1-year enrollment period. Initial datasets were collected at BRH admission; weaning outcome was scored at discharge. Telephone contact was used to determine 12-month post-admission functional status. Functional status was determined using the Zubrod Score (0 ⫽ Fully active to 4 ⫽ Bedridden with no self-care). Zubrod scores of 0-2 were determined to be good functional status; scores of 3-4 were poor functional status. Discharge Zubrod was not scored for patients who died. RESULTS: 186 patients were enrolled from 3/1/02 - 2/28/03. Patients’ age: 74 [22-98] years. Patients spent 32 [1-216] days at the transferring facility, with 31[1-215] days of mechanical ventilation. Total days of hospitalization (transferring facility ⫹ BRH): 70 [8-388] days. Interactive with staff on admission: 66%. Weaning outcome: 49% weaned, 22% remained ventilator-dependent, 29% died; 23% of survivors were discharged directly home. There was no significant difference in weaning outcome between patients with good premorbid functional status and those with poor premorbid functional status. Patient functional status at selected time points: Pre-morbid (n⫽180): 66.1% good, 33.9% poor; BRH admission (n⫽186): 0% good, 100% poor; BRH discharge (n⫽116): 11.2% good, 88.8% poor; 12-months post BRH admission (n⫽48): 43.8 % good, 56.2% poor. CONCLUSION: Patients admitted to BRH were elderly, but largely independent before their catastrophic illnesses and PMV. Functional status at discharge in the surviving 71% of patients was less than pre-morbid, but improved from that at transfer to BRH. At 12-months post-admission to BRH, nearly half of survivors reported good functional status. CLINICAL IMPLICATIONS: Functional status falls to expected lows in an elderly population with PMV following a catastrophic illness. Gains in functional status are demonstrated as long as 12-months postadmission to an LTAC specializing in weaning from PMV. DISCLOSURE: D.J. Scheinhorn, None.

DISCHARGE DESTINATION IN OLDER SURVIVORS OF CRITICAL ILLNESS: PREDICTING THE INABILITY TO RETURN HOME Brian K. Gehlbach, MD*; Joe Levitt, MD; Victor Salamanca, BS; Mary K. Mohan; Anne Pohlman, MSN; Ajeet Vinayak, MD; John Kress, MD; Greg Sachs, MD; Jesse Hall, MD; University of Chicago, Chicago, IL PURPOSE: Studies of ambulatory and hospitalized older patients show that functional decline is predicted by the interaction of baseline risk (vulnerability) with acute events (noxious stimuli). We hypothesized that chronic medical conditions and acute illnesses predict which older survivors of critical illness (CI) will not return home on hospital discharge. To test this we developed a prediction model using information commonly available to intensivists. METHODS: Using an existing database, we retrospectively analyzed all first admissions of medical ICU patients ⱖ 65 yrs, excluding patients not living at home prior to admission. Chronic medical conditions (neurodegenerative disorder; diabetes mellitus ⬎5 years; stage IV solid organ malignancy; advanced heart, lung, liver, or kidney disease) and acute (first 72hrs intensive care) illnesses (mechanical ventilation [MV], acute renal failure requiring dialysis, and severe neuromuscular dysfunction) were recorded, along with age, APACHE II score, and body mass index. Logistic regression was performed, with discharge to a location other than home serving as the dependant variable. RESULTS: 737/789 charts were available; 167 met study criteria. 61/167 (36.5%) older survivors of CI did not return home on discharge. These patients were older (76 [71-80] vs. 72 [67-77], p⫽.003), sicker (APACHE II score 23.7 ⫾ 6.8 vs. 17.3 ⫾ 5.5, p⬍.001), and received more MV (52.5% versus 16%, p⬍.001). None of the chronic medical conditions analyzed predicted not returning home on discharge. After adjustment, odds ratios for not returning home on discharge were: age (2.2/10yrs),

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APACHE II (4.8/10 pts), MV (4.2). Our model was only 60.7% sensitive for predicting this outcome. CONCLUSION: Even if survival could be predicted, routinely available information about chronic medical conditions does not predict which older patients will be unable to return home on discharge. CLINICAL IMPLICATIONS: Assessment of baseline physical and cognitive function may be necessary to more accurately predict functional decline and transfer to other health care facilities following CI. DISCLOSURE: B.K. Gehlbach, None.

EVALUATION OF THE APACHE II SCORING SYSTEM AND HOSPITAL OUTCOMES IN AN INNER CITY HOSPITAL INTENSIVE CARE UNIT Vinette E. Coelho-D’Costa, MD*; Peter Spiro, MD; Samuel DarteyHayford, MD; Javed Iqbal, MD; Harlem Hospital Center / Columbia University College of Phys, New York, NY PURPOSE: A number of physiologic scoring systems have been developed worldwide for estimating outcomes of critically ill patients. Using the Apache II system, we attempted to determine disease severity and outcome of critically ill patients and to assess their relationship to the clinical characteristics of the population admitted to the Medical Intensive Care Unit (MICU). This data was then compared with a similar study done in the same ICU 10 years ago. METHODS: Prospective survey of 60 patients admitted to the MICU at Harlem Hospital over 2 months. The Apache II scores were evaluated at 24 and 48 hours and hospital outcomes were assessed. RESULTS: There were 22(36.6%) females and 38(63.3%) males; Age range 18 –92 yrs(mean 58.2). Five patients(8.3%) had HIV infection and 39(65%) had three or more co-morbidities. The Apache II scores ranged from 4 –36(mean 18.6) at 24hrs, and 0-39(mean 16.8) at 48hrs. The length of ICU stay ranged from 1– 42 days(average 8 days); 46 patients(76.6%) stayed for 10 days or less(average 3.6 days). Eighteen patients(30%) died in the hospital with Apache II scores of 9-39; 23% women and 34% men died. Twelve(20%) deaths occurred in ICU. The Apache II scores of survivors were 0-29. However the average scores of survivors versus(vs)non-survivors were significantly different (Graphic 1): at 24 hours 16.4 vs 24 (p ⫽ 0.0004); at 48 hours 14.5 vs 22.4 (p ⫽ 0.0006). In the similar study done previously in this population, more than 80% had significant co-morbidities; 20% had HIV infection. But the average Apache II scores at 24hrs and 48hrs of survivors vs non-survivors were not significantly different. CONCLUSION: In our patients, Apache II scores of survivors versus non-survivors were significantly different overall. However in individual patients the scores were not always predictive of the outcome. CLINICAL IMPLICATIONS: As the cost of ICU care continues to rise and with the decline of available resources, improving our ability to accurately predict the outcome of critically ill patients is crucial.

APACHE II SCORES OF SURVIVORS VS NONSURVIVORS Survivors At 24 hrs

At 48 hrs

Mean Males Females Mean Males Females

16.4 17 16 14.5 15 14

Non-Survivors

P Value

24 24 25 22.4 20 28

0.0004

0.0006

DISCLOSURE: V.E. Coelho-D’Costa, None.


Wednesday, October 27, 2004 Critical Care Outcomes, continued RESPIRATORY FAILURE: DATA FROM THE PNEUMOSTAR PROJECT Licia Ballerin, MD*; Anna Maria Moretti, MD; Alfredo Potena, MD; Franco Falcone, MD; Carlo Sturani, MD; Walter Arossa, MD; Ciro Rampulla, MD; Giovanna Magni; Carlo Buniolo; AO Universitaria Arcispedale S. Anna, Ferrara, Italy

ACHIEVING HOUSESTAFF COMPETENCE IN EMERGENCY AIRWAY MANAGEMENT: STANDARD TRAINING VERSUS TRAINING USING A COMPUTERIZED PATIENT SIMULATOR Mari Adachi, MD*; M. Rosenthal, DO, MPH; J. Mueck, DO; V. Ribaudo, MD; R. Schneider, MD; Paul Mayo, MD; Beth Israel Medical Center, New York, NY PURPOSE: Airway management is critical to resuscitation. Medical housestaff are initial responders to cardiorespiratory arrest and their competence in airway management is essential. We have previously shown that use of a Computerized Patient Simulator (CPS) is effective at training medical interns in initial airway management skills. These skills could also be acquired during medical residency without formal training through observation and practice in clinical situations. We examine whether this is the case. METHODS: Subjects: 49 new internal medicine interns compared to 30 senior residents in Jul-Aug, 2003. Intervention: Interns were tested and trained using the CPS (SimMan) in initial airway skills. One month later, they were retested to determine training effect. Senior residents who had not received prior CPS training were tested in identical fashion. They had extensive clinical experience including 12 weeks of critical care rotation. Testing with the CPS was done with standard clinical scenario. Initial airway management was divided into specific scorable steps. Performance was scored under video control by two observers. Following testing all senior residents were trained using the CPS. RESULTS: Interns had poor airway management skills before training; these improve following training. Senior residents also had low skill level. Interns who trained using the CPS scored significantly better than senior residents. (See table). CONCLUSION: Two years of clinical experience was insufficient trainig to achieve proficiency in initial airway management. CPS training

Steps Identifies apnea Calls code team Position at head of bed 02 to BVM and on full Inserts oral airway correctly 2 person BVM ventilation Effective BVM seal Attaches pulse oximeter Places towel under head Attaches suction Positions intubation tray

Intern pre training

Intern post training

Senior Resident

N⫽49 42 (86%) 18 (37%) 3 (6%)

N⫽49 48 (98%) 47(96%) 46 (94%)

N⫽30 26 (87%) 15 (50%) 8 (27%)

0

(0%)

40

(82%)

5

(17%)

3

(6%)

44

(90%)

6

(20%)

12

(24%)

45

(92%)

12

(40%)

1

(2%)

45

(92%)

6

(20%)

34

(69%)

44

(90%)

23

(77%)

0

(0%)

33

(67%)

2

(7%)

1 (2%) 13 (27%)

23 (47%) 38 (78%)

2 (7%) 4 (13%)

DISCLOSURE: M. Adachi, None.

DO ERYTHROPOIETIN AND A BLOOD TRANSFUSION GUIDELINE REDUCE THE AMOUNT OF PACKED RED BLOOD CELLS TRANSFUSED IN A MAJOR TEACHING HOSPITAL? Nam T. Ly, MD*; Brian Cuneo, MD; William L. Jackson, MD; Nagla Wahab, PharmD; Linda Gery; Robin Howard; Karen Whitman; Walter Reed Army Medical Center, Washington, DC PURPOSE: Recent literature has suggested that recombinant human erythropoietin alfa (rHuEPO) administered to critically ill patients reduces the number of units of packed red blood cells (PRBCs) transfused in the medical intensive care unit (MICU). We compared the number of units of PRBCs transfused in the MICU before and after the institution of a blood transfusion guideline and subcutaneously administered rHuEPO in critically ill patients in 2003. METHODS: This is a retrospective record review for the years before and after the use of rHuEPO and the blood transfusion guideline. This blood-conservation guideline recommends transfusion of PRBCs at specific hematocrit levels. Patients with a hematocrit of less than 38% and an anticipated stay in the MICU of greater than four days were eligible to receive rHuEPO. The transfusion rate and number of units transfused in the MICU at our institution were reviewed for 2002 and 2003. RESULTS: The transfusion rate was 32.1% in 2002 and 33.2% in 2003 (p⫽0.71) for all patients admitted. The transfusion rate for patients who stayed five days or more were 52.8% in 2002 and 54.0% in 2003. For all patients, the mean number of units transfused per patient day was 0.36 in 2002 and 0.30 in 2003 (p⫽0.84). The mean units transfused per patient day for patients with length-of-stay greater than 4 days was 0.29 in 2002 and 0.29 in 2003 (p⫽0.966). CONCLUSION: The institution of a blood transfusion guideline a major teaching institution, along with the concurrent administration of rHuEPO, did not result in a significant reduction in either the transfusion rate or the blood transfused per patient day. CLINICAL IMPLICATIONS: rHuEPO has been shown to reduce the amount of blood transfused in the critical care setting in previous CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: To characterize the different typologies of Respiratory Failure (RF) in terms of frequency, mean length of stay (LOS), type of discharge, comorbidity, procedures. METHODS: The Italian PneumoSTAR project provides discharge forms (DFs) of patients from respiratory care units since 1999 (236,000 total DFs). Since June 2003, the project focused also on RF, differentiating between Acute RF (ARF), chronic (CRF), acute on chronic RF (ACRF). We examined DFs in the period June-December 2003, reporting RF as principal (PD) or secondary (SD) diagnosis. RESULTS: DFs with RF as PD or SD resulted 3,848 (27.6%): 38.6%-ARF, 28.6%-CRF, 32.8%-ACRF. M/F rate was 1.8; 84.9% was⬎60 years (68.9-ARF, 72.0-CRF, 72.0-ACRF). In 54.2% of cases RF was reported in PD (48.5%-ARF, 54.1%-CRF, 61.1%-ACRF). COPD was the prevalent SD (60.7%): 48.0% with exacerbation, 12.7% without exacerbation. RF was reported in SD in 45.8% (51.5%-ARF, 45.9%-CRF, 38.9%-ACRF); the prevalent PDs were: COPD (18.4%, with exacerbation 17.4%), pneumonia (26.6%). Prevalent procedures were: 32.2% oxygen therapy, 72.1% arterial blood gas-analysis, 16.8% mechanical ventilation, 11.5% non-invasive mechanical ventilation (14.2% for RF in PD, 8%ARF, 10.7%-CRF, 22.7%-ACRF). DRG87 was the prevalent DRG for RF in PD: 91.8%. When RF was in SD the prevalent DRGs were: DRG88 (19.5%), DRG89 (17.0%), DRG92 (13.7%), DRG82 (9.8%), DRG79 (7.2%). The mean LOS was 12.1 (12.1-ARF, 11.3-CRF, 12.9-ACRF) and was significantly lower for RF in PD vs SD: 11.3 vs 13.2 (p⬍0.01). For RF in SD, DRGs 79 and 89 showed a mean LOS significantly higher than DRG88 (15.3 and 12.2 vs 10.5 p⬍0.01). Admission was mainly from emergency department (81.8%). Mortality rate was 7.2% for RF in PD (8.9%-ARF, 4.7%-CRG, 7.5%-ACRF) and 11.2% for RF in SD (15.4%ARF, 6.9%-CRF, 9.2%-ACRF). CONCLUSION: The DFs studied are mainly characterized by chronic, exacerbated pathology. Pneumonia seems to be responsible for a higher LOS, and is more represented in ARF. Nevertheless, further considerations are needed about comorbidity, e.g. COPD. CLINICAL IMPLICATIONS: RF in SD is associated with a higher hospital mortality, specially when it is ARF. DISCLOSURE: L. Ballerin, None.

is a more effective means of training housestaff in initial airway management than standard clinical residency training. CLINICAL IMPLICATIONS: The CPS may be utilized effectively to train internal medicine residents in high-risk, low-frequency events like initial airway management.

Wednesday, October 27, 2004 Critical Care Outcomes, continued clinical trials that excluded many subpopulations. This study, which considered transfusion in all patients, suggests that there may be no difference in the general ICU population. This study has limitations associated with other retrospective non-randomized studies. DISCLOSURE: N.T. Ly, None.

ICU Diagnostics and Therapeutics 12:30 PM - 2:00 PM ROLE OF MAGNESIUM SULFATE IN HYPERTENSIVE ENCEPHALOPATHY Abhijit K. Dam, MD, FCCP*; Jagdish C. Mishra, MD; Bokaro General Hopspital, Bokaro Steel City, India PURPOSE: To assess the effectiveness of intravenously administered MgSO4 as an adjunct to nitroglycerine infusion in hypertensive encephalopathy. METHODS: 18 patients with hypertensive encephalopathy(HE) admitted in the CCU over a period of 3 years. Randomly assigned to two groups viz.Group A(n ⫽ 10): patients with HE receiving MgSO4 as an adjunct to NTG infusionGroup B(n ⫽ 8): patients with HE receiving only NTG infusion for control of BPNTG infusion was started at a dose of 0.5ug/kg/min & gradually titrated up till desired level of BP control was acheived in both the groups. Patients in Group A were given MgSO4 as a 2g I/V bolus when the requirement of NTG infusion was greater than 2ug/kg/min.The end point of therapy was considered to be a 30% reduction in admission mean arterial pressure(MAP) values or to a BP of 160/90mm og Hg, whichever was higher. RESULTS: Patients in Grp.A had a more rapid and smoother control of BP compared to Grp.B. The requirement of NTG infusion was lesser in Grp.A compared to Grp.B.One patient in Grp.B had intracerebral haemorrhage which was diagnosed at 24 hrs. after admission.Patients in Grp.A required lesser amount of sedation for restlessness than in Group B. CONCLUSION: MgSO4 is a useful adjunct to NTG in the acute control of BP in patients with HE. Its use also results in a reduction of the dose of NTG needed.It proably also potentiates the action of sedatives & analgesics. CLINICAL IMPLICATIONS: MgSO4 has documented cerebroprotective effectsalong with its potential to relax smooth muscle. It is also a physiological antagonist of Ca⫹⫹. These properties makes its use in controlling the BP in HE, as an adjuvant to NTG,very useful.Its use in our study was not associated with any serious adverse effects other than to cause flushing & a feeling of warmth on injection. DISCLOSURE: A.K. Dam, None. THE ROLE OF ABDOMINAL COMPUTERIZED TOMOGRAPHY IN THE MEDICAL INTENSIVE CARE UNIT Andrew J. Stiehm, MD*; Bekele Afessa, MD; Mayo Clinic College of Medicine, Rochester, MN PURPOSE: To determine the diagnostic yield and safety of abdominal computerized tomography (CT) in the medical intensive care unit (MICU). METHODS: This retrospective study included 95 MICU patients who received CT for suspected infection. We collected demographics, symptoms, APACHE III score and predicted mortality, selected laboratory data and mortality. CT related findings, their impact on patient management and CT related complications were noted. RESULTS: Mean patient age 64.4 years. Mean admission and CT day APACHE III scores were 82 and 75 with predicted mortality rates of 38.5% and 45%, respectively. Fever was present in 34%, abdominal pain in 59%, nausea/vomiting in 8% and diarrhea 30%. Leukocyte count was elevated in 67%, alkaline phosphatase in 84%, total bilirubin in 57% and lipase in 22%. The main CT findings included colitis 8, gall bladder disease 4, diverticulitis 3, incarcerated hernia 3, pancreatitis 2, bowel perforation 2, bladder distention/obstruction 2. There were management changes based on the CT in 16%. No airway or vascular access loss was documented. The mean PaO2 to FIO2 ratio was 267 and 242, before and after CT respectively (p ⫽ 0.08). The serum creatinine increased over a 3-day period by more than 2 mg/dL in 1 patient and between 1-2 mg/dL

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in 3 patients. The hospital mortality rate was 35%: 33% in patients who had management change compared to 36% in the others (p⫽0.8492). There was no independent association between management change and hospital outcome when adjustment was made for APACHE III predicted mortality. CONCLUSION: Abdominal CT changed patient management in 16%. Management change did not have significant impact on hospital mortality. CT scanning was not associated with any significant adverse patient outcomes including vascular access loss, airway loss, post contrast renal dysfunction or change in arterial oxygenation. CLINICAL IMPLICATIONS: Abdominal CT in selected ICU patients is a safe diagnostic procedure. However, it leads to management changes only in the minority of patients. When it leads to management changes mortality outcomes are not significantly effected. DISCLOSURE: A.J. Stiehm, None.

EARLY HIGH ANION GAP METABOLIC ACIDOSIS IN PATIENTS WITH ACETAMINOPHEN OVERDOSE: CLINICAL SIGNIFICANCE Joe Zein, MD*; Christine Kakoulas, MD; Nagib Toubia, MD; Gary Kinasewitz, MD; The University of Oklahoma, Health Sciences Center, Oklahoma City, OK PURPOSE: Acetaminophen (APAP) overdose can cause metabolic acidosis and coma before overt hepatic injury. We sought to determine the incidence and clinical significance of early high (⬎15) anion gap metabolic acidosis (EHAGMA)in patients with APAP overdoses. METHODS: We identified 145 patients (⬎14 years) presenting within 24 hours of APAP overdose to OUHSC or Saint Vincent’s Hospital of NY from January 1998 until November 2003 by review of hospital discharge logs. We excluded 69 with polysubstance overdose. Clinical characteristics and outcome were determined by review of the medical record. Data are presented as mean ⫾ SEM. Comparisons between groups were done using the Student t-Test for continuous variables. Categorical variables were compared using the Pearson chi-square test. A p value ⬍0.05 was considered statistically significant. RESULTS: Most patients (81%) presented within 15 hours of ingestion. Vital signs were stable. APAP level at 4 hours was 194⫾9 mg/ml. EHAGMA was present in 41% of patients on admission and persisted for 1.5⫾0.1 days. The lactate level increased in proportion to the acetaminophen concentration (r ⫽0.86, p⬍0.05). The AG was associated with an elevated lactate level (4.5⫾1 mmol/L) (r ⫽0.82, p⬍ 0.05), which persisted for 1 day. Patients with increased AG had a higher incidence of confusion (48%vs.3%; p⬍0.001) and lethargy (39%vs.6%; p⫽0.003) EHAGMA was found in the absence of shock or liver failure. Gender, vital signs, glucose, peak AST, ALT, bilirubin, creatinine, and PT were similar in the normal and high AG groups. All patients were treated with N-acetylcysteine and despite the EHAGMA, no patient developed hepatic failure. Patients were discharged after 3.6⫾0.2 days. The highest AST and ALT values were found in patients where therapy was delayed (⬎24 hours). CONCLUSION: EHAGMA is frequently seen in acetaminophen overdose and is probably related to impaired mitochondrial function. CLINICAL IMPLICATIONS: Acetaminophen poisoning should be considered in the differential diagnosis of metabolic acidosis of unknown etiology. EHGMA has minimal impact on outcome, and does not predict liver failure probably because of the effective therapy available with N-acetylcysteine.

Variable Ingested dose (gm) HCO3-day 1 (mEq/ L) HCO3-day 3 (mEq/ L) ALT-max (U/L) PT-max (sec) Hospital LOS (days)

High AG n⫽30

Normal AG n⫽44

P Value

12.9⫾1.2 19.4⫾0.6

10.1⫾0.95 23.4⫾0.4

0.16 0.001

24.1⫾0.6

24.4⫾0.5

0.7

198⫾94 12.8⫾0.4 3.8⫾0.3

112⫾32 12.6⫾0.2 3.5⫾0.2

0.32 0.7 0.4

DISCLOSURE: J. Zein, None.


Wednesday, October 27, 2004 ICU Diagnostics and Therapeutics, continued PROGNOSTIC SIGNIFICANCE OF ELEVATED SERUM LACTATE DEHYDROGENASE (LDH) IN PATIENTS WITH SEVERE SEPSIS Joe G. Zein, MD*; Gregory L. Lee, RN; Maroun Tawk, MD; Mohammed Dabaja, MD; Gary T. Kinasewitz, MD; The University of Oklahoma, Health Sciences Center, Oklahoma City, OK

Variable MODS APACHE II HCO3 (mEq/L) SGOT (U/L) CK (␮mol/L) Platelets x103 Lactate (mmol/L) Creatinine (mg/dl)

Normal LDH (n ⫽ 17)

High LDH (n ⫽ 65)

P Value

6.75 ⫾ 0.9 23 ⫾ 2.2 23.5 ⫾ 1.9 36 ⫾ 8 96 ⫾ 31 257 ⫾ 27 2.1 ⫾ 0.3 2.4 ⫾ 0.8

9.2 ⫾ 0.4 27 ⫾ 0.8 18.7 ⫾ 0.9 197 ⫾ 52 997 ⫾ 157 180 ⫾ 14 4.1 ⫾ 0.6 2.9 ⫾ 0.4

0.02 0.05 0.012 0.001 0.04 0.004 0.03 0.03

DISCLOSURE: J.G. Zein, None. CENTRAL VENOUS PRESSURE FROM PERIPHERALLY INSERTED CENTRAL CATHETERS CORRELATES WELL WITH THAT OF CENTRALLY INSERTED CENTRAL CATHETERS Mariam Alansari, MD, FRCSI; Mohammed Hijazi, MD, FCCP*; KFSH RC, Riyadh, Saudi Arabia PURPOSE: To compare CVP measured by CICCs through the distal port of a triple lumen catheter size ; with the transducer at the level of the heart; with CVP measured via distal port of the PICCs with transducer level at – 4, -2, 0, ⫹2, and ⫹4 from heart. METHODS: Measurements of central venous pressure were recorded from patients who had an indwelling CICC and PICC concomitantly. Pressure measurements were taken from 18-gauge dual-lumen PICCs and from 16-gauge CICCs all with continuous pressure infusion devices. Central venous pressure measurements, using a pressure infusion device to overcome the natural resistance of the PICC, were taken from both the

Table 1 Rc values in the 20 patients Measurements Peripherally Inserted heart level Peripherally Inserted heart level Peripherally Inserted Peripherally Inserted heart level Peripherally Inserted heart level

RC

Central Catheter at 4 cm above the

0.906

Central Catheter at 2 cm above the

0.972

Central Catheter Central Catheter at 2 cm below the

0.992 0.941

Central Catheter at 4 cm below the

0.834

Table 2 Rc values in the subgroup of patients (femoral acess vs neck lines)

Femoral lines

IJ and SC lines*

at

0.8961

0.9239

at

0.9673

0.9822

at

0.9922 0.9393

0.9935 0.9515

at

0.8326

0.8442

Measurements Peripherally Inserted Central Catheter 4 cm above the heart level Peripherally Inserted Central Catheter 2 cm above the heart level Peripherally Inserted Central Catheter Peripherally Inserted Central Catheter 2 cm below the heart level Peripherally Inserted Central Catheter 4 cm below the heart level IJ ⫽ intrnal jugular SC ⫽ SubClavian DISCLOSURE: M. Hijazi, None.

ASSESSMENT OF GLYCEMIC CONTROL IN CRITICAL ILLNESS USING A CONTINUOUS GLUCOSE MONITORING SYSTEM Mary Jo S. Farmer, MD*; Hardy Kornfeld, MD; UMass Memorial Medical Center, Worcester, MA PURPOSE: The importance of intensive insulin therapy in critical illness has been widey accepted since Van den Berghe (2001) demonCHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Elevated serum levels of the intracellular enzyme LDH in sepsis might result from various mechanisms including cellular injury related to bacterial toxins, ischemia and cytotoxic-reactive oxygen species generated during reperfusion. The clinical and prognostic significance of elevated LDH in severe sepsis remains to be defined. We hypothesized that increased LDH in patients with severe sepsis and septic shock would reflect the extent of tissue injury and be associated with a worse prognosis. METHODS: Clinical data and outcome variables were extracted from the medical records of 82 adult patients admitted to the intensive care unit at the University of Oklahoma, Health Sciences Center or the Oklahoma City VA medical center with severe sepsis, for whom informed consent was obtained. Data are presented as mean ⫾ SEM. Comparisons between groups were done using the Student t-test for continuous variables. Categorical variables were compared using the Pearson chi-square test. A p value ⬍0.05 was considered statistically significant. RESULTS: The LDH level was elevated in 65 patient (79%) on admission. Increased LDH was associated with more physiologic abnormalities (higher APACHE II score), and organ failure (higher MODS score), and a higher lactic acid, SGOT, creatine kinase, creatinine, and lower platelet count and plasma bicarbonate level (p⬍0.05) (Table -1). There was significant correlation between LDH and lactic acid levels (r ⫽0.76; p⬍0.01), and between LDH and MODS score(r ⫽0.6; p⬍0.01). Death was associated with a higher LDH level (656⫾79; p⬍0.001 vs. 369⫾72 U/L). LDH levels that are increasing 48 hours after ICU admission(observed in 37 of 82 patients) were sensitive (0.72) and specific (0.77) in predicting mortality. CONCLUSION: Increased plasma LDH levels are commonly seen in patients with severe sepsis. It is a marker of cell injury which reflects the degree of tissue damage. CLINICAL IMPLICATIONS: Failure to improve LDH levels at 48 hours is a strong predictor of mortality in patients with severe sepsis.

CICC and the PICC at the level of the heart simultaneously. Two more readings were taken from the PICC, both at 2 and 4 cm above and below the heart respectively. This cycle was repeated 6 times in each patient. Measurements were recorded at end-expiration. RESULTS: 120 pairs of CVP readings were obtained from 20 paients. Among these, 12 had femoral access and 8 were mixed between internal jugular and subclavian.For measuring and comparing the agreement between CVP from CICC and CVP FROM PICC , concordence correlation (Rc) was calculated. The Rc was 0.99 at the level of the heart (Rc value between 0.9-1, means substantial agreement). See the table below. CONCLUSION: Central venous pressure measured through a peripherally inserted central catheter at the level of the heart had substantial agreement with central venous pressure measured through centrally inserted central catheter, at the same level. This applies to femoral internal jagular and subclavian access. CLINICAL IMPLICATIONS: Measuring CVP from PICCs is possible without subjecting the patient to invasive procedures.With an additional benefit of central venous pressure monitoring from PICCs, more institutions may adopt increasing use of PICCs in acute settings. Nurse led PICC line insertion was found to be successful, which would be of great help in decreasing the work load on physician in intensive care units.

Wednesday, October 27, 2004 ICU Diagnostics and Therapeutics, continued strated that maintaining blood glucose ⱕ 110 mg/dl reduced morbidity and mortality in SICU patients. We assessed glycemic control achieved with a simplified insulin infusion protocol using a Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed) in an MICU. METHODS: Therapy was initiated with regular insulin bolus followed by continuous insulin infusion titrated according to a standard protocol with a target glucose of 80 - 110 mg/dl. Traditional monitoring included morning laboratory blood glucose measurements plus glucometer measurements every 2 - 4 hours. The CGMS sampled interstitial fluid, recording glucose values every 5 minutes for 72 hours. Data analysis focused on the number of excursions and percentage of time above or below the target range. Factors contributing to periods of hypo- and hyper-glycemia were identified. RESULTS: Fifty patients were studied, yielding ⬃35,000 CGMS glucose readings. Overall, only 50% of values were in the target range. Patients could be stratified retrospectively into those with predominantly tight control and those with poor control. Factors contributing to poor glycemic control included elevated blood glucose on admission, corticosteroids and antibiotic therapy, gastroparesis, prior history of diabetes, interruption of enteral tube feeding, bacteremia, and multiple organ involvement as reflected by elevated serum creatinine and liver enzyme studies. CONCLUSION: Tight glycemic control in MICU patients is desirable but difficult to achieve in clinical practice. We evaluated the implementation of a simplified insulin infusion protocol feasible for general use. Retrospective analysis of CGMS data identified patient characteristics associated with poor control. These data may permit the prospective identification of patients requiring more intensive monitoring, and will contribute to the development of more effective infusion strategies specifically targeted to this population. CLINICAL IMPLICATIONS: Continuous glucose monitoring data is helpful in achieving tight glycemic control in MICU patients. DISCLOSURE: M.S. Farmer, None.

USE OF THE ESOPHAGEAL DOPPLER AND SUBLINGUAL CAPNOMETER IN THE HEMODYNAMIC ASSESSMENT OF MECHANICALLY VENTILATED SURGICAL PATIENTS Gene Grindlinger, MD; Salman Ahmad, MD*; Steven Desjardins, RRT; Maine Medical Center, Portland, ME PURPOSE: Circulatory failure in the critically ill is difficult to assess with the pulmonary artery catheter (PAC). Criticism of this technology has focused on erroneous interpretation of PAC measurement especially in mechanically ventilated patients. The Esophageal Doppler (ED) has emerged as a potential alternative to the PAC. Sublingual Capnometry (SC) allows assessment of end-organ perfusion and therefore provides additional information about circulatory failure. METHODS: The ED was placed in 28 mechanically ventilated patients with PAC in place. A total of 54 simultaneous ED, PAC and SC measurements were obtained. Arterial blood gases (ABG) were measured concurrently. Hemodynamics, mixed venous oxygen saturation (SvO2), serum lactate and ventilator mode settings were recorded. The Pearson correlation was used to compare measurements. Significance was defined as a p value ⬍ 0.05. RESULTS: PAC cardiac output and ED correlated well (r⫽0.71, p⬍0.001) as did cardiac index (r⫽0.77, p⬍0.001). ED corrected flow time, a measure of LV filling volume, correlated with PAC cardiac index (r⫽0.83, p⬍0.001). While the Pulmonary Artery Wedge Pressure (PAWP) correlated with the End-Diastolic Volume Index (EDVI) (r⫽0.61, p⬍0.05), it did not vary with PAC cardiac index (r⫽0.19, p⬎0.1) as would be predicted by the Starling mechanism. Similarly, the EDVI did not predict the PAC cardiac index (r⫽-0.12, p⬎0.1). As a marker of end-organ perfusion, the difference between the SC PCO2 and arterial PCO2 (PCO2 gap) correlated with the SvO2 (r⫽-0.49, p⬍0.05) but not with serum lactate (r⫽0.20, p⬎0.05). The serum lactate did not vary with the PAC cardiac index (r⫽-0.34, p⬎0.05). The PCO2 gap had the expected inverse correlation with PAC cardiac index (r⫽-0.68, p⬍0.01) as did the SvO2 (r⫽-0.63, p⬍0.01). CONCLUSION: The ED provides a fast alternative to the PAC and may obviates the technical limitation imposed by fluctuating intrathoracic pressures. The SC appears to track end-organ perfusion more predictably than serum lactate.

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CLINICAL IMPLICATIONS: The ED and SC may be effectively substituted for the PAC and other measures of end-organ perfusion in some critically ill patients. DISCLOSURE: S. Ahmad, None. UTILIZATION OF PERIPHERALLY INSERTED CENTRAL CATHETERS (PICC) FOR MONITORING CENTRAL VENOUS PRESSURES Marie K. Arnone, MS*; Swedish Medical Center-Providence Campus, Seattle, WA PURPOSE: To determine if peripherally inserted central catheters are a viable alternative to physician inserted central lines for monitoring of central venous pressures in the intensive care setting (ICU. METHODS: Simultaneous hard copy recordings of central venous pressure by physician inserted central lnes and PICC lines inserted by specially trained RN’s were studied for reliability and simularity of tracings. Comparison of waveform analysis and numerical value of both catheters was performed on all subjects in the study. RESULTS: Limited study of intensive care patients showed no difference in numerical value or hard copy waveform alanysis. CONCLUSION: PICC lines can be used to monitro central venous pressures in critically ill patients in the ICU setting. CLINICAL IMPLICATIONS: PICC lines have a lower incidence of infection than central venous catheters and may stay safely incerted for longer periods, this would decrease the risk of nosocomial infections. PICC lines as an alternative for short term monitoring of central venous pressure would decrease hospital costs and provide accurate information regarding the patient’s volume status. DISCLOSURE: M.K. Arnone, None. NON-INVASIVE MONITORING OF CYANIDE TOXICITY USING DIFFUSE OPTICAL SPECTROSCOPY IN A RABBIT MODEL Jennifer Armstrong, BA*; Jangwoen Lee, PhD; Andrew Duke, MD; Hamza Beydoun, BS; Kelly Kreuter, BS; Tom Waddington, MD; Bruce Tromberg, PhD; Mattew Brenner, MD; University California, Irvine, Irvine, CA PURPOSE: Currently, there are no reliable non-invasive methods for monitoring the severity of in-vivo cyanide (CN) toxicity and concurrent physiological changes. Broadband diffuse optical spectroscopy (DOS) is theoretically an ideal diagnostic technique to monitor a range of pathologic conditions. DOS allows quantitative analysis of tissue chromophore concentrations such as oxyhemoglobin, deoxyhemoglobin, methemoglobin, water, and lipid. We developed an in-vivo broadband DOS prototype system that combines multi-frequency domain photon migration (FDPM) with timeindependent near infrared (NIR) spectroscopy to accurately measure bulk tissue absorption and scattering spectra between 600 nm and 1000 nm. In this study the DOS prototype was used to monitor cyanide toxicity by quantifying the redox state changes of cytochrome-c oxidase, (since the redox state of cytochrome-c has a distinguishable absorption spectrum) in an animal model to test the feasibility of this concept.


Wednesday, October 27, 2004 ICU Diagnostics and Therapeutics, continued CORRELATION BETWEEN HEAD COMPUTED TOMOGRAPHY SCANS AND THE NEUROLOGICAL EXAM IN THE MEDICAL INTENSIVE CARE UNIT (MICU) Raymonde Jean, MD; Amir Harandi, MD*; Erin Sullivan, MD; Sameer Mahesh, MD; Sripal Bangalore, MD; Leo Polosajian, MD; St. Luke’sRoosevelt Hosptial Center, New York, NY

DISCLOSURE: A. Harandi, None.

EXTRACORPOREAL LIFE SUPPORT (ECLS) FOR ARDS CAUSED BY SEVERE PNEUMONITIS Robert H. Bartlett, MD*; Mark R. Hemmila, MD; Fresca C. Swaniker, MD; Jonathan W. Haft, MD; Ronald B. Hirschl, MD; Stephen A. Rowe, MD; University of Michigan Medical Center, Ann Arbor, MI PURPOSE: To report a single center experience with ECLS for severe ARDS pathophysiology caused by pneumonitis. METHODS: ECLS (ECMO) supports cardiac and pulmonary function in the absence of native organ function allowing time for treatment of primary pulmonary disease. Between 1990 and 2003 we treated 132 moribund patients with ECLS. Patient characteristics AaDO2 612, shunt fraction 55%, P/F rtio 54, all despite and after optimal treatment (3.8 ventilator days). Average time on ECLS was 9 days. Septic shock and multiple-organ failure were common complications. RESULTS: The cause of pneumonia, numbers of patients, and hospital discharge survival was: bacterial N79, 57%; viral N33, 55%; aspiration N13, 62%; fungal N7, 29%; overall cases N132, 55% survival. CONCLUSION: Extracorporeal life support resulted in recovery and survival in 55% of 132 patients with overwhelming pneumonitis. CLINICAL IMPLICATIONS: ECLS should be considered in patients with high mortality risk from pneumonitis. DISCLOSURE: R.H. Bartlett, None.

CONCORDANCE OF THE ACTIVATED PARTIAL THROMBOPLASTIN TIME AND THE ANTI-ACTIVATED FACTOR X ASSAY IN MONITORING UNFRACTIONATED HEPARIN THERAPY IN CRITICALLY ILL PATIENTS Jonathan A. Rettmann, MD*; Boaz A. Markewitz, MD, FCCP; Lori Wilson, MS, MT; Jeanmarie Mayer, MD; Christopher M. Lehman, MD; University of Utah Health Sciences Center, Salt Lake City, UT PURPOSE: The ideal method for monitoring unfractionated heparin (UH) therapy is unknown. The activated partial thromboplastin time (aPTT) does not measure a heparin level, but rather its ex-vivo “physiologic” response. The anti-activated factor X (Xa) assay measures heparin levels indirectly, and is considered the “gold standard” to which laboratories reference their aPTT therapeutic ranges. Critically ill patients have alterations in the level of multiple proteins theorized to lower the accuracy of the aPTT. Anti-Xa assays are recommended for monitoring of UH therapy in several clinical situations, but there is little information on its use in the intensive care unit (ICU). We sought to determine the concordance between the aPTT and an anti-Xa assay in ICU patients receiving UH. METHODS: Prospective evaluation of forty-one consecutive ICU patients receiving continuous UH infusions. Blood samples drawn to monitor UH therapy had both an aPTT and an anti-Xa level measured. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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METHODS: New Zealand White rabbits (NZW) were used in this study. The DOS prototype probe was placed on the inner thigh muscle of the hind leg. After Sodium Cyanide solution of 2mg increments were injected into ear venous line, the systemic blood pressure, arterial, and venous blood gases were monitored. Blood samples were taken to assess the blood cyanide level. RESULTS: Broadband DOS measurements of tissue hemoglobin (Hb), Oxyhemoglobin (HbO2), water, and, cytochrome c oxidase redox state changes are shown in the below figures. In Figure (a), the reduced state of cytochrome-c increased after CN was injected. In Fig. (b), the changes in cytochrome-c redox state correlated with increasing doses of injected CN. CONCLUSION: Broadband DOS has far greater spectral capacity compared to current non-invasive optical spectroscopic modalities. We have demonstrated the feasibility of broadband DOS in-vivo as a monitoring technique for cyanide toxicity using its full spectral capacity and distinct absorption spectrum of cytochrome c oxidase redox state difference. CLINICAL IMPLICATIONS: Non-invasive in vivo monitoring capability of broadband DOS may be a useful advance for monitoring not only in cyanide toxicity but also mitochondrial diseases associated with cytochrome oxidase functions. DISCLOSURE: J. Armstrong, None.

PURPOSE: To identify clinical indicators that assist in predicting acute abnormalities on head computed tomography (CT) scans in patients with altered mental status in the MICU. METHODS: This is a retrospective study of 100 patients admitted to the MICU between January 2001 and March 2002. Patients who developed altered mental status 48 hours or more after admission and subsequently had a head CT scan were reviewed. Data abstracted from the medical records were used to investigate the association between abnormal head CT scans and factors such as patients’ demographics, medical history, admitting diagnosis, length of stay, laboratory abnormalities (white blood cell count, coagulation profile, ammonia levels, blood urea nitrogen and creatinine), sedation, and focal neurological deficits. RESULTS: Head CT scans were positive for acute abnormalities in 29% (29/100) of patients. Univariate analysis revealed age ⬎ 65 years (p⫽0.015), presence of a neurological deficit on physical examination (p⬍0.0001, and a history of myocardial infarction (p⫽0.030) as positive predictors for an abnormal head CT scan. Multivariate (Logistic Regression) analysis confirmed that age greater than 65 years (p⫽0.007; OR⫽9.9, 95% CI⫽1.9-52.2) and an abnormal neurological exam (p⬍0.0001; OR⫽21.0, 95% CI⫽4.1-106.6) as strong predictors for a positive head CT scan. The presence of a neurological deficit had a sensitivity of 59.7%, specificity of 87.9%, positive predictive value (PPV) of 66%, and a negative predictive value (NPV) of 84.9%. CONCLUSION: In patients admitted to the MICU, who subsequently developed altered mental status, age greater than 65 years and a focal neurological deficit on physical examination were strong predictors for an abnormal head CT scan. CLINICAL IMPLICATIONS: Older age and presence of a neurological exam are positive predictors of an abnormal head CT scan in critically ill patients.

Wednesday, October 27, 2004 ICU Diagnostics and Therapeutics, continued

Thromboembolic Disease: Diagnosis, Risk Groups, and Treatment 12:30 PM - 2:00 PM

Our laboratory’s therapeutic aPTT during the time of the study was defined as 56-94 seconds. The therapeutic anti-Xa level was defined as 0.3-0.6 U/mL. RESULTS: A total of 273 simultaneous aPTTs and anti-Xa levels were analyzed. The aPTT and anti-Xa level were in agreement (i.e. both in therapeutic or both out of therapeutic range) only 50.9%. The measure of agreement beyond the amount expected by chance alone, determined by the Kappa statistical test, was poor (k⫽0.24). CONCLUSION: The concordance of the aPTT and an anti-Xa assay in determining if critically ill patients receiving UH are in the therapeutic range is extremely poor. CLINICAL IMPLICATIONS: Although, anti-Xa assays are considered the gold standard, the paucity of clinical outcomes data using the anti-Xa for monitoring of UH therapy in critically ill patients, combined with the poor concordance with the aPTT (for which there are clinical outcomes data) prevents us from recommending routine anti-Xa monitoring of critically ill patients receiving UH therapy at this time. DISCLOSURE: J.A. Rettmann, None.

THE INCIDENCE AND PROPHYLAXIS OF VENOUS THROMBOEMBOLISM IN A COMMUNITY INTENSIVE CARE UNIT John G. Muscedere, MD*; Louise Roberts, RN; Julie Trpkovski, RN; Carol Diemer, RN; Deborah Cook, MD; Hotel-Dieu Grace Hospital, Windsor, ON, Canada

INTRAVITAL MICROSCOPY DEMONSTRATES HYPOXIA AND IRON CHELATION SHARE MICROVASCULAR RESPONSES BUT NOT GENERATION OF FREE RADICALS Sonja D. Bartolome, MD*; Amy R. O’Brien-Ladner, MD; A. J. Casillan; John G. Wood, PhD; University of Kansas School of Medicine, Kansas City, KS PURPOSE: The program of genes induced by hypoxia appears, at least in part, to be shared by that induced by Deferoxamine (DFA), a chelator of iron. A number of these genes are integral to the regulation of the microvasculature and may have a protective role against continued hypoxia-related injury. In order to develop therapeutic targets for these advantageous effects, we sought to identify which physiologic responses are shared at the microvascular level. METHODS: To characterize the microvascular response to DFA exposure, 4 rat groups were utilized: saline control, DFA (7.1mg/hr/kg 6h), DFA/a´ -lipoic acid (an antioxidant), and hypoxia (10% FiO2 4h). Measurements of leukocyte adherence (# per 100mm venule), capillary leak by fluorescein isothiacyanate-labeled albumin (Fi/Fo), and generation of ROS (reactive oxygen species) by DHR fluorescence (an oxidantsensitive probe [% control]), were performed during intravital microscopy of the rat mesenteric venular bed. RESULTS: Results: (⫹- SEM). CONCLUSION: DFA infusion and hypoxia regulate capillary leak and white blood cell adherence at similar levels. However, in contrast to hypoxia, the generation of ROS was not detectable above normoxia in the DFA groups. In addition, the microvascular responses in the DFA group were not inhibited by an antioxidant (a´ -lipoic acid). In conclusion, although DFA and hypoxia appear to regulate microvascular responses similarly, our experiments do not elucidate ROS-related mechanisms in common. Additional experiments are underway to fully characterize the unique aspects of iron chelation-related signaling. CLINICAL IMPLICATIONS: This may have particular importance in developing protective strategies during hypoxia.

Normoxia Hypoxia DFA DFA ⫹ alpha-lipoic acid

ROS

Capillary Leak

WBC Adherence

100 182⫹- 16 107⫹-3.1 106⫹-6.2

.14⫹-.04 .82⫹-.14 .71⫹-.10 .91⫹-.07

0.4⫹-0.1 14.5⫹-1.2 12.7⫹-2.0 8.7⫹-2.2

DISCLOSURE: S.D. Bartolome, None.

PURPOSE: Venous thrombo-embolism (VTE) can be a life threatening complication of critical illness. Screening studies have demonstrated high rates of VTE in the ICU. There is little information on the rates of clinically diagnosed VTE and there is even less information on VTE rates in community ICU’s. The clinical diagnosis of VTE is problematic in the ICU since the signs and symptoms of VTE may be absent. Most studies of VTE have been done in teaching centers and the generalisability to community ICU’s is questionable. The purpose of this study was to study the incidence of clinically diagnosed VTE and thromboprophylaxis in a tertiary community ICU. METHODS: In a tertiary care medical, surgical, trauma and neurosurgical community ICU we conducted a retrospective chart review, identifying 600 consecutive, adult admissions who were admitted to the ICU ⬎ 48 hours, without an admission diagnosis of VTE, between January 2001 and December 2002. The primary endpoints were: VTE events, VTE diagnostic studies and prophylaxis regimens. The charts were reviewed for the whole hospital stay. RESULTS: Patient characteristics were as follows: Age 59.5 ⫾ 0.7 years, Apache II score 17.0 ⫾0.3, ICU LOS 9.3 ⫾0.3 days and overall hospital mortality rate was 22.2%. The total VTE rate (ICU ⫹ hospital) was 8.3% (ICU 3.0%, hosp 5.7%). The VTE rates varied dramatically between diagnostic catagories. For medical/surgical patients the rate was 4.8% (ICU 2.6%, hosp. 2.5%), for trauma patients 6.1% (ICU 3.0%, hosp. 3.2%), for neurosurgical patients 18.2% (ICU 4.1%, hosp. 15.3%). See table for thromboprophylaxis regimens and rates. CONCLUSION: Among critically ill patients, VTE risk a) is significant b) varies depending on the ICU population c) occurs despite thromboprophylaxis and d) continues as critical illness resolves and thromboprohylaxis rates drop. Further research on the diagnosis of VTE and better thromboprophylaxis regimens are neeeded. CLINICAL IMPLICATIONS: VTE remains a significant problem in critically ill patients, occuring despite thromboprophylaxis. Increased attention to prevention is needed in the ICU, as well as after ICU discharge.

LDUH (Low LMWH (Low Mechanical Prophylaxis (% Dose molecular (pneumatic of days with Unfractionated weight compression prophylaxis) Heparin) heparin) stockings) ICU (all patients) Ward (all patients) ICU (Medsurgical patients) Ward (Medsurgical patients) ICU (Neurosurgical patients) Ward (Neurosurgical patients) ICU (Trauma patients) Ward (Trauma patients)

Total

11.2⫾1.1

42.1⫾1.7

34.3⫾2.3 87.6⫾3.1

14.4⫾1.4

41.9⫾1.9

3.5⫾0.6 59.8⫾2.4

58.0⫾2.0

10.3⫾1.3

17.6⫾1.7 85.9⫾2.9

50.6⫾2.4

9.4⫾1.4

1.3⫾0.5 61.3⫾3.2

9.9⫾1.8

5.8⫾1.5

71.0⫾2.8 86.7⫾3.7

26.4⫾3.3

15.9⫾2.9

10.3⫾2.0 52.6⫾4.8

20.9⫾3.9

26.5⫾4.5

23.6⫾4.4 71.0⫾7.4

27.0⫾5.2

37.9⫾5.6

1.8⫾1.1 66.7⫾7.7

DISCLOSURE: J.G. Muscedere, None.

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Wednesday, October 27, 2004 Thromboembolic Disease: Diagnosis, Risk Groups, and Treatment, continued A PROBABILISTIC APPROACH TO THE DIAGNOSIS OF DEEP VENOUS THROMBOSIS IN HOSPITALIZED PATIENTS Nicola Mumoli, MD*; Marco Cei, MD; Alberto Busoni, MD; Franco Papini, MD; Emergency Medicine Department, Livorno, Italy

CAUSES OF PULMONARY INFARCTIONS: ANALYSIS OF 43 SURGICALLY RESECTED CASES Joseph G. Parambil, MD*; Mayo Clinic, Rochester, MN PURPOSE: To identify potential causes of pulmonary infarcts, we identified 43 such cases diagnosed by surgical lung biopsy over a period of seven years, January 1996 through December 2002. METHODS: Patients with pulmonary infarctions diagnosed by surgical lung biopsy at Mayo Medical Center, Rochester, MN were identified by a computer-assisted search of medical records. RESULTS: For the purpose of identifying potential causes of pulmonary infarcts, we identified 43 such cases diagnosed by surgical lung biopsy over a period of seven years, January 1996 through December 2002. Histopathologic changes of pulmonary infarction were identified in the resected lung specimen in all cases. The median age of these patients was 55 years (range 22 years to 85 years); 17 (40%) were women and 26 (60%) were men. Thirty-five patients (81%) had a smoking history. An underlying malignancy was present in 17 patients (40%). The underlying causes were identifiable in 32 cases (74%) based on review of clinical, laboratory, radiologic and histopathologic data. These causes included pulmonary thromboembolism in 17 cases (40%), pulmonary infection in 6 cases (14%), non-infectious inflammatory lung disease in 4 cases (9%), pulmonary torsion in 2 cases (5%), iatrogenic causes in 2 cases (5%), and tumor embolism in 1 case (2%). In 11 cases (26%), the underlying causes were not directly identifiable but were probably due to previous pulmonary thromboembolism. CONCLUSION: We conclude that although pulmonary thromboembolism is the commonest cause of pulmonary infarction, a variety of other causes exist including angioinvasive infections, infective endocarditis, inflammatory lung diseases, pulmonary torsion, tumor or foreign body embolism, and pulmonary artery catheter deployment. CLINICAL IMPLICATIONS: Although pulmonary thromboembolism is the commonest cause of pulmonary infarction a thorough review of clinical, laboratory, radiologic and histopathologic data is required to identify other potential causes. Based on our data we also feel that

A USEFUL CLINICAL MODEL TO PREDICT PULMONARY EMBOLISM AMONG PATIENTS WITH ACUTE DYSPNEA Ju-Yi P. Chen, MD*; Ting-Hsing Chao, MD; Yueliang L. Guo, MD, MPH; Chih-Hsin Hsu, MD; Yao-Yi Huang, MD; Jyh-Hong Chen, MD, PhD; Li-Jen Lin, MD; National Cheng Kung University Medical Center, Tainan, Taiwan ROC PURPOSE: Developing a simple clinical prediction of pulmonary embolism (PE) among patients with acute dyspnea in the emergency room. METHODS: Fifty-six patients with diagnosis of PE and 92 consecutive patients without PE, both presented with acute dyspnea in emergency room, were enrolled in this study. Primary physicians in emergency room assessed the initial evaluation and interpretation of various laboratory findings. Some significantly independent predictors of PE were identified and integrated to a clinical model of pretest probability. The probability was categorized as low (⬍30%), intermediate (⬎30%, ⬍70%), and high (⬎70%). RESULTS: Clinical parameters associated with increased likelihood of PE were female, unilateral low leg edema, high alveolar-arterial oxygen gradient, clear chest roentgenogram, and electrocardiographic findings of right ventricular strain. On the other hand, variables associated with decreased likelihood of PE included cough, chest tightness, and unclear breathing sound. 95% of patients with PE were categorized into high or low probability based on our clinical model. The positive predictive value for high probability and negative predictive value for low probability were 94.1% and 94.4%, respectively. Less than 5% patients were fit in the intermediate probability group. CONCLUSION: This simple and easily available prediction model was useful in estimating the pretest probability of PE in this clinical setting. CLINICAL IMPLICATIONS: This simple and easily available prediction model was useful in estimating the pretest probability of PE in this clinical setting. DISCLOSURE: J.P. Chen, None. THE ROLE OF ECHOCARDIOGRAM IN THE MANAGEMENT OF NORMOTENSIVE PATIENTS WITH PULMONARY EMBOLISM Rammohan Gumpeni, MD, FCCP; Debasish Roychoudhury, MD; Thu Yein, MD*; The New York Hospital Queens, Weill Medical College at Corne, Flushing, NY PURPOSE: To evaluate short-term prognosis of normotensive patients with pulmonary embolism diagnosed by spiral CT and RV dysfunction by echocardiogram. Prognostic value of RV dysfunction in this group of patients is not fully evaluated. METHODS: Retrospective medical record analysis was performed in patients with documented PE and echocardiogram. Total of 21 patients met the inclusion criteria. Patient’s data include symptoms, vital signs, clinical history, ABG’s, EKG, CXR and spiral CT. Echocardiograms were reviewed by a cardiologist. Patients with one or more of the following criteria were considered to have acute RV dysfunction (1) RV dilatation (RVEDD⬎30 mm or RV/LV end-diastolic diameter ratio ⬎1 in fourchamber view) (2) septal flattening and paradoxical septal motion (3) McConnell’s sign (normokinesis or hyperkinesis of RV apex with right ventricular free wall hypokinesis) (4) pulmonary arterial hypertension detected with tricuspid regurgitation jet (5) RVOT acceleration time value of ⬍60 msecs in presence of TR pressure gradient ⬍60 mmHg (60/60 sign) (6) Patent foramen ovale (7) direct visualization of thrombus. RESULTS: RV/LV end-diastolic diameter ratio ⬎1 in four-chamber view positive in 18 patients (85.7%), septal flattening and paradoxical motion positive in 17 patients (80.9%) and McConnell’s sign positive in 15 patients (71.4%). Average pulmonary arterial pressure 53.1 mmHg and average RVEDD 4.6 cm. Patent foramen ovale was found in 3 patients (14.2%), thrombus was visualized in 3 patients (14.2%) and 60/60 sign positive in 1 patient (4.7%). 17 patients received heparin or enoxaparin with wafarin, 2 patients received heparin with IVC filter and 2 patients received heparin, wafarin and IVC filter. There were 4 deaths in the group who met at least five echocardiographic criteria. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Although clinical diagnosis of deep-vein thrombosis (DVT) has been regarded as equivocal, the use of symptoms scores may increase the probability of instrumental confirmation and help the clinician in therapeutic decisions, expecially when a compression ultrasound scanning is not immediately available. We propose a new and simple score, based on a retrospective analysis of our inpatients. METHODS: 154 patients, out of 1650 consecutively admitted in our emergency medicine department, were submitted to a doppler – ultrasound evaluation for suspected DVT. We revised hystories, clinical examinations, and laboratory data of all patients. Odds ratios (with confidence intervals) were calculated for all rilevant variables (age, risk factors, physical examination, alternative diagnosis, D-dimer). Statistical analysis was performed employing the X2. A new score, named HOOD (Hystory, Objective, Other diagnosis and Dimer), was then developed. RESULTS: A DVT was confirmed in 96/154 patients (62.3%). Sex and age over 70 years (OR 0.69) were not predictive of DVT. The presence of two o more risk factors (OR 3.15), as one or more signs of DVT (OR 6.2) and Dimer value greater than cut-off (OR 4.2) were all strong predictors of the ultrasound results. A HOOD score of 1 or less was not associated with thrombosis, whereas a score of 2 or more was highly predictive of DVT (OR 6.41; sensivity 0.96, specificity 0.52; positive and negative predictive value 0.75 and 0.88 respectively). CONCLUSION: DVT can been predicted by a simple, clinical score. When a CUS is not immediately avalaible, a treatment with eparin should not delayed in patients with high clinical probability of DVT. CLINICAL IMPLICATIONS: The clinical suspicion of DVT is made by gestalt or by use of scores that divide cases in three groups of risk (i.e., low, intermediate and high risk). We propose a clinical method that segregate patients in two clearly distinct groups of risk, in one of which initial treatment could be probably safely omitted. DISCLOSURE: N. Mumoli, None.

investigations for venous thromboembolism should be performed on all patients with a surgical biopsy specimen showing pulmonary infarction. DISCLOSURE: J.G. Parambil, None.

Wednesday, October 27, 2004 Thromboembolic Disease: Diagnosis, Risk Groups, and Treatment, continued CONCLUSION: Among echocardiographic criteria, RV/LV end-diastolic diameter ratio ⬎1 in four chamber view, septal flattening, paradoxical motion and McConnell’s sign were seen in more than 70% of the patients. The normotensive patient with five or more criteria probably should receive thrombolytic therapy or other intervention. CLINICAL IMPLICATIONS: Echocardiography may play a significant role in making therapeutic decision in normotensive pulmonary embolism patients.

DISCLOSURE: T. Yein, None.

ELEVATED SOLUBLE VASCULAR CELL ADHESION MOLECULE-1 LEVELS AT SUBACUTE PHASE OF VENOUS THROMBOEMBOLISM EVEN AFTER ACHIEVEMENT OF COMPLETE THROMBOLYSIS Satoshi Ota, MD*; Norikazu Yamada, MD; Akihiro Tsuji, MD; Ken Ishikura, MD; Mashio Nakamura, MD; Masaaki Ito, MD; Naoki Isaka, MD; Takeshi Nakano, MD; The First Department of Internal Medicine, Mie University, Tsu, Japan

NOVEL STREPTOKINASE NANODEVICES FOR ENHANCED THROMBOLYSIS: PREPARATION, IN VITRO AND IN VIVO STUDIES Sujatha Kannan, MD*; Omathanu P. Perumal, PhD; Rangaramanujam M. Kannan, PhD; Rajyalakshmi I; Jayant Khandare, PhD; Mary Lieh-Lai, MD; Children’s Hospital of Michigan/Wayne State University, Detroit, MI PURPOSE: Venous thromboemboli constitute an increasing problem in children with complex medical problems. The treatment of thromboemboli in children is challenging because unlike in adults, the use of thrombolytics is not well studied and is often associated with bleeding. These risks can be minimized by delivering the thrombolytic agent specifically and directly to the clot. Our objective is to use novel dendritic nanodevices loaded with streptokinase (SK) to achieve enhanced clot lysis. We hypothesize that these nanodevices enhance clot lysis by improving the stability of streptokinase, decreasing its immunogenicity and allowing more effective diffusion of the nanodevice into the clot to deliver the drug. METHODS: Three different nanodevices were designed: Hydroxyl terminated nanopolymers that were (1)complexed with SK and (2)conjugated with SK and (3)polylactic acid-glycolic acid nanoparticles loaded with SK. Drug loading was determined by Lowry protein estimation, and streptokinase activity evaluated using a chromogenic assay kit. A rabbit model of jugular venous thrombus using time, extent of reperfusion (measured by doppler flowmetry) and decrease in clot weight as therapeutic end points was established for in vivo testing of nanodevices. RESULTS: In vitro studies showed that streptokinase was present in the nanodevices. Streptokinase activity was measured using a chromogenic assay and it was found to be active. From kinetic analysis, it was found that the streptokinase nanodevices took a longer time than free streptokinase to hydrolyse the peptide substrate nanoparticle⬎conjugate⬎complex⬎free SK. In vivo studies, showed that treatment with saline did not produce any significant reperfusion. Upon treatment with free streptokinase 30% of baseline blood flow was restored in 60 minutes. The clot weight with streptokinase treatment was 60% of control. CONCLUSION: These results indicate that novel streptokinase loaded nanodevices can be successfully prepared and that they achieve sustained and controlled delivery of streptokinase. The in vivo model has been established and the nanodevices will be tested. CLINICAL IMPLICATIONS: Nanodevices can non-invasively enhance clot lysis and minimize side effects by achieving controlled delivery of thrombolytics. DISCLOSURE: S. Kannan, None.

PURPOSE: It has been considered that venous thromboembolism (VTE) and vascular endothelial cell inflammation are directly interrelated and are mediated in part by cell adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1). Purpose of this study is to prove the relationship between VTE and soluble form of VCAM-1(sVCAM-1) at acute or subacute phase. METHODS: We prospectively measured serum sVCAM-1 concentration at 23 consecutive patients diagnosed VTE (average age 55.2 ⫾ 19.3 years old, 8 males) at acute phase (before treatment) and subacute phase (4 weeks after treatment). We also analyzed 8 healthy volunteers (average age 39.4⫾17.0 years old, 4 males) as control. Patients with obvious arteriosclerosis such as ischemic heart disease, cerebrovascular disease, diabetes mellitus and so on were excluded. The concentration of sVCAM-1 at acute phase was compared with that of controls. Patients were also measured d-dimer level at subacute phase and were classified into complete-thrombolysis(C) group (d-dimer⬍500 ng/ml) and incompletethrombolysis(I) group. Then the concentration of sVCAM-1 was compared at each group. RESULTS: The patients had significantly higher sVCAM-1 concentration than controls at acute phase (2522.8 ⫾ 1274.2ng/ml vs 1353.4 ⫾ 772.7ng/ml, p⬍0.01). The sVCAM-1 concentration of patients with acute pulmonary thromboembolism (APTE) had no difference from the patients without APTE (3085.3 ⫾ 1628.4ng/ml vs 2222.8⫾973.9ng/ml p⫽0.2). At subacute phase, the patients kept high sVCAM-1 concentration (2097.1⫾878.0ng/ml) and there are no difference between C group and I group (1772.1⫾838.1ng/ml vs 2347.2⫾854.8ng/ml, p⫽0.1). CONCLUSION: This findings showed that the sVCAM-1 concentration of VTE patients was elevated at acute phase. This elevation was recognized at subacute phase whenever d-dimer elevated or not. This result indicates that the inflammation of vascular endothelial cell still continue until subacute phase in spite of achievement of complete thrombolysis. CLINICAL IMPLICATIONS: In our study, the inflammation persists in vascular endothelial cell at least for a month whenever thrombus had dissolved or not. Therefore we considered patients still have a high risk of VTE recurrence and need anticoagulation therapy at this period. DISCLOSURE: S. Ota, None.

PURPOSE: Plasma viscosity, a major determinant of blood flow in microcirculation is determined by macromolecules, eg, fibrinogen, immunglobulins, lipoproteins. Risk factors for pulmonary embolism can not be detected in majority of the patients with pulmonary embolism, and the recurrence takes places in some of them. In this study we aimed to investigate the plasma viscosity levels in patients who had previously attack of pulmonary embolism. METHODS: Nineteen patients (5 women 14 men, mean age:52 from 35 to 72) who had only one attack of pulmonary embolism and 21 healthy subjects were included in the study. Patients who had coronary artery disease, peripheral arterial disease, chronic obstructive lung disease, connective tissue disease and genetic predisposition for pulmonary embolism were not included in this study. Blood samples were drawn from all patient and the plasma viscosity were measured at 37°C. Mean time interval between completion of treatment for pulmonary embolism and blood sampling was 9⫾2 months. RESULTS: Plasma viscosity of patients who had pulmonary embolism attack was significantly higher than that of healthy subjects (1.73⫾0.23 mPa.s, and 1.23⫹0.06 mPa.s respectively p⬍0.001). There were no statistically significant differences between patients and control subjects in respect to routine hematological and biochemical parameters.

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INCREASED PLASMA VISCOSITY IN PATIENTS WITH HISTORY OF PULMONARY EMBOLISM Levent C. Mutlu, MD; Ibrahim Tek, MD; Suleyman S. Hacievliyagil, MD; Hakan Gunen, MD; Akin Kaya, MD; Numan Numanoglu, Prof; Ozkan Yetkin, MD*; Inonu University Faculty of Medicine Department of Pulmonary, Malatya, Turkey

Wednesday, October 27, 2004 Thromboembolic Disease: Diagnosis, Risk Groups, and Treatment, continued CONCLUSION: We have shown that patients who had pulmonary embolism attack had increased plasma viscosity levels compared to control subjects even long after completion of the treatment. CLINICAL IMPLICATIONS: Role of increased plasma viscosity in the pathogenesis of pulmonary embolism should be evaluated in further clinical studies. DISCLOSURE: O. Yetkin, None.

INCIDENCE OF POSTOPERATIVE PULMONARY EMBOLISM (PE) DETECTED BY MULTI-SLICE COMPUTERIZED TOMOGRAPHY(MSCT)IN LUNG SURGERY FOR CANCER Mark Ragusa, MD*; Giuliano Daddi, MD; Giulia Milillo, MD; Luciano Lupattelli, MD; Angelo Lemmi, MD; Francesco Puma, MD; Filippo Calzolari, MD; Giancarlo Agnelli, MD; Division of Thoracic Surgery, University of Perugia, Perugia, Italy

ANTI-ACTIVATED FACTOR X HEPARIN ASSAYS IN CRITICALLY ILL PATIENTS WITH ANTITHROMBIN DEFICIENCY Boaz A. Markewitz, MD*; Jonathan Rettmann, MD; Lori Wilson, MS, MT; Christopher M. Lehman, MD; University of Utah, Salt Lake City, UT PURPOSE: Antithrombin (AT) levels are frequently decreased in critically ill patients. It has been suggested that reduced AT levels result in underestimation of plasma heparin levels. Due to this concern, anti-activated factor X (Xa) assays may add excess AT to the sample to compensate for the AT deficiency. We sought to determine whether this added step, the addition of excess AT, was clinically useful by assessing the concordance between two Xa assays in ICU patients with reduced AT levels receiving continuous unfractionated heparin (UH) infusions; the STA-Chrom® Heparin assay adds excess AT to the sample before assessing the heparin level, whereas the STA-Rotachrom® assay does not. METHODS: We conducted a prospective evaluation of forty-one consecutive ICU patients receiving continuous UH infusions. Blood

UPPER EXTREMITY DEEP VENOUS THROMBOSIS IN CRITICALLY ILL PATIENTS: RISK FACTORS AND OUTCOMES Peter Lee, MD*; Ann Weinacker, MD; Michael Gould, MD, MS; Stanford University Medical Center, Stanford, CA PURPOSE: Critically ill patients have multiple risk factors for deep venous thrombosis (DVT), a leading preventable cause of death among hospitalized patients. Upper extremity (UE) DVT occurs more commonly than previously thought, and some UEDVT may result in pulmonary embolism (PE). We examined risk factors and outcomes among ICU patients with UEDVT. METHODS: We performed a retrospective case-control study of 147 critically ill patients from July 2000 through June 2003 in a 64 bed multidisciplinary ICU of a large university hospital to evaluate risk factors for UEDVT, including previous DVT, UE central venous catheterization (CVC), obesity (BMI ⬎ 30), malignancy, mechanical ventilation , DVT prophylaxis, surgery within 30 days, and vasopressor use. Cases were all patients with ultrasound evidence of UEDVT (n⫽ 45). One control group included all patients with negative UE ultrasounds (n⫽ 57), and another control group included ICU patients matched by age, gender, and primary diagnosis (n⫽ 45). We excluded patients with known DVT or PE, or anticoagulant use prior to admission. Outcomes included documented PE, duration of mechanical ventilation, mortality, hospital length of stay (LOS), and ICU LOS. RESULTS: Significant risk factors for UEDVT included history of DVT, UE CVC, requirement for vasopressors, and mechanical ventilation . 6 patients had documented PE, all of whom had UEDVT. There were no differences in mortality or ICU LOS (Tables 1 and 2). CONCLUSION: Critically ill patients with history of DVT, UE CVC, need for vasopressors, or mechanical ventilation are at greater risk for development of UEDVT. UEDVT appears to be a risk factor for PE in critically ill patients. CLINICAL IMPLICATIONS: Critically ill patients with prior DVT, UE CVCs, or prolonged mechanical ventilation should be closely monitored for the development of UEDVT and pulmonary embolism.

Table 1. Case vs. control. Odds Ratio (95% CI) Risk factor History of DVT Upper extremity CVC Outcomes Pulmonary embolism

P

6.8 (1.4-33.7) NC1.

⬍.01 07

2.8 (0.6-11.8)

.18

1. Not calculated. 45 out of 97 (46%) patients with upper extremity CVC had UEDVT, 0 out of 5 (0%) patients without upper extremity CVC had UEDVT. Odds ratio could not be calculated. P value trended towards significance by Fisher’s Exact Test CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: The incidence of pulmonary embolism (PE) in patients undergoing lung surgery for cancer remains undefined. In these patients the risk for venous thromboembolism is potentially high due to the combination of prothrombotic effects of cancer, extensive surgery, prolonged immobilization and parietal and endothelial local alteration consequent to surgery. The aim of this study was to assess the incidence of PE after lung surgery for cancer using MSCT scan. METHODS: PE was detected by MSCT (GE Light-Speed 4x1,25) scan performed 7-15 days after surgery. Diagnostic criteria for PE were complete or partial intraluminal filling defect. Patients were scheduled to receive pharmacological prophylaxis for venous thromboembolism with low-molecular-weight heparin (LMWH) starting the first post-operative day, until discharge. RESULTS: Fifty patients were included in this study. The average age was 66,5 (range 26 to 90). Diagnosis of cancer was confirmed in all except one patient found to be affected by tuberculosis. Thirty-six patients underwent lobectomy, 11 pneumonectomy, and the remaining 3 patients wedge resection. Histology showed epidermoid carcinoma in 20 cases, adenocarcinoma in 15, anaplastic carcinoma in 7, and other types in the remaining 8 cases. All patients but two received prophylaxis for venous thromboembolism. Seven patients (14%) showed PE at MSCT scan. Of the PE, 5 involved central arteries (principal, lobar and segmentary) and 2 subsegmentary arteries. Two of the patients with MSCT scan detected PE were symptomatic. CONCLUSION: PE is a common complication in patients undergoing lung surgery for cancer, despite antithrombotic prophylaxis. CLINICAL IMPLICATIONS: In such high-risk population prophylactic regimens should be optimized. DISCLOSURE: M. Ragusa, None.

samples drawn to monitor UH therapy had heparin levels measured (by the two different assays listed above), as well as AT activity levels. The concordance between the Xa assays in AT depleted patients was determined. RESULTS: 13 of the 41 patients were noted to have an AT level less than 60% of normal human plasma activity. A total of 30 pairs of Xa levels were determined from this population. In AT depleted patients, Xa levels measured by the STA-Chrom® and STA-Rotachrom® assays were similar (correlation between paired values was 0.87). CONCLUSION: The concordance between Xa assays in AT depleted ICU patients is high. We found no benefit in an assay that adds excess AT to the sample prior to measuring plasma heparin levels in patients treated with UH. CLINICAL IMPLICATIONS: The management of anticoagulation with UH, in critically ill patients deficient in AT, would not be altered by this Xa assay that added excess AT to plasma samples. DISCLOSURE: B.A. Markewitz, None.

Wednesday, October 27, 2004 Thromboembolic Disease: Diagnosis, Risk Groups, and Treatment, continued Table 2. Case vs. matched control Odds Ratio (95%CI) Risk factor History of DVT Upper extremity CVC Vasopressor requirement Mechanical ventilation Outcomes Pulmonary embolism

P

11.0 (1.390.5) NC1 2.8 (1.26.6) 6.3 (2.56.0)

.02

NC2

.03

⬍.01 .02 ⬍.01

1. Not calculated. 45 out of 79 (57%) patients with upper extremity CVC had UEDVT, 0 out of 11 (0%) patients without upper extremity CVC had UEDVT. Odds ratio could not be calculated. P value obtained significance by Fisher’s Exact Test. 2. Not calculated. 6 out of 45 (13.3%) patients with UEDVT had PE, 0 out of 45 (0%) patients without UEDVT had PE. Odds ratio could no be calculated. P value obtained significance by Fisher’s Exact Test. DISCLOSURE: P. Lee, None.

INITIAL HEMODYNAMICS WITHIN THE FIRST THREE HOURS OF PRESENTATION DETERMINE ULTIMATE OUTCOME IN PATIENTS WITH PULMONARY EMBOLISM Aaron M. Joffe, DO*; Rosa P. Mak, MS; Kenneth E. Wood, DO; St. Francis Medical Center, Honolulu, HI

Tele-Education 12:30 PM - 2:00 PM THE ROLE OF TARGETED EDUCATION IN THE AWARENESS, EXPERIENCES AND ADHERENCE OF MEDICAL PROFESSIONALS WITH HOSPITAL PROTOCOLS Tuhina Raman, MBBS*; Brett Gerstenhaber, MD; Elizabeth Moore, RRT; Hospital of St. Raphael, West Haven, CT PURPOSE: There is poor knowledge among medical professionals regarding the roles and functions of the respiratory therapists (RTs) and this leads to inappropriate use of Respiratory care services (RCS). The advent of RT driven protocols have shown these to be superior to physician orders with reduced cost and improved utilization of services. METHODS: The pre intervention assessment included two questionnaires administered to a group of medical professionals, the first was to assess the awareness of the functions of the RTs and the second was to assess the effectiveness of the RTs performance at the hospital. One hundred orders for nebulised bronchodilators were reviewed prospectively to assess adherence to the protocol. This was followed by a three educational interventions didactic lecture given to all groups and two interventions targeting medical residents including a teaching module and pocket cards detailing the ordering of RCS. A post intervention assessment was done. Outcomes included the awareness and experiences with RCS among residents, attendings and physician assistants, their adherence with the protocol for bronchodilators and the effect of the education on their awareness, experiences and adherence with the protocol. RESULTS: A total of 105 individuals participated in pre intervention assessment and 75 in the post intervention assessment. There were no differences in awareness post intervention. Less than 50% were aware of RT training and that protocol driven care improved RCS. In the post intervention assessment residents were less satisfied with RTs in the areas of bronchial hygiene, suctioning and oxygen titration. Most agreed that RTs were effective in all areas with the exception of hemodynamic monitoring, education and end of life care. Of the orders reviewed, 72 % were on protocol, which decreased to 53% after the intervention. CONCLUSION: There is poor awareness of RCS among medical professionals and poor adherence to evidence based protocols and this cannot be improved by education alone. CLINICAL IMPLICATIONS: For protocol implementation to be successful, a multifaceted approach of education, periodic auditing, provider feedback and practice reconstruction is necessary. DISCLOSURE: T. Raman, None.

PURPOSE: Pulmonary embolism (PE) represents a disease with disparate outcomes. Despite a paucity of data showing clear benefits, aggressive therapy with thrombolytics and pulmonary thromboembolectomy are accepted treatments in hemodynamically unstable PE (MPE) patients while efficacy data is equally lacking and additionally contentious in stable PE (HS-PE) patients. The current study was designed to examine the relationship between demographic variables, hemodynamic status, time to initial presentation, and treatment modality on PE-related mortality. METHODS: Data regarding age, gender, history of pre-existing cardiopulmonary disease (CPD), hemodynamic status within 3 hours of presentation, time from symptom onset to initial evaluation, and treatment modality were collected retrospectively in consecutive patients with diagnostically confirmed PE. Early treatment was defined as time to evaluation 0-6 hours and late as ⬎6 hours. Aggressive care was defined as thrombolysis or embolectomy while heparin therapy, inferior vena cava interruption, or both was considered routine care. Using multivariable logistic regression, the effects of these predictive variables on mortality were examined. RESULTS: 562 patients were included in the final regression model. Overall mortality was 8.5% (513 alive, 48 dead). Adjusted odds ratios and their corresponding 95% CI for each variable are as follows: age 0.997 (0.974-1.020), gender 0.706 (0.336-1.484), CPD 2.614 (1.189-5.747), shock 11.156 (5.226-23.813), early versus late treatment 1.393 (0.6433.017), aggressive versus routine therapy 4.161 (0.209-82.2922). Only CPD and shock remained significant, both with p-values of ⬍ 0.001. CONCLUSION: Despite adjustment for age, gender, delays in presentation, and use of more aggressive therapies, only CPD and the presence of shock or hemodynamic instability within 3 hours of presentation remained significant predictors of death. More aggressive therapy did not alter outcome. CLINICAL IMPLICATIONS: Given the substantial cost and potential morbidity, aggressive therapy with thrombolysis or pulmonary embolectomy should be reserved for MPE patients. Further study into the interaction between embolus size and underlying cardiopulmonary function is needed to define the subset of HS-PE patients at highest risk and likely to benefit from more aggressive treatments. DISCLOSURE: A.M. Joffe, None.

PURPOSE: Previous studies from our institution demonstrated dramatic improvements identifying cardiac sounds after listening to 400 repetitions of each sound recorded on audio compact disc (CD). This follow-up study investigated if similar results could be obtained using identical content placed on the Internet for student download. METHODS: Twenty-four first-year medical students in a traditional curriculum at an urban east coast medical school were randomized to one of two groups. Both groups received instruction on 5 basic cardiac murmurs (AS, AR, MS, MR, Innocent Murmur) and 2 extra heart sounds (S3, S4). Group A was given a one-hour CD with 200 repetitions of the above heart sounds interspersed with didactic material. Group B was given instructions to download an internet-based digital audio file (DAF) containing content identical to Group A. Both groups were instructed to listen to their CDs or DAFs exactly twice. Computer-based testing was used to assess proficiency at identifying 10 heart sounds played in random order before and after educational intervention. RESULTS: On completion, twenty-three students were available for analysis (12 in Group A, 11 in Group B). Group A improved from a pre-test proficiency score (M ⫾ SD) of 21.7 ⫾ 11.9% to a post-test score of 69.2 ⫾ 22.3% (p⬍.001). Group B improved from a pre-test proficiency of 20.0 ⫾ 14.8% to a post-test score of 61.8 ⫾ 21.8% (p⬍.001). Mann-Whitney testing showed no statistical difference between the two groups (p⫽.534). CONCLUSION: Medical students demonstrated dramatic improvement recognizing cardiac sounds after listening to 400 repetitions of each abnormality. Post-test results were similar and significant regardless of whether the student used a CD or DAF downloaded over the Internet.

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MASTERING CARDIAC AUSCULTATION OVER THE INTERNET: USE OF COMPUTER-BASED TESTING TO DEMONSTRATE THE POWER OF REPETITION Tyler C. Seto, MD*; Michael Barrett, MD; Jason Bradley, MD; Robert Lee; UCLA-San Fernando Valley Medical Center, San Marino, CA

Wednesday, October 27, 2004 Tele-Education, continued CLINICAL IMPLICATIONS: These results confirm previous studies demonstrating cardiac auscultation is partially a technical skill requiring repetition for mastery. This study shows delivery of content via the Internet is as effective as delivery via CD. Internet-based distribution allows an effective teaching tool to be made available to many students over multiple clinical sites. DISCLOSURE: T.C. Seto, Astra-Zeneca

DETECTION OF PNEUMOTHORAX BY COMPUTERIZED BREATH SOUND ANALYSIS Hansen A. Mansy, PhD; Silas J. Hoxie, BS; William H. Warren, MD; Robert A. Balk, MD; Richard H. Sandler, MD; Hesham A. Hassaballa, MD*; Rush University Medical Center, Chicago, IL

PURPOSE: Many factors affect stethoscope sound transmission. Although bench measurements with an artificial pure tone make for a straightforward measurement, chest sounds have many different simultaneous frequencies. We compared stethoscope output using a 50-3000 Hz pure tone sweep and pink noise (50-10K Hz). METHODS: The sound transmission characteristics of a pure tone sweep and pink noise through a double-tubed diagnostic stethoscope were measured in an anechoic chamber using a computerized signal analysis system (CoolEdit™ and MATLAB®). The reference signal was measured at the chest piece and the earpiece (other earpiece occluded). A plot of frequency vs. decibel change is given below. RESULTS: The plot shows a difference between the shape of the pure tone sweep output and the pink noise output. The sweep output appears to develop periodic additive and subtractive nodes that would create signal distortion. CONCLUSION: Real use conditions would involve listening to multiple frequencies simultaneously. Using concurrent, multiple frequencies during bench testing appeared to limit confounding variables that are more likely to occur with pure tones. CLINICAL IMPLICATIONS: Clinicians using stethoscope comparisons for selection of a stethoscope should pay careful attention to the methodology employed and seek comparisons that use simultaneous multi-frequency analysis (natural or artificial).

DISCLOSURE: J.B. Waugh, None.

Geriatrics 12:30 PM - 2:00 PM

THE EFFECT OF NUTRITIONAL STATUS ON VASOMOTOR STABILITY IN THE SICK ELDERLY William D. Marino, MD*; Serat Kuppachi, MD; Malathi Akula, MD; Anna Pankratov, MD; T.S. Dharmarajan, MD; Our Lady of Mercy Medical Center, Bronx, NY DISCLOSURE: H.A. Hassaballa, None.

PURPOSE: We have observed that there is a large subset of geriatric patients who develop relative hypotension during physiologic stress and, when treated with vasopressors, are difficult to wean from them. This phenomenon has been especially noted in malnourished individuals. The vasomotor component of peripheral resistance mediated by the sympathetic nervous system deteriorates with age and metabolic derangements, particularly diabetes mellitus. Since malnutrition has substantial effects on peripheral nervous system function, we evaluated the effect of nutritional status on sympathetic vasomotor competence utilizing the cold pressor response (CPR). CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Pneumothorax is a potentially life-threatening condition, especially in critically ill patients. Although usually diagnosed clinically, physical signs may be equivocal, thus leading to delayed diagnosis and possible adverse clinical outcomes. Chest radiography may not always establish the diagnosis, and CT scanning may be impractical given cost, availability and scheduling considerations. We hypothesized that pneumothorax can be accurately detected by computerized analysis of breath sounds. METHODS: After IRB approval and informed consent, breath sounds of 10 subjects (5 controls and 5 with pneumothorax) were recorded using an electronic stethoscope. Subjects were studied in the semi-upright position with the stethoscope placed over the mid clavicular line just inferior to the clavicle. Breath sound signals were digitized and “bandpass” filtered (300-700 Hz ) using a personal computer. The breath sound amplitude variation was calculated as the ratio between mean and minimum sound amplitude during inspiration. This ratio was compared between the control and pneumothorax groups using the Wilcoxon signed ranks test. RESULTS: The inspiratory breath sound variability was smaller in the pneumothorax group, which is consistent with decreased airflow and airflow variation with pneumothorax. Using this criterion, 100% separation of the pneumothorax and control group was possible (p ⬍ 0.008). CONCLUSION: Pneumothorax may be accurately detected by computerized analysis of breath sounds, suggesting that further research into these methods is warranted. CLINICAL IMPLICATIONS: Simple bedside devices may use computerized breath sound analysis to rapidly alert clinicians to the occurrence of a pneumothorax, leading to more rapid diagnosis and earlier intervention.

STETHOSCOPE TRANSMISSION CHARACTERISTICS USING A PURE TONE SWEEP VERSUS PINK NOISE INPUT Jonathan B. Waugh, PhD*; Dale C. Callahan, PhD; George A. Mathew, MS; Wesley M. Granger, PhD; University of Alabama at Birmingham, Birmingham, AL

Wednesday, October 27, 2004 Geriatrics, continued METHODS: Study Design: Prospective data collection. A complete nervous system evaluation was performed, with special attention to mental status and peripheral sensation of pain and cold in order to assure the integrity of the sensory limb of the CPR. Blood pressure was measured in both arms, and the cuff placed on the arm with the higher pressure. The contralateral hand was then immersed in ice water for 70 seconds, and the blood pressure determination repeated. Clinical and laboratory data were collected from the clinical record. The magnitudes of the systolic, diastolic and mean arterial pressure responses to cold challenge were correlated graphically with albumin level(ALB), total lymphocyte count(TLC), body mass index(BMI), age and other clinical data. RESULTS: 22 nondiabetic patients were evaluated (13 women, 9 men; age 73⫾7yr). None were on vasopressors. All had normal mental status and peripheral nervous system function. All CPRs were lower than normal (diastolic response 3.5⫾6mm Hg, systolic 0.8⫾13 mm Hg) but within the group there was no correlation between CPR and either age or use of vasodilating medications. There was an inverse relationship between BMI and CPR (CPR⫽-0.7BMI) and a direct relationship between CPR and ALBxTLC (CPR⫽0.75xALBxTLC). There were weaker relationships between CPR and individual variables. CONCLUSION: Sympathetic competence is impaired in older adults and is further adversely affected by malnutrition and obesity. CLINICAL IMPLICATIONS: The sick elderly should be evaluated for nutritional deficiency and for vasomotor incompetence to stratify their risk for hemodynamic destabilization. DISCLOSURE: W.D. Marino, None.

Pulmonary Hypertension 12:30 PM - 2:00 PM PROTOCOL FOR REDUCTION OF SITE PAIN IN THE ADMINISTRATION OF TREPROSTINIL Loretta K. Ashby, BSN*; Kathy Hague, BSN; Lian Latham, RN, BA; Caremark RX, Northbrook, IL PURPOSE: Remodulin (Treprostinil) is a SQ drug used in the treatment of Pulmonary Hypertension. The most common side effect of the drug is site pain. The Site pain does seem to taper off at about 8 weeks but the management of the patient for the first several weeks can be a struggle. Our study compares two groups – a control group which did not utilize the pain management protocol and a new protocol group which did. METHODS: Our study was based on a historic control group that was compared to a study group using a special site management protocol and observation of current new Treprostinil “starts.” We utilized two groups for the study. The control group consisted of patients started on Remodulin form 3/15/03- 07/15/03 utilizing miscellaneous pain medications. The study group consisted of patients from 08/18/03 – 12/31/03. The special pain management in the study group consisted of adding Duoderm patches with PLO GEL, adding oral drugs and being much more psychologically supportive with the patients and families. The authors have found a 90-day improvement after the start of Treprostinil therapy for site pain reduction and getting the patient to the 15ng dose seems to be the point at which most patients stay on therapy. RESULTS: There were 9 patients started on Treprostinil in the control group from 3/15/03 through 7/15/03, 7 or a 77% discontinued therapy due to site pain during the 16-week period. From the period of 8/18/03 through 12/18/03, 12 patients started Remodulin therapy. ALL of the patients are still on the therapy in the study group for a 0% rate of discontinuation during the 16-week trial. CONCLUSION: Our study demonstrates that the pain protocol used in this study can keep patients on drug with 100% compliance VS a 77% discontinution rate. CLINICAL IMPLICATIONS: Our study demonstrates that this pain protocol can influence patient discontinuation rate, maintains patient comfort, reduces site pain and keeps the patient on therapy, which increases the long-term survival of the patient. DISCLOSURE: L.K. Ashby, None.

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INCREASED PHOSPHORYLATION OF ENOS AND IMPAIRED VASCULAR FUNCTION OF PULMONARY ARTERY IN A RAT MODEL OF INCREASED PULMONARY BLOOD FLOW Timothy Peterson, MS; Anthony Croatt; Karl Nath, MD; Zvonimir Katusic, MD, PhD; Chen-Fuh Lam, MD, PhD*; Mayo Clinic, Rochester, MN PURPOSE: Pulmonary hypertension may develop in patients with left-to-right shunt congenital heart disease and systemic arteriovenous shunt. Abnormal vasoreactivity of pulmonary artery (PA) secondary to increased blood flow may responsible for the high perioperative mortality of these patients. Utilizing an aortocaval (AC) fistula, we studied the functional and morphological changes of PA in rats with chronic increased pulmonary blood flow. METHODS: Eight weeks after sham (n⫽8) or AC fistula (n⫽10) operation, PA of each rat was examined. Rings of second generation PA were contracted with phenylephrine (PE) in organ chambers. Concentration-response curves were obtained by cumulative addition of acetylcholine (Ach), and a nitric oxide (NO) donor (DEA-NONOate) to the pre-contracted rings. Protein expression and morphological changes of PA were examined. RESULTS: Contractions to PE were significantly increased in the PA of rats with the AC fistula. Relaxation of PA to Ach was significantly impaired in the fistula rats with reduced maximal relaxation (96.9⫾0.9 versus 81.5⫾3.3%; P⬍ 0.001). DEA-NONOate-induced relaxation of the PA was less affected in these rats. PA of fistula rats expressed higher levels of endothelial NO synthase (eNOS) and phosphorylated eNOS (ser1177). H&E and Verhoeff’s stains showed remarkable medial thickening of the PA, without significant changes in the intima. Thickening of internal elastic lamina and widening of subendothelial space with deposition of collagen fibers were found in the PA of rats with the fistula under an electron microscope. CONCLUSION: Chronic increased blood flow causes vascular smooth muscle hypertrophy and enhances the contractility of PA. Endotheliumdependent relaxation is impaired in the PA with increased blood flow, while the endothelium-independent relaxation is preserved. Increased pulmonary blood flow also up-regulates the expressions of eNOS and phosphorylated eNOS in the PA. Remodeling in the subendothelium, which limits the diffusion of endothelium-released NO may responsible for the flow-induced vascular dysfunction of PA. CLINICAL IMPLICATIONS: Subendothelium remodeling may lead to the vascular dysfunction of PA in patients with flow-induced pulmonary hypertension. DISCLOSURE: C. Lam, None. CARDIAC MUSCLE MASS AND WALL THICKNESS IN FETAL LAMBS WITH PULMONARY HYPERTENSION Frederick C. Morin, MD; Vicki L. Mahan, MD*; Women and Children’s Hospital of Buffalo, Buffalo, NY PURPOSE: In our fetal lamb model of PPHN, created by prenatal ligation of the ductus arteriosus, we found that endothelial NO gene expression is attenuated and that this may contribute to abnormal vasoreactivity and muscularization of the pulmonary circulation in fetal hypertension. This study characterizes changes in the cardiac muscle mass and wall thickness and pulmonary physiology in this model. METHODS: Six experimental fetuses who had their ductus arteriosus ligated, three control fetuses who had sham ligation of the ductus arteriosus before delivery, and six control fetuses who had no prenatal surgery were delivered by cesarean section. Each was instrumented to measure pulmonary artery pressure and systemic arterial pressure and pulmonary blood flows. Each newborn lamb was ventilated with room air during the first 45 minutes after delivery and then with decreasing amounts of inspired oxygen. RESULTS: Pulmonary arterial pressure decreased significantly when ventilation was begun in the control lambs but not in the study animals. Pulmonary arterial pressure and total pulmonary resistance were higher, and pulmonary blood flow was lower in the ligated lambs. Similarly, a group of lambs 133 to 142 days gestation, 11 control and 11 ligated for 4 to 17 days were used for heart measurement comparisons. Right ventricular wall thickness was increased in the lambs that had their ductus arteriosus ligated. Left ventricle, right ventricle, and septal weights were also higher in the ligated animals. CONCLUSION: These pathologic and physiologic changes are most likely due to the intra-uterine development of pulmonary hypertension. Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Pulmonary Hypertension, continued CLINICAL IMPLICATIONS: Intra-uterine pulmonary hypertension may result in pathologic and physiologic changes in neonatal myocardium with subsequent poor outcomes. Prenatal treatment and management of pulmonary hypertension may improve outcome of this high risk population of patients. DISCLOSURE: V.L. Mahan, None. THE EFFECT OF 100 % OXYGEN ON THE PULMONARY VASCULAR HEMODYNAMICS IN PULMONARY ARTERIAL HYPERTENSION Tji-Joon Gan, MS; Anco Boonstra, MD, PhD, F; Frank P. Oosterveer; Anton Vonk-Noordegraaf, MD, PhD*; Pieter E. Postmus, MD, PhD; Frances S. de Man, MS; VU University Medical Centre, Amsterdam, the Netherlands

LONG TERM EFFICACY OF COMBINATION THERAPY WITH SILDENAFIL AND BERAPROST SODIUM FOR PRIMARY PULMONARY HYPERTENSION Ken Ishikura, MD*; Norikazu Yamada, MD; Akihiro Tsuji, MD; Satoshi Ota, MD; Mashio Nakamura, MD; Masaaki Ito, MD; Naoki Isaka, MD; Takeshi Nakano, MD; First Department of Internal Medicine, Mie University School, Tsu, Japan PURPOSE: Sildenafil and beraprost sodium have different mechanism for pulmonary vasodilatation. We evaluated the long term efficacy and safety of combination therapy of oral sildenafil and beraprost sodium for patients with primary pulmonary hypertension, which is hypothesized to be more effective than each agent alone. METHODS: Four patients with primary pulmonary hypertension (4 female, mean age ⫾ SEM, 39 ⫾ 12 years) were orally administered 50mg of sildenafil bid and 120 or 180 microgram of beraprost sodium qid. We assessed hemodynamics, arterial blood gas, ANP, BNP and NYHA functional class at baseline, 3 months and 12 months after treatment. No patients received neither sildenafil and beraprost sodium before this study. RESULTS: The NYHA functional class was kept improved in all cases until 12 months (from IV, III to II). Pulmonary vascular resistance was significantly decreased to 664.5 ⫾ 246.6 dyne●sec●cm-5 at 3 months (-40.7%, p⫽0.0098) and 737.5 ⫾443.5 dyne●sec●cm-5 at 12 months

ACCURACY OF DOPPLER ECHOCARDIOGRAPHY IN THE HEMODYNAMIC EVALUATION OF PULMONARY HYPERTENSION Micah R. Fisher, MD*; Paul R. Forfia, MD; Elzbieta Chamera, MD; Traci Housten, MD; Hunter C. Champion, MD; Jon Resar, MD; Mary Corretti, MD; Reda E. Girgis, MB,Bch; Paul Hassoun, MD; Johns Hopkins University, Baltimore, MD PURPOSE: Transthoracic Doppler Echocardiography (TDE) is routinely used to estimate pulmonary artery systolic pressure (PASP) in patients suspected of having pulmonary hypertension (PH). However, there is conflicting data as to the accuracy of these pressure estimates when compared to right heart catheterization (RHC). We sought to determine the accuracy of TDE in estimating PASP and cardiac output (CO) among patients seen in a PH clinic. METHODS: We enrolled consecutive patients referred for RHC for the diagnosis or management of PH. Subjects underwent RHC followed within one hour by TDE performed by a dedicated echocardiographer blinded to RHC results. Measurements included right atrial pressure (RAP), PASP, and CO (determined by thermodilution for RHC and Doppler interrogation of the left ventricular outflow tract for TDE). Paired results from both studies were compared using Bland-Altman analysis. We calculated the average difference between RHC and TDE measurements (bias) and the expected range of differences for 95% of values (95% limits of agreement). RESULTS: To date, 16 patients (94% female; median age 51 yrs) have completed the study. Seventy-five percent of patients had PH; the most common diagnoses were idiopathic pulmonary arterial hypertension (PAH) and PAH related to scleroderma. RHC yielded a median RAP of 8mmHg (range: 2-19), PASP of 70mmHg (range: 28-113), and CO of 4.1L/min (range: 1.6-8.7). TDE tended to overestimate RAP and PASP (bias 3.63mmHg and 8.22mmHg, respectively) with 95% limits of agreement of -4.3 to 11.6mmHg and -20.4 to 36.9mmHg, respectively. In 44% of patients, the TDE estimate of PASP had a difference of greater than ⫾10mmHg compared to RHC. TDE bias for CO estimates was 0.02L/min with 95% limits of agreement of -2.4 to 2.5L/min. CONCLUSION: In patients with known or suspected PH, TDE estimates of RAP, PASP, and CO can vary significantly from RHC measurements. CLINICAL IMPLICATIONS: While TDE plays an important role in the evaluation of PH, clinicians should not rely solely on TDE estimates to inform management decisions. DISCLOSURE: M.R. Fisher, None.

PATTERNS OF PULMONARY HYPERTENSION CLINICAL PRACTICE IN CANADIAN CENTERS Carol Storseth, RN; John Granton, MD; David Langleben, MD; Sanjay Mehta, MD; David Ostrow, MD; Tawimas Shaipanich, MD*; Duncan Stewart, MD; Robert D. Levy, MD; University of British Columbia, Vancouver, BC, Canada PURPOSE: The diagnosis and management of pulmonary hypertension (PH) varies amongst physicians. The objective of this survey was to determine the patterns of PH practice in programs across Canada, specifically targeting program structure, access, referral patterns, diagnostic workup and treatment approach. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Our study aims to evaluate the effect of 100 % oxygen on the pulmonary vascular hemodynamics in pulmonary arterial hypertension(PAH) and to analyse the main determinants of this response. METHODS: Fifty-four PAH patients (11 male, 43 female)underwent right heart catheterisation. Mean pulmonary artery pressure (mPap) and pulmonary capillary wedge pressure were measured. Arterial and mixed venous saturations and oxygen pressures were obtained from the femoral and pulmonary artery. All measurements were performed at baseline and after reversibility testing. Cardiac output was calculated by the Fick method and the pulmonary vascular resistance (PVR) was calculated from the cardiac output and pressure measurements. Reversibility was tested by means of inhaling 100% oxygen for a time period of 5 minutes followed by a refractory time of 5 minutes. In addition, 20 ppm Nitric Oxide (NO) was inhaled for 5 minutes. Reversibility to 100% oxygen was defined as a decrease of the PVR (dPVR) more than 20%. Differences between the groups were statistical analysed by use of the non parametric Mann Witney t test. RESULTS: Thirty-three patients showed reversibility to 100% oxygen inhalation(dPVR⫽ 37 ⫾ 11%). Arterial oxygen pressure was at baseline (PaO2 ⫽ 77 ⫾ 16 mmHg) for the patients showing reversibility and (PaO2 ⫽ 66 ⫾ 16 mmHg) for the non reversible patients(p ⬍ 0.02). Mixed venous oxygen pressure (PvO2)did not differ significantly between the two groups. PaO2 showed a weak relation with dPVR (r⫽0.34, p ⬍ 0.02). PvO2 was not related to dPVR. Oxygen caused a significant larger (p ⬍ 0.001) decrease of the PVR (dPVR ⫽ 26 ⫾ 14%) than NO (dPVR ⫽ 13 ⫾ 16%). CONCLUSION: These data show that the higher the systemic arterial oxygen pressure the greater the respons to oxygen therapy and that the improvement of pulmonary hemodynamics in PAH is more pronounced for 100% oxygen inhalation than for NO. CLINICAL IMPLICATIONS: The extent of the systemic arterial oxygen pressure might be the main determinant for the decision to initiate oxygen therapy in PAH patients. DISCLOSURE: A. Vonk-Noordegraaf, None.

(-37.2%, p⫽0.042) from baseline (1105.5 ⫾ 291.9 dyne●sec●cm-5). Pulmonary vascular resistance at 12 months was decreased more than that at 3 months in 2 cases. Systemic blood pressure was not changed at 3 months (111.3 ⫾ 4.3 mmHg) and at 12 months (120.5 ⫾ 18.0 mmHg) compared with baseline (111.0 ⫾ 10.2 mmHg). Compared with baseline (72.2 ⫾ 9.8 Torr), partial pressure of arterial blood oxygen was increased both at 3 months (92.0 ⫾ 11.9 Torr, ⫹29.7%) and at 12 months (91.3 ⫾ 16.7 Torr, ⫹30.8%). ANP and BNP were correlated with mean pulmonary artery pressure. No adverse events were observed. CONCLUSION: These data suggest that beneficial effects of improving oxygenation and functional class as well as decreasing pulmonary vascular resistance continued after 12 months of combination therapy with sildenafil and beraprost sodium. CLINICAL IMPLICATIONS: This combination therapy should be considered before introducing continuous intravenous PGI2 infusion. DISCLOSURE: K. Ishikura, None.

Wednesday, October 27, 2004 Pulmonary Hypertension, continued METHODS: The 66 question survey was developed by a Canadian working group of PH experts and distributed to the 12 established Canadian PH centers in September 2003. RESULTS: Ten of the 12 PH centers completed the survey. The annual number of referrals to Canadian PH programs increased substantially from an average of 24 (range 0-120) cases in 2000 to 72 (6-240) cases per year in 2003. Of patients referred, 25% had primary (idiopathic) PH and 34% had PH related to connective tissue diseases. At the time of referral, 51 ⫾ 18(SD) % of patients were in WHO functional class 3. The investigation of choice for diagnosis and assessment of PH severity was echocardiogram with assessment of right ventricular systolic pressure and function. In 70% of centers, acute vasodilator responsiveness was determined either as an absolute reduction of pulmonary vascular resistance (PVR) to close to normal or a reduction of 20% of systolic pulmonary artery pressure and PVR. For vasodilator responders, calcium channel blockers were the initial treatment of choice in 70% of the centers. For WHO class 3 vasodilator non-responders, endothelin receptor antagonists (bosentan) were the first choice in 80% of programs. All centers considered the initiation of epoprostenol, or WHO class 3/4 symptoms despite optimal medical therapy, as indications for transplant referral in suitable patients. Transplant programs were easily accessible to 80% of the PH centers. CONCLUSION: This survey provides practical information describing the patterns of PH practice in Canada. There are many areas of both agreement and divergence in terms of diagnostic and therapeutic management approach. CLINICAL IMPLICATIONS: The survey provides an environmental scan useful for the development of Canadian PH practice guidelines related to program structure, access, referral patterns, diagnostic workup and treatment approach. DISCLOSURE: T. Shaipanich, None. BOSENTAN IN PULMONARY ARTERIAL HYPERTENSION RELATED TO CONNECTIVE TISSUE DISEASE WITH MODERATE TO SEVERE PULMONARY FIBROSIS Zoheir Bshouty, MD*; University of Manitoba, Winnipeg, MB, Canada PURPOSE: Endothelin-1 is a potent vasoconstrictor but also can promote fibrosis, cell proliferation and remodeling. Bosentan, an ETA and ETB receptor antagonist, has demonstrated potential benefits in animal models of pulmonary hypertension and pulmonary fibrosis (PF). The two pivotal clinical studies evaluating bosentan in patients with pulmonary arterial hypertension (PAH) included patients with idiopathic PAH and PAH related to connective tissue disease (CTD). However, the CTD patients with significant PF were excluded. The purpose of this pilot study was to evaluate the safety and potential benefit of bosentan in patients with PAH related to CTD with moderate to severe PF. METHODS: Patients with PAH related to CTD with significant underlying PF and WHO functional class III or IV were included in this study. PAH was suspected by echocardiography and confirmed by right heart catheterization. Bosentan, 62.5mg bid for 4 weeks followed by 125mg bid for 5 months, was added to the patient’s usual medication. Pulmonary function tests and echocardiography were done at baseline and after 6 months. Six minute walk test (6MWT) was done at baseline, 3 and 6 months. Laboratory assessments were carried out monthly.

Table 1: Baseline Demographics Pt#

Age

Gender

Diagnosis

VC (% pred)

TLC (% DLco WHO RVSP pred) (% pred) Class(mmHg) 6MWT (m)

1

33

F

Scleroderma

41

41

19

III

55

340

2

68

F

MCTD

53

42

32

III

50

260

3

65

F

MCTD

60

62

36

III

95

440

4

60

M

Scleroderma

54

52

19

IV

85

240

5

47

M

MCTD

IV

50

20

67⫾ 21.4

260⫾ 155.5

Mean54.6⫾14.5 ⫾ SD

62

72

25

54 ⫾ 8.2

53.8⫾ 13.2

26.2⫾ 7.6

RESULTS: During the 6 month period, all patients tolerated the treatment without significant elevation in liver transaminases levels or unexpected adverse events. WHO functional class was maintained (2 pts) or improved (3 pts). Over the 6 month period, the 6MWT distance mildly deteriorated in 2 patients and increased in 3 patients, resulting in a mean increase of 69.2 ⫾ 127.4 meters. CONCLUSION: The use of bosentan in patients with PAH related to CTD with moderate to severe PF appears safe and may induce a significant improvement in exercise tolerance. These findings should be further assessed in a larger cohort. CLINICAL IMPLICATIONS: These patients should be considered for a trial treatment with bosentan in an attempt to improve their exercise tolerance, quality of life, and survival. DISCLOSURE: Z. Bshouty, None.

CONTROLLED PULMONARY ARTERY BANDING: A NOVEL HYDRAULIC DEVICE TO INCREASE RIGHT VENTRICULAR SYSTOLIC PRESSURE Luis E. Santos-Martinez, MD, FCCP; Jose Gotes, MD*; Carlos Tena, VD; Pedro Flores, VD; Samuel Ramirez, MD; Arturo Carrillo, MD; Veronica Graullera, VD; Tomas Pulido, MD; Edgar Bautista, MD; M.L. Martinez-Guerra, MD; Alicia Castan˜ on, RN; Mauricio Soule, MD; Gerardo Rojas, MD; Mateo Porres, MD; Julio Sandoval, MD; Instituto Nacional de Cardiologia Ignacio Chavez, Mexico DF, Mexico PURPOSE: The banding of the pulmonary artery (PAB) has been done previously with diverse materials. An Hydraulic Device (HD) has been designed to band, in a controlled fashion, the main pulmonary artery of animals weighing more than 18 kilograms. We introduce an HD for smaller animals. METHODS: The components of the HD are: a valve, a reservoir, a teflon tape and a silastic conector. We built an artificial silicone tube and increased it⬘s internal pressure with water from the baseline condition [(20 mmHg (A)] to 40 (B), 60 (C) up to 80 mmHg (D). With each of this prefixed pressures, the volume and pressure of the HD was recorded after the addition of 0.1 ml of water in the HD reservoir, until it reached 1.0 ml. We followed the preceding procedure in a canine model of PAB. By introducing water to the HD reservoir, we obtained the increase of the right ventricular systolic pressure (RVSP), the systolic pulmonary artery pressure (sPAP) and the RVSP and sPAP difference (RVSP-sPAP). RESULTS: We studied 10 mongrel dogs weighing 12.6 ⫾ 2.2 kgs. There were no complications in the construction or in the HD positioning procedure. The HD behavior with every increase of the artificial tube internal pressure is shown in Figure 1. The maximum RVSP developed with the HD was 50.3 ⫾ 6.9 mmHg, it behavior, and the sPAP and RVSP-sPAP difference are observed in Figure 2. CONCLUSION: The HD it⬘s capable of overcoming the artificial tube prefixed pressures and provoking an acute increase in RVSP.

VC⫽vital capacity; TLC⫽total lung capacity; DLco⫽diffusing capacity for carbon monoxide; RVSP⫽right ventricular systolic pressure; MCTD⫽mixed connective tissue disease 884S


Wednesday, October 27, 2004 Pulmonary Hypertension, continued CLINICAL IMPLICATIONS: This HD has the potential to be used in congenital disorders, particularly in ventricular preparation for surgical correction of transposition of the great vessels. DISCLOSURE: J. Gotes, None.

A POSSIBLE ETIOLOGY OF CHRONIC THROMBO-EMBOLIC PULMONARY HYPERTENSION Timothy A. Morris, MD*; James J. Marsh, PhD; Peter G. Chiles, BS; University of California, San Diego, San Diego, CA

Pt.

Baseline

Baseline

12 wk

12 wk

Change

L1 L2 L3 1 2 3 4 5 6 7

WHO 3 3 2 3 3 2 3 2 3 3

6MWT 359 275 579 390 294 470 330 320 466 387

WHO 2 3 2 3 3 2 3 2 3 3

6MWT 408 372 600 432 294 477 390 342 461 459

6MWT ⫹49 ⫹97 ⫹21 ⫹42 0 ⫹7 ⫹60 ⫹22 -6 ⫹72

DISCLOSURE: A.E. Frost, Encysive,Actelion

PROFILING OF GENE EXPRESSION IN PULMONARY HYPERTENSION INDUCED BY LEFT VENTRICULAR HEART FAILURE Song M. Hong, MD*; David Dostal, PhD; Scott & White Memorial Hospital, Temple, TX

DISCLOSURE: T.A. Morris, None.

SITAXSENTAN SODIUM FOR THE TREATMENT OF PULMONARY HYPERTENSION (PAH) IN PATIENTS FAILING BOSENTAN: PRELIMINARY SINGLE CENTER DATA Adaani E. Frost, MD*; Helena Purl, RN; Baylor College of Medicine & The Methodist Hospital, Houston, TX PURPOSE: Bosentan (BOS) is an oral endothelin A&B receptor antagonist effective for PAH treatment. Patients (Pts.) with initial benefit

PURPOSE: Although basic pathological, physiological, and signal transduction mechanisms associated with secondary pulmonary hypertension have been elucidated, underlying genes responsible for these phenotypes remain to be discovered. The goal of this study was to identify gene expression profiles in lung parenchyma of rat model during development of pulmonary hypertension induced by left ventricular dysfunction using microarray. METHODS: Male Sprague-Dawley rats were divided into two groups: sham-operated control, and surgically induced pulmonary hypertension by partially constricting the abdominal aorta with a silk ligature. The rats were followed by serial echocardiography at 4 weeks, 6 weeks and 28 weeks. Samples of lung RNA was extracted and amplified using MessageAmpTM (Ambion). Gene expression analysis, using competitive hybridization, and dye-swap techniques were performed. Microarray scanning and data acquisition were done with an Axon 4000A scanner and Axon GenePix 5.0 software. Data normalization and bioinformatic analysis was performed with Gene Spring 6.1 software from Silicon Genetics, Inc. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a debilitating and potentially fatal sequelae of acute pulmonary embolism. The etiology of CTEPH has not been determined, resulting in a lack of predictive or preventive strategies for CTEPH after acute pulmonary embolism. We speculate that the N-terminus of the fibrin beta chain (residues 15-21) is a potent stimulator of pulmonary endothelial cells and fibroblasts and could be involved in pulmonary vascular scarring in CTEPH. We studied fibrinogen purified from patients with CTEPH to determine the susceptibility of the beta chain N-terminus to lysis by plasmin. METHODS: The kinetic patterns of fibrin polymer digestion by plasmin were compared between five CTEPH patients and five healthy volunteers. Non-cross-linked fibrin clots (50 ug) were incubated with plasmin (1.25 ug) for various times (0-6 hours) at 37 degrees C. Aliquots from each time point were subjected to SDS-PAGE under reducing conditions, and the gels were western blotted using antibodies specific for the fibrin beta chain N-terminus or stained with Coomassie blue. RESULTS: Western blotting disclosed that plasmin lysed the fibrin beta chain N-terminus more slowly in CTEPH patients than in controls (see figure). A two way ANOVA of western blot densitometry, considering patient group and digestion time, disclosed a significant persistence of fibrin beta-chains with intact N-termini in the CTEPH group compared to the controls (p ⫽ 0.025). Coomassie blue disclosed trends toward resistance of the CTEPH alpha, beta and gamma chains to plasminmediated lysis, relative to the controls (p values of 0.12, 0.17 and 0.23, respectively). CONCLUSION: These results indicate that fibrin from CTEPH patients may be digested more slowly and perhaps less completely by plasmin, particularly at the N-terminus of the beta chain. This phenomenon may be due to an alteration in the structure or accessibility of its plasmin cleavage site. CLINICAL IMPLICATIONS: Structural variances of fibrinogen, which make it relatively resistant to normal fibrinolysis, may be one of the mechanisms responsible for the development of CTEPH after acute pulmonary embolism.

can deteriorate or develop liver function test abnormalities (LFab) requiring drug cessation. Sitaxsentan (SITAX) is a selective oral endothelin A receptor antagonist in clinical trials. Between 10/01/03 and 1/23/04 13 pts. enrolled at this center in an open-label safety study of SITAX. 11 pts. were previously treated with BOS which was discontinued due to LFab (3) or deteriorating functional capacity and walk test (6MW)(8). We present their short term response to SITAX. METHODS: Pts with LFab on BOS (L1-L3)remained off BOS prior to SITAX intiation until LFab normalized. In pts. transitioned due to clinical deterioration (1-7), baseline values were on BOS. 10 pts. have been followed for 12 weeks with 6MW, exam and WHO. The change in 6MW was compared to baseline values using two-sided paired t-test. RESULTS: The mean improvement (⫾ SE) in 6MW with SITAX was 36.5 ⫾ 10.56m (p⫽0.0072). No Pts. with LFab on BOS experienced signficant LFab with SITAX. One pt. (not included due to no efficacy measurements)who refused epoprostenol for clinical deterioration transitioned to SITAX from BOS. This pt. worsened at wk 5 started epoprostenol and subsequently died. CONCLUSION: SITAX appears to offer potential as oral therapy for pts. with PAH who fail BOS due to LFab or clinical deterioration. CLINICAL IMPLICATIONS: Failure or complications with one endothelin receptor antagonist does not presuppose failure with another. Different endothelin receptor antagonists may offer unique advantages.

Wednesday, October 27, 2004 Pulmonary Hypertension, continued RESULTS: An interrogation of gene lists identified 93 genes upregulated in lungs of rats with acute diastolic dysfunction (4 weeks), 45 genes up-regulated in pulmonary tissue from rats with compensated hearts (6 weeks) and 69 genes up-regulated in lung tissue from rats with systolic heart failure (28 weeks). An interrogation of gene lists also identified 91 genes down-regulated at 4 weeks, 17 genes at 6 weeks, and 28 genes at 28 weeks. CONCLUSION: The study indicates a dynamic changes in the expression of genes in lung tissue secondary to heart failure fall into 4 distinct patterns of gene expressions: 1) Initial gene activation, followed by suppression, then reactivation (Cellular metabolism, structural proteins) 2) Initial gene quiescence, followed by activation, then suppression (Signal transductions, inflammation and immunoregulators, adhesion/extracellular proteins and transport proteins, intracellular transport proteins) 3) Continued increase in gene activation (Transcription regulators) 4) Continued decrease in gene activation (Cell cycle and cell differentiation). CLINICAL IMPLICATIONS: Gene expression profiles using microarry is an important diagnostic and prognostic markers of pulmonary hypertension and could be used to identify new therapeutic targets.

28 had no change in FC. Sensitivity of a 10% or more deterioration in 6MWT to predict FC deterioration is 66% with a specificity of 71%. 92 patients did not change their 6MWT more than 10%, 21 improved their FC, 1 worsened and 70 had no change in FC. Sensitivity of no change in 6MWT to predict no change in FC is 56% and a specificity of 50%. CONCLUSION: Sensitivity and specificity of improvement, deterioration or no change in 6MWT was poor to predict a similar directional change in FC. CLINICAL IMPLICATIONS: Modified or integrated endpoints may be needed to assess study outcomes and patient response to intervention.

Improvement ⬎ 10% in 6MWT Change within 10% in 6MWT Deterioration ⬎ 10% in 6MWT

Improvement ⬎ 10% in 6MWT / Yes Improvement ⬎ 10% in 6MWT / No

DISCLOSURE: S.M. Hong, None.

Deterioration ⬎ 10% in 6MWT / Yes Deterioration ⬎ 10% in 6MWT / No

CORRELATION OF CHANGE IN 6MWT AND NYHA FUNCTIONAL CLASS IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) Nabeel Y. Hamzeh, MBBS*; Adaani E. Frost, MD; Baylor College of Medicine, Pearland, TX PURPOSE: The Six Minute Walk Test (6MWT) correlates with mortality in PAH. NYHA functional class (FC) and 6MWT are used as endpoints and to guide individual patient therapy. 6MWT is fairly reproducible, FC is subjective in the mid-range (Classes II & III). In patient management, this subjectivity can impact therapy. In studies, endpoints might be impacted. Consistent functional classification is expected by the same observers assessing the same patients in these studies. Change in one assessment should theoretically be in the same direction as the other. In PAH studies, discrepancies have been observed . Our study aims to assess the sensitivity and specificity of a change in the 6MWT to predict a change in NYHA FC. METHODS: Data was derived from the STRIDE-1 study. 178 PAH patients were enrolled testing the safety and efficacy of Sitaxsentan. 6MWT and FC were recorded at baseline, 6 and 12 weeks. A change in 6MWT was defined ⬎10% from baseline. Complete data was available on 168 patients. RESULTS: 45 patients had more than 10% improvement in their 6MWT, 19 improved their FC, none worsened, 26 did not change their FC. Sensitivity of a 10% and more change in 6MWT to predict FC improvement is 48% with a specificity of 73%. 31 patients had more than 10% deterioration in their 6MWT, 2 worsened their FC, 1 improved and

886S

Change within 10% in 6MWT / Yes Change within 10% in 6MWT / No

Improved FC

Worse FC

No Change in FC

19

0

26

21

1

70

1

2

28

FC improved / Yes 19

FC improved / No 26

21

70

FC worsened / Yes 2

FC worsened / No 28

1

70

FC unchanged / Yes 70

FC unchanged / No 22

54

22

Sens ⫽ 48% Spec ⫽ 73%

Sens ⫽ 66% Spec ⫽ 71%

Sens ⫽ 76% Spec ⫽ 71%

DISCLOSURE: N.Y. Hamzeh, Dr. Frost Received grants from Encysive


Wednesday, October 27, 2004 Pulmonary Hypertension, continued DEVELOPMENT OF A MURINE BLOOD OUTGROWTH ENDOTHELIAL CELL CULTURE SYSTEM Arif Somani, MD*; Julia Nguyen, BSC; Liming C. Milbauer, PhD; Anna Solovey, MD; Judy Enenstein, PhD; Robert P. Hebbel, MD; University of Minnesota, Minneapolis, MN

Interstitial Lung Disease - Idiopathic Pulmonary Fibrosis 12:30 PM - 2:00 PM CORRELATES OF SIX-MINUTE WALK TEST IN IDIOPATHIC PULMONARY FIBROSIS Rajay K. Jain, MD*; Charlie Strange, MD, FCCP; James Ravenel, MD; Lejla Aganovic, MD; Steven A. Sahn, MD, FCCP; Medical University of SC, Charleston, SC PURPOSE: To evaluate the utility of Six-Minute Walk Test (6MWT) for Idiopathic Pulmonary Fibrosis (IPF) and determine correlates with spirometry, diffusion, high resolution CT (HRCT), and dyspnea scores. METHODS: We retrospectively evaluated all patients with IPF seen at MUSC from 1999 to 2003 to find those with concurrent HRCT, spirometry, diffusion, and 6MWT. HRCT was evaluated by two reviewers and summary scores for fibrosis obtained. Desaturation was defined by ⬎ 3% drop in oxygen saturation. Univariate correlations were performed on the initial set of tests with p-values ⬍ 0.05 judged significant. RESULTS: 27 patients had all the required tests for study inclusion performed. Twelve individuals had OLB diagnosis with the remainder meeting the ATS defination of probable IPF. Patient demographics

A CRITICAL ASSESSMENT OF TREATMENT OPTIONS FOR IDIOPATHIC PULMONARY FIBROSIS Nirav R. Shah, MD*; Paul Noble, MD; Robert W. Dubois, MD, PhD; New York University School of Medicine, New York, NY PURPOSE: To convene a diverse panel of physicians to formally review available data on treatment options for idiopathic pulmonary fibrosis (IPF) and to rate the “appropriateness,” “inappropriateness,” or “uncertainty” of some of the available therapeutic options. METHODS: A formal literature review was conducted on the risks and benefits of commonly used treatment options for IPF. The Medline and Cochrane databases were searched through September 2003, and supplemental information was obtained from specialty societies, pharmaceutical companies, and investigators. Unpublished, pertinent and new data from a just completed clinical trial presented at a recent international society meeting was included in abstract form. The panel comprised nine selected physicians from geographically diverse areas who practiced in communitybased settings and academic institutions. The RAND/UCLA Appropriateness Method was used to review and rate multiple clinical scenarios for the treatment of IPF. The consensus method did not force agreement. RESULTS: Please see Table 1. CONCLUSION: The panel concluded that corticosteroids alone are always “inappropriate.” Cyclophosphamide plus steroids are “inappropriate” for those aged 65-79 and “uncertain” as initial therapy for those under 65. Azathioprine plus steroids are “appropriate” as initial therapy in those under 65 (unless they showed signs of severe objective impairment when it was “uncertain”), and “uncertain” as initial therapy in those 65-79. Interferon gamma is “appropriate” for patients who have failed initial therapy with either steroids or cytotoxic agents and have mild to moderate objective impairment, “uncertain” as initial therapy, and “inappropriate” as initial therapy in patients with severe objective impairment. The appropriateness of pirfenidone is “uncertain” in all scenarios. Providing no therapy is “inappropriate” for most scenarios. Referring patients for enrollment in randomized trials is “appropriate” in all scenarios. Referring patients for transplant evaluation is “appropriate” for patients under 65 and “inappropriate” for those over 65. CLINICAL IMPLICATIONS: In patients with known IPF, the use of corticosteroids alone is inappropriate, referral for enrollment in randomized trials should be strongly considered, and patients under 65 should be referred for transplant evaluation. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Vascular endothelial cells provide a critical interface between the vessel wall and blood borne elements. They modulate clot formation, vascular tone, chemotaxis, angiogenesis; and consequently, have the potential ability to aid in revascularization therapy, prosthetic cardiac valve or stent coverage, and as an autologous vector in gene therapy. In order to address these future goals, our study attempted to establish a reliable and reproducible system to culture endothelial cells from murine blood samples for use in further modeling studies. METHODS: Mouse blood was collected via intercardiac aspiration from CO2 anaesthetized animals. Anticoagulation, buffy coat suspension, cellular washing, plating and incubation were undertaken to optimize cell isolation. Additionally, cell specific marker panning with antibody coated magnetic beads were used in cell isolation. Various plating conditions, media growth factors, nutritional additives, and serum supplements were manipulated to optimize cell expansion. Phase Contrast microscopy, immuno-histochemical staining and flow cytometry were undertaken to confirm cellular characterization. RESULTS: The murine blood outgrowth endothelial cells (BOECs) that we obtained take up acetylated low-density lipoprotein (AcLDL) and stained positive for multiple endothelial cell markers including von Willebrand factor (VWF), platelet/endothelial cell adhesion molecule (PECAM), vascular-endothelial (VE) – cadherin, and vascular cell adhesion molecule (VCAM). They are negative for CD11b - a marker of granulocytes, monocytes, and natural killer cells; and negative for CD14 a marker of monocytes and polymorphonuclear leukocytes. Moreover, these cells demonstrate proliferative potential, tolerate cryopreservation, and are amenable to gene transfer with a retroviral vector for the expression of Green Fluorescent Protein (GFP) and human factor VIII. CONCLUSION: A reliable and reproducible culture method was successfully developed to grow murine blood outgrowth endothelial cells. These cells have a potential use as a gene therapy delivery tool. CLINICAL IMPLICATIONS: Murine BOECs can be utilized in modeling studies for gene therapy, limb and tissue revascularization, and coverage for prosthetic valves and stents. DISCLOSURE: A. Somani, None.

included age 67 ⫾ 12 years, male 66%, FVC% predicted 68 ⫾ 21%, and DLCO% predicted 42 ⫾ 17%. Correlates of 6MWT distance included high FVC % predicted (p⬍0.01) high FEV1% predicted (p⬍0.02), low DLCO% predicted (p⬍0.03), high Borg dyspnea score at rest (p⬍0.02), and no need for supplemental oxygen (p⬍0.01). Oxygen desaturation occured in 24 of 27 patients. Correlates of the difference between maximal and minimal oxygen saturation included a high Borg dyspnea score at maximal exercise (p⬍0.02) and low DLCO% predicted (p⬍0.005). Nonsmokers had more desaturation (p⬍0.02) than those who were smokers despite similar measures of FVC, FEV1, and DLCO. The HRCT fibrosis score failed to correlate with any measure of 6MWT (p⫽NS). CONCLUSION: The 6MWT measures a walk distance and degree of oxygen desaturation that have independent correlates in IPF. Neither of the measures are strongly correlated with HRCT fibrosis score. The determination of which tests are best as clinical outcome measures remain unknown. The correlation between cigratte smoking and less oxygen desaturation implies lead time bias. CLINICAL IMPLICATIONS: A 6MWT measures variables that are independent from lung fibrosis. Oxygen desaturation is correlated with measures of vascular patency and dyspnea. Walk distance is more correlated with measures of lung mechanics. A 6MWT integrates important variables in IPF. DISCLOSURE: R.K. Jain, None.

Wednesday, October 27, 2004 Interstitial Lung Disease - Idiopathic Pulmonary Fibrosis, continued Table 1. Appropriateness of various treatments for IPF by age and severity subgroups. IFN ⫹ IFN Steroids

No Steroids Azathioprine Cyclophos Treatment alone ⫹ Steroids ⫹ Steroids ⬍65, mild

No prior steroids or cytotoxic agents

–

–

⫹

0

0

0*

Failed prior steroids

–

–

⫹

0

⫹

0

Failed prior cytotoxic agents

–

–

0

–

⫹

⫹

Failed prior steroids and 0* cytotoxic agents

–

–

–

⫹

⫹


–

⫹

0

0*

0*

⬍65, moderate –


–

–

0

0

⫹

0


–

–

0

–

⫹

⫹

Table 2. Consensus Panel Members for: A critical assessment of treatment options for idiopathic pulmonary fibrosis. This work was supported by an unrestricted grant from the Coalition for Pulmonary Fibrosis (CPF). The Coalition did not play any role in the design or conduct of the study, in the collection, analysis or interpretation of the data, or the preparation of the manuscript. The majority of the authors have received honoraria from companies that manufacture and distribute therapies mentioned in this report; several also serve as consultants and are on the advisory board and steering committee for clinical trials sponsored by pharmaceutical companies, received honoraria for giving lectures sponsored by InterMune, Inc. and are on the Board for the CPF. Panel Members 1

Paul Noble, MD

Failed prior steroids and – cytotoxic agents

–

–

–

⫹

⫹


–

–

0

0

–

0

Robert M. Jackson, MD2


–

–

0

0

0*

0

Talmadge E. King, Jr., MD3


0*

–

–

–

0*

0


–

–

–

0*

0


–

–

0

–

0

0*


0

–

0*

–

⫹

0


0*

–

–

–

0

0


–

–

–

⫹

0


–

⬍65, severe

65-79, mild

Steven D. Nathan, MD4 Maria Padilla, MD5 Ganesh Raghu, MD6 Melissa Bruce Rhodes, MD7 Marvin Schwarz, MD8

65-79, moderate –

0

–

0

0*


–

–

0*

–

⫹

0


0*

–

–

–

⫹

0


–

–

–

⫹

0


0*

–

0*

–

–

–


0*

–

0*

–

–

0


0*

–

–

–

–

0


–

–

–

0

0

65-79, severe

*0 ⫽ panelist disagreement ⫹ ⫽ Appropriate, – ⫽ Inappropriate, 0 ⫽ Uncertain, Steroids ⫽ Corticosteroids, Cyclophos ⫽ Cyclophosphamide *0 ⫽ panelist disagreement

⫹ ⫽ Appropriate, – ⫽ Inappropriate, 0 ⫽ Uncertain, Steroids ⫽ Corticosteroids, Cyclophos ⫽ Cyclophosphamide

888S

Gregory Tino, MD9

Institutions 1

Yale University School of Medicine Department of Internal Medicine, New Haven, CT 2 University of Alabama at Birmingham, Birmingham, AL 3 Department of Medicine, University of California San Francisco, San Francisco, CA 4 Inova Fairfax Hospital, Falls Church, VA 5 North Shore University Medical Center, Manhasset, NY 6 Department of Medicine, University of Washington, Seattle, WA 7 Georgia Lung Associates, Austell, GA 8 University of Colorado Health Sciences Center, Denver, CO 9 University of Pennsylvania Medical Center, Philadelphia, PA

DISCLOSURE: N.R. Shah, None. DISTANCE-SATURATION PRODUCT AS A MARKER OF DISEASE PROGRESSION AND MORTALITY IN IDIOPATHIC PULMONARY FIBROSIS Christopher J. Lettieri, MD*; Robert F. Browning, MD; Andrew F. Shorr, MD, MPH; Shahzad Ahmad, MD; Steven D. Nathan, MD; Walter Reed Army Medical Center, Washington, DC PURPOSE: Desaturation during six-minute walk test (6MWT) is associated with increased mortality in idiopathic pulmonary fibrosis (IPF) and distance walked has been shown to have prognostic value in various forms of advanced lung disease. We defined a new index, the distancesaturation product (DSP), which is the product of total distance walked and final oxygen saturation (SpO2) during 6MWT. We hypothesized that for IPF, the DSP is a more reliable predictor of mortality than other physiologic variables. METHODS: Prospective analysis of serial 6MWTs with contemporaneous pulmonary function tests (PFTs), in IPF patients, seen between 1998 and 2004. Oxygen saturation and distance walked were recorded at baseline and throughout 6MWT. The DSP was calculated in each test. We compared PFTs, the occurrence of hypoxia at each minute during 6MWT, the DSP, and the decline in DSP over time in survivors and non-survivors. RESULTS: 63 patients (35 survivors, 28 non-survivors) were identified. Median period of observation was 23.3 months. Hypoxia was common, but occurred earlier during 6MWT and with greater magnitude among non-survivors. Desaturation ⬎8% from baseline and the development of Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Interstitial Lung Disease - Idiopathic Pulmonary Fibrosis, continued hypoxia (SpO2 ⬍88%) within 3 minutes of walking were both more common among non-survivors (p⬍0.05). Final SpO2 declined by 10% in survivors and 14% in non-survivors (p⬍0.05). Average distance declined 10% in survivors and 21% in non-survivors (p⬍0.05). Mean DSP measured 256 (%-meters) among survivors vs. 176 in non-survivors (p⫽0.001). During follow-up, the average DSP declined in survivors by 23% compared to 45% in non-survivors (p⫽0.036). Neither initial PFTs nor changes in PFTs over time, differentiated survivors from non-survivors. CONCLUSION: The DSP represents a simple, non-invasive test that is a sensitive predictor of mortality. Timing and degree of hypoxia during 6MWT also correlates with mortality. Each of these functional measurements was a better predictor of outcome than either PFTs or serial changes in PFTs over time. CLINICAL IMPLICATIONS: Physicians should consider utilizing 6MWTs to identity subjects at increased for death. The DSP may be a useful marker of disease severity in IPF. DISCLOSURE: C.J. Lettieri, None.

PURPOSE: IPF is a crippling disease that impairs gas exchange in the lung due to excessive accumulation of extra cellular matrix (ECM). IPF is thought to result from epithelial cell injury followed by aberrant wound healing. Numerous resident and recruited cell types, including lung epithelial cells, fibroblasts, activated macrophages, platelets, and lymphocytes, are known to release transforming growth factor beta (TGF-beta) in lung tissue in individuals with IPF. TGF-beta, in turn, enhances the deposition and accumulation of ECM, which leads to fibrotic lesions. To examine the molecular consequences of therapeutic application of IFNgamma1b, we studied the effect of IFN-gamma1b on TGF-beta-modulated ECM turnover in a cellular model for IPF. METHODS: A human lung epithelial cell line (A549) was cultured in DMEM containing 10% serum, washed with PBS and serum-free medium added. After overnight incubation, cells were treated with increasing concentrations of IFN-gamma1b or left untreated, and then stimulated with 5 ng/ml TGF-beta. Both cell culture supernatant and cell lysate were collected, and ELISA assays were used to quantify secreted collagen and intracellular tissue inhibitor of metalloproteases 1, TIMP1. RESULTS: Relative to untreated cells, TGF-beta induced the expression of collagen by 30% and TIMP1 by 60%. TGF-beta-induced expression of both collagen and TIMP1 was suppressed in a concentrationdependent fashion by adding IFN-gamma1b (p⬍0.01 for TIMP1, 0.03 for collagen). Importantly, these effects were statistically significant at the therapeutically relevant Cmax concentrations of IFN-gamma1b obtained from clinical trials. CONCLUSION: Our results indicate that IFN-gamma1b inhibits both TGF-beta-induced collagen synthesis and TGF-beta-induced accumulation of TIMP1. Since both of these components are integral to deposition and accumulation of ECM, the likely net result may be a substantial decrease in the rate of ECM accumulation. CLINICAL IMPLICATIONS: These results suggest that IFNgamma1b may be beneficial in the treatment for IPF in certain patients by reducing the rate of TGF-beta-induced ECM accumulation. Further study of IFN-gamma 1b in IPF patients is warranted and may provide a means for early assessment of response to IFN-gamma1b therapy. DISCLOSURE: O. Ozes, InterMune, Inc. OUTCOMES OF LUNG TRANSPLANTATION IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS RECEIVING GAMMA-INTERFERON 1B Nelson B. Burton, MD; Robert F. Browning, MD*; Christopher J. Lettieri, MD; Vincent G. Valentine, MD; Shahzad Ahmad, MD; Steven D. Nathan, MD; National Naval Medical Center, Bethesda, MD PURPOSE: Mortality rates are high among patients with idiopathic pulmonary fibrosis (IPF) awaiting lung transplantation (LTx). GammaInterferon 1b(IFN) has been used in these patients, with evidence suggesting an improvement in mortality in patients with mild to moderate disease. The role of IFN in LTx candidates was assessed by comparing

Survival From Listing

␥-IFN⫹ group (n⫽ 22) ␥-IFN- group (n⫽78)

1-mo

3-mo

6-mo

12-mo

91% 94%

91% 82%

91% 77%

91% 69%

p ⫽ 0.12 by Gehan-Wilcoxon

Survival after LTx

␥-IFN⫹ group (n⫽17) ␥-IFN- group (n⫽59)

1-mo

3-mo

6-mo

12-mo

100% 92%

100% 86%

100% 81%

100% 81%

p ⫽ 0.14 by Gehan-Wilcoxon DISCLOSURE: R.F. Browning, None.

Interstitial Lung Disease - Various Topics 12:30 PM - 2:00 PM INHIBITION OF BLEOMYCIN-INDUCED PULMONARY FIBROSIS BY OKAM EXTRACT J201 Handong Jiang, MD*; Tong Li; Affiliated Hospital of Medical College, Qingdao University, Qingdao, Peoples Republic of China PURPOSE: To explore the inhibitory effect of okam extract J201 on bleomycin-induced pulmonary fibrosis and its underlying mechanism of action. METHODS: Inhibition of proliferation and collagen synthesis of human lung fibroblast by okam extract J201 and its effect on PDGF were measured by MTT assay and Sircol Soluble Collagen Assay in vitro. Using bleomycin-induced pulmonary fibrosis animal model, its effects on mouse lung index, concentration of serum IL-4, INF-r were measured with ELISA. The concentrations of MDA and hydroxyproline in supernant of lung tissue were measured and microscopic pathology of lung was evaluated at the same time. RESULTS: Okam extract J201 significantly inhibited the proliferation and collagen synthesis of lung fibroblast induced by PDGF with its peak inhibitory rate at concentration above 50ug/ml. Serum IL-4 was significantly lower and INF-r higher in okam group than those in controls. The contents of MDA and hydroxyproline in mouse lung supernant were CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

889S


EFFECT OF INTERFERON-GAMMA 1B IN CELLULAR MODELS OF LUNG FIBROSIS: IMPLICATIONS FOR THE TREATMENT OF IDIOPATHIC PULMONARY FIBROSIS (IPF) Osman Ozes, PhD*; Tim Tran, BS; Tony Wang, MD; Sarah Stevens, MS; Scott Seiwert, PhD; Lawrence M. Blatt, PhD; InterMune, Inc., Brisbane, CA

outcomes of listed IPF patients who were treated with IFN and those who were not. METHODS: Retrospective review of all patients with IPF listed for LTx at two large centers (1992-2004). Endpoints were defined as mortality from listing to 90 days post LTx along with survival to LTx and survival post LTx. Outcomes were compared between those patients who did and did not receive IFN pretransplant. RESULTS: During the study period, 101 patients with IPF were listed and 76 underwent LTx. Among the IFN⫹ cohort, 10% (n⫽2) died prior to LTx vs 21% (n⫽17) of the IFN- cohort (p⫽0.20). The median duration of IFN treatment was 359 days (range 42-867). The waiting list time was shorter for the IFN⫹ group, 86 vs 136 days in the IFN- group, (p⫽0.09). The mortality rates from listing to 90 days post LTx for the IFN⫹ and IFN- groups were 5% and 24%, respectively (p ⫽ 0.23). Survival from listing and post LTx are seen in the tables below. CONCLUSION: IFN appeared to have a clinically relevant reduction in mortality for IPF transplant candidates although statistical significance was not achieved. This study is limited by its retrospective design, small sample size, and historically different eras in the pooled dataset. CLINICAL IMPLICATIONS: We speculate this trend to improved survival in IFN⫹ group may be due to a combination of improved pretransplant survival and the IFN⫹ patients being less ill at the time of transplant.

Wednesday, October 27, 2004 Interstitial Lung Disease - Various Topics, continued significantly lower in okam group than in controls. Mouse lung index as measured by lung weight divided by body weight were significantly lower in okam group than that in control. Light microscopic examination revealed less inflammatory cell infiltration and fibrosis of the lung. CONCLUSION: Okam extract J201 inhibits bleomycin-induced pulmonary fibrosis in mouse possibly by inhibition on fibroblast proliferation and Th2 cell cytokines. CLINICAL IMPLICATIONS: Okam extract J201 may be used for the treatment of pulmonary fibrosis. DISCLOSURE: H. Jiang, None. SERUM ANTIBODY IN SARCOIDOSIS DEMONSTRATES ANTIGENIC PROFILE SIMILAR TO INTRATRACHEAL UREASE Courtney D. Langdon, MD*; Rebecca L. Shriver, MD; Betty Herndon, PhD; University of Missouri-Kansas City, Kansas City, MO PURPOSE: Our group has a long-standing interest in Helicobacter pylori (Hp) and its enzyme urease, and the pulmonary inflammation which occurs following micro-aspiration of Hp and its byproducts. We have established an animal model in which urease was delivered intratracheally via an osmotic pump for 1 month. Histopathology showed prominent peribronchial germinal centers and, in vitro analysis of urease showed cross-reactivity with a well-known lymphocyte mitogen, Concanavalin A (ConA). Urease, in a non-acidic milieu, increases in ConA reactivity as shown by Western blot. (ATS report 2004, Langdon and Herndon). With the hypothesis that enigmatic pulmonary inflammation may relate to aspiration of urease/ConA or its bacterial source, antibody capture was performed on the sera of fourteen subjects with sarcoidosis. We have previously reported that subjects with sarcoidosis often have high levels of antibody against Hp, as did these 14 (93%). METHODS: Eight 2x dilutions of the 14 serum samples were analyzed for specific IgG on microtiter plates coated with one of three capture antigens: Hp, urease, or ConA. Serum titer was the log10 mean dilution producing linear antigen binding. ConA (a putative breakdown product of urease) was analyzed on the subjects divided by Hp and urease reactivity: High Hp responders, low Hp responders, high urease responders, and low urease responders. RESULTS: All 14 subjects with sarcoidosis had elevated antibody titers to both Hp and urease when plated against ConA. The subjects who were high urease responders showed a signigicant increase in ConA reactivity compared to subjects who were high Hp responders, p⬍0.02, student t-test. Our schematic interpretation of these results is: urease ⬍zpi; ●⬎“pH related breakdown ⬍zpi;●⬎” ConA-like mitogen ⬍zpi;●⬎” pulmonary inflammation ⬍zpi;●⬎“ disease (and antigenic recognition). CONCLUSION: Patients with sarcoidosis have a high immunologic response to a breakdown product of urease that has known mitogenic pulmonary effects in animals. The relationship to the etiology of their disease is unknown at this time. CLINICAL IMPLICATIONS: Data providing evidence for the etiology of sarcoidosis would be a major advance in medicine. DISCLOSURE: C.D. Langdon, None. ACUTE EOSINOPHILIC PNEUMONIA IN SOLDIERS DEPLOYED AS PART OF OPERATIONS IRAQI FREEDOM & ENDURING FREEDOM Andrew F. Shorr, MD*; George D. Shanks, MD; Stephanie L. Scoville, DrPH; Steven B. Cersovsky, MD; Bruno P. Petruccelli, MD; Walter Reed Army Medical Center, Washington, DC

person-years. The majority of subjects (88%) were male and the median age was 23 years (range 20-43). Six subjects underwent bronchoalveolar lavage (median eosinophilia of 41%). All subjects developed peripheral eosinophlia (range 8% to 42%). There was no geographic or temporal clustering of cases. An extensive search for known causes of pulmonary eosinophilia (e.g., drug exposures, parasitic disease) did not identify any secondary etiologies. All patients used tobacco with 2/3rds recently beginning to smoke. MV was required in 71% for a median of 7 days (range: 2 to 16 days). Two soldiers died. The remainder responded to corticosteroids. Twelve individuals were re-evaluated a median of 3 months after diagnosis. At this point subjects were: off treatment and had either normal or nearly normal spirometry. None had recurrent eosinophilia or developed chronic eosinophilic pneumonia. CONCLUSION: The rate of AEP appears high in this population of otherwise healthy subjects and not all suffer fulminant respiratory failure. Corticosteroids if initiated promptly appear effective. CLINICAL IMPLICATIONS: Physicians caring for soldiers returning from OIF/OEF should consider AEP in patients who develop pneumonia. Early use of bronchoscopy may aid in identification of cases. DISCLOSURE: A.F. Shorr, None.

INTERSTITIAL LUNG DISEASE AND PULMONARY EMPHYSEMA ASSESSED BY HIGH RESOLUTION COMPUTED TOMOGRAPHY ANALYSIS OF PIXEL DENSITY DISTRIBUTION Antonio Castagnaro*; Elisa Calabro`; Emilio Marangio; Olga Torre; Matteo Maestrelli; Nicola Sverzellati; Alfredo Chetta; Dario Olivieri; Maurizio Zompatori; Respiratory Diseases Section, University of Parma, Parma, Italy PURPOSE: Pulmonary emphysema extension can be reliably evaluated by histogram of density based on HRCT pixel density distribution. To date, there are no data on ILD and HRCT pixel density distribution. We evaluated the diagnostic role of the HRCT pixel density distribution to differentiate ILD patients from patients with pulmonary emphysema. METHODS: We studied 6 patients (3 M, age range: 43 to 83 yrs) with ILD and 6 patients (5 M, age range: 60 to 72 yrs) with pulmonary emphysema. Spirometry, lung volumes, diffusing capacity and blood gases were measured in all patients. The histogram of density provided a frequency distribution of voxels with specific attenuation numbers (in Hounsfield units) in the lung. We analyzed the voxel distribution vs hounsfield units plots in all patients. RESULTS: We found that the 1/slope of pixel density values vs hounsfield units value were significantly steeper in patients with emphysema than those with ILD patients (-844 ⫾ 91 vs -622 ⫾ 91, p⬍ 0.05). CONCLUSION: Our results showed that the histogram of density based on HRCT pixel density distribution in ILD patients was significantly different from that of pulmonary emphysema patients. CLINICAL IMPLICATIONS: HRCT pixel density distribution may be clinically useful to assess ILD patients. DISCLOSURE: A. Castagnaro, None.

SERUM IGE-LEVELS IN PATIENTS WITH CHRONIC SARCOIDOSIS VS. PATIENTS WITH ACUTE DISEASE AND HEALTHY CONTROLS Violeta V. Vucinic, MD, PhD*; Jelica Videnovic, MD, PhD; Vladimir Zugic, MD; Branislav Gvozdenovic, MD; Jasmina Zivkovic, MD; Snezana Filipovic, MD; Institute of Pulmonary Diseases, University Clinical Center, Belgrade, Serbia

PURPOSE: Eosinophilic lung diseases include a variety of conditions ranging from tropical eosinophlia to drug reactions. Acute eosinophilic pneumonia (AEP) is a rare disease usually characterized by respiratory failure and alveolar infiltration with eosinophils. We describe a series of US military personnel who developed AEP while deployed. METHODS: We identified military personnel diagnosed with AEP while serving in Operations Iraqi Freedom and Enduring Freedom (OIF/OEF). After a retrospective evaluation (March – June 2003), prospective surveillance commenced in July 2003. We defined AEP based on the acute onset of pulmonary infiltrates coupled with either pulmonary eosinophilia or peripheral eosinophilia. We required that known causes of eosinophilia be excluded. Endpoints included: epidemiologic features, need for mechanical ventilation(MV), and mortality. RESULTS: Between March 2003 and March 2004, 17 cases were identified yielding an estimated annualized incidence of 9.7 per 100,000

PURPOSE: The thesis on allergy and atopy in sarcoidosis patients has been present as a challenge considering different immunology pathways of sarcoidosis for years. The aim of this study is to present the correlation of the low serum IgE levels in patients with chronic sarcoidosis and the serum IgE levels of the healthy control subjects, and to introduce into the discussion different possibilities of the immune response in sarcoidosis. METHODS: 459 biopsy positive sarcoidosis patients and 100 healthy controls are analyzed. The patient group was divided into two subgroups: patients with acute sarcoidosis and patients with chronic sarcoidosis. Patients with positive history of allergy were excluded from the study as well as the patients with extremely high levels of the serum IgE (500 IU/ml and above). All patients and healthy controls were non-smokers, with the mean age of 46,48 years (SD 11,50) for the patients group and 48,72 years for healthy controls (SD 9,60).

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Wednesday, October 27, 2004 Interstitial Lung Disease - Various Topics, continued RESULTS: The mean value of the serum IgE of all analyzed patients (459pts) was 51,57 IU/ml (SD 75,55). In the group with chronic sarcoidosis (259 pts) the mean value of the serum IgE was 43, 86 IU/ml (SD 73,78) while in the group of sarcoidosis patients with acute disease (200pts) the mean serum IgE level was 61,75 IU/ml (SD 76,96) The serum IgE mean value in the control group was 137, 56 IU/ml (SD 194,84). CONCLUSION: Patients with chronic sarcoidosis have significantly lower values of the serum IgE compared with the patients with acute disease and healthy controls (statistic. sign p⬍ 0,01). CLINICAL IMPLICATIONS: The low values of the serum IgE might enlighten the new approach of the immunology in sarcoidosis patients. DISCLOSURE: V.V. Vucinic, None.

LUPUS PERNIO ACTIVITY AND SEVERITY INDEX (LUPASI) SCORE IN SARCOIDOSIS PATIENTS Robert P. Baughman, MD*; Marc A. Judson, MD; Elyse E. Lower, MD; Rozsa Schkenker-Herceg, MD; Elliott Barnathan, MD; University of Cincinnati, Cincinnati, OH

INTEGRATING CLINICAL ASSESSMENT AND IMAGING IN INTERSTITIAL LUNG DISEASE (ILD) Roberto G. Carbone, MD, FCCP*; Rosangela Filiberti, PhD; Giovanni Bottino, DSc; Pneumology, Regional Hospital, Aosta, Italy PURPOSE: The research deals with non-invasive methods for the diagnosis of ILD, aimed at avoiding surgical procedures and reducing medical costs. METHODS: We evaluated clinical symptoms, signs, and imaging of 71patients (pts) with ILD (median age 60 years, 42 % males). ILD subgroups included: usual interstitial pneumonia (UIP ⫽ 34), non-specific idiopathic pneumonia (NSIP⫽13), Wegener granulomatosis (WG ⫽14), and extrinsic allergic alveolitis (EAA ⫽ 10), all pathologically confirmed. Surgical diagnosis performed by open pulmonary biopsy (n ⫽ 31), VATS (n⫽27) or percutaneous biopsy (n ⫽13). A periodical imaging evaluation has been carried out independently by two radiologists and two respiratory physicians, and a high-resolution CT (HRCT) severity score (degrees ⫽ 04) has been calculated.

INITIAL HEMODYNAMIC DESCRIPTION IN 20 CASES OF EXTRINSIC ALERGIC ALVEOLITIS Erick Bringas, MD*; Yolanda Mares, MD; Hospital General de Mexico, Tlalpan, Mexico PURPOSE: Analyze the initial hemodynamic behavior of the illness and determine if exist any data for differentiate this illness from others interstitial lungs diseases. METHODS: We reviewed the hemodynamic characteristic at rest as in exercise with right cardiac catheterization (RCC) of 20 patients with the diagnostic of EAA in a retrospective and observational study with statistical analysis of the hemodynamic of these patients. RESULTS: From October of 1996 to June of 2002 we found 200 patients with interstitial diseases, 21 with diagnostic of EAA (10.5%). 20 patients were included in the study, 19 females and 1 man with a mean age of 51.5 ⫾ 16.5, 18 had histological diagnostic by open lung biopsy the remaining two had clinic-tomography (One patient did not accept the procedure and one more was rejected for sever pulmonary hypertension). 60% of the 20 patients evaluated presented pulmonary hypertension (The mean pulmonary pressure was at rest 25.7 mmHg. ⫾ 13.45) without significant increase during exercise (40.2 mmHg. ⫾ 15.54 p⫽0.276). The mean pulmonary wedge pressure was 5.29 mmHg at rest and 7.61 mmHg in exercise without statistical significance.The mean cardiac index was 3.58 L/min./m2 at rest and 4.79 L/min./m2 in exercise with a p⫽ 0.628 and 0.564 respectively (been significant with p ⱕ 0.05). The were not hemodynamic findings that reached statistical significance but in the other hand the data of the blood gas exchange did it, like Qs/Qt%, PvCO2, PvO2, G a-vO2. CONCLUSION: In Conclusion our study showed that even we found similar results in the hemodynamic at rest and exercise, there were only differences in the blood gas exchange and that theses differences were more significant in the venous blood gas exchange. CLINICAL IMPLICATIONS: We hypothesized that the hemodynamic of the patient with EAA can be a determinant for differentiate it form others interstitial pneumopathies but the result showed the opposite. More hemodynamics studies are needed to better understand the illness and offer other therapies that render in the best life quality and expectancy. DISCLOSURE: E. Bringas, None.

Pleural Disease: Bench to Bedside 12:30 PM - 2:00 PM SAFETY AND EFFICACY OF INTRAPLEURAL INSTILLATION OF ALTEPLASE IN THE MANAGEMENT OF HEMOTHORAX George Thommi, MBBS*; Chris Shehan, MD; Patrick Meyers, MD; Mathew Mcleay, MD; Creighton University/ Methodist Hospital, Omaha, NE PURPOSE: To determine if Alteplase can be safely instilled intrapleurally in patients with hemothorax, and who are poor surgical candidates. METHODS: Ten patients with hemothorax were evaluated for intrapleural Alteplase instillation. These patients were either postoperative CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Lupus pernio is a chronic facial lesion due to sarcoidosis with a minimal rate of spontaneous remission. In order to quantitate response to therapy for lupus pernio, we developed a specific lupus pernio activity and severity index (LuPASI) based on the psoriasis activity and severity index. METHODS: We evaluated 10 patients with lupus pernio at one institution, were seen at least on two separate visits, and evaluated by two investigators (RPB and EEL) when possible. The face was divided into specific areas and each area was separately scored on a five point scale for erythema (E), induration (I), and desquamation (D). The total amount of the area (A) involved was also assessed on a 7 point scale. The divisions were the four quadrants of the face, with the division of upper and lower being through the mid eye, with the nose should be scored separately. RESULTS: All 10 patients had one or more areas of involvement. There were 297 comparisons between the areas involved. The table below shows the difference between the median determination for each area and the discrepancy for the individual score for different days for the same patient. Level of Difference: None: E⫽76.4%,I⫽74.4%,D⫽77.1%, A⫽83.8%, All⫽77.9%; One: E⫽20.2%, I⫽23.2%, D⫽20.9%, A⫽16.2%, All⫽20.1%; Two: E⫽3.4%, I⫽2.0%; D⫽1.3%, A⫽0.0%, All⫽1.7%. Three: I⫽0.3%, All⫽0.1%. For all four descriptors, the agreement was with one point of the median in over 95% of cases. When we compared two observers (RPB vs EEL), there was less agreement, but in less than 5% of cases in which there was a 3 point or higher difference noted between the readers. The LuPASI score was then used at another institution. It was judged to simple to understand and easily completed in less than two minutes. CONCLUSION: We conclude that the use of a LuPASI score can provide objective evidence of response to therapy. CLINICAL IMPLICATIONS: When the same reader evaluates the patient, a greater than 1 point difference probably reflects response to therapy, rather than chance. DISCLOSURE: R.P. Baughman, Centocor

RESULTS: NSIP pts were younger than UIP (p⫽0.001) or WG (p ⫽ 0.01). Cracklers were less common in NSIP than UIP (38% vs 100%; p⬍0.001), and were absent in WG and EAA. Fever was much more common in EAA than in NSIP (p⫽0.002), UIP (p⫽0.001), and WG (p⬍0.001). All UIP showed Octreoscan uptake index (UI) ⬍10 (normal value ⱕ10). UI ranging from 10 to 12 UI was indicative of NSIP. It was indicative of WG and EAA when it was higher than 15 UI. A CT score with degree ⫽ 4 was indicative of UIP, while 100% of WG and EAA had score degree ⫽ 2. CONCLUSION: Age, signs (cracklers), fever and Octreoscan may be useful to differentiate among ILD subgroups. The diagnosis of UIP, the commonest ILD subgroup, may be achieved by using these parameters. CLINICAL IMPLICATIONS: Clinical parameters as well as imaging must be considered in assessing ILD. Diagnosis of UIP is possible avoiding surgical procedure and reducing medical costs. DISCLOSURE: R.G. Carbone, None.

Wednesday, October 27, 2004 Pleural Disease: Bench to Bedside, continued patients or poor surgical candidates with the following characteristics: Three patients had spontaneours hemothoraces secondary to anticoagulation; two patients had thoracotomies with decortication and postoperatively were noted to have large hematomas in the pleural space; five patients with malignant pleural effusions that were frankly bloody with multiple loculations documented on CT scan and/or ultrasound of the chest. Patients were anemic and needed transfusion prior to Alteplase instillation. All patients had 28-F or 30-F chest tube catheter placed without any improvement of the hemothorax. Patients were monitored for at least fourty eight hours prior to Altelplase instillation. Initially, 10 mg of Alteplase was instilled intrapleurally. If no complications occured then further doses of 10 mg to 25 mg of Alteplase was administered daily until significant clearing of the hemothorax was noted. Most patients required three to four doses of Alteplase therapy. RESULTS: All patients tolerated the procedure well and marked clearing of the hemothorax was noted. No patients needed surgical intervention or any other medical therapy. CONCLUSION: Intrapleural instillation of Alteplase can be safely used in patients with hemothorax occuring spontaneously, with malignant pleural effusions, or in postoperative patients, providing no trauma or acute bleeding is noted. CLINICAL IMPLICATIONS: Alteplase is an alternative to surgical intervention in the management of patients with hemothorax. DISCLOSURE: G. Thommi, Supported by Genetech, Inc

SAFETY PROFILE OF VARIOUS DOSES OF ALTEPLASE INSTILLED INTRAPLEURALLY IN THE MANAGEMENT OF COMPLICATED PLEURAL EFFUSIONS/EMPYEMA George Thommi, MBBS*; Chris Shehan, MD; Patrick Meyers, MD; Mathew Mcleay, MD; Creighton University/ Methodist Hospital, Omaha, NE PURPOSE: To evaluate the safety of various doses of Alteplase in the management of complicated pleural effusions(CPE)/empyema. METHODS: One hundred twenty patients admitted to Methodist Hospital with CPE/empyema that failed standard medical treatment and simple chest tube drainage were treated with intrapleural Alteplase in doses ranging from 10mg to 100mg. A total of 330 doses of Alteplase were instilled intrapleurally as follows: 17 doses of 100mg of Alteplase, 70 doses of 50mg alteplase, 211 doses of 25mg alteplase and 10 doses of 10mg alteplase. Alteplase was administered daily through the chest tube intapleurally in 100cc of normal saline. Alteplase instillation was stopped when the drainage was less than 150cc in 24 hours, or if the drainage fluid appeared to be more bloody with each instillation, or if any complications occurred. A few patients received pre-and post coagulation profile with Alteplase instillation. Patients were monitored for any adverse events during, and for 24 hours after the procedure. RESULTS: Two patients had significant bleeding post procedure (over 1gm Hemoglobulin), one needing transfusion. One patient had an intrapleural hematoma that resolved over a few days. One patient with severe COPD and respiratory failure had progressive shortness of breath several hours after Alteplase instillation, but when rechallenged a few days later had no adverse events. Seven patients experienced chest pain with only the first dose of Alteplase. Five had mild chest pain, one had moderate chest pain and one had severe chest pain. No significant change in coagulation was noted pre and post-Alteplase instillation in the patients that were monitored. CONCLUSION: Intrapleural instillation of Alteplase is safe in doses up to 100mg administered daily. Side effects are minimal, with chest pain and bleeding at the chest tube site being the most common. CLINICAL IMPLICATIONS: Alteplase in doses of up to 100mg daily can be safely instilled intrapleurally in complicated pleural effusions/ emyema. DISCLOSURE: G. Thommi, Supported by Genetech, Inc

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INTRAPLEURAL INSTILLATION OF ALTEPLASE IN COMPLICATED MALIGNANT PLEURAL EFFUSIONS PRIOR TO PLEURODESIS George Thommi, MBBS*; Chris Shehan, MD; Patrick Meyers, MD; Mathew Mcleay, MD; Creighton University/ Methodist Hospital, Omaha, NE PURPOSE: To document the safety and efficacy of Alteplase in the management of malignant pleural effusions prior to pleurodesis. METHODS: Eighteen patients with malignant pleural effusions continued to have persistent fluid drainage after chest tube placement. Chest radiograph showed persistent pleural fluid and infiltrates, and/or loculated pleural fluid documented on CT scan and/or ultrasound. All eighteen patients were treated with Alteplase instilled intrapleurally in doses ranging from 10mg to 50mg (diluted in 100cc of normal saline) daily or every second or third day. The chest tube was flushed after Alteplase instillation with 30cc to 50cc of normal saline. Alteplase was continued until significant improvement of pleural fluid and loculations/pulmonary infiltrates were noted. Two to four doses of Alteplase was usually required. RESULTS: Pleural fluid drainage decreased with clearing of loculations and/or pulmonary infiltrates after Alteplase instillation. Pleurodesis was performed only when the pleural fluid drainage was less than 150 cc in 24 hours, using either talc or bleomycin. All patients that were sclerosed after Alteplase instillation had no recurrence of their malignant pleural fluid. CONCLUSION: Malignant pleural effusions that are loculated, have pulmonary infiltrates and continue to have persistent fluid drainage may benefit from intrapleural instillation of fibrinolytic agents to help facilitate pleurodesis. CLINICAL IMPLICATIONS: Fibrinolytics may have a role in the management of complicated malignant pleural effusions prior to pleurodesis. DISCLOSURE: G. Thommi, Genetech DIAGNOSIS OF PNEUMOTHORAX (PTX) BY MEANS OF TRANSTHORACIC ULTRASOUND – A PROSPECTIVE TRIAL Felix J. Herth, MD*; Ralf Eberhardt, MD; Heinrich D. Becker, MD; Armin Ernst, MD; Thoraxklinik, Heidelberg, Germany PURPOSE: X-ray of the thorax represents so far the standard diagnostic procedure to evaluate for a PTX, but is associated with radiation exposure and logistic delays. Portable ultrasound is now widely and easily available and may present an attractive alternative to conventional CXR in the evaluation for that disorder. The typical ultrasonic finding is typically the lack of respiration-dependent sliding of the pleura. Prospective investigations of the value of ultrasound in the diagnosis of PTX are missing. METHODS: Patients undergoing transbronchial biopsy were included in the study, as all patients undergo post procedure imaging to rule out PTX. All patients were evaluated by ultrasound and conventional CXR in 2 views. The results were compared. RESULTS: In the observation period (01/03-01/04) 1023 patients (321 female, 702 men and mean age 47.2 years) were examined. In 36 cases a PTX was assumed by ultrasound, in 30 cases (2.9 %) a pneumothorax was radiologically proven. This corresponds to a sensitivity of 100 % and a specificity of 83 %. There were no wrong negatives. CONCLUSION: Transthoracic ultrasound represents a highly sensitive procedure for the diagnostic of pneumothorax. It is easily performed, does not expose patient and staff to radiation and is increasingly available. It is not possible to quantify the free amount of air. CLINICAL IMPLICATIONS: Transthoracic ultrasound allows the diagnosis of PTX. DISCLOSURE: F.J. Herth, None. EFFICACY OF ULTRASOUND IN THE DIAGNOSIS OF PLEURODESIS IN RABBITS Edwin Donnelly, MD; Zhiwen Zhu, MD*; Kirk B. Lane, PhD; Richard W. Light, MD; Saint Thomas Hospital, Nashville, TN PURPOSE: The treatment of recurrent pleural effusion or recurrent pneumothorax frequently involves the creation of a pleurodesis. Advances in the technology have greatly improved the imaging capabilities of ultrasound (US). Ultrasound is an efficient imaging modality for the evaluation of a wide variety of chest diseases. The purposes of this study Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Pleural Disease: Bench to Bedside, continued

IATROGENIC PNEUMOTHORAX: ETIOLOGY, MORBIDITY, AND MORTALITY Alexsander Kogos, MD; Mazen Alakhras, MD*; Zakia Hossain, MD; Vijay Rupangudi, MD; Karthikeyan Kanagarajan, MD; Padmanabhan Krishnan, MD; Coney Island Hospital, Brooklyn, NY PURPOSE: The purpose of this study is to review the cases of pneumothorax (PTX) in our community hospital, and to determine the frequency, causes, morbidity, and one-month mortality rate (MR) of iatrogenic pneumothorax. METHODS: Retrospective study of all patients with pneumothorax in our community hospital between January 1999 and December 2003. Patients with iatrogenic PTX were identified, and data on the causes, need for chest tube (CT), need for mechanical ventilation (MV), and onemonth MR were collected. RESULTS: Iatrogenic PTX occurred in 86 patients (56%) out of 151 patients identified with PTX. The most common cause of iatrogenic pneumothorax was central venous catheter (CVC) placement (32 patients), followed by thoracentesis (26 patients), MV (17 patients), transthoracic needle aspiration (TTNA) (10 patients), and transbronchial biopsy (TBB) (1 patient). Among the patients with PTX following thoracentesis 9 patients (35%) were on MV. Need for CT, MV, and one-month MR is shown in the table. CONCLUSION: Iatrogenic pneumothorax accounts for a large proportion of the PTX seen in our hospital. Central line insertion, thoracentesis, and MV are the main causes resulting in substantial morbidity and significant mortality in this group of critically ill patients. CLINICAL IMPLICATIONS: When iatrogenic PTX occurs, it carries significant morbidity and mortality. In order to decrease the incidence of iatrogenic PTX, emphasis should be placed on prevention. Measures should include: 1) Proper choice of site of CVC insertion , internal jugular and femoral instead of subclavian, 2) Thoracentesis on patients on MV should be avoided if possible, or done under ultrasound guidance, and 3) Ventilator adjustments known to reduce barotrauma must be used in all patients on MV.

DISCLOSURE: M. Alakhras, None.

THORACENTESIS PERFORMED BY AN EXPERIENCED PULMONOLOGIST WITHOUT ULTRASOUND Yossef Aelony, MD*; KaiserPermanente, Rancho Palos Verdes, CA PURPOSE: Recent publications suggest that pleural ultrasound (U/S) needs to be routinely performed at the time of thoracentesis. (see CHEST: Feb,2003). We decided to contrarily assess the risks of NOT using U/S in a real world setting. METHODS: Consecutive thoracentesis procedures using a commercial kit (Pharmaseal*) & a #14 angiocatheter without U/S guidance were prospectively analyzed for success and morbidity in an inpatient/outpatient pulmonary practice, with 100% followup. The usual end-point of fluid removal was cessation of drainage, achievement of 1500 ml, or symptoms of severe cough, chest tightness, or dyspnea. Monometric measuresments were not used. RESULTS: A total of 123 Thoracenteses in 85 patients were performed, equally divided between males and females, right & left side. Simultaneous cope needle pleural biopsy was done in 7 instances. Large effusions (⬎1000 ml ) were removed in 32 cases (26%). A prior chest CT scan had been done in 16 patients (13%). There were 4 (3%) small pneumothoraces , 2 of which were associated with pleural biopsy. None required placement of a chest tube or any other intervention for the small air pocket. No patients had ‘re-expansion pulmonary edema’. No pleural hemorrhage or cutaneous hematoma was observed. No vasovagal reactions, although atropine was not given prophylactically Four ‘failings’ occurred:one dry tap with 30 mL hemoptysis–indicating an inaccurate choice of site for puncture–required further imaging to localize an anteriorly loculated parapneumonic effusion. Three dry or insufficient taps required a 2nd puncture at the same sitting in order to reach the fluid. The first case (1%) & possibly the last 3 (2%) might have benefited from ultrasonic guidance. CONCLUSION: In this real world setting of inpatient and outpatient thoracenteses performed by an experienced pulmonologist, situations where U/S could benefit patients were rare (ⱕ 3%). CLINICAL IMPLICATIONS: Although U/S is helpful in difficult presentations of pleural disease and in training programs, this study suggests it is superfluous for routine cases in a pulmonary practice. DISCLOSURE: Y. Aelony, None.

MOVING LUNG SIGN - A NEW WAY TO DIAGNOSE AND FOLLOW MODERATE PNEUMOTHORAX Lalit Kanaparthi, MD*; Mehboob Chaudhry, MD, FCCP; Rodney Landreneau, MD; University of Pittsburgh Medical Center, McKeesport, PA PURPOSE: To describe a new sign that may be useful in the detection and follow-up of patients with moderate pneumothorax called the moving lung sign. METHODS: Thirteen patients with pneumothorax were examined. In the moving lung sign, the patients with moderate pneumothorax felt the lung movement when they were made to stand and bend forwards at the waist. This movement was also felt as a light tap by the palm of the examiner’s hand applied lightly to the chest. All the patients were followed daily from the day of diagnosis until the pneumothorax resolved. RESULTS: Of the thirteen patients studied, nine with ⬍30% pneumothorax had a positive moving lung sign. The rest were negative possibly secondary to small lung size in three patients with ⬎50% pneumothorax, adhesions in two other patients which included one with CABG and the other with malignancy. This sign disappeared in all our patients when the pneumothorax resolved. CONCLUSION: Moving Lung sign is a new clinical sign in moderate pneumothorax. This finding can be used to detect pneumothorax immediately, facilitating prompt treatment. Although the sensitivity, specificity of this sign should be evaluated in larger studies, clinically this sign could be used as an additional diagnostic tool. As Dr Chaudhry himself personally experienced this sign, we call it the “Chaudhry’s sign”. CLINICAL IMPLICATIONS: This sign can lead the clinician further along this potential diagnosis in the early evaluation of acute chest pain which would potentially change the triage order of such patients seen in the emergency room and also lead the physician seeing the patient in the office setting to investigate this further with urgent chest x-ray. Further this sign could be used to follow patients with pneumothorax. DISCLOSURE: L. Kanaparthi, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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are: (1)To investigate whether US can be used for the diagnosis of pleurodesis. (2)To confirm which US image is the most important feature to diagnosis pleurodesis. METHODS: The utility of US in documenting pleurodesis was assessed in New Zealand white rabbits that were given a single intrapleural injection of TGF-␤ at doses of 1.70 ␮g in a volume of 2.5 ml. The side that received the injection was randomized and a sham procedure was performed on the alternate side. The ultrasonographer was blinded as to which side received the injection. All rabbits had an ultrasonic examination at three marked places on each side on days 0, 5, 9 and 14 after the intrapleural injection. At each of the three places on both sides, three US features (absence of gliding sign, pleural thickenings and pleural effusion) were evaluated and graded. The animals were sacrificed on day 14 and the macroscopic pleurodesis score was subsequently determined. RESULTS: All rabbits were found to have absence of the lung gliding sign in the side receiving the pleurodesis at five days and subsequently. The lung gliding sign was present on the control side at all examinations. There was a high correlation between pleurodesis score and the absence of the gliding sign in all rabbits. CONCLUSION: US is an efficient imaging modality for the evaluation of pleurodesis in rabbits. Absence of gliding sign is the most important feature to indicate the presence of a pleurodesis. CLINICAL IMPLICATIONS: US should be assessed in humans for it utility in assessing pleurodesis. DISCLOSURE: Z. Zhu, None.

Wednesday, October 27, 2004 Pleural Disease: Bench to Bedside, continued COMPARING THE SYSTEMIC ACUTE EFFECTS OF THE PLEURODESIS AGENTS TALC AND SILVER NITRATE Evaldo Marchi, MD*; Francisco Vargas, MD, FCCP; Leila Antonangelo, MD; Lisete R. Teixeira, MD; Milena M. Acencio, BS; Eduardo H. Genofre, MD; Pulmonary Division, Heart Institute (InCor), University of Sao Paulo, Brazil PURPOSE: We have previously shown that talc (TL) induces an acute systemic inflammatory response even in doses considered ineffective (100 mg/kg) in producing pleurodesis. Silver nitrate (SN) has been used as an effective pleurodesis agent, but its systemic effects are still unknown. The aim of this study was to determine the systemic response to SN in doses considered effective (0.5%) and ineffective (0.1%) in an experimental model of pleurodesis and compare with the findings previously described with talc. METHODS: Groups of six rabbits were injected intrapleurally with TL 100 or 400 mg/kg and SN 0.1% or 0.5% and after 6 and 24 hours samples of blood were assayed for leukocytes (WBCx103), percent neutrophil and the inflammatory cytokines interleukin-8 (IL-8; pg/mL) and vascular endothelial growth factor (VEGF; pg/mL). Pre-injection blood samples were used as controls. Statistics: ANOVA (all groups compared to control). CONCLUSION: The WBC increased at 6 hours for both agents only for the higher doses and decreased after 24 hours. The percent neutrophils increased at 6 hours in the TL100 and TL400 groups, but not in the SN0.1% and SN0.5% groups. The IL-8 and VEGF levels were greater for all groups at all times, even in doses considered ineffective in producing pleurodesis. CLINICAL IMPLICATIONS: Intrapleural SN induced an acute systemic inflammatory response characterized by a low cellular response when compared to talc.

6 hours Control

TL100

24 hours

TL400

SN0.1

SN0.5

TL100

TL400

SN0.1

SN0.5

WBC5.1⫾1.6*

7.6⫾2.1

9.7⫾ 3.6

5.8⫾ 1.0

8.1⫾ 2.1

4.7⫾ 1.3

6.8⫾3.1 7.7⫾1.9 6.7⫾1.2

%N 53⫾ 6*

74⫾ 9

73⫾

39⫾25*

60⫾ 12

61⫾

45⫾ 11

IL-8 90⫾ 31* VEGF⬍

15*

890⫾ 390 65⫾ 35

10

620⫾ 380 52⫾

15

5

1955⫾365 2250⫾307 1461⫾610 955⫾ 515 33⫾ 14

47⫾ 13

66⫾ 43

56⫾6.0

39⫾ 7 990⫾ 245 48⫾ 14

36⫾ 13 1512⫾ 510 53⫾9.0

WBC: *p⬍ 0.05 TL400 6hours vs. Control; SN0.5 6hours vs. Control. %N *p⬍ 0.05 TL100 and TL400 6hours vs. Control; SN0.5 6hours vs. Control. IL-8: *p⬍ 0.05 TL100 and TL400 at all times vs. Control; *p⬍ 0.001 SN0.1 and SN0.5 at all times vs. Control. qVEGF: *p⬍ 0.05 All groups of TL and SN at all times vs. Control.

DISCLOSURE: E. Marchi, None.

but its incidence continuously growed to an almost 30% of total number of pneumotoraces in the last years. Al the parameters taken into consideration show a much more difficult evolution of these patients: prolonged air leaks and drainage, higher rate of complications, longer hospitalisation and later recovery. CONCLUSION: Spontaneous pneumothorax due to tuberculosis has a growing incidence, which paralells with the incidence of tuberculosis. These patients are very fragile and require a different approach compared with other types of pneumothorax. CLINICAL IMPLICATIONS: Considering the actual growing incidence of tuberculosis we expect also a raise of number of patients with spontaneous pneumothorax caused by this disease. Full recovery requires a specific complex medical and surgical treatment. DISCLOSURE: P.V. Botianu, None.

INFLUENCE OF ANTI-INFLAMMATORY DRUGS IN THE EXPERIMENTAL PLEURODESIS INDUCED BY SILVER NITRATE OR TALC Pedro F. Paz*; Milena M. Acencio, BS; Francisco S. Vargas, MD, FCCP; Carlos S. Silva; Leila Antonangelo, MD; Evaldo Marchi, MD, FCCP; Lisete R. Teixeira, MD; Pulmonary Division - Heart Institute (InCor) University of Sao Paulo, Brazil PURPOSE: Pleurodesis is frequently considered for the management of recurrent malignant pleural effusions and pneumothorax. A significant percentage of patients who are candidates for pleurodesis may be receiving anti-inflammatory drugs at the time pleurodesis is attempted. We have previously shown in rabbits that the use of corticosteroids decreases the initial inflammatory process and diminishes the efficacy of pleurodesis induced by talc or doxycycline (Am J Respir Crit Care Med 1998,157:1441-44, Chest 2002,121:216-9). The aim of this study was to evaluate the influence of steroidal and nonsteroidal anti-inflammatory drugs in the effectiveness of pleurodesis induced by silver nitrate or talc. METHODS: Rabbits received intrapleural injection of silver nitrate (SN) 0,5% or talc slurry (TS) 400 mg/kg. The animals were subdivided in groups that received intramuscular injection of metilpredinisolone (Cort) (1mg/Kg/weekly) or Diclofenac (Dicl)(1.2 mg/Kg/daily during the first seven days). After 28 days, the animals were sacrificed and macroscopic analysis for pleural adhesions, atelectasis and hemothorax was done. Statistical analysis: t test. RESULTS: The pleural adhesions were significantly reduced (*p ⬍ 0.05) in the talc group that received anti-inflammatory drugs (TS x TS Cort and TS x TS Dicl). CONCLUSION: In rabbits, metilprednisolone and diclofenac inhibited the pleurodesis induced by talc. Silver nitrate induced an efficient pleurodesis despite the use of systemic anti-inflammatory drugs. CLINICAL IMPLICATIONS: If these results can be extrapolated to clinical practice, anti-inflammatory drugs should be avoided with talc pleurodesis. Our results indicate that these drugs may not affect the final result of pleurodesis with silver nitrate.

SPONTANEOUS PNEUMOTHORAX IN TUBERCULOSIS Petre V. Botianu, MD*; Surgical Clinic no. 4 (Abdominal and Thoracic Surgery), Roma, Targu Mures, Romania PURPOSE: This study analyses spontaneous pneumothorax occuring in the natural evolution of lung tuberculosis, focusing on the main differences compared with other types of spontaneous pneumothorax. METHODS: We retrospectively analysed patients with spontaneous pneumothorax treated in our unit between 1985 and 2004 and selected patients with lung tuberculosis as the cause of intrapleural presence of air. Diagnosis of tuberculosis was based on history and radiological and CT aspect after lung reexpansion and confirmed by bacteriological studies and evolution after tuberculostatic treatment. Out of a total number of 272 patients with spontaneous tuberculosis, 67 had lung tuberculosis. The treatment protocol was based on immediate chest drainage, full tuberculostatic treatment and thoracotomy in case of prolonged air leaks and lack of reexpansion. RESULTS: There was a dramatically raise of incidence of spontaneous pneumotorax caused by lung tuberculosis. In the first years of our study, this entity was very rare (less than 3% of total number of pneumothoraces)

894S

Pleural adhesions SN SN⫹Cort SN⫹Dicl TS TS⫹Cort TS⫹Dicl Data were expressed as mean ⫾ SD

3.2⫾1.1 3.5⫾0.6 4.0⫾0.0 2.2⫾0.8 * 1.3⫾0.7 1.3⫾1.1

Atelectasis

Hemothorax

1.9⫾1.6 1.2⫾0.8 1.2⫾0.3 0.0⫾0.0

0.8⫾1.5 0.8⫾1.5 0.7⫾1.2 0.0⫾0.0

0.0⫾0.0 0.0⫾0.0

0.0⫾0.0 0.0⫾0.0

TS vs TS⫹Cort and TS⫹Dicl DISCLOSURE: P.F. Paz, None.


Wednesday, October 27, 2004 Pleural Disease: Bench to Bedside, continued CAN TUBE DRAINAGE REDUCE THE PLEURAL THICKENING IN LOCULATED PLEURAL EFFUSION OF TUBERCULOUS PLEURISY ? Moon J. Na, MD*; Ji W. Son, MD; Eu G. Choi, MD; Won Y. Lee, MD; Konyang University Hospital, Daejon, Korea

PLEURAL FLUID FROM PATIENTS WITH SUCCESSFUL PLEURODESIS CAUSES INCREASED PROLIFERATION AND DEPOSITION OF COLLAGEN BY PLEURAL FIBROBLASTS Michael A. Jantz, MD*; Najmunnisa Nasreen, PhD; Kamal A. Mohammed, PhD; Mark L. Brantly, MD; Veena B. Antony, MD; University of Florida, Gainesville, FL PURPOSE: Pleurodesis is frequently employed to manage malignant pleural effusions. Talc induces pleurodesis by directly initiating inflammation in the pleural space. The injury to the pleura results in intense inflammation with secondary collagen deposition. The aim of this study was to compare fibroblast proliferation and collagen deposition by pleural fibroblasts exposed to pleural fluid from patients with successful pleurodesis (SP) versus failed pleurodesis (FP). Pleurodesis was termed “successful” when the effusion did not recur at any time during follow-up to death of the patient, while it was deemed a “failure” if the pleural effusion recurred at any time. METHODS: Pleural fluid was collected from 23 patients with malignant pleural effusions and 6 patients with congestive heart failure (control group). The pleural fluid was obtained at the beginning of thoracoscopy (baseline), immediately after thoracoscopy, and at 2, 4, 12, and 24 hours post thoracoscopy. A grading scale (1-9) was used to quantitate the extent of tumor burden. Soluble collagen was estimated using the Sircoll assay. The proliferation of pleural fibroblasts was determined by [3H] thymidine incorporation. RESULTS: Pleural fluids from patients with SP following intrapleural talc insufflation have a significantly higher capacity to stimulate fibroblast proliferation as compared to pleural fluid from patients with FP (P⬍0.05). The pleural fibroblasts exposed to pleural fluids from SP patients also demonstrated higher collagen deposition over time when compared to pleural fluids from FP patients. In addition there was an inverse correlation between tumor burden and proliferative activity of the fluids.

PROTEOMIC PROFILES DIAGNOSTIC FOR MALIGNANT PLEURAL EFFUSIONS Pinar Yildiz, MD*; Noel Wardwell, MD; Yu Shyr; Bashar Shakhtour; David P. Carbone, MD; Richard W. Light, MD; Pierre P. Massion, MD; Vanderbilt University, Nashville, TN PURPOSE: The diagnosis of malignant pleural effusion suffers from low sensitivity of its cytological evaluation. We therefore asked whether proteomic profiles obtained by matrix assisted laser desorption ionizationmass spectrometry (MALDI-MS) can discriminate malignant from nonmalignant effusions. METHODS: MALDI-MS profiles were obtained from 49 cytologically proven malignant effusions and from 48 cytologically-negative exudative pleural effusions. We compared the two groups first in a training set of 27 malignant and 26 non-malignant exudative effusions, built a prediction model and tested its accuracy in a leave-one-out cross-validation class prediction analysis. We then tested the selected features in an independent test set of 22 malignant and 22 non-malignant effusions and estimated the misclassification rate. RESULTS: In a training set of effusions, we identified a profile discriminating malignant effusions from others based on 897 MS features. Class prediction models based on the discriminatory protein peaks allowed correct classification of pleura from malignant and nonmalignant patients in 98% of the patients in the training set with a sensitivity of 96%, a specificity of 100%. This derviation set of discriminant features was validated in the remaining half of the samples. This model allowed correct classification in our blinded test set in 66% of the patients. We then compared the list of discriminant features obtained in pleural effusions to the one obtained in the serum distinguishing cases of lung cancer from matched controls. We identified 9 features that are likely to represent the same proteins or peptides between the discriminants in these two independent datasets. CONCLUSION: We used MALDI-MS directly on 1␮l of 1:10 diluted unfractionated pleural fluid to obtain protein expression profiles and distinguish individuals with cytologically proven pleural effusions from cytologically negative exudative effusions with 66% accuracy in the blinded set. We hope to further improve our prediction model in a larger cohort of patients with and without malignant effusions. CLINICAL IMPLICATIONS: If these results are confirmed, such profiling may have important implications in the management of patients with malignant pleural effusions. DISCLOSURE: P. Yildiz, None. ASBESTOS-INDUCED PLEURAL INFLAMMATION IN MICE GENETICALLY SELECTED FOR MAXIMUM OR MINIMUM INFLAMMATORY RESPONSE Evaldo Marchi, MD*; Francisco S. Vargas, MD; Milena M. Acencio, BS; Mauro Canzian, MD; Orlando G. Ribeiro, PhD; Olga M. Ibanez, PhD; V. Courtney Broaddus, MD; Pulmonary Division - Heart Institute (InCor), University of Sao Paulo, Brazil PURPOSE: Asbestos fibers injected into the pleural space induce pleural inflammation by activation of macrophages and neutrophils, leading to apoptosis, cell proliferation, fibrosis and eventually the tumor mesothelioma. The degree of the local inflammatory response may play a role in the overall injury induced by asbestos. We investigated if crocidolite asbestos, a toxic mineral fiber, would produce different degrees of inflammation in mice genetically selected for minimum (AIRmin) or maximum (AIRmax) acute inflammatory response. METHODS: Three groups of 5 mice were injected intrapleurally with 3 ug/cm2 crocidolite (Cro) asbestos (Control, AIRmin or AIRmax) and one control group with wollastonite (Wol). After 1, 2 or 3 months the animals were sacrificed, the thorax was removed and the lungs expanded CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

895S


PURPOSE: In patients with tuberculous pleurisy, the residual pleural thickening(RPT) that produce symptoms like dyspnea and chest discomfort is the common sequelae after treatment of tuberculous pleurisy. But there are not known predictable factors and preventable methods for pleural thickening. We studied about the effects of tube drainage on RPT. METHODS: 70 patients who treated with anti-tuberculous medication for at least 6 months, were included for study. We performed tube drainage that include chest tube and pig tail drainage, in 34 patients (group I) at a point of anti-tuberculous treatment. 36 patients (group II) treated only with anti-tuberculous treatment after diagnostic thoracentesis. In group I performed with tube drainage (n⫽34), we divided to two subgroups that are with initial loculation (group Ia, n⫽26) and without initial loculation (group Ib, n⫽8). In initial loculated pleural effusion (n⫽35), the tube drainage group is group A (n⫽26), and the no tube drainage group is group B (n⫽9). We used residual pleural thickness as average value of residual pleural thickening at the 3 points of lateral chest wall. RESULTS: RPT in group I is larger than in group II (2.53⫾1.86mm vs 2.40⫾5.28mm), but it’s not statistically significant (p⬎0.05). RPT in initially loculated subgroup (group Ia) is significantly smaller than RPT in initially not-loculated subgroup (group Ib) (p⬍0.05). In initial loculated pleural effusion (n⫽35), RPT in tube drainage group (group A) is smaller than RPT in no tube drainage group (group B) (3.92⫾1.82mm vs 4.33⫾9.46mm), but it’s not statistically significant (p⬎0.05). CONCLUSION: Tube drainage is helpful in reducing the RPT in initial loculated group than initial not-loculated group, statistically significant. Tube drainage can reduce theoretically pleural thickening as a sequelae of tuberculous pleurisy. As our results, tube drainage is helpful in reducing RPT only in patients with initial loculated pleural effusion rather than not-loculated effusion. CLINICAL IMPLICATIONS: Tube drainage will be helpful in reducing RPT in especially loculated pleural effusion. We expect further large studies about factors related with residual pleural thickening in tuberculous pleurisy. DISCLOSURE: M.J. Na, None.

CONCLUSION: We found significantly increased proliferation and increased collagen deposition by pleural fibroblasts when exposed to pleural fluids from patients with SP as compared to pleural fluids of patients with FP. There was an inverse correlation between fibroblast proliferative activity and tumor burden. CLINICAL IMPLICATIONS: The mechanism of action of talc involves the laying down of matrix proteins. Given the negative correlation between success and extent of pleural tumor involvement, earlier diagnosis and treatment of patients may be justified. DISCLOSURE: M.A. Jantz, None.

Wednesday, October 27, 2004 Pleural Disease: Bench to Bedside, continued and fixed in formalin. The specimens were paraffin embedded and the three more representative transversal sections were stained with HE and analyzed for the presence of inflammatory infiltrate, giant cell reaction, mesothelial cell proliferation, fibrosis and macrophage infiltrate. A score (0-4) was attributed to evaluate the morphological findings: 0: none; 1: slight; 2: mild; 3: moderate; 4: intense. Statistics: ANOVA on Ranks. RESULTS: Inflammatory Infiltrate: Cro Control, Airmax and AIRmin at all times vs. Wol (*p⬍ 0.05); GCR: AIRmax and AIRmin vs. Wol at all times (*p⬍ 0.05); AIRmax vs. Cro Control at 1mo. (#p⬍ 0.05). CONCLUSION: All groups of crocidolite-injected mice had more inflammatory infiltrate and giant cell reaction than wollastonite-injected animals at all time-points. No difference was found among subgroups of the crocidolite-injected animals. The giant cell reaction was more evident in animals with maximum inflammatory response in the first month in comparison to crocidolite control animals. Mesothelial cell proliferation, fibrosis and macrophage infiltrate were not different among groups. CLINICAL IMPLICATIONS: Determination of the crocidoliteassociated inflammatory pleural reaction may be significant in understanding the pathogenesis of asbestos-related pleural diseases, including the tumor mesothelioma. Inflammatory Infiltrate Cro Control

Giant Cell Reaction

1mo.

2mo.

3mo.

1mo.

2mo.

3mo.

2.0 ⫾ 0.0

1.3 ⫾ 0.6

2.0 ⫾ 00

0.3 ⫾ 0.6#

0.7 ⫾ 0.6

0.7 ⫾ 0.6

AIRMin

2.0 ⫾ 1.1

2.0 ⫾ 0.9

1.9 ⫾ 0.8

1.3 ⫾ 0.5

1.1 ⫾ 0.6

1.3 ⫾ 0.9

AIRMax

2.7 ⫾ 1.2

2.6 ⫾ 1.0

2.5 ⫾ 1.4

2.7 ⫾ 1.2

1.7 ⫾ 0.9

1.3 ⫾ 1.1

Wol

0.2 ⫾ 0.4*

0.3 ⫾ 0.5*

0.5 ⫾ 0.3*

0.0 ⫾ 0.0*

0.0 ⫾ 0.0*

0.0 ⫾ 0.0*

CONCLUSION: Oral TET/DOX is more cost-effective than and as safe as parenteral DOX in producing pleurodesis in rabbits. CLINICAL IMPLICATIONS: Oral TET/DOX can be used for pleurodesis in humans when parenteral forms of these drugs are not available. DISCLOSURE: S. Bilaceroglu, None. CYTOKINES IN PLEURAL EFFUSION IN FIRST 48 HOURS AFTER CORONARY ARTERY BYPASS SURGERY (CABG) Marcelo A. Vaz, MD*; Antonio M. Chibante, MD; Daniela G. Mont’Alverne; Milena M. Acencio, BS; Lisete R. Teixeira, MD; Francisco S. Vargas, MD, FCCP; Pulmonary Division - Heart Institute (InCor) University of Sao Paulo, Brazil PURPOSE: To evaluate the participation and behavior of cytokines in pleural fluid after 2, 24 and 48 hours after the CABG. METHODS: Patients were separated into two groups: Control (16 patients with transudative pleural effusion) and CABG (43 patients submitted to CABG). Pleural samples were collected from CABG patients after 2, 24 and 48 hours of the end of surgery. The cytokines TNF-␣, IL-1Beta, IL-6, IL-8, VEGF and TGF-beta were measured in pleural fluid samples. Transudates effusions were considered according to Light’s criteria. Statistical analysis were done using SPSS software. RESULTS: IL-1beta, IL-6, VEGF and TGF-beta were analyzed in logarithmic form (Ln) to obtain normality. Results are presented in graphs, and showed that TNF-␣ is not mobilized in the first 48 hours after surgery. IL-1beta increased between 2 and 24 hours after CABG. IL-6 and IL-8 presented expressive levels during 48 hours as well as VEGF. Nevertheless, the TGF-beta levels increased in the first 2 hours and decreased significantly in subsequent times as the transudates levels after 48 hours. CONCLUSION: Pleural effusion in CABG is related to inflammatory response mediated by IL-1 beta, IL-6, IL-8, VEGF and TGF-beta. CLINICAL IMPLICATIONS: This profile may be considered in future studies over persistent pleural effusion after CABG.

DISCLOSURE: E. Marchi, None. PLEURODESIS INDUCED BY ORAL FORMS OF TETRACYCLINE AND DOXYCYCLINE IN RABBITS Semra Bilaceroglu, MD*; Yubiao Guo, MD; Michael Hawthorne, MD; Zhiwen Zhu, MD; Georgios T. Stathopoulos, MD; Kirk Lane, PhD; Richard Light, MD; Dept. of Pulmonary Medicine, Vanderbilt University, Nashville, TN PURPOSE: Parenteral tetracycline (TET) and doxycycline (DOX) are cost-effective and safe in producing pleurodesis but mostly unavailable currently. We investigated whether oral forms of TET/DOX can produce pleurodesis as does parenteral DOX. METHODS: Parenteral DOX (10 mg/kg), or filtered oral TET (35 mg/kg)/DOX (10 mg/kg) was injected intrapleurally in 2 cc saline through a chest tube in 3-kg rabbits. When daily aspirated pleural fluid volume was below 5 cc/24 hour, the chest tube was removed. The fluid volumes, and white blood cell (WBC), lactate dehydrogenase (LDH) and protein levels on the 1st day after the injection were recorded. After sacrificing on the 14th day, pleurodesis was graded from 1 (none) to 8 (complete symphysis) by two observers blinded to treatment groups. RESULTS: Oral TET (capsule/tablet-n:6) and DOX (capsule/tabletn:7) were as effective as parenteral DOX (n:10) in producing pleurodesis [right pleurodesis scores: TET capsule- 7.50 (6.00), tablet- 6.50 (6.00); DOX capsule- 4.00 (1.00), tablet- 8.00 (5.00); parenteral DOX- 7.50 (6.00); p⫽0.235]. The left scores were 1.00 in all 36 rabbits. A positive correlation existed between right scores and fluid total volume (r⫽0.523, p⫽0.001) or protein level (r⫽0.577, p⫽0.0004). Fluid total volume, WBC, LDH and protein levels were comparable excluding WBC in TET tablet versus DOX parenteral groups (p⫽0.047). Only fluid 24-hour volume and WBC level differed (p⬍0.05) between oral (n:26) and parenteral groups (n:10), and only 72-hour volume between TET and DOX capsule groups in four oral groups. The complications were non-fatal [right hemothoraxTET capsule (3) / tablet (2); DOX tablet (2); parenteral DOX (2); left hemothorax- TET capsule (1); ascites- parenteral DOX (1)]. There was no growth on culture of filtered oral specimens. TET/DOX capsule/tablet costed less than parenteral DOX (⬍$1 versus $4.72/rabbit). Filtering oral forms increased the cost by $1.12/rabbit.

896S

DISCLOSURE: M.A. Vaz, None.

THE PATHOGENESIS OF SPONTANEOUS PNEUMOTHORAX IN SMOKERS Taine T. Pechet, MD; Shamus R. Carr, MD*; Michael G. Santomauro, BS; Monica E. de Baca, MD; John L. Farber, MD; Thomas Jefferson University, Philadelphia, PA PURPOSE: The pathogenesis of subpleural bleb formation in patients with a spontaneous pneumothorax is poorly defined. In an attempt to define the causal mechanisms of bleb formation, we studied the pathology in a cohort of young smokers with a pneumothorax. METHODS: We examined clinical records and pathology specimens from a consecutive series of 12 patients with a history of cigarette smoking who presented with a spontaneous pneumothorax. All failed conservative therapy with tube thoracostomy and underwent thoracoscopic bleb resection with mechanical pleurodesis and/or partial pleurectomy. RESULTS: The patients (8 males and 4 females) ranged in age from 20 to 30 years (mean 21.3). There were 8 Caucasians, 2 African-Americans, and 2 Asians. The Body Mass Index of the group ranged from 15.5 to 20.3 (mean 19.1). The patients had a smoking history of 1 to 16 pack-years (mean 6.9). The pulmonary pathology was remarkably similar in all the Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Pleural Disease: Bench to Bedside, continued patients. In each case, there was pleural fibrosis with a sub-pleural chronic pneumonitis characterized by interstitial inflammation and fibrosis with collections of tar-laden macrophages in the airspaces. In 4 patients, sub-pleural emphysema was evident. The interstitial pneumonitis varied in severity and extended to a variable degree into the sub-pleural parenchyma. In 4 patients, the interstitial pneumonitis was present diffusely throughout the biopsied lung. The pathology here closely resembled that of desquamative interstitial pneumonitis. CONCLUSION: There are young individuals with a thin body habitus and smoking history who present with a pneumothorax that is associated with a peripheral interstitial pneumonitis. It is proposed that the pathogenesis of smoking-associated pneumothorax begins with the accumulation of tar-laden macrophages that are toxic to the dependent lung parenchyma beneath the pleura. This pneumonitis and fibrosis in the context of the greater mean distending pressures associated with an asthenic body habitus result in the formation of subpleural blebs and consequent pneumothorax. CLINICAL IMPLICATIONS: The proposed causal sequence between cigarette smoking and spontaneous pneumothorax should allow further focused efforts aimed at defining the specific mechanisms and thus permit targeted therapy. DISCLOSURE: S.R. Carr, None.

MAAS Score

Description

0

Unresponsive

1

Responsive only to noxious stimuli

2

Responsive to touch or name

3

Calm and cooperative

4

Restless and cooperative

5

Agitated

6

Dangerously agitated, uncooperative

THE CORRELATION BETWEEN THE BISPECTRAL INDEX (BIS) AND MOTOR ACTIVITY ASSESSMENT SCALE (MAAS) IN SEDATED AND MECHANICALLY VENTILATED CRITICALLY ILL PATIENTS Mohammed H. Hijazi, MBBS*; Ashraf Chaudhary, BESC, PhD; King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia PURPOSE: Measure the corrolation between BIS and MAAS in mechanically ventilated critically ill patients. METHODS: A prospective observational study was performed in sedated, mechanically ventilated medical and surgical patients (ⱖ14 yr) with a MAAS of 0-1(see the table below for details on MAAS). Patients with stroke, closed head injury, forehead wounds, and undergoing muscular paralysis were excluded. Bispectral index was recorded using a BIS Monitor Model A-2000 with XP software (Aspect Medical Systems, USA) and a sensor (BIS Quatro) placed on the patient’s forehead. The investigator documented MAAS four times daily, but was blinded for data concerning BIS and sedative doses administered. Recording of BIS was done just prior (n⫽157), and 5 minutes after (n⫽153) the assessment of MAAS. The patients were followed until MAAS reached 3 or death. Statistical analysis of the correlation between BIS and MAAS was done using Pearson’s correlation coefficient. RESULTS: Twenty patients (60% males) with a mean age of 47.3 yr were included. The utilization of sedative agents at the time of recordings was as follows: fentanyl (70.7%), midazolam (49.7%), and propofol (17.2%). The correlation coefficients between both pre- and post BIS and MAAS was 0.87 (p⬍0.0001).No patient with BIS index of ⬍50 and quite few with BIS of ⬍ 60 had a MAAS of 2 or more (see graph below). CONCLUSION: The study shows a strong correlation between BIS and MAAS, supporting the use of BIS as a monitoring tool of sedation in critically ill patients. CLINICAL IMPLICATIONS: BIS of ⬍ 50 to 60 can be used as a reasonable target in paralyzed mechanically ventilated patient in the ICU setting.

Definition Does not move with noxious stimulus Opens eyes OR raises eyebrows OR turns head toward stimulus OR moves limbs with noxious stimulus Opens eyes OR raises eyebrows OR turns head toward stimulus OR moves limbs when touched or name is loudly spoken No external stimulus is required to elicit movement AND patient is adjusting sheets or clothes purposefully and follows commands No external stimulus is required to elicit movement AND patient is picking at sheets or tubes or uncovering self and follows commands No external stimulus is required to elicit movement AND attempting to sit up OR moves limbs out of bed AND does not consistently follow commands (e.g. will lie down when asked but soon reverts back to attempts to sit up or move limbs out of bed No external stimulus is required to elicit movement AND patient is pulling at tubes or catheters OR thrashing side to side OR striking at staff OR trying to climb out of bed AND does not calm down when asked

DISCLOSURE: M.H. Hijazi, None. RENAL FUNCTION AND WEANING FROM PROLONGED MECHANICAL VENTILATION Debapriya Datta, MD*; Paul Scalise, MD; Manchester Hospital, Manchester, CT PURPOSE: Renal failure requiring hemodialysis has been associated with a poor outcome in patients on prolonged mechanical ventilation (PMV). Serum creatinine (Cr) ⬎ 1.3 mg% has been implicated in failure-to-wean from PMV. Literature on the impact of renal failure on weaning is limited. Creatinine clearance (CrCl)provides a better estimate of renal function than serum creatinine. However, no prior studies have examined the relationship of CrCl on weaning outcome in patients on PMV. The objective of this study was to determine the effect of renal function, particularly CrCl, on weaning from PMV. METHODS: We retrospectively studied 167 patients on PMV, admitted to a long term acute care facility between 1999-2002, for weaning. These patients had CrCl measured routinely on admission. The following data was obtained: age, sex, cause of respiratory failure and admission BUN, Cr and CrCl. Random urine creatinine (RUCr) and 24-hour urinary creatinine (24-UCr), obtained with CrCl estimation, were also noted. Outcome was liberation from PMV, defined as being off ventilator for ⬎ 7 days. Univariate analysis was performed to determine relation between above parameters and outcome. p ⬍0.05 was statistically significant. RESULTS: Mean age of patients: 67.5⫾16 years; 49% were males and 51% females. Cause of respiratory failure was cardiovascular surgery in CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

897S


Mechanical Ventilation 12:30 PM - 2:00 PM

Motor Activity Assessment Scale (MAAS)

Wednesday, October 27, 2004 Mechanical Ventilation, continued 27%; other surgery in 15.5%; COPD in 21%; pneumonia in 9%; ARDS in 5.5%; neurological disease in 18.5% and heart failure in 3.5%. Sixty-four percent were liberated and 36% failed-to-wean. The studied parameters and outcome in the 2 groups of patients are shown in Table 1. CONCLUSION: Renal function as measured by BUN, CrCl, and 24-UCr has a statistically significant impact on weaning from PMV. Serum creatinine, by itself, doesnot appear to affect weaning. CLINICAL IMPLICATIONS: Renal function as measured by BUN, CrCl and 24-UCr can be used to prognosticate liberation form PMV. Apart from renal function, BUN and 24-UCr provide an estimate of patients’ nutritional status and positive nitrogen balance, which could also affect weaning outcome.

Parameters

Weaned

Failed

p

BUN (mg/dL) Cr (mg/dL) CrCl (ml/min) RUCr mg/dL 24UCr (mg)

29⫾17 0.85⫾0.9 69.3⫾35 43⫾28 646⫾284

33⫾21 0.84⫾0.5 61⫾32 44⫾28 593⫾262

0.003 0.7 0.0001 0.8 0.009

DISCLOSURE: D. Datta, None.

CAN BREATHING PATTERN PARAMETERS ASSESS RESPONSE TO NONINVASIVE MECHANICAL VENTILATION (NIMV)? Bornali Datta, MD*; B. Datta, MD; H.S. Heera, MD; Pilgrim Hospital, Boston, Lincolnshire, United Kingdom PURPOSE: NIMV is commonly used in treating respiratory failure in patients with COPD and CHF. Response to NIMV is assessed by arterial blood gases. Whether breathing pattern parameters can adequately assess clinical response to NIMV has not been evaluated. This study aimed at determining the efficacy of breathing pattern parameters as compared to ABGs in assessing response to NIMV. METHODS: Twenty patients with Type II Respiratory Failure were treated with NIMV using a Kimura KV3 ventilator delivered via a nasal CPAP mask. ABG and breathing pattern parameters were determined before, 4 hours after and on day 3 on NIMV. Breathing parameters studied included respiratory rate (RR), Percent ribcage contraction (%RC), Mean inspiratory flow (Vt/Ti), Total compartment displacement/ tidal volume(TCD/VT), Fractional inspiratory time (Ti/T), Tidal volume(TV) and Minute ventilation(MV). RESULTS: Mean age was 56⫾ 10.6 years; 80% were males, 20% females.The studied parameters are shown in Table 1. CONCLUSION: The improvement in respiratory failure with NIMV, as evident by ABG parameters was also reflected by changes in certain breathing pattern parameters such as percent rib cage contraction and respiratory rate.

Parameters pH PCO2 PO2 O2 SAT(%) RR VT(%) VE (%) %RC Ti/T TCD/VT VT/Ti

898S

Pre-NIMV

4HRS- Post

3 Days

p

7.26 85 52 79.7 30 95.5 91 62 .34 1.04 101.5

7.35 69 58 84.4 26 105 104 48 .34 1.04 111

7.42 50 58.5 89.5 23 99.3 97.4 51 .34 1.03 98

⬍0.00005 ⬍0.00005 ⬍0.005 ⬍0.05 ⬍0.05 NS NS ⬍0.00005 NS NS NS

CLINICAL IMPLICATIONS: Instead of frequent ABGs, certain breathing pattern parameters such as percent ribcage contraction and respiratory rate could be used to assess response to NIMV. Larger studies are needed to confirm this. DISCLOSURE: B. Datta, None. VENTILATOR-ASSOCIATED PNEUMONIA AND FREQUENCY OF CIRCUIT CHANGES Tsung P. Tsai, MD, PhD*; Yen T. Lin, RRT; Yao C. Wang, MD; Jang M. Su, MD; Shih M. Taso, MD; Chung-Shan Medical University Hospital, Taichung, Taiwan ROC PURPOSE: Mechanical ventilator circuits are commonly changed at 2 to 7 day intervals. This study is to evaluate the incidence of ventilatorassociated pneumonia and compare the results of ventilator circuitchanges between 3-day and 7-day changes in acute care environment. METHODS: 235 patients were admitted to an adult intensive care unit who required mechanical ventilator for more than 2 days. 128 patients had their ventilator circuit changed at 3-days interval (Group I) during the first 6 months compared to 7-day interval in 107 patients (Group II) during the subsequent 6-month period. Study patients were evaluated as ventilatorassociated pneumonia by clinical criteria for the presence of leukocytosis, fever, purulent secretion, evidence of new infiltrate on chest film. RESULTS: Ventilator-associated pneumonia was seen in 5 patients (5/235, 2.12%) and pneumonia rate was of 1.53 per 1000 ventilator days in a total of 3269 ventilator days. In 128 patients receiving 3-day circuitchanges (Group I), the pneumonia was seen in 4 patients (4/128, 3.13%). There were 1704 ventilator days and a pneumonia rate of 2.35 per 1000 ventilator days. In 107 patients receiving circuit-changes every 7 days (Group II), the pneumonia was seen in only one patient (1/107, 0.93%) and there were 1565 ventilator days, and a pneumonia rate of 0.64 per 1000 ventilator days. No statistically significant difference was found between the two groups (P⫽0.376). CONCLUSION: There is no significant difference in the incidence of ventilator-associated pneumonia with ventilator circuit-changes at 3-day and 7-day intervals. Ventilator circuits can be safely changed at weekly intervals without any increased incidence of pneumonia. CLINICAL IMPLICATIONS: For ventilator-dependent patients, ventilator circuits can be safely changed at a 7-day interval without increasing the incidence of pneumonia. DISCLOSURE: T.P. Tsai, None.

VOLUME DEPENDENCE OF RESPIRATORY MECHANICS DURING MECHANICAL VENTILATION IN COPD PATIENTS Argyro Amygdalou, MD; Miltiadis P. Vassiliou, MD; Christos Katsanos, MD; Christina Koubaniou, MD; Emanouil Mitrovassiliou, MD; Stavros H. Constantopoulos, MD, FCCP; Costas Mandragos, MD; Panagiotis K. Behrakis, MD, FCCP*; Exper. Physiology Lab, Medical School, Athens, Greece PURPOSE: To investigate the influence of VT size on respiratory mechanics during mechanical ventlation (MV) in COPD patients. METHODS: Airway pressure (Pao) and flow (V’) were recorded from 8 pts without respiratory disorder (WRD) and 8 pts with COPD exacerbation. They were under MV, sedation and muscle relaxation during measurements, performed at 6 levels of VT (300-800 ml) and 0 hPa of PEEPe. Data were analysed according to: Pao⫽EEP ⫹ E1.V⫹E2.V2 ⫹ k1.V’ ⫹ k2.V’.|V’| ⫹ k3.V.V’, where E1 & k1 are the linear coefficients of elastance and resistance, k2 the V’ dependence of resistance coefficient, E2 & k3 the volume dependence of elastance & resistance, respectively and EEP the end-expiratory pressure. Root Mean Square Difference (RMSD) of the regression was also calculated. All coefficients were compared between the two groups of pts and between the 6 levels of VT with the aid of two ways ANOVA with replication (p⫽0.05). RESULTS: -Significant higher values for all calculated coefficients (except E1) between WRD and COPD patients at all VT levels (k3 more negative in the COPD group). -k2 negative at all VT levels in the COPD group. -k3 negative at all VT levels in both groups. -E1 showed a tendency to increase on both groups. -E2 decreased significantly with VT increase in both groups. -k1 decreased non significantly with VT increase in both groups. -k2 decreased non significantly in the WRD group, while correAbstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Mechanical Ventilation, continued sponding changes in the COPD group were not homogenous. -k3 turned significantly to more positive values with increasing VT. -EEP increased non-significantly with increasing VT in both groups. -RMSD increased with increasing VT in both groups, non-significantly in the COPD group. CONCLUSION: The present results suggest that tidal volume size influences strongly respiratory mechanics in mechanically ventilated COPD patients, specifically their dependencies on flow and volume. CLINICAL IMPLICATIONS: Careful monitoring, with the aid of the proposed non-linear model may help for better adjustment of the tidal volume in COPD patients under MV. DISCLOSURE: P.K. Behrakis, None.

BNP IS NOT A PREDICTOR OF SUCCESSFUL EXTUBATION David Hersh, MD*; Ken B. Mandell, MD; Athena M. Remolina, DO; Neil Coplan, MD; Elijovich Fernando, MD; Lenox Hill Hospital, New York City, NY

AVERAGE TEMPERATURE AND FLOW USING THE VAPOTHERM IN AN ADULT POPULATION David C. Lain, PhD*; Lain Candace, BS(c); Jonathan B. Waugh, PhD; Sleep Safe, Murrysville, PA PURPOSE: The Vapotherm device uses membrane transfer technology to generate a high flow of warm humidified gas. Gas can be delivered via nasal cannula at flows of 5-40 L/min and at temperatures of 33-43°C. We reviewed patient records to determine typical flow and temperatures used in the clinical setting with the Vapotherm device and collected patient feedback on comfort of the device. METHODS: Thirty-three data records, taken during prospective evaluations, across 10 medical centers were recorded and analyzed for patient demographics, gas flow, temperature, respiratory rate and SaO2 %. Subjective data was collected by respiratory therapists describing comfort for all patients using the Vapotherm. RESULTS: Records were studied from 14 females and 19 males, mean age 71 years (range 29- 90). Mean flow rate was 21 lpm (range 5– 40 L/min: 2 subjects 5 lpm, all others 10 - 40 lpm). Mean temperature was 36.4°C (range 28-43°C). On Vapotherm therapy, mean respiratory rate was 23 bpm and mean SaO2 was 96% (range 90-100%), vs. 27bpm and 90.9% on conventional supplemental oxygen. No patient discomfort from the Vapotherm device was reported or observed by respiratory therapy data collectors. Paired t-test indicates significance for SaO2% and respiratory rate at p⫽ .0001 and .0002, respectively. CONCLUSION: The Vapotherm system delivers oxygen-enriched gas at high flows. These high flows may reduce deadspace, add small amounts of PEEP, and decrease the work of breathing. The average flow rate used in this group to maintain hemoglobin saturation was about half of the maximum Vapotherm capability. It is noteworthy that no discomfort was

COMPARISON OF PATIENT COMFORT DURING PRESSURE SUPPORT(PSV) AND ASSIST CONTROL(AC) MECHANICAL VENTILATION Imran Khalid, MD*; Robert Pensler, MD; John Crawford, RRT; Alan D. Betensley, MD; Henry Ford Hospital, Detroit, MI PURPOSE: PSV has been reported to be more comfortable than AC during non-invasive ventilation(1). This may be due to the ability of PSV to allow the patient to control rate, flow, volume and pattern. A previous report has compared physiologic parameters of PSV versus AC in intubated patients, but patient comfort levels were not assessed(2). Our study aims at comparing comfort levels in these modes in intubated patients. METHODS: We enrolled twelve patients who were intubated, stable, and able to mark a line on a 100 mm visual analog scale(VAS). After randomization, they were ventilated in PSV and AC for 30 minutes each with a washout period between modes. AC volume was 8cc/kg and pressure support level was set at (Plateau Pressure-PEEP) or enough pressure for tidal volume of 8cc/kg. After each mode, patients were asked to mark their comfort level on the VAS (Very comfortable⫽100, Uncomfortable⫽0). Physiologic parameters were also recorded. Paired t-testing was used to compare means between the two groups. RESULTS: After analyzing the data, we have found PSV(mean⫽83) to be a more comfortable mode than AC(mean⫽68), with a difference of 15 between the means(p⫽0.029). However, we didn’t find any statistical difference between the two modes in terms of physiologic parameters including blood pressure, heart rate, respiratory rate, mean airway pressure and minute ventilation. CONCLUSION: Our data shows that PSV is a more comfortable mode of ventilation for stable intubated patients than AC. Our study is limited by difficulty in finding mechanically ventilated patients who are both clinically stable and able to use a VAS to accurately mark their comfort level. In addition, other modes of mechanical ventilation such as volume support, proportional assist, and pressure-regulated volume control may potentially be more comfortable, but our study is designed only to evaluate PSV and AC. CLINICAL IMPLICATIONS: Patient comfort is an essential component of medical critical care. Physicians can use this information in making a decision regarding the choice of a specific mode of ventilation for their intubated patients.

Parameter

AC

Comfort (0-100 scale) Blood pressure-systolic (mmHg) Blood pressure-diastolic (mmHg) Heart rate /min Respiratory rate /min Mean airway pressure (cm H2O) Minute ventilation (L/min)

68 126 63 84 12 9.6 8.09

PSV 83 130 64 83.5 14 10.4 8.54

p Value 0.029 0.179 0.673 0.757 0.404 0.366 0.367

REFERENCES: 1- Girault C et al. Chest 1997; 111:1639-48 2- Tejada M et al. Chest 1997; 111:1322-25 DISCLOSURE: I. Khalid, None.


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PURPOSE: Likelihood of successful extubation in critically ill patients is estimated by respiratory parameters, the predicitive power of which is only modest. Although the sensitivity of a rapid shallow breathing index (RR/TV) is 100%, its specificity is only 63%. We hypothesized that brain natriuretic peptide (BNP), a marker of pressure or volume overload of the heart, could improve this prediction in the cardiac population. METHODS: Baseline BNP (Triage BNP, Biosite) was measured in 23 consecutive CCU patients who had reached the point of attempted extubation according to usual clinical criteria. RESULTS: Extubation failed in two patients (F). The 21 patients with successful extubation (S) had age 69 ⫾ 4 years, mean arterial pressure 74 ⫾ 3 mmHg, hemoglobin 10.4 ⫾ 0.3 g/l, creatinine 1.3 ⫾ .14 mg/dl, period of intubation 5.5 ⫾ 1 days, ejection fraction 32 ⫾ 3% and RR/TV 35 ⫾ 6.1 breaths*min-1. Baseline BNP was 1212 ⫾ 254 pg/ml and its increase in response to a 60 minute spontaneous breathing trial (SBT) was 308⫾184 pg/ml. In the failure group (n⫽2) none of the individual parameters were outside the 95% confidence intervals. CONCLUSION: In summary, the preliminary data of this ongoing trial suggest that BNP is not predictive of which patients will fail extubation. CLINICAL IMPLICATIONS: Our data suggests that BNP measurement is not useful in determining a patient’s likelihood for successful extubation. DISCLOSURE: D. Hersh, None.

reported from the Vapotherm compared to oxygen masks or standard nasal cannula therapy (at ambient temperature and pressure saturated) using lower flow rates. CLINICAL IMPLICATIONS: High flow humidified gas delivered by nasal cannula, was well tolerated by patients even though gas flows were considerably higher than in traditional nasal cannula therapy. Patients had significant increases in SaO2% and decreases in respiratory rate while using the Vapotherm device. DISCLOSURE: D.C. Lain, Vapotherm, Inc

Wednesday, October 27, 2004 Mechanical Ventilation, continued THE CHANGES OF CUFF PRESSURE FROM ENDOTRACHEAL INTUBATION FOR LONG-TERM MECHANICAL VENTILATION Bock H. Jung, MD*; Me-ae Kim, MD; Younsuck Koh, MD; Gangneung Asan Hospital, Gangwon Do, South Korea PURPOSE: Tracheal stenosis is caused by mucosal ischemic injury. Contrary, aspiration of upper airway secretion and impaired gas exchange due to cuff leakage is related to low Pcuff. To prevent these complications, Pcuff should be kept appropriately. But the constant cuff volume(Vcuff) has been frequently instilled to the cuff balloon to maintain the optimal Pcuff. To address the necessity of continuous Pcuff monitoring, we evaluated the change of Pcuff in various level of Vcuff daily basis in patients with long-term mechanical ventilation. We also investigated the usefulness of mercury column sphygmomanometer for the continuous Pcuff monitoring. METHODS: In 17 patients with prolonged endotracheal intubation for mechanical ventilation for 2 week or more, we observed the change of Pcuff according to the increase in Vcuff. We repeated this maneuvor measuring the change of Pcuff daily during mechanical ventilation days. And we compared the Pcuff measured by mercury column sphygmomanometer with the Pcuff measured by automatic cuff pressure manager. RESULTS: There was no statistically significant changes of Pcuff during more than 14 days of intubation for mechanical ventilation. However the Vcuff required to maintain the appropriate Pcuff vary from 1.9 cc to 9.6 cc individually. And the intra-individual variation of the Pcuff was observed from 10 cmH2O to 46 cmH2O at constant 3 cc Vcuff. The Pcuff measured by bedside mercury column sphygmomanometer is well coincident with that measured by automatic cuff. CONCLUSION: It is thought that continuous monitoring and management of Pcuff should be necessary to maintain the appropriate level of Pcuff for preventing cuff related problems during long-term mechanical ventilation. For this purpose, mercury column sphygmomanometer could replace the specific cuff pressure monitoring equipment. CLINICAL IMPLICATIONS: It’s known that appropriate Pcuff managements can prevent cuff related complications of endotracheal tube. But Pcuff seems to change according to patient’s respiratory mechanics. Therefore the constant cuff volume(Vcuff) instillation maneuvor may be inappropriate to maintain the optimal Pcuff and continuous Pcuff monitoring is necessary. DISCLOSURE: B.H. Jung, None. NORMAL LIMITS FOR RESPIRATORY FUNCTION TESTING IN MECHANICALLY VENTILATED PATIENTS Robyn L. Proffitt, MD*; James E. Johnson, MD; University of Alabama, Birmingham, AL

and abnormal subjects. VE X PaCO2/Ht is abnormal in over half of ARDS patients and warrants further study as a predictor of mortality. CLINICAL IMPLICATIONS: Indexing common ventilator parameters may aid in diagnosis and prognosis in the intensive care unit.

Normal Range

% Abnormal (n⫽227)

Parameter

Mean

COV(%)

Cstat (cc / cmH2O) Cstat/Ht (cc / cmH2O / cm) Cdyn (cc / cmH2O) Cdyn/Ht (cc / cmH2O / cm) Raw (cmH2O / L / sec) Raw X Ht (cmH2O X cm / L / sec) VE X PaCO2 (L X Torr / min) VE X PaCO2 / Ht (L X Torr /min / cm)

48.8 0.283

24.6 22.4

⬎29.1 35.7 ⬎0.179 36.6

29.7 0.172

21.4 19.9

⬎19.2 32.2 ⬎0.116 33.5

13.0

28.9

⬍19.1

2,205

24.8

⬍3,100 22.9

320

44.3

⬍553

16.8

1.83

39.3

⬍3.00

18.6

15.4

DISCLOSURE: R.L. Proffitt, None.

IDENTIFICATION OF BRONCHIAL INTUBATION USING COMPUTER-ASSISTED CHEST AUSCULTATION Robert A. Balk, MD*; Hansen A. Mansy, PhD; Christopher J. O’Connor, MD; Richard H. Sandler, MD; Rush University Medical Center, Chicago, IL

PURPOSE: Ventilators are capable of assessing certain aspects of lung function such as static and dynamic compliance (Cstat and Cdyn) and airway resistance (Raw). We sought to determine the normal limits of these parameters and a new easily determined parameter minute ventilation (VE)X PaCO2, as a reflection of dead space. We attempted to see if simple corrections would increase the separation between normal and abnormal subjects. Increased dead space by the Bohr method is predictive of death in acute respiratory distress syndrome (ARDS), but is difficult to measure. METHODS: Mechanically ventilated patients were evaluated. Cstat and Cdyn were measured as well as Raw. PaO2/FiO2 and VE X PaCO2 were calculated. Patients intubated for non-pulmonary reasons with normal radiographs, no history of lung disease, and a PaO2/FiO2 ⬎ 400 mm Hg were used as controls. The coefficient of variation (COV) and 95% confidence interval (CI) were determined based on the controls for the parameters Cstat, Cdyn, Raw, and VE X PaCO2. A series of corrections were then applied to see if these reduced the COV and increased the number of patients outside the 95% CI. RESULTS: There were 17 controls and 227 patients studied. The groups had similar demographics and ventilator settings, but patients weighed more than controls. Dividing Cstat and Cdyn by the patient’s height reduced COV and increased the number of patients classified as abnormal. Indexing Raw for patient size also improved performance. For VE X PaCO2, height resulted in more ARDS patients being classified as abnormal. The mean, COV, range of normal and percentage of patients classified as abnormal are given as follows:. CONCLUSION: Indexing commonly performed ventilator parameters for patient height reduces variability and increases separation of normal

PURPOSE: Bronchial intubation may produce significant hypoxemia. Current methods of detecting this condition include radiography, auscultation, and direct visualization. While radiography and direct visualization may involve delays and be unavailable outside the hospital, auscultation may have limited accuracy. The purpose of this study is to measure breath sound asymmetry caused by bronchial intubation, and assess the utility of that asymmetry for bronchial intubation detection. METHODS: After IRB approval and informed consent, breath sounds were recorded in 19 healthy subjects undergoing general surgery. While patients were supine, 2 electronic stethoscopes were placed at the right and left intersections of the axillary and nipple lines. After anesthesia induction, breath sounds were recorded for tracheal and bronchial intubation, which were confirmed fiberoptically. The acoustic signals were converted into digital form using a PC. The breath sound signal energy before and after filtering out certain acoustic frequencies (300-600 Hz) was calculated, along with the ratio of the acoustic energy between the left and right stethoscopes to assess breath sound asymmetry. Energy ratios for the tracheal and bronchial intubations were compared using the Wilcoxon signed-rank sum test. RESULTS: Accuracy for separating tracheal and bronchial intubation was 100% when the acoustic signals were filtered (p⬍0.00001). The 100% separation using computer-assisted breath sound measurements suggest a high sensitivity and specificity for bronchial intubation detection. CONCLUSION: These preliminary results suggest that devices implementing this technology may be a reliable, accurate, portable, and inexpensive. Such devices can be used for both online monitoring of ETT position and during initial intubation, and may be most useful when radiographs are unavailable, unpractical or unreliable. Further studies will determine the applicability of this device to a wider range of patients with more diverse medical conditions and different body weights and sizes. CLINICAL IMPLICATIONS: Improved bronchial intubation detection may assist clinicians in accurate and inexpensive assessment of patient status, thereby lowering morbidity, mortality and financial costs.

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Wednesday, October 27, 2004 Mechanical Ventilation, continued

DISCLOSURE: R.A. Balk, None.

PURPOSE: Positive end-expiratory pressure (PEEP) is commonly used during mechanical ventilation in several clinical settings. Such a change in mechanical environment will affect the mechanosensory input from pulmonary slowly adapting receptors (SARs), altering cardiopulmonary function. However, we know little about how SARs behave during prolonged, graded PEEP application. METHODS: We systematically examined the SAR response to PEEP application in anesthetized, open-chest and mechanically ventilated rabbits. We recorded single-unit activities from 18 SARs in the cervical vagus nerve and examined their response to increase of PEEP from 4 to 10 cm water for 20 minutes. RESULTS: The mean activity of the units increased immediately from 35.7⫾4.2 to 80.5⫾7.3 imp/s at the fifth breath after PEEP application (n⫽14, p⬍0.001) and then gradually returned to 56.5⫾5.7 imp/s at the end of 20 minute of PEEP application (p⬍0.001). Similarly, the unit activities at the peak and valley of cyclic airway pressure increased from 84.2⫾5.2 (peak) and 8.5⫾3.7 (valley) to 137.1⫾11.4 and 47.8⫾6.2 imp/s, respectively (p⬍0.001). The activities gradually adapted to 118.5⫾9.3 (p⬍0.05) and 22.1⫾4.9 (p⬍0.005) imp/s after 20 minutes. The rest four units ceased firing at 34.7 seconds (ranging 10-56 seconds) after their activity reached peak and the cyclic airway pressure maintained high during PEEP application. These inactivated units could be reactivated by lowering PEEP and inactivated again by returning PEEP to the high level. Activation and inactivation occurred abruptly, i.e., the unit activity oscillated between high frequencies and 0, suggesting that over-excitation inactivates the sensory units. CONCLUSION: Sustained high PEEP stimulates SARs and the SAR activity habituates through multiple mechanisms including receptor inactivation by over-excitation. CLINICAL IMPLICATIONS: Understanding of the sensory inputs in the regulation of cardiopulmonary function during PEEP application will assist in developing better strategies of mechanical ventilation. DISCLOSURE: J.J. Guardiola, None. USE OF NONINVASIVE POSITIVE AIRWAY PRESSURE DURING WAKEFULNESS FOR THE TREATMENT OF HYPERTENSION IN PREGNANCY Deborah A. Hutter, MD*; S. Edward Davis III, MD; Manuel Alvarez, MD; Hormoz Ashtyani, MD; Hackensack University Medical CenterUMDNJ, Fort Lee, NJ PURPOSE: To measure the effect of noninvasive positive airway pressure ventilation on maternal hypertension and fetal blood flow in women with pregnancy-associated hypertension during wakefulness.

EVALUATION OF SUBGLOTTIC IRRIGATION IN CONJUNCTION WITH THE CONTINUOUS ASPIRATION OF SUBGLOTTIC SECRETIONS (CASS) John J. Hill, BA, RRT; David M. Murphy, MD*; Michael J. Neary, MD; Caroline Panichello, CRT; Joseph Bestic, CRT; Charlotte Sims, CRT; DEBORAH Heart and Lung Center, Browns Mills, NJ PURPOSE: To determine the effect of irrigating and draining subglottic secretions on the bacterial load of the lower respiratory tract of mechanically ventilated patients. METHODS: We performed a randomized study of subjects on mechanical ventilation in a critical care setting. One hundred and forty six patients were enrolled in the study. All patients were intubated with an endotracheal tube containing a dorsal lumen to allow for the aspiration of subglottic secretions. Patients in the control group had subglottic secretions removed by continuous suction (CASS). Patients in the experimental group had subglottic secretions removed by continuous suction and also received a 7ml sterile saline bolus to irrigate the subglottic space every four hours. Patients still intubated after 72 hours had a non-bronchoscopically obtained protected specimen brush (NB-PSB) sample taken from the lower respiratory tract. The NB-PSB was cut and placed into 1ml of sterile saline, and a 0.01ml aliquot was plated for quantitative culture. RESULTS: NB-PSB samples from fourteen patients (7 experimental, 7 control) were evaluated. Patients in the control group showed an average growth of 840 cfu/ml. Patients in the experimental group had an average growth of 15 cfu/ml. None of the patients in this study developed Ventilator Associated Pneumonia (VAP). CONCLUSION: Irrigation with CASS serves to reduce the bacterial load on the lower respiratory tract of mechanically ventilated patients. The small sample size limits the statistical power of this study. CLINICAL IMPLICATIONS: CASS has been shown to be effective in reducing the bacterial colonization of the lower respiratory tract and the subsequent occurrence of VAP. Irrigation in combination with CASS may accentuate these benefits. Further studies should include more subjects and be geared towards subglottic irrigation’s effect on VAP. DISCLOSURE: D.M. Murphy, None.


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AIRWAY STRETCH RECEPTOR BEHAVIOR DURING EXPOSURE TO PROLONGED POSITIVE END-EXPIRATORY PRESSURE Juan J. Guardiola, MD*; Jingwen Zhang, MD; Rajeesh S. Punnakkattu, MD; Musa A. Haxhiu, MD, PhD; Jerry J. Yu, MD, PhD; Univ. of Louisville, Louisville, KY

METHODS: Pregnant women hospitalized with new onset pregnancyassociated hypertension were screened for participation. Women were excluded with multiple gestations, fetal anomalies, sleep disorder or comorbid illness. Two women were enrolled. Both patients underwent a comprehensive sleep/wake history and performed an Epworth Sleepiness Scale. Both patients had blood pressure and umbilical artery dopplers performed with and without 15 cmH2O continuous positive airway pressure(CPAP). RESULTS: The first patient was a 35 year-old at 32 weeks gestation with an Epworth score of 7 and no snoring. She had a mean arterial blood pressure (MAP)of 97, fetal heart rate of 156 beats per minute (bpm), and a mid-cord umbilical artery systolic/diastolic (S/D) ratio of 1.88. On CPAP 15 cmH2O, her MAP decreased to 85 with a fetal heart rate of 174 bpm and a S/D ratio of 1.81. She continued to use an auto-titrating CPAP with an average pressure of 5-6 cmH2O. She underwent Cesarean section at 37 weeks to deliver a viable 2860 gram baby with an APGAR score of 8. The second patient was a 26 year-old at 35 weeks with an Epworth score of 8 and loud snoring. Her MAP was 121, with a fetal heart rate of 156 bpm and S/D ratio of 2.61. On CPAP 15 cmH2O, her MAP decreased to 110, with a fetal heart rate of 136 bpm and S/D ratio of 2.66. Her blood pressure was inadequately controlled and she also underwent Cesarean section. She delivered a viable 2565 gram baby with an APGAR of 7. CONCLUSION: In our patients, the use of CPAP resulted in improved daytime maternal-fetal hemodynamics. It would appear that even a small amount of positive pressure may result in an improvement in hemodynamics. CLINICAL IMPLICATIONS: We propose that the use of continuous positive airway pressure in pregnancy-associated hypertension may result in an improvement in maternal-fetal hemodynamics. DISCLOSURE: D.A. Hutter, None.

Wednesday, October 27, 2004 Mechanical Ventilation, continued THE VALIDITY OF THE MEAD EQUATION FOR PREDICTING OPTIMAL RESPIRATORY RATE IN THE SETTING OF MECHANICAL VENTILATION Anna Bass, MD*; Eric Gluck, MD, FCCP; Finch University/CMS, North Chicago, IL PURPOSE: To date there has been little evidence to guide clinicians in their choice of ventilator settings for non-ARDS patients. Approximately 40 years ago, Mead et al, developed an equation that calculates an optimal respiratory rate (ORR) to minimize work of breathing. We attempt to verify this equation in a mechanically ventilated mixed medical/surgical ICU patient population. METHODS: All patients admitted to a single mixed medical/surgical ICU who underwent mechanical ventilation with a Drager, Evita 4, ventilator were included. Parameters to satisfy the Mead equation–minute ventilation, tidal volume, peak expiratory flow, and measured respiratory rate (MRR) were measured daily and during spontaneous breathing trials when possible. For patients being ventilated with combined SIMV and PS modes, calculations were made only for the spontaneous (PS) parameters. ORR was then calculated using the Mead equation. Weaning and ventilator settings were determined by individual practitioners. All measurements were made by a single observer. Data obtained from post CABG patients was analyzed separately. RESULTS: A total of 73 measurements, 16 on PS and 57 on AC, were completed on 17 patients. The mean difference between MRR and ORR was 3.1 breaths/min (25.4 vs 22.3 breaths/min), p⫽0.02, r⫽0.78. When analyzed separately for mode, the mean difference between MRR and ORR during PS mode was 6.0 breaths/min (22.9 vs 16.9 breaths/min), r⫽0.70. The mean difference between MRR and ORR with AC mode was 2.5 breaths/min (26.4 vs 23.9 breaths/min), p⫽0.08, r⫽0.84. Analysis of post CABG data showed a mean difference between MRR and ORR to be 6.6 breaths/min (17.7 vs 11.1 breaths/min), p⫽0.01, r⫽0.76. CONCLUSION: The Mead equation for predicting ORR correlates with MRR in a mixed medical/surgical mechanically ventilated population. MRR during AC mode ventilation correlated best with the Mead predicted ORR. CLINICAL IMPLICATIONS: AC mode ventilation may provide superior patient-ventilator interactions allowing for decreased work of breathing. Further quantification of modifiable factors that may contribute to deviation from the ORR maybe be helpful to guide clinicians in the choice of ventilator parameters and is warranted. DISCLOSURE: A. Bass, None. RELATIONSHIP BETWEEN NON-INVASIVE VENTILATION (NIV) TIME AND CLINICAL AND FUNCTIONAL RESULTS IN PATIENTS WITH ACUTE EXACERBATIONS OF COPD (AECOPD) Nicolino Ambrosino, MD*; Soo-Kyung Strambi, PT; Ilaria D’Amico, MD; Massimiliano Serradori, MD; Marzia Pedreschi, MD; Daniele Giannini, MD; Cardio-Thoracic Department. Pulmonary Unit, Pisa, Italy PURPOSE: To evaluate clinical and functional findings in 23 patients undergoing a successful first trial of NIV in a pneumological ward for AECOPD. METHODS: We studied 23 patients undergoing a successful first trial of NIV in a pneumological ward for AECOPD without any other comorbidity [pH: 7.34⫾0.03, PaCO2 65.2⫾11.4 mmHg PaO2: 50.3 ⫾11.2 mmHg respiratory rate (RR): 26⫾4 bpm, dyspnea (by Borg scale BS): 5.9⫾1.9, Glasgow Coma Scale (GCS): 14.9⫾0.2, heart rate (HR): 97.1⫾11.7 bpm and systolic arterial blood pressure (ABP) 140.3⫾10.0 mmHg]. NIV was considered as successful and stopped when pH was normalized without tachypnoea or signs of respiratory muscle fatigue for more than 1 day and NIV time were the hours elapsed from starting of NIV to the last hour of actual ventilation. For each patient length of COPD (LD: 17.0⫾13.0 years), number of AECOPD as defined by worsening in symptoms requiring change in medical therapy in the last two years preceding NIV (2.3⫾1.5) were recorded. RESULTS: NIV time was 72.7⫾10.7 hours and showed a significant high correlation with number of AECOPD in the 2 years preceding NIV (R2: 0.69, p⫽ 0.0001) No correlation was found between NIV time and blood gases, BS GCS, RR, HR, and ABP before starting of NIV nor with LD respectively. CONCLUSION: We conclude that high number of annual AECOPD may influence the time of NIV required to recover from ARF due to AECOPD.

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CLINICAL IMPLICATIONS: All pharmacological, and non pahrmacological tools should be used to reduce frequency of exacerbations. DISCLOSURE: N. Ambrosino, None.

Sleep Investigations 12:30 PM - 2:00 PM PREVALENCE OF SLEEP-RELATED BREATHING DISORDERS IN RURAL POPULATION OF DELHI, INDIA V. K. Vijayan, MD*; Anshu Mittal, MBBS; Puneet Tyagi, MD; Muhammed Fahim, PhD; Mujeeb U. Rahman, PhD; VP Chest Instiute, University of Delhi, Delhi, India PURPOSE: To study the prevalence of sleep-related breathing disorders in adults of rural population of Delhi. METHODS: Nineteen out of 232 villages in Delhi were randomly selected. Households were then selected randomly to obtain a sample of 350-400 subjects of either sex from each village. The study was done using a questionnaire. The field investigators made house-to-house visits and administered the questionnaire to all over 18 years of age. A repeat visit was made by the Investigators to contact the members absent during the first visit. The questionnaire had fifteen multiple-choice questions and each question was scored depending on the severity of symptoms. Each subject has to choose one of five possible alternatives for each question: “never”, “less than once a week”, “once or twice a week”, “three to five nights/days a week”, or “almost everyday/night”. The respondents were classified as having sleep-related breathing symptoms if they had loud snoring (scores 4 or 5) and/or daytime sleepiness (scores 4 or 5). Age, weight and height were recorded. RESULTS: A total of 6908 subjects from the rural area of Delhi were studied. There were 3562 (51%) males and 3346 (49%) females. A history of sleep-related breathing symptoms was present in 763 (11%) of 6908 subjects. Of these, 448 (12%) were males and 315 (9%) females. Further analysis had shown that subjects with sleep-related breathing symptoms were older (p⬍0.001) and had weight (p⬍0.001) and body mass index (p⬍0.001) higher in both sexes compared to subjects without such symptoms. In subjects with sleep-related symptoms, snoring was significantly more in males (p⬍0.001) compared to females. However, the daytime sleepiness and morning headache were more in females (p⬍0.001). CONCLUSION: Eleven percent of adult subjects in the rural area of Delhi had sleep-related breathing symptoms. The symptoms increased with age in both sexes and the prevalence of snoring was more in males. CLINICAL IMPLICATIONS: The study makes the physicians aware the magnitude of the problem of sleep-related breathing disorders which has not received adequate attention till recently. DISCLOSURE: V.K. Vijayan, None.

CARDIOPULMONARY EXERCISE TESTING IN PATIENTS OF SLEEP APNEA SYNDROME Ching-Chi Lin, MD*; Mackay Memorial Hospital, Taipei, Taiwan ROC PURPOSE: To evaluate whether cardiac dysfunction or abnormal measurements on cardiopulmonary exercise testing (CPET) are present in patients with obstructive sleep apnea syndrome (OSAS), and to evaluate what factors are responsible for exercise limitations in these patients. METHODS: Two groups of subjects were enrolled. The OSAS group consisted of 20 patients with moderate or severe OSAS. The control group consisted of 20 healthy subjects without OSAS. All subjects underwent spirometric, cardiac evaluation by radionuclide scanning, CPET and an overnight sleep study. RESULTS: The results showed that there was no difference in left ventricular ejection fraction (VEF) between the OSAS and control groups, but the OSA group had a lower right VEF. Patients in the OSAS group had a lower VO2peak, VO2peak/kg and workpeak than the control group. The OSAS group had a higher breathing reserve and a greater decrease in anaerobic threshold and oxygen pulse. CONCLUSION: In conclusion, moderate to severe OSAS patients had abnormal CPET as reflected by low VO2peak/kg, workpeak, anaerobic Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Sleep Investigations, continued threshold and oxygen pulse. These abnormalities may have been due to cardiac disease or possible lack of fitness. CLINICAL IMPLICATIONS: In the future, we intend to use cardiopulmonary exercise test to evaluate cardiac function in moderate to severe OSAS patients.

OSAS Group RDI, times / hour RVEF, % VO2peak, L/min,

*

44.01⫾8.16 38.05⫾4.08* 1.69⫾0.21*

Control Group 5.14⫾1.60 44.20⫾3.36 2.34⫾0.20

DISCLOSURE: C. Lin, None. THE ASSOCIATION BETWEEN THE NECK CIRCUMFERENCE, THE EPWORTH SLEEPINESS SCALE, AND THE APNEA-HYPOPNEA INDEX Ramzi M. Shaqareq, MD*; John A. Ashkar, MD; Samir Fahmy, MD; SUNY Downstate Medical Center, Brooklyn, NY

TOLERABILITY OF MODAFINIL IN DISORDERS OF SLEEP AND WAKEFULNESS Jed Black, MD; Jonathan R. Schwartz, MD, FCCP; Michael J. Thorpy, MD*; Milton K. Erman, MD; Sleep Disorders Center, Montefiore Medical Center, Bronx, NY PURPOSE: Excessive sleepiness in disorders of sleep and wakefulness can be caused by sleep-wake dysregulation (eg, narcolepsy), circadian misalignment (eg, shift work sleep disorder [SWSD]), or sleep disruption (eg, obstructive sleep apnea/hypopnea syndrome [OSAHS]). Modafinil, a novel wake-promoting agent with low abuse potential, is indicated to improve wakefulness in patients with excessive sleepiness in narcolepsy, SWSD, and OSAHS (when used as adjunctive treatment of residual sleepiness in regular nCPAP users). The tolerability of modafinil was evaluated from placebo-controlled studies in these disorders. METHODS: Tolerability data were combined from 6 placebo-controlled studies: 2 studies each in narcolepsy, chronic SWSD, and residual excessive sleepiness in OSAHS. Assessments included adverse events and effects of modafinil on blood pressure/heart rate, electrocardiogram intervals, and clinical laboratory parameters. RESULTS: 369 patients with narcolepsy, 273 with SWSD, and 292 with OSAHS received modafinil; 567 received placebo. The most com-

SYMPTOMS OF SLEEP DISORDERED BREATHING AND ADHD IN PREADOLESCENT HISPANIC CHILDREN. PRELIMINARY REPORT Youngran Chung, MD*; M. Corso, MD; A. Ivanenko, MD; Loyola University Medical Center, Maywood, IL PURPOSE: Obstructive sleep apnea syndrome(OSAS), a disorder characterized by partial or complete upper airway obstruction, leads to disruption of sleep. Prevalence varies from 2.2% in Caucasians to 8.7% in African-American children (Redline, 1997). OSAS are frequently associated with symptoms of ADHD in the general pediatric population, suggesting a mechanistic link between these conditions. However, there is no data on prevalence rates of sleep disordered breathing in Hispanic children, or its association with neurobehavioral disturbances. METHODS: A cross-sectional survey was performed in 1 to 11 year old Hispanic children recruited from the general pediatric clinic. The survey queried snoring and breathing patterns suggestive of sleep apnea, nocturnal arousals, excessive daytime sleepiness, and diagnosis or symptoms of attention deficit hyperactivity disorder (ADHD). Parents rated the frequency of their children’s symptoms in each of the first three categories using a likert scales: no symptoms in the last 6 months; 1/week; 3-4/week; ⬎4/week. For data analysis, symptoms occurring 3 or more times per week were considered as persistent. RESULTS: 30(15 boys)patients were recruited. Age range: 1 to 9, average 5 years. 17% had persistent snoring, 6.7% had snoring and another persistent symptom, i.e. nocturnal arousals or excessive daytime sleepiness. None reported a diagnosis of ADHD or symptoms of hyperactivity. CONCLUSION: This preliminary study provides initial estimates of the prevalence rate of snoring and symptoms of sleep disordered breathing in preadolescent Hispanic children. The risk for OSAS appears to be in the reported range of the general population. Furthermore, the prevalence seems to be higher than in Caucasians and lower than in African Americans (Redline, Am. J. Resp Crit. Care Med., 1997). Contrary to other ethnical groups, none of the patients had ADHD or hyperactivity symptoms by parental report, thereby suggesting a role for genetic and/or environmental/cultural factors in the mechanisms of OSAS and their neurobehavioral sequelae in children. CLINICAL IMPLICATIONS: This data shows the importance of environmental/cultural factors, and the need to explore internalizing symptoms also, when associating sleep disordered breathing and external behavioral changes. DISCLOSURE: Y. Chung, None. MODAFINIL DOSING DURING LONG-TERM TREATMENT OF EXCESSIVE SLEEPINESS IN NARCOLEPSY AND OBSTRUCTIVE SLEEP APNEA Jonathan R. Schwartz, MD*; Max Hirshkowitz, PhD; Wolfgang SchmidtNowara, MD; Integris Sleep Disorders Center of Oklahoma, Oklahoma City, OK PURPOSE: Modafinil is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, shift work sleep CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: The size of the patient’s neck, as measured by the neck circumference, has been studied in the past in evaluating patients with obstructive sleep apnea (OSA). To the best of our knowledge there has been no studies done to investigate if the neck circumference is related to the patient’s symptoms. The purpose of this study is to evaluate the association between the neck circumference, the Epworth sleepiness scale, and the Apnea-Hypopnea Index (AHI). METHODS: We reviewed the sleep studies of 73 patients referred to our sleep lab for suspected obstructive sleep apnea (OSA) and compared their demographic data, their AHI, their neck circumferences, and their Epworth sleepiness scales. RESULTS: We found that there was a strong association between the neck circumference and the sleepiness scale (p value of 0.0003), and a weaker association between the neck circumference and the AHI (p value of 0.0010). The higher the neck circumference, the higher the Epworth sleepiness scale and the more likely these patients are to have sleepiness symptoms. CONCLUSION: We conclude that patients with higher neck circumferences are more likely to be symptomatic than patients with lower neck circumferences regardless of the level of AHI. The size of the neck appears to predict the severity of sleepiness symptoms that these patients display as indicated by the Epworth sleepiness scale. Further studies are needed with larger numbers of patients to evaluate the usefulness of this observation. CLINICAL IMPLICATIONS: The size of the Patient’s neck as indicated by the measurement of the neck circumference appears to predict the severity of symptoms in patients with obstructive sleep apnea. DISCLOSURE: R.M. Shaqareq, None.

mon adverse events that occurred in ⱖ 5% of patients and were greater for modafinil than placebo were headache (34% vs 23%), nausea (11% vs 3%), rhinitis (7% vs 6%), nervousness (7% vs 3%), back pain (6% vs 5%), and diarrhea (6% vs 5%). Most adverse events were transient, mild to moderate in nature, and occurred within the first month of treatment. The adverse event profile for modafinil was similar among the disorders studied, except for headache, which was more frequent in narcolepsy. Overall, 8% of modafinil and 3% of placebo patients discontinued treatment due to adverse events. Modafinil had no clinically significant adverse effects on blood pressure/heart rate, electrocardiogram intervals, or clinical laboratory evaluations compared with placebo. CONCLUSION: Modafinil is well tolerated in patients with excessive sleepiness associated with specific disorders of sleep and wakefulness with a low incidence of adverse events, most of which were transient and mild-to-moderate in severity. CLINICAL IMPLICATIONS: Modafinil is a well-tolerated therapy that can be used in effectively improving wakefulness in patients with specific sleep-wake disorders without evidence of effects on blood pressure, heart rate, ECG intervals, or laboratory measures. DISCLOSURE: M.J. Thorpy, Cephalon, Inc.

Wednesday, October 27, 2004 Sleep Investigations, continued disorder (SWSD), and obstructive sleep apnea (OSA) (when used as an adjunct to nCPAP to treat residual excessive sleepiness). The modafinil dose necessary to sustain wakefulness may relate to excessive sleepiness severity. Patients with narcolepsy are usually sleepier than nCPAP-treated OSA patients. This meta-analysis evaluated open-label extension studies to determine whether the modafinil dose necessary to optimize wakefulness differed between the narcolepsy and OSA patient populations. METHODS: Patients with narcolepsy or residual excessive sleepiness in nCPAP-treated OSA who had completed 1 of 3 randomized, doubleblind, placebo-controlled studies entered open-label extension phases (40 weeks for both narcolepsy studies, 12 months for the OSA study). The effect of modafinil (200-400 mg per day) on excessive sleepiness was assessed using the Epworth Sleepiness Scale (ESS). RESULTS: 478 narcolepsy patients and 266 OSA patients received modafinil in open-label studies; 453 (95%) narcolepsy and 175 (66%) OSA patients completed the studies. Body mass index was 28.8⫾6.3 kg/m2 in narcolepsy patients versus 36.2⫾7.6 kg/m2 in OSA patients (p⬍0.0001). Mean baseline ESS score was 17.4⫾4.1 in narcolepsy patients versus 14.5⫾3.6 in OSA patients (p⬍0.001). Change from baseline in ESS at endpoint was -4.5⫾4.7 for OSA and -4.4⫾4.9 for narcolepsy. The percent of patients titrated to average doses of 400, 300, and 200 mg were 50, 34, and 16, respectively, for narcolepsy and 33, 43, and 24 for OSA. Modafinil was well tolerated. Adverse events were similar in both patient populations. CONCLUSION: When titrated for both efficacy and tolerability, a greater percentage of patients with narcolepsy were treated at higher doses of modafinil than nCPAP-treated OSA patients with residual excessive sleepiness. This difference may relate to differences in excessive sleepiness at baseline. CLINICAL IMPLICATIONS: Modafinil is effective for treating excessive sleepiness in narcolepsy and OSA (as an adjunct to nCPAP). Knowledge of the effective dose range for different patient populations will assist clinicians in making dosing decisions. Sponsored by Cephalon, Inc. DISCLOSURE: J.R. Schwartz, Cephalon,

SNORING AND RISK OF SLEEP DISORDERED BREATHINGA PILOT STUDY IN BANGLADESH A.K.M. M. Hossain, MBBS, FCPS*; M.A. Hasnat, MBBS, MD; M.A.J. Chowdhury, MBBS, FCPS; S.A. Haq, MBBS, FCPS; M. Hasan, MBBS, FCPS; Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh PURPOSE: Bangladesh is a developing country in south-east Asia where there is no polysomnography (PSG) facilities even in a tertiary care hospital. This pilot study reports about snoring and sleep disordered breathing (SDB) for the first time among Bangladeshi population. METHODS: The Berlin questionnaire and Epworth sleepiness scale (ESS) were used to identify patients of snoring and SDB. Subjects [ N: 96; sex ( male/female): 66/30]; age [ ( yrs, m ⫾ SD):33 ⫾ 8] were selected from Chest clinic and Medicine OPD of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. The Berlin questionnaire and ESS were translated and validated into Bengali language for easy interpretation. RESULTS: Snoring was observed in 35%, while daytime sleepiness in 46%. BMI (kg/m2) and neck circumference (inch) was 23 ⫾ 3 and 14.3 ⫾ 3.7 respectively. Both witness apnea and waketime tiredness was in 25%. Where as drowsiness during chatting (replaced for drowsy driving) was seen in 8%. ESS score revealed significant differences between groups having snoring (5.06 ⫾ 0.07 Vs 4.72 ⫾ 0.016, P⫽0.016), witness apnea (11.17 ⫾ 4.02 Vs 8.63 ⫾ 5.18, P⫽0.032), tiredness ( 11.75 ⫾ 4.32 Vs 8.42 ⫾ 4.91, P⫽0.042), daytime sleepiness ( 11.86 ⫾ 4.10 Vs 7.04 ⫾ 4.57, P⫽ ⬍0.001), drowsiness (12.50 ⫾ 2.20 Vs 7.59 ⫾ 4.00, P⫽ ⬍0.001) and HTN ( 11.25 ⫾ 4.56 Vs 8.81 ⫾ 5.01, P⫽ 0.19) when compared with respective counterparts. About 41% subjects showed ESS score ⱖ 11. Regression analysis of BMI, neck circumference, snoring, witness apnea, tiredness, daytime sleepiness, drowsiness and HTN for significant ESS score (ⱖ 11) showed daytime sleepiness ( P ⬍ 0.001) as independent predictor. CONCLUSION: Snoring, daytime sleepiness, waketime tiredness are not less frequently seen in Bangladeshi population. Study encompassing large population with PSG evaluation could illuminate the problem.

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CLINICAL IMPLICATIONS: Awareness of SDB, an unidentified problem in Bangladesh, can help overall health care and curtail accidents in vehicles and industries, attributable to sleep apnea. DISCLOSURE: A.M. Hossain, None.

DO ADDITIONAL FRONTAL EEG LEADS (FZ-A2), IN SLEEP STUDIES, LEAD TO DETECTION OF CORTICAL AROUSALS FOLLOWING PERIODIC LIMB MOVEMENTS THAT ARE CLINICALLY RELEVANT? Siva K. Ramachandran, MBBS; Eduardo A. DeSousa, MD*; Liliane M. Bastos, MD; Ajay Pillai, MD; Sindhu Kammath, MD; Fred Jaffe, DO; Drexel University College of Medicine, Philadelphia, PA PURPOSE: Periodic limb movements (PLM) are characterized by repetitive leg movements, detected by surface EMG of tibialis anterior muscles, during sleep. EEG arousals are considered to be associated with leg movements if they occurred before, simultaneously or 10 s after a PLM. Studies have indicated that PLM’s are not primary but rather an epiphenomenon associated with an underlying arousal disorder. Recently O’Malley et. al. 2003 postulated that the addition of a single frontal EEG lead yielded additional respiratory related arousals that were physiologically relevant. We hypothesized that PLM related arousals detected by an additional Fz-A2 EEG lead would correlate with a measure of excessive daytime sleepiness(EDS) and offer clarity when reporting PLM’s. METHODS: 12 subjects (6 males) who had symptoms of excessive daytime sleepiness (EDS) with an apnea-hypopnea index of ⬍ 10 and a PLM index ⬎ 10 were recruited. A full overnight polysomnography (with additional Fz -A2) was performed using a complete computerized system (Sandman). Sleep was staged as per standard criteria (Rechtschaffen A, Kales A.1968) EEG arousals were scored as per the report from Sleep Disorders Atlas Task Force of the American Sleep Disorders Association (1992). Daytime sleepiness was measured by the Epworth Sleepiness score (ESS). RESULTS: The age of our subjects were 54 ⫾ 15(mean ⫾ SD), ESS 11 ⫾ 5 (mean ⫾ SD), mean total PLM’s 201, mean PLM index 36. More PLM arousals were detected by Fz-A2 than C3-A2 EEG leads (456 vs 257).There was a significant correlation between ESS and total PLM’s (Pearson correlation, r⫽0.57, p⫽0.05), however there was no difference between C3-A2 or Fz-A2 related PLM arousals during specific sleep stages, CPAP usage or by severity (PLM index ⬎ or ⬍ 20). CONCLUSION: There was a significant relationship between total PLM’s and a clinical measure of EDS. CLINICAL IMPLICATIONS: In reporting PLM’s, the absolute number of PLM is more relevant than the commonly reported PLM arousal index, and measures to improve arousal detection by an additional frontal EEG lead may not be relevant. DISCLOSURE: E.A. DeSousa, None.

A CONTROLLED EVALUATION OF THE CLINICAL CHARACTERISTICS OF CENTRAL SLEEP APNEA Imran Sharief, MBBS*; Rohit Budiharaja, MBBS; David W. Hudgel, MD; Henry Ford Hospital, Section of Sleep Medicine, Detroit, MI PURPOSE: The clinical characteristics of Central sleep apnea (CSA)are thought to be similar, but usually less severe, to those of patients with OSA but these characteristics have not been examined in a controlled fashion. Purpose of this study was to compare clinical and polysomnographic (PSG) data between CSA and OSA populations after matching for age, race and gender. METHODS: CSA was defined as central AH index ⱖ5/hr and OSA index ⱕ5/hr. Retrospectively we reviewed charts and PSG’s of all patients diagnosed with CSA in last 2 years (n ⫽ 38) and compared data with OSA patients selected to match (n ⫽ 38) for age (57 vs. 55), race (C 26/26, AA 12/12), and gender (M 31/31, F 7/7) from our data base. RESULTS: Compared to OSA patients, CSA patients presented less commonly with snoring (23/38 vs. 32/38 P ⫽ .005), and witnessed apnea (19/38 vs. 27/38 P ⫽ .04). There was no difference in Epworth Sleepiness Scale (12 ⫾ 5 vs. 12 ⫾ 6 P ⫽ NS). BMI was similar in both groups (38 ⫾ 36 vs. 37 ⫾ 36 P ⫽ NS). A history of coronary artery disease (CAD) was more prevalent in CSA patients (18/38 vs. 6/38 P ⫽ .003). Review of PSG data revealed AH index was not different between CSA and OSA (27 ⫹ 20 vs. 24 ⫹ 20 P ⫽ NS). Periodic leg movements were more prevalent in CSA as compared to OSA (27 ⫹ 89 vs. 9 ⫹ 30 P ⫽ .027). Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Sleep Investigations, continued CONCLUSION: After controlling for age, race and gender a comparison of CSA and OSA patients revealed that CSA patients presented less commonly with a history of snoring and observed apneas, but more commonly had a history of CAD. CSA patients had a similar degree of day time sleepiness and obesity to matched OSA patients. CLINICAL IMPLICATIONS: Evaluation of day time sleepiness with a PSG should be considered in obese patients with a history of CAD even in those without snoring or witnessed apneas. DISCLOSURE: I. Sharief, None.

ROLE OF SLEEPINESS IN VEHICLE AND LABOR ACCIDENTS IN HEALTH CARE WORKERS IN THE HOSPITAL UNIVERSITARIO DE CARACAS IN VENEZUELA Gur Y. Levy, MD*; Yumaira Hernandez, MD; Maria Lozada, MD; Jose M. Lopez, MD; Hospital Universitario de Caracas, Caracas, Venezuela

Somnolence

Age Gender (F) IBM (Kg/m2) Hours of sleep Snorers Labor accidents in the last 5 years Vehicle accidents in the last 5 years Night shift Epworth scale

p

Yes (n:63) (31%) 32,9⫾6,71 32 (50,8%) 23,8⫾3,73 5,97⫾1,14 11 (17,5%) 13 (20,6%)

No (n:139) (69%) 35,9⫾9,49 74 (53,2%) 24,98⫾3,52 6,40⫾1,15 17 (12,2%) 4 (2,9%)

ns ns ns ns ns p⬍(0,001)

0,6⫾1,14

0,41⫾0,81

ns

51 (81%) 12,49⫾2,66

81 (58,3%) 6,14⫾2,19

p⬍(0,01) p⬍(0,001)

DISCLOSURE: G.Y. Levy, None.

THE INFLUENCE OF 8 MONTHS OF THERAPY WITH NASAL CONTINOUS POSITIVE AIRWAY PRESSURE (NCPAP) ON LEPTIN SERUM CONCENTRATION AND SYMPATHETIC ACTIVITY IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME(OSAS) Ryszarda Chazan, Prof*; Piotr Bielicki, PhD; Krzysztof Byskiniewicz, PhD; Renata Rubinsztajn, PhD; Marta Kumor, MD; Department of Pneumonology Med. University, Warsaw, Poland PURPOSE: to evaluate the leptin (LE) serum concentration and the sympathetic activity by the serum concentration of adrenaline (A) and noradrenaline (NA) in patients with OSAS before and after 8 months of therapy with nCPAP.

A COMMUNITY-BASED STUDY OF THE RELATIONSHIP BETWEEN METABOLIC SYNDROME AND SLEEP-DISORDERED BREATHING IN CHINESE SUBJECTS Jamie Lam, MBBS*; Bing Lam, FRCP, FCCP; Chi-leung Lam, MRCP; Julie K. Wang, MRCP; Hung-fat Tse, MD, FRCP; Karen S. Lam, MD, FRCP; Mary S. Ip, MD, FRCP; Queen Mary Hospital, Hong Kong, Hong Kong PRC PURPOSE: Sleep-disordered breathing in Asian populations is being increasingly recognized. This prospective cross-sectional study investigated the relationship of the metabolic profile or cardiovascular risk factors to obstructive sleep apnoea(OSA) in Chinese subjects in Hong Kong. METHODS: 255 consecutive Chinese subjects of either sex, aged between 30-60 years old, were recruited from staff in public institutions and visitors to community centers. Demographic and anthropometric data, blood pressure, metabolic parameters(fasting blood glucose, LDL & HDL-cholesterol and triglycerides), and polysomnographic findings were collected. RESULTS: The major dependent outcome variable was the apnoeahypopnoea index(AHI), the average number of apnoeas and hyponoeas per hour of sleep. Obstructive sleep apnoea was defined as AHIⱖ 5. Independnet variables were anthropometric measurement, blood pressure, serum lipoproteins, fasting blood glucose, age and sex. Significant linear relationship of AHI with age, BMI, waist circumference , systolic and diastolic blood pressure, triglycerides and HDL-cholesterol could be established. Multiple regression analysis identified age and obesity , in particular, central obesity as major determinants of AHI. OSA was also highly associated with more than one risk factor of the metabolic syndrome , as defined by clinical criterai (American Medical Association. Summary of the NECP adult treatment panel III report).JAMA 2001;285: 19. CONCLUSION: Among community-based subjects, presence of OSA is associated with a cluster of metabolic risk factors known to contribute to cardiovascular mortality or morbidity. CLINICAL IMPLICATIONS: Are OSA and Metabolic Syndrome one disease? Are they associated in a vicious cycle: More severe OSA subjects are highly associated with Metabolic syndrome or subjects with Metabolic syndrome do suffer from OSA? We should further investigate the effects of Continuous positive pressure treatment on the metabolic profile of those OSA subjects, and look into the preventive measures. DISCLOSURE: J. Lam, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Evaluate the influence of diurnal chronic somnolence and snoring in transit and labor accidents in the Health Team Workers (HTW) from the Hospital Universitario de Caracas. METHODS: A self reported questionnaire was obtained from HTW, which involved the following items: Short form sleep outcomes evaluation, Epworth sleepiness scale, alcohol consumption, labor and, vehicles accidents during the last five years, snoring history and employment status. RESULTS: 202 HTW were recruited, 106 females and 96 males. Thirty one per cent has somnolence according to the Epworth sleepiness scale greater than 10 points. CONCLUSION: This study shows that HTW from the Hospital Universitario de Caracas with diurnal chronic somnolence have seven-fold increase of labor accident. This finding could be related to labor shifts, sleep deprivation and other biological rhythm effect. CLINICAL IMPLICATIONS: Labor accidents attempt against the patient and HTW, therefore it is necessary to provide anchor sleep periods during the execution of prolonged labor shifts and better legislation on work hours for the HTW.

METHODS: The study group was consisted of 40 men with OSAS (mean age 50.6⫾10.0 yrs, range 30-71) with the following antropometrical parameters: mean body mass 97.8 ⫾ 23.8kg, mean height 175.7⫾ 8.3cm, BMI 31.5⫾6.3kg/m2, WHR 0.99⫾0.07. 14 patients were overweight, 23 were obese. Arterial hypertension was diagnosed in 7 cases, 3 patients were treated due to ischaemic heart disease. The control group was consisted of 12 men without OSAS. Methods: the diagnosis of OSAS (AHI ⬎ 10) was confirmed by polisomnography. Blood samples were taken after overnight fasting. The serum concentration of LE by RIA method, A and NA by HPLC were evaluated and basic biochemical investigations were performed. RESULTS: After 8 months 33 patients underwent control blood investigations, among them 20 subjects were treated with nCPAP. At the begining of the study the midlle serum concentrationof A, NA and LE were 64,0⫾30,4 pg/mL : 517,0 ⫾158,0 pg/mL : 16,2⫾ 12,8 ng/mL in the study group. Results of A, NA, LE before and after 8 months of 20 treated by CPAP patients were 55,7⫾20,4 pg/mL: 521,4⫾142,8pg/mL : 14,6⫾4,2 ng/mL vs 52,66⫾26,52pg/mL:472,48⫾160,97pg/mL:12,31⫾3,87ng/mL. The concentration of A, NA and LE in control group were 46,0⫾28,2pg/ mL: 430,8⫾106,5 pg/mL :11,38⫾6,93 ng/ml. CONCLUSION: In patients with OSAS comparing to the control group an increased sympathetic activity and higher leptin concentration were observed. There were tendency to decrease of sympathetic activity and leptin concentration, but there was not significant. CLINICAL IMPLICATIONS: The nCPAP therapy seems to have influence on sympathetic activity and leptin concentration in patients with OSAS. This kind of therapy could have ability to lower the risk of cardiovascular diseases in patients with OSAS. DISCLOSURE: R. Chazan, None.

Wednesday, October 27, 2004 Sleep Investigations, continued

SLEEP DISORDERED BREATHING IN PATIENTS ADMITTED TO A TERTIARY HOSPITAL WITH CONGESTIVE HEART FAILURE David A. Neumeyer, MD*; Ann T. Wilkinson; Charles Gbadouwey, MD; Al Levin, MD; Lahey Clinic, Burlington, MA PURPOSE: Untreated sleep apnea and other sleep disorders in patients with congestive heart failure are known to be associated with an increased mortality.1 Studies have shown an increased prevalence of OSA in patients with CHF, however little data exists on the prevalence of OSA on in-patients with CHF. This pilot study attempts to define the prevalence of sleep disordered breathing in patients with congestive heart failure admitted at a teaching hospital. The study was obtained with the use of an unmonitored four-channel recording (Stardust-Respironics, Inc). METHODS: Patients with the primary diagnosis of CHF admitted to our facility were selected for enrollment in this study. Enrollment criteria included resolution of acute heart failure. Other acute medical problems were required to be under adequate control, as not to significantly interfere with the sleep evaluation. Verbal consent was obtained from all patients entered into the study for the unmonitored four-channel Stardust recording (heart rate, pulse oximetry, nasal/oral air flow, and respiratory effort). The diagnosis of sleep disordered breathing was defined as an Apnea/Hypopnea Index (AHI of ⱖ5/hr, based on the results of the Stardust recording. RESULTS: Our data suggests a high prevalence of sleep disordered breathing amongst patients admitted to the hospital with the diagnosis of CHF. In 5 patients studied to date, all had evidence of sleep disordered breathing, based on a 4-channel sleep recording device (see table one). The mean AHI ⫽ 19.4. CONCLUSION: There is a high prevalence of sleep disordered breathing in patients with congestive heart failure admitted to our facility. CLINICAL IMPLICATIONS: Sleep disordered breathing in patients with congestive heart failure is associated with an increased risk of morbidity and mortality. Unmonitored sleep studies may play an important role in identifying this subset of patients with CHF who are at increased risk of death. 2, 3.

Patient

Age

Sex

AHI

Diagnosis

1 2 3 4 5

51 85 73 75 83

male female male male male

22/hr. 9.6/hr. 16.5/hr. 36.4/hr. 12.4/hr.

CHF, CAD CHF, Pneumonia CHF CHF, s/p AVR, MVR CHF

DISCLOSURE: D.A. Neumeyer, None.

Pulmonary Function in Various Clinical Situations 12:30 PM - 2:00 PM HEPATIC AND PULMONARY CORRELATES Giosue` Catapano, MD*; Francesca Mannucci, MD; Edo Fornai; Cristina Carli; Renato Prediletto, MD; Institute of Clinica Physiology, National Research Council, Pisa, Italy PURPOSE: The aim of this study was to develop a logistic model to predict the clinical probability of liver impairment based on a series of tests of respiratory function,in order to characterize those cirrhotic patients being more hypoxemic and thus at risk for the successfull of the liver transplant. METHODS: More than 500 patients with liver cirrhosis of different degree and classifed differently according Child-Pugh (32% in A class, 48% in B class, 20% in C class) have been evaluated by measure of

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spirometry, lung volumes, single breath CO test, gas exchange and hyperoxia test for the evaluation of intrapulmonary shunt. Out of these, 202 patients were transplanted and their rate of mortality was around 11% in the first 6 months later on. We used logistic regression analysis to estimate the probability of having a more severe hepatic disease (B and C) based on patient’s functional characteristics according the values of the respiratory tests. RESULTS: The most frequent respiratory abnormalities were hypocapnia (PaCO2⬍35mmHg), low TLCO (⬍80% pred.), increase of alveolar to arterial gradients for oxygen (A-aPO2⬎18mmHg) and shunt (⬎9%) present in more than 30%, 40%, 37% and 17% of patients, respectively. After transplant, those who died had more severe gas exchange impairment, in terms of A-aPO2, PaCO2 and shunt. FIO2 100% breathing test was able to predict a favoreable outcome after transplant mostly on 89% (predictive negative values of 94%). Abnormal values of five parameters, TLCO, A-aPO2, PaCO2, pH and hemoglobin were associated with an increased risk of more severe liver disease. With this model, when abnormal shunt was introduced, the correct classification of patient with a more severe liver damage was approximately around 86% (sensitivity 91.5). CONCLUSION: This structured logistic model may be useful for estimating the probability of having a more severe hepatic derangement from simple functional respiratory tests and to predict the survival after the transplant by the assessment of the shunt in the complex contest of the liver-lung scenario. CLINICAL IMPLICATIONS: Outcome of liver transplant. DISCLOSURE: G. Catapano, None.

PULMONARY FUNCTION AND EXERCISE CAPACITY IN MODERATE TO SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS AFTER LUNG CANCER RESECTION Alessia Verduri; Antonio Castagnaro*; Alfredo Chetta; Paolo Carbognani; Elisa Calabro`; Eveline Internullo; Francesca Greco; Emilio Marangio; Michele Rusca; Dario Olivieri; Respiratory Diseases Section, University of Parma, Parma, Italy PURPOSE: Exercise capacity may be reduced in patients with COPD. We evaluated patients with COPD who underwent lung cancer reduction in order to examine how surgery influences pulmonary function and exercise capacity. METHODS: We studied 13 patients (2 F; age range: 51 to 74 yr) with moderate to severe COPD and lung cancer. Before and after surgery, FEV1, FEV1/VC, TLC, and TLCO were recordered. Exercise capacity was also assessed by an incremental symptom limited exercise test on cycle ergometer. O2 uptake at peak of exercise (V’O2max) and at anaerobic threshold (V’O2@AT) values were recordered. Via standard posterolateral thoracotomy patients underwent lobectomy or bilobectomy according to lung cancer extension. RESULTS: Before surgery mean⫾SD values of FEV1, FEV1/VC, TLC, and TLCO were 47% of pred⫾18, 46%⫾14, 129% of pred⫾37, and 72% of pred ⫾39, respectively. O2 uptake at peak of exercise (V’O2max) and at anaerobic threshold (V’O2@AT) values were 1,337mL/min⫾353 and 1,010mL/min⫾235, SpO2 fall value during exercise was 2.4%⫾3. After 109days⫾39 from surgery, FEV1, FEV1/VC, TLC, and TLCO values did not significantly differ (50%⫾19, 50%⫾15, 108%⫾23, and 57%⫾20). V’O2max value significantly decreased, as compared to that before surgery (987ml/ min⫾219, p⬍0.05). In three patients, the AT was not detectable, in the remaining patients V’O2@AT value was significantly less that before surgery (797ml/min⫾155, p⬍0.05). SpO2 fall value did not change (3%⫾3). CONCLUSION: In patients affected by lung cancer and moderate to severe COPD, lobectomy or bilobectomy can significantly affect the exercise capacity in spite of no significant changes in pulmonary function. CLINICAL IMPLICATIONS: Both deconditioning and circulatory limitation may occur after surgery in patients with lung cancer and COPD. DISCLOSURE: A. Castagnaro, None.


Wednesday, October 27, 2004 Pulmonary Function in Various Clinical Situations, continued USE OF END-TIDAL CARBON DIOXIDE MONITORING TO DETECT OCCULT HYPOVENTILATION IN PATIENTS RECEIVING OPIOIDS IN THE PRE-HOSPITAL AND EMERGENCY DEPARTMENT SETTINGS Andrew A. Aronson, MD*; Stephen H. Thomas, MD; Tim Harrison, MPH; Mark Saia, EMTP; Hanh Bach; Massachusetts General Hospital, Boston, MA

VENTILATOR FUNCTION IMPROVEMENT IN PATIENTS RECEIVING REGULAR HEMODIALYSIS: RELATION TO SEX DIFFERENCES Pedja M. Kovacevic, MD*; Amela Matavulj, MD, PhD; Slavimir Veljkovic, MD, PhD; Mirjana Djekic-Cadjo, MD; Zvezdana Rajkovaca, MD, PhD; Nenad Ponorac, MD; Medical Faculty, University of Banja Luka, Banja Luka, Bosnia-Herzegovina PURPOSE: Uremic lung is different entity then oedema present in cardiovascular diseases or in adult respiratory distress syndrome as well. This state is one of the possible complications in patients with chronic renal failure (CRF) receiving regular hemodialysis (HD). It appears upon hydrostatic and colloidal pressure disbalance in lung capillaries and interstitial space leading to accumulation of oedematous liquor in interstitum and alveols. There are several studies suggesting that in these patients in 30-40% cases pulmonary hypertension was developed. The data also showed that primary as well secondary pulmonary hypertension are more often developed in females; even real reason is still unknown. The aim of the study was to estimate the ventilator function improvement in patients with CRF receiving regular HD related to sex differences. METHODS: The study population consisted in 39 patients (males, females koliko?) with CRF, with no cardiac and pulmonary diseases. These patients were treated by regular hemodialysis using bicarbonate or acetate mode, respectively (Table 1). They were divided into two groups according to the sex. Spirometry parameters as vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), before and after onset of hemodialysis were recorded. The results were analyzed using Student t-test and presented as mean ⫾SD. All p values ⬍0,05 were considered significant.

Table 1. Sex

Males

Females

Bicarbonatei modul Acetatei modul

79% 21%

65% 35%

Table 2. Spirometry

Males

Function pareameters Before HD VC 3.6 L FVC 3.8 L/s FEV1 3.2 L/s

Females

After HD Before HD 4.0 L* 2.5 L 3.8 L/s 2.53 L/s 3.4 L/s* 2.29 L/s

After HD 2.5 L 2.57 L/s 2.26 L/s

* p ⬍ 0.05 DISCLOSURE: P.M. Kovacevic, None.

CHRONIC COUGH: RETROSPECTIVE EVALUATION OF 472 CASES Elie Fiss, MD*; Alberto A. Monteiro Filho, MD; Regina M. Carvalho Pinto, MD; Adriano C. Guazzelli, MD; Faculdade de Medicina do ABC, Sao Paulo, Brazil PURPOSE: Cough is a very frequent symptom and is considered a very common cause of visits to the doctor. It causes great discomfort and should not been treatded without investigation of its cause. When cough lasts three or more weeks it can be called chronic cough. It is an essencial defense mechanism to protect the airways and to facilitate the drainage of airways secretions.But couhging in not always a protective mechanism and may be the first manifestation of a disease in several parts of the body , not only in the chest ,requiring investigation and treatment. Some studies demonstrated that the association of bronchial hyperreativity , sinusitis and gastroesophageal reflux account for aproximately 90% of teh causes of chronic cough (pathogenic triad in chronic couhg ). In order to achieve success in diagnosing patients with chronic cough , a well-defined protocol should be followed to investigate it. Our study analises retropectively the causes of chronic cough in 472 patients who seek medical attention for chronic cough. METHODS: Using an algorithm focusing on the most common causes of chronic cough we examined the date of 472 patients who underwent to a medical attention because of chronic cough and whose identification of the factors of cough and institution of adjust treatment results in a successful therapy. RESULTS: The analyses of the results showed this correlation : pos-nasal drip syndrome : 310 (65,7%), gastroesophageal reflux : 58 (12,3%) and asthma : 40 (8,5%). The less frequent causes appeared in 11,4% and 8,0% did not do all exams. CONCLUSION: In our patients the three most common causes of chronic cough were post-nasal drip syndrome ( 65,7%) , gastroesophageal reflux disease (12,3%) and asthma (8,5%), with a total of 86,5% of the patients with one of the components of the pathogenic triad of chronic cough. CLINICAL IMPLICATIONS: The proposal of an algorith focusing of the most common causes of chronic cough may be helpful in this initial approach. DISCLOSURE: E. Fiss, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Opioids are frequently given to patients in the prehospital and acute care setting to relieve pain. A known adverse effect of opioid administration is respiratory depression. This is particularly worrisome for patients with head injuries as hypercarbia is detrimental to these patients. This study attempts to determine if clinically significant respiratory depression occurs in the acute care setting from opioid administration. METHODS: Conscious, nonintubated patients presenting to Boston Medflight and the Massachusetts General Hospital Emergency Department were enrolled. A nasal cannula was applied to patients prior to opioid administration and end-tidal carbon dioxide monitoring via the Necllor Puritan Bennett NPB-75 (Pleasanton, California) occurred continuously. Opioids included morphine, fentanyl, meperidine and hydromorphone. The opioid was administered intravenously and post administration end-tidal carbon dioxide levels were obtained for up to ten minutes. Multiple doses were often recorded. RESULTS: The mean age of patients in the study was 38.5 years old with a standard deviation of 14.0. The average end-tidal carbon dioxide level before an opioid was administered was 34.2 millimeters of mercury with a standard deviation of 4.3. After opioid administration, the average end-tidal carbon dioxide level was 34.9 millimeters of mercury with a standard deviation of 4.6. The mean change was 0.78 millimeters of mercury. There was no difference between the pre and post end-tidal carbon dioxide levels based on the Wilcoxon signed-rank test which had a p-value of 0.15. CONCLUSION: The administration of intravenous opioids to nonintubated patients in the pre-hospital and emergency department has no effect on ventilatory status as evident by lack of a significant change to end-tidal carbon dioxide levels. CLINICAL IMPLICATIONS: Based on these results, it is safe to administer opioids to nonintubated injured or ill patients due to the lack of significant respiratory depression or hypercarbia caused by analgesia. Monitoring acute care patients end-tidal carbon dioxide levels can aid in early detection of an opioid toxicity. DISCLOSURE: A.A. Aronson, None.

RESULTS: The result showed that ventilatory function in male patients is significantly improved, especially VC and FEV1, whereas in female patients improvement had not statistical significance (Table 2). CONCLUSION: It can be concluded that one of the possible reasons for slight improvement of ventilator function in female patients is greater random usage of acetate mode for HD. CLINICAL IMPLICATIONS: Recommendation refers to preferable use of bicarbonate mode in HD treatment in patients diagnosed uremic lung.

Wednesday, October 27, 2004 Pulmonary Function in Various Clinical Situations, continued LOW FREQUENCY OF POSTOPERATIVE PULMONARY COMPLICATIONS AFTER ELECTIVE GYNECOLOGIC SURGERY Basel Khoury, MD*; P. R. Smith, MD, FCCP; S. Shah, MD; V. Brito, MD; M. Bergman, MD, FCCP; S. Pappachen, MD; D. Gal, MD; N. Hanif, MD; Long Island College Hospital, Brooklyn, NY PURPOSE: In a previous prospective study(Am J Respir Crit Care Med.2004;169:A105) we reported a low incidence (3.1%) of postoperative pulmonary complications (PPCs) after elective gynecologic surgery (EGS) for non-malignant disorders. This was considerably less than the incidence of PPCs (11%) after hysterectomy for all causes reported by BrooksBrunn (Clin Nurs Res. 2000;9:27-46). To assess whether the low frequency of PPCs that we found was due in part to the study itself (study team encouraged appropriate use of incentive spirometry or deep breathing exercises), we performed a retrospective study of PPCs after EGS for malignant and non-malignant disorders in the period immediately preceding our prospective study. METHODS: We reviewed the records of all patients (Pts) at our 450 bed community hospital undergoing EGS from 11/1/01 through 10/31/02. PPCs were defined as 2 or more of the following for 2 or more consecutive days: 1) new cough/sputum, 2) exam c/w atelectasis or pneumonia, 3) Temp greater than 38C, 4) chest radiograph showing atelectasis or new infiltrate. Statistical analyses utilized Fishers exact test. P⬍0.05 was the level of significance for all comparisons. RESULTS: 440 records were reviewed. 56 Pts not undergoing open abdominal procedures were excluded. Of 384 remaining Pts, PPCs occurred in 7 (1.8%). Variables which might influence the risk for PPCs are compared in Pts with and without PPCs in the Table. CONCLUSION: This retrospective data confirms the results of our prospective study. PPCs after elective gynecologic surgery are infrequent. Older age, smoking, history of lung disease, and gynecologic malignancy were not statistically significant risks for development of PPCs, although age and malignancy approached the level of significance. CLINICAL IMPLICATIONS: The incidence of PPCs after EGS is low. The risk for PPCs in Pts undergoing EGS does not appear to be influenced by age, smoking, history of lung disease, or diagnosis of gynecologic malignancy.

Characteristics of Patients With and Without Postoperative Pulmonary Complications After Gynecologic Surgery Age (mean) PPCs (n⫽7) No PPCs (n⫽377) P value for difference

48.7 43.0 0.088

Smoke

Lung Disease

2 (28.6%) 0 54(14.3%) 33 (8.8%) 0.27

0.83

Pathology (No. Malignancies) 2 (28.6%) 27(7.16%) 0.09

DISCLOSURE: B. Khoury, None. ASSESSMENT OF GLOBAL AND REGIONAL VENTILATION BY THE PALISCOPE, AN ACOUSTIC IMAGING DEVICE THAT ASSEMBLES A DYNAMIC IMAGE OF THE LUNG Issahar B. Dov, MD*; Meir Botbol, MSc; Igal Kushnir, MD; Ariela Velner, MT; Pnina Yaron, MSc; Hector Roizin, MD; Chaim Sheba Medical Center Tel Hashomer, Tel Aviv, Israel PURPOSE: Auscultation has been the basis for diagnosis lung diseases, but supplementation by imaging is often required. Our goal is to describe the PALIScope (Passive Acoustic Lung Imaging), an array of acoustic sensors and an algorithm that assembles a dynamic image that is useful for diagnosis and monitoring lung diseases. METHODS: The PALIScope is composed of 42 microphones, attached to the back by gentle negative pressure that records sounds during tidal breathing. An algorithm filters interferences and selects, from lung sounds frequencies, a band that carries the information required to assemble a consistent lung image. The signals are converted to energy over every 0.17 seconds at each sensor. To smooth the transitions between

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sensors, the dissipation of the signals was fitted to a mathematical function, and a gray level frame is constructed (white ⫽ no signal, black ⫽ maximal signal). The final image is one breath sequence of these frames. Subjects: Healthy nonsmoker adults and patients with space occupying processes. RESULTS: Normal image: As inspiration starts, the intensity and spatial distribution of the image increase, almost symmetrically, firstly at the upper zones. During expiration, which is of lower sound, the intensity fades towards the center. Image 1. Disease states: Changes in tissue composition or alteration of airflow may modify 1-3 characteristics of the image, intensity, distribution or dynamics/symmetry. Space occupying process affects the intensity and distribution. Image 2. Airway and parenchymal diseases affect the time sequence and symmetry. Image 3. CONCLUSION: The PALIScope processes sounds and assembles a dynamic lung image that is consistent in healthy subjects and possesses distinct abnormalities in diseases. Therefore, it offers easily obtainable, quantifiable, functional and potentially structural information on the lung, some of which can otherwise be obtained only by combining multiple imaging modalities. CLINICAL IMPLICATIONS: The PALIScope may facilitate bedside diagnosis and physiological studies of the lung.Images are shown at: http://www.sheba.co.il/lung-image. DISCLOSURE: I.B. Dov, Deep Breeze Ltd.

MEASUREMENT OF EXHALED NITRIC OXIDE BEFORE AND AFTER SIX-MINUTE WALK TESTS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Kian C. Ong, MBBS*; Wai Fung Chong, BN, MBA; Cindy Soh, BSc; Seow Pek Tan; Tan Tock Seng Hospital, Singapore, Singapore PURPOSE: Many factors are known to influence exhaled nitric oxide (eNO) values. In healthy subjects, eNO levels are known to markedly increase during physical exercise. Spirometric manoeuvres have also been shown to transiently reduce eNO levels. The purpose of this study is to determine whether there is a change in eNO levels after performing six-minute walk tests in patients with chronic obstructive pulmonary disease (COPD). METHODS: Twelve consecutive male patients with stable COPD (mean FEV1 50 ⫹ 23% predicted) each performed 2 six-minute walk tests with a 30-minute rest period in between. eNO was measured by chemiluminiscence to obtain eNO concentration (FeNO) and output (VNO) at rest 10 minutes before the start and 10 minutes after the end of the 2 six-minute walk tests. RESULTS: In 6 patients, there were increases in the FeNO and VNO after the exercise tests and in 5 patients there were reduction in FeNO and VNO after the exercise tests. In the remaining patient, the FeNO and VNO were the same after the exercise tests. The overall changes in the mean FeNO (1.1 ⫹ 0.3 parts per billion) and in the mean VNO (3.9 ⫹ 1.1 parts per billion) after the exercise tests were not significant (P⫽0.899 and P⫽0.872 respectively). There was also no significant correlation between the change in FeNO and the six-minute walk distance (r ⫽ 0.42, P⫽0.176) and between the change in VNO and the six-minute walk distance (r ⫽ 0.44, P⫽0.157). CONCLUSION: No significant changes in eNO levels were detected after six-minute walk testing in this series of patients with COPD. CLINICAL IMPLICATIONS: In patients with COPD, analysis of eNO may be performed shortly after performance of six-minute walk tests as the eNO levels do not appear to be significantly affected by the exercise testing. DISCLOSURE: K.C. Ong, None. PULMONARY FUNCTION AND VOCAL AERODYNAMICS OF FEMALE PROFESSIONAL SOPRANOS AND NONSINGERS Chul Min Ahn, MD*; Do Hyun Nam; Hong-Shik Choi, MD; Pulmonary Division, Department of Internal Medicine, Seoul, South Korea PURPOSE: Singing requires exquisite coordination between the respiratory and phonatory system to efficiently control glottal airflow. Our study determines both pulmonary function and vocal aerodynamics in classically trained professional singers and compares the data obtained Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Pediatric Chest 12:30 PM - 2:00 PM

from singers with normal female subjects who had had no professional vocal training. METHODS: Pulmonary function and vocal aerodynamic tests were carried out on six professional singers and seven female subjects who had had no professional vocal training. All singers had at least 15 years of formal classical vocal training and were active professional sopranos. Mean flow rates were obtained from all the subjects to assess glottal efficiency. Additionally, maximum phonation time and phonation quotients were obtained. RESULTS: No differences were found in physical characteristics between sopranos and non-singers. We also found no significant differences between groups in FEV1, FVC, FEV1/FVC, TLC, VC, and FRC. There was a trend for sopranos to exhibit an increment in inspiratory capacity than the nonsingers. In addition, respiratory muscle power was strengthened in singers compared to non-singers, as shown by increased MIP and MEP. The sopranos exhibited higher maximum phonation time and lower phonation quotient than do the nonsingers, while no differences were found in vital capacity between the groups. The sopranos exhibit higher mean flow rate in low pitch (C3) than do the nonsingers. When the pitch changes to high (C4), singers did not show any change in MFR levels, whereas a higher MFR levels were found for the nonsingers. CONCLUSION: The result suggested that classically trained professional sopranos did not have exceptional pulmonary function, but compartment of lung volume related to singing might be changed. CLINICAL IMPLICATIONS: Singers have strengthened their respiratory muscle power through vocal training and use air more efficiently in high-pitched sound than do the non-singers. DISCLOSURE: C. Ahn, None.

ASSOCIATION OF PASSIVE SMOKING ON THE PULMONARY FUNCTION OF STUDENTS AGED 9-12 YEARS AT THE UNIVERSITY OF SANTO TOMAS ELEMENTARY SCHOOL Marion P. Santos, MD*; Olivia C. Go, MD; University of Santo Tomas Hospital, Manila, Philippines

RESPIRATORY MUSCLE WEAKNESS FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANT Alexander C. White, MD*; Anna Kovalszki, MD; Helen Ryan, MD; Tufts-New England Medical Center, Newton, MA PURPOSE: Pulmonary complications are a major cause of morbidity and mortality following allogeneic/matched unrelated hematopoietic stem cell transplant (HSCT). Respiratory muscle weakness may contribute to pulmonary morbidity in subjects who develop pulmonary complications or graft versus host disease (GVHD) following HSCT. We routinely test inspiratory (PI) and expiratory (PE) respiratory muscle strength in all HSCT subjects who are having pulmonary function testing (PFT) and the purpose of this study was to analyze these data. METHODS: We combined the databases in the pulmonary function laboratory and in the HSCT and identified 46 subjects who underwent full PFT and the additional PI and PE measurements following allogeneic/ matched unrelated HSCT between 1999 and 2003. The data were de-identified, entered into an Excel spreadsheet and analyzed using SAS. This study was approved by the Human Investigation Review Committee. RESULTS: The distribution of values obtained for PI, PE and maximal voluntary ventilation (MVV) were as follows(A⫽values ⬍60% predicted, B⫽ 60-79% predicted, C⫽ ⬎79% predicted). PI: 9 (19.57%)(A), 15 (32%)(B), 22 ( 47%)(C); PE:33 (71%)(A),7 (15%)(B),6 (13%)(C); MVV:12 (26%)(A),13 (28%)(B),21 (45%)(C). We then compared patients with PI ⬍ 59% predicted (n⫽9) with those with PI ⱖ60% predicted (n⫽37) to better define the clinical relevance of a moderate reduction in muscle function. Patients with PI⬍59% predicted had significantly lower values ( p ⬍ 0.05) for FVC, MVV, PE and Dlco. There was no significant difference between groups for age, body mass index, time elapsed from HSCT to PFT and FEV1. GVHD was present in 58% of all patients, with no difference in incidence between these two PI groups. CONCLUSION: Conclusion: Respiratory muscle weakness is present in a significant percentage of patients undergoing PFT testing following HSCT. These findings may help identify patients at increased risk of increased pulmonary morbidity in the post HSCT period. (Supported by HL: 04411-02). CLINICAL IMPLICATIONS: Respiratory muscle weakness may contribute to pulmonary morbidity following HSCT. Chronic GVHD may be a risk factor for respiratory muscle weakness in this population. DISCLOSURE: A.C. White, None.

PURPOSE: The health consequences of exposure to environmental tobacco smoke (ETS) among children have been the subject of intense scientific and public health concern. This is a cross-sectional study to determine the association of exposure to parental passive smoking to changes in pulmonary function. METHODS: 578 students aged 9-12 y/o from the University of Santo Tomas Elementary school were given questionnaires to assess ETS exposure. 309 students who had acceptable spirograms based on the American Thoracic Society (ATS) guidelines were included in the analysis. The Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), FEV1/FVC ratio, Peak Expiratory Flow (PEF) and Forced Expiratory Flow at 25%-75% (FEF25-75) were the pulmonary function parameters measured. RESULTS: Forty five percent of the students who submitted the questionnaire had exposure to passive smoking; 5.5%, 23.6% and 33.7% were exposed to maternal, paternal and other sources of ETS in the home respectively. Majority of the parents smoked 1-5 cigarette sticks per day. The decrease in the pulmonary function parameters of these students was not statistically significant. However a statistically significant decrease in FEV1 (p⬍0.049), FVC (p⬍0.026) and PEF (p⬍0.038) was evident among children exposed to maternal smoking. CONCLUSION: Forty five percent of the students 9-12 years of age at the University of Santo Tomas Elementary school are exposed to passive smoking. Maternal smoking is associated with statistically significant deficits in FEV1, FVC and PEF. CLINICAL IMPLICATIONS: ETS is a serious health burden for children. Every effort should be made to reduce their exposure to passive smoking to give them a chance to grow up in a healthier environment. DISCLOSURE: M.P. Santos, None.

THE BOOSTER EFFECT OF A REPEAT MANTOUX TUBERCULIN SKIN TEST AS A DIAGNOSTIC CRITERION OF TUBERCULOSIS IN CHILDREN Clara R. Rivera, MD; Maita B. Zerda, MD*; Olivia C. Go, MD; UST Hospital, SJDM Bulacan, Philippines PURPOSE: To determine if the booster effect of a repeat Mantoux tuberculin skin test can be used as a diagnostic criterion of tuberculosis in children and to determine the factors affecting the booster phenomenon. METHODS: This is an experimental study conducted at a University Hospital out patient department and non goverment organization (NGO) medical clinic. Six hundred seventy four (674) children aged 6 months to 19 years old seen as out patients were screened for tuberculosis. A two step tuberculin test was done to determine if the initial tuberculin reaction was truly negative. Factors affecting booster response in patients who were given a booster test were assessed. RESULTS: Out of the 339 non reactors to the initial Mantoux tuberculin skin test, 240 (70.8%)had a positive booster result. Neither BCG vaccination,time of boosting and nutritional status were related to the incidence of boosting. There was a correlation between age, sex, presence of tuberculosis disease and positivity of a repeat tuberculin skin test. Factors such as history of exposure, signs and symptoms suggestive of tuberculosis (TB) and abnormal chest radiographs are important parameters that helped distinguish between boosting secondary to other causes from true conversion which indicates recent infection with M. tuberculosis. CONCLUSION: The presence of TB disease is related to the positivity of a repeat Mantoux Tuberculin skin test. Factors such as exposure, abnormal radiographs, signs and symptoms suggestive of TB are important parameters that affected the booster effect. CLINICAL IMPLICATIONS: There is a need to do a repeat tuberculin skin test in contacts of active cases of TB who had an initial negative reaction. DISCLOSURE: M.B. Zerda, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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Pulmonary Function in Various Clinical Situations, continued

Wednesday, October 27, 2004 Pediatric Chest, continued RISK OF TUBERCULOSIS IN CHILDREN FROM SMEAR NEGATIVE SOURCE CASES R. K. Elwood, MD*; Eduardo Hernandez-Garduno, MD; Victoria J. Cook, MD; University of British Columbia, Vancouver, BC, Canada

CLINICAL IMPLICATIONS: Dosing may have to be adjusted to take into account the poorer efficiency of the non-conducting VHC. DISCLOSURE: J.P. Mitchell, Mark W. Nagel and Jolyon P. Mitchell

PURPOSE: To determine the frequency of smear negative tuberculosis transmission events from adults to children in epidemiologically-linked pairs and to determine the predictors for identifying the source case. METHODS: We extracted demographic, clinical and mycobacteriology information of 190 children with TB and their 83 source cases who were reported from 1990 to 2001 in the province of British Columbia, Canada. Smear negative transmission events from adults to children were determined by identifying the smear results of epidemiologically-linked source cases. We compared the gender, age, ethnicity, contact history, site of disease and TST results of children who had a source case identified with those who had not. RESULTS: Smear negative source cases transmitted the disease to 10% of children (95%CI 5-17). Aboriginals (OR⫽4.9, 95% CI 1.5-13.4), those with primary TB (OR⫽7.3, 95% CI 3.3-16.0) and those with a positive TB skin test (OR⫽2.9, 95% CI 1.2-7.0) were independent predictors for source case identification. CONCLUSION: This study suggests lower rates of transmission of disease to children from smear negative sources compared to other studies involving all ages. Ethnicity of children, site of disease and a positive TST predict source case identification. CLINICAL IMPLICATIONS: Contact investigation of smear negative cases retains a low priority in most public health departments. Our findings illustrate a potential weakness in current infection control practices for smear negative TB patients and highlight potential challenges when secondary cases are diagnosed in children. The importance of these findings requires local interpretation after considering the impact of smear negative disease on local transmission. DISCLOSURE: R.K. Elwood, None.

A RANDOMIZED CONTROLLED TRIAL OF DIRECTLY OBSERVED TREATMENT SHORTCOURSE (DOTS) FOR CHILDHOOD TUBERCULOSIS BY USING AN OFFICIAL DOTS PROVIDER AND NON GOVERNMENTAL ORGANIZATIONS Meenu Singh, MD*; Lata Kumar, MD, FIAP; Advanced Pediatric Centre, Post Graduate Institute of Medical, Chandigarh, India

IN VITRO COMPARISON OF VALVED HOLDING CHAMBERS (VHCS) WITH FACEMASKS USING AN INFANT FACE MODEL Allan L. Coates, B.Eng; Emily Louca, BSc; Kitty Leung, BSc; Mark W. Nagel, HBSc; Jolyon P. Mitchell, PhD*; Trudell Medical International, London, ON, Canada

PURPOSE: Traditionally DOTS is provided by an officially appointed accountable individual who should not be the parent of the child. Recently, non governmental organizations (NGO’s) have been recommended to be involved in provision of anti tuberculosis treatment by DOTS. This randomized controlled trial was undertaken as there are no trials comparing the two in India. METHODS: Children (n:128) upto 12 years of age diagnosed with tuberculosis were allotted by computerized random allocation into two groups. Group 1(n:62) was given anti tuberculosis treatment (ATT) by direct supervision provided by an officially appointed and trained DOTS provider employed under a project funded by Department of Science and Technology, UT, Chandigarh, India. Group 2 (n: 66) was given ATT by workers belonging to two locally active NGO’s. The treatment protocols used were according to the recommendations of World Health Organization (WHO) for different categories of the disease. RESULTS: The distribution of patients in Category I and Category III as defined by WHO was similar in the two groups (P⬎.05). There were no patients belonging to Category II and IV. One drop out occurred in Group 1 as the family migrated to another state. All others completed the recommended duration of treatment and showed favourable clinical and radiological response. Six months after the completion of treatment of last case randomized there are no recurrences in either group. CONCLUSION: DOTS provided by an NGO’s is as effective as provided by an official provider when carried out in a project setting. Acknowledgement: The project was funded by Department of Science and Technology UT, Chandigarh, India. CLINICAL IMPLICATIONS: Treatment of tuberculosis in children by DOTS is equally effective when given by an official Dots provider or a commited workers from NGO in India. Hence NGO’s must be involved in the Revised National Tuberculosis Programme. DISCLOSURE: M. Singh, None.

PURPOSE: The delivery of aerosolized medication from pressurized metered-dose inhalers (pMDIs) by VHC with facemask that is often prescribed for infants and small children, is influenced by surface electrostatic charge. Our study attempted to examine medication delivery via VHC with facemask attached, using a model infant face (ADAM) based on a Laerdal head mannequin, modified to simulate natural facial texture. METHODS: VHCs manufactured from a transparent, electrostatic charge dissipative polymer (AeroChamber Max™ with child mask, Monaghan Medical Corp., Plattsburgh, NY [AC-MAX]) were compared with similar sized VHCs manufactured from non-conducting polymer (OptiChamber® Advantage with medium facemask, Respironics Inc., Cedar Grove, NJ [OPT-ADV]) [n⫽3-devices/group, 3-replicates/device]. The AC-MAX VHCs were tested out-of-the-package and pre-washed with detergent solution followed by rinsing. The OPTI-ADV VHCs were pre-washed but not rinsed to confer the maximum benefit of detergent coating as a means of reducing electrostatic charge. An electret filter was located immediately behind the lips of the model and breathing simulated at 155-ml tidal volume, 25-breaths/min with inspiration duration of 0.8-s. The facemask was applied with a pressure of 1.6-kg to the face, based on practice at a university pediatric asthma clinic. An acceptable facial seal was confirmed by comparing volumes from the inspiratory flow-time profile determined by a pneumotachograph located at the pMDI adapter of the VHC with that indicated by the breathing simulator. 2-actuations of fluticasone propionate ([FP], 125 ␮g/actuation, Flovent® HFA, GSK Inc., Canada) were delivered 10 to 12-s apart. The filter was removed from the model and assayed for FP content by HPLC-UV spectrophotometry. RESULTS: TM via AC-MAX VHCs with no pre-treatment was 55.1 (2.29) ␮g (mean (95%CI)), comparable with 51.3 (3.29) ␮g with pretreatment. TM via OPTI-ADV VHCs was 19.4 (4.76) ␮g. CONCLUSION: The use of electrostatic charge dissipative materials for the VHC is more effective than pre-treatment of a non-conducting VHC by washing in ionic detergent.

PURPOSE: To compare the efficacy of an improvised cardboard cone with a conventional spacer (NebuChamber, AstraZeneca) for the delivery of inhaled bronchodilator for children with acute asthma. METHODS: Sixty-two patients, aged 5 to 17 years with acute exacerbation of bronchial asthma, seen at the Children’s Asthma Unit and Pediatric Out-Patient Department in the University of Santo Tomas Hospital were included in the study. A single-blind (investigator blind) randomized controlled trial was conducted for 7 months. Terbutaline was given by the co-investigator via metered-dose inhaler (MDI) using either of the randomly assigned NebuChamber or cardboard cone constructed from pharmaceutical flyers. History was taken and clinical assessment before and 15 minutes after use of the MDI-spacer was done by the primary investigator using the following parameters: (1)respiratory rate; (2)accessory muscles and suprasternal retractions; (3)wheeze; and (4)peak expiratory flow (PEF). The primary investigator was unaware as to the type of spacer used. RESULTS: Patients who used the NebuChamber and cone with MILD exacerbation showed statistically significant differences in respiratory rate (NebuChamber p⫽0.004, cone p⫽0.019), wheeze (NebuChamber p⫽0.001, cone p⫽0.002) and PEF (NebuChamber p⫽0.000, cone p⫽0.000) between pre and post-bronchodilator. With regard to the use of accessory muscles and suprasternal retractions, there was no statistically significant difference between pre and post-bronchodilator (NebuChamber p⫽1.000, cone p⫽1.000). Among those who used the NebuChamber and cone with MODERATE exacerbation, there were likewise statistically significant differences in respiratory rate (NebuChamber p⫽0.013, cone

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INEXPENSIVE SPACER FOR BRONCHODILATOR THERAPY IN YOUNG ASTHMATICS Jessica J. Quetulio, MD*; University of Santo Tomas Hospital, Manila, Philippines

Wednesday, October 27, 2004 Pediatric Chest, continued p⫽0.000), wheeze (NebuChamber p⫽0.000, cone p⫽0.000) and PEF (NebuChamber p⫽0.000, cone p⫽0.000) between pre and post-bronchodilator. However, there was no statistically significant difference in the use of accessory muscles and suprasternal retractions between pre and post-bronchodilator (NebuChamber p⫽0.317, cone p⫽0.180). CONCLUSION: There was significant improvement in the lung findings and PEF of patients who used both the NebuChamber and coardboard cone. The cardboard cone , as an improvised spacer, is comparable with the NebuChamber. CLINICAL IMPLICATIONS: The improvised cardboard cone can be used as an inexpensive alternative spacer particularly in developing countries. DISCLOSURE: J.J. Quetulio, None. EFFECTS OF OVERWEIGHT ON LUNG FUNCTION IN INNERCITY CHILDREN Rashed A. Hasan, MBChB; George Y. Zureikat, MBBS*; Brian M. Nolan, MBBS; Jenny L. La Chance, BA, MA; Raouf Amin, MBBS; Raouf Amin, MBBS; Michigan State University, Hurley Medical Center, Flint, MI

THE SAFETY OF FLUTICASONE PROPIONATE/SALMETEROL DISKUS® IN PEDIATRIC PATIENTS AGES 4 – 11 WITH ASTHMA Karen House, MS; Paul M. Dorinsky, MD*; John Stauffer, MD; Lynne Schoaf, RN; Anna Ellsworth, BS; GlaxoSmithKline, Research Triangle Park, NC PURPOSE: Treatment options for asthma are limited for patients 4-11 years of age. Current guidelines recommend adding an inhaled longacting beta2-agonist to an inhaled corticosteroid (ICS), as a preferred option versus increasing the ICS dose, thus ensuring the lowest effective dose of ICS is used. Hence, a clinical study was conducted to evaluate the safety of fluticasone propionate/salmeterol 100/50mcg (FSC) BID compared with fluticasone propionate (FP) 100mcg BID, both via Diskus®, in patients 4-11 years of age with asthma. METHODS: A 12-week, randomized, double-blind, parallel-group study was conducted in 40 patients 4 and 5 years of age, and 163 patients 6 to 11 years of age with asthma, who were symptomatic on an ICS. RESULTS: No patient had an abnormal clinically significant ECG during treatment. CONCLUSION: This study demonstrated that FSC 100/50mcg via Diskus twice daily has a favorable risk/benefit profile in patients 4-11 years of age with asthma and a similar safety profile to FP 100mcg Diskus twice daily.

FSC 100/50mcg BID

Adverse events, n (%) # Pts with drugrelated adverse events # Pts withdrawn due to an asthma exacerbation FEV1 (L) at Baseline FEV1 (L) at Endpoint

FP 100mcg BID

4 and 5

6 to 11

4 and 5

6 to 11

n⫽21

n⫽80

n⫽19

n⫽83

15 (71) 3

45 (56) 9

15 (79) 2

43 (52) 7

1

1

3

2

n/a n/a

1.70 1.88

n/a n/a

1.65 1.77

DISCLOSURE: P.M. Dorinsky, None.

CHARACTERISTICS OF PEDIATRIC PATIENTS WITH PARADOXICAL VOCAL CORD DYSFUNCTION THAT PRESENT WITH COMPLAINTS OF WHEEZING OR SHORTNESS OF BREATH Alice Gu, MD*; Kevin D. Maupin, MD; University of Florida Department of Pediatrics, Pensacola, FL PURPOSE: Patients with paradoxical vocal cord dysfunction(PVCD) frequently present with complaints of wheezing or shortness of breath(SOB) and are frequently diagnosed with asthma and treated unnecessarily for asthma. Our study examines patients referred to a Pediatric Pulmonary Clinic for uncontrolled asthma or SOB who were diagnosed with PVCD. METHODS: We retrospectively reviewed patient charts with a diagnosis of PVCD that were seen in our Pediatric Pulmonary Clinic over a 27-month period. We reviewed twenty charts for the following parameters: age, race, SOB, insurance, spirometry, hospital admission, participation in strenuous activities, anxiety, school performance, stressors, fiberoptic bronchoscopy(FOB), and complaints during the episodes (chest pain, stridor, headache, parasthesia, hyperventilation, and dizziness). RESULTS: All the patients presented with a complaint of SOB. The average age of the patients was 13.4 years old. Nineteen (95%) of the patients had private insurance. Sixteen (80%) of the patient were female and 17(85%) of the patients were Caucasian. Eight(40%) of the patients complained of stridor, parasthesias, or dizziness during the episodes. Thirteen(65%) complained of hyperventilation during the episodes. Nine(45%) of the patients were participating in sports or choir. Eleven(55%) complained of been anxious. Thirteen(65%) had known stressors such as sports, divorce, illness or moving that coincided with the onset of the complaints. Fourteen(60%) admitted to an “A” average in school. Nineteen(95%) had normal spirometry and 15(65%) had diagnostic FOB. Only 5(25%) were admitted to the hospital and 2 of those admissions were to the intensive care unit. The one patient that had asthma and PVCD was a black male. CONCLUSION: In this study, the majority of the patients were Caucasian females with private insurance presenting with a complaint of chest pain, headache, or hyperventilation during the episodes. They were “A” students and anxious. CLINICAL IMPLICATIONS: PVCD should be considered in adolescent Caucasian female patients presenting with complaints of asthma or SOB. This may decrease the unnecessary utilization of asthma medications in this patient population. DISCLOSURE: A. Gu, None. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: The purpose of this study was to describe the proportion of overweight (body mass index ⬎ 85th percentile) inner-city children who have objective measures of airway obstruction as determined by spirometry. METHODS: After an informed consent was obtained,one hundred nine children healthy children (age: 14.7 ⫾ 1.6 years) from one secondary school were enrolled into the study. Children with recent respiratory infections or chest deformities were excluded. The standing heights and weights were measured, and body mass index (BMI) was calculated. Spirometry was performed according to the American Thoracic Society guidelines. We defined asthma as a forced expiratory volume in one second (FEV1) ⬍ 80% predicted, and FEV1/forced vital capacity (FVC) ⬎ 5% lower than predicted for age, sex, and race. RESULTS: Eighty children (74%) were African-American and 29 children (26%) were white, with a mean BMI of 26 ⫾ 7.8 kg/m2 (BMI percentile: 77 ⫾ 23). There were 61 female and 48 male. 58 (53%) children were overweight. 12 (11%) children met the criteria for asthma, of which 9 (9.5%) were overweight. Baseline FEV 1 percent predicted (87⫾ 6 vs. 83 ⫾ 7 %, p⫽0.03), FEV 1 /FVC (93 ⫾ 6 vs. 87 ⫾ 8, p⬍0.001), and FEV 1 percent predicted following albuterol administration (94 ⫾ 7 vs. 89 ⫾ 7 %, p⫽0.03) were all lower in children who were overweight compared to lean children. CONCLUSION: In inner-city minority children, overweight is associated with reduced lung function as demonstrated by spirometry. CLINICAL IMPLICATIONS: Many overweight inner-city children could benefit from diagnosis and treatment of asthma to improve symptoms and quality of life. DISCLOSURE: G.Y. Zureikat, This study was supported, in part, by a grant from GlaxoSmithKline

CLINICAL IMPLICATIONS: FSC 100/50mcg via Diskus twice daily provides added clinical benefit in pediatric patients 4-11 years of age with asthma indicating that treatment of the two main components of asthma (inflammation and smooth muscle dysfunction) in children is more effective than treatment of a single component (i.e., inflammation) alone. (SAS30031).

Wednesday, October 27, 2004 Pediatric Chest, continued SAFETY OF MOMETASONE FUROATE DRY POWDER INHALER AND COMPARISON WITH BECLOMETHASONE DIPROPIONATE IN CHILDREN WITH ASTHMA PREVIOUSLY MAINTAINED ON INHALED CORTICOSTEROIDS (ICS) Michael Noonan, MD*; Jonathan Corren, MD; Jeffrey Leflein, MD; Allergy Associates Research, Portland, OR

FACTORS ASSOCIATED WITH SUPRAVENTRICULAR ARRHYTHMIAS IN THE EARLY POST-PULMONARY RESECTION PERIOD Makoto Takahama, PhD*; Keiji Kushibe, MD; Michitaka Kimura, MD; Takeshi Kawaguchi, MD; Yamato Tamura, MD; Shigeki Taniguchi, MD; Nara Medical University, Kashihara, Japan

PURPOSE: To assess the long-term pediatric safety of mometasone furoate dry powder inhaler (MF-DPI) and compare it with that of beclomethasone dipropionate metered dose inhaler (BDP-MDI). METHODS: Children (N ⫽ 233) aged 4 – 11 years were randomized to 52 weeks of treatment with MF-DPI 200 mcg qd AM, MF-DPI 100 mcg bid, or BDP-MDI 168 mcg bid. Subjects had used ICS daily for ⱖ 30 days before the screening visit, and were on stable ICS doses for ⱖ 2 weeks before screening. The primary safety variables were adverse events. Secondary safety variables included vital signs and physical examination. RESULTS: The incidences of treatment-emergent adverse events were similar in all three treatment groups. The most frequently reported adverse event was upper respiratory tract infection, reported by 47% to 51% of subjects. Most adverse events were considered unrelated to study drug, and those considered related to treatment were consistent with all treatmentemergent adverse events. The most frequently reported related adverse events were headache (MF-DPI 200 mcg qd AM, 8%; MF-DPI 100 mcg bid, 4%; BDP-MDI 168 mcg bid, 2%) and oral candidiasis (4% in each treatment group). No clinically relevant changes in laboratory values, vital signs, or physical examinations were noted in any treatment group. CONCLUSION: Both MF-DPI doses were well tolerated, with no unusual or unexpected adverse events or safety concerns, and had a similar adverse event profile to that of BDP-MDI 168 mcg bid. CLINICAL IMPLICATIONS: MF-DPI is a well-toleratd ICS for the treatment of pediatric asthma. DISCLOSURE: M. Noonan, Schering-Plough Research Institute

PURPOSE: Supraventricular arrhythmias (SVA) following pulmonary resection have been well documented, although their reported incidence has varied widely. The purpose of this study was to retrospectively evaluate patients who have undergone a pulmonary resection in an effort to determine the incidence of and factors related to the development of postoperative SVA during the early post-pulmonary resection period (the first 7 postoperative days). METHODS: During the study period (1999-2003), 337 patients (244 men, 93 women) were included to this study. The primary end point with respect to efficacy was sustained (⬎15 minitues) or clinically significant SVA during the first 7 days after the operation. Frequencies observed in patients who experienced SVA and those who did not were compared by means of a chi-square test and Student’s t test for unpaired data. RESULTS: The study comprised 337 patients whose age ranged from 39 to 83 years (mean age, 66.4 years). Four patients underwent pneumonectomy, 12 bilobectomy, 263 lobectomy, and 58 segmentectomy. Forty (11.9%) of the 337 patients developed SVA. One patient developed atrial flutter, 22 patients atrial fibrillation (af), 10 paroxysmal supraventricular tachycardia (PSVT), and 7 af & PSVT. The incidence of SVA in patients having pneumonectomy, bilobectomy, lobectomy, or segmentectomy was 0%, 0%, 13.3%, and 8.6%, respectively. SVA occurred in 32 (13.1%) men and in 8 (8.6%) women (N.S.). Patients experiencing SVA were older (p⬍0.05). Patients with SVA did not differ in preoperative pulmonary functional parameters from patients without SVA. Seventeen of 40 (42.5%) patients with SVA and 30 of 297 (10.1%) without SVA required bronchial toileting after operations (p⬍0.05). There was no difference in the incidence of major postoperative complications between patients with and without SVA. CONCLUSION: Patients who developed SVA were older and almost half of them required bronchial toileting. CLINICAL IMPLICATIONS: Since the causes of postoperative rhythm disturbances and the treatment of these arrhythmias will be completely understood, the prophylactic use of cardiac active drugs should be considered as the way to secure low-risk procedures, especially in elderly patients. DISCLOSURE: M. Takahama, None.

Thoracic Oncology 12:30 PM - 2:00 PM LUNG MANIPULATION HAS NO EFFECT ON MEDIUM-TERM SURVIVAL IN RESECTABLE NON-SMALL CELL LUNG CANCER Sudip Ghosh, PhD*; Gaetano Rocco, MD; Northern General Hospital, Sheffield, United Kingdom PURPOSE: Although it is well-known that excessive surgical stress augments the growth of residual cancer and metastasis, whether surgical stress is increased according to the degree of surgical manipulation and can consequently lead to the enhancement of cancer metastasis has not been examined in lung cancer. The aim of this study was to examine whether lung manipulation has an effect on the survival of patients undergoing resection for non-small cell lung cancer (NSCLC). METHODS: Data was collected prospectively on 164 patients undergoing open lung resection and mediastinal nodal dissection by a single surgeon in a thoracic unit between 2001 and 2003 for Stage 1-IIIA NSCLC. Pre,intra-, and postoperative variables were collected from medical records and survival data obtained from follow-up files and personal confirmation. The patients were sub-divided into two groups; G1 - frozen section ⫹ lung resection (n⫽69) and G2 - lung resection only (n⫽95). RESULTS: Both groups were equally matched for sex and age. FEV1 of patients in G1 was 2.43 ⫹ 0.86L vs 1.97 ⫹ 0.69L in G2 (p⫽0.07). 23 patients had pre-operative chemotherapy and 3 patients had chemoradiotherapy in G2. There was no significant difference in the pathological staging of patients in either groups (Stage I-43% vs 46%; Stage II - 38% vs 32%; Stage IIIA - 18% vs 23%). Observed 3-year stage specific survival was not significantly different between the two groups (Stage I-73% vs 70%; Stage II - 57% vs 54%; Stage IIIA - 16% vs 17%; p⫽0.4). CONCLUSION: Lung manipulation to obtain histological confirmation prior to resection appears not to have a definite deleterious effect on medium term survival in patients with surgically resected NSCLC. CLINICAL IMPLICATIONS: This study may have far reaching implications for patients undergoing VATS lobectomies. DISCLOSURE: S. Ghosh, None.

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PROGNOSIS OF STAGE I NON-SMALL CELL LUNG CANCER PATIENTS WITH POSITIVE PLEURAL LAVAGE CYTOLOGY Ryoji Yamamoto, MD; Takashi Tojo, MD, FCCP*; Ryu Nakajima, MD; Kan Ideguchi, MD; Hirohito Tada, MD; Osaka City General Hospital, Osaka, Japan PURPOSE: The purpose of this study is to clarify the prognosis of resected stage I non-small cell lung cancer patients with positive pleural lavage cytology (PLC). METHODS: From January 1994 to December 2001, 1025 patients underwent resections for primary lung cancer, and PLC was performed by washing with 50 ml of physical saline solution immediately after a thoracotomy in the patients with little or no pleural effusion. 490 patients were in pathological stage I, and 15 patients (3.1%) of them had positive PLC. Four patients were male and 11 female, with a mean age of 65.3 years (range 47 to 75 years). Six patients were in stage IA, and 9 in stage IB. Ten were adenocarcinoma, and 5 were squamous cell carcinoma. The pleural involvement (P factor) was 8 in p0, 4 in p1, and 3 in p2. RESULTS: Of 15 positive PLC patients, 4 had a recurrence of the disease, 2 in the pleural cavity, 1 in the cervical lymphnode and 1 in the lung. All four were in stage IB. 3 were adenocarcinomas, and 3 were in p2. The survival of positive PLC at 3 and 5 years were 84.4% and 57.9%. Survival was significantly poorer in patients with positive PLC results than in those with negative results (93% at 3 years, 82% at 5 years) (p⬍0.0001). CONCLUSION: Even in stage I Of 490 non-small cell lung cancer patients, 15 patients (3.1%) had positive PLC. And 4 had a recurrence of the disease, 2 in the pleural cavity, 2 in the distant lesion. All four were in stage IB. Survival was significantly poorer in patients with positive PLC results than in those with negative results. CLINICAL IMPLICATIONS: Even in stage I Of 490 non-small cell lung cancer patients, 15 patients (3.1%) had positive PLC. And 4 had a Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 Thoracic Oncology, continued recurrence of the disease, and all four were in stage IB. Survival was significantly poorer in patients with positive PLC results than in those with negative results. DISCLOSURE: T. Tojo, None.

CLINICAL IMPLICATIONS: We recommend sCEA measurement before treatment as an additional predictor of life expectancy in advanced NSCLC. DISCLOSURE: M. Szturmowicz, None.

STAGING OF LUNG CANCER WIH SUSPECTED N2 DISEASE: THE ROLE OF VIDEO ASSISTED THORACOSCOPY Pier P. Brega-Massone, MD*; Barbara Magnani, PhD; Franca Ferro, MD; Cosimo Lequaglie, MD; Thoracic Surgery, S. Rita Clinic, Milan, Italy

WHAT IS THE CLINICAL SIGNIFICANCE OF INCREASED SERUM CYFRA 21-1 AND CEA CONCENTRATIONS IN THE PATIENTS WITH ADVANCED NSCLC? Monika Szturmowicz, MD.ACCP*; Monika Zaleska, MD; Jacek Zych, MD,PhD; Barbara Roszkowska, MD,PhD; Renata Langfort, MD,PhD; Urszula Demkow, MD,PhD; Kazimierz Roszkowski-Sliz, Prof; National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland PURPOSE: Inoperable NSCLC is associated with poor prognosis. Response to chemotherapy and survival depend on biologic properties of tumor. We asked a question if serum (s) Cyfra 21-1 and CEA estimation is helpful in predicting response to chemotherapy and survival in this group of patients (pts). METHODS: Tumor markers were measured before treatment in 162 NSCLC pts: 93 stage IIIa⫹b, 69 stage IV. All the patients received cisplatin based chemotherapy. The response to treatment assessed before the third course was: PR in 46 pts, MR in 33, SD in 40 and PD in 43. RESULTS: sCyfra 21-1⬎3.3 ng/ml was found in 89(52%) of pts and correlated significantly with disease extension (DE) and performance status (PE). PD was more frequent in the group of 23 pts with Cyfra 21-1⬎10 ng/ml than in remaining pts. sCEA⬎3 ng/ml was found in 74(46%) of pts and correlated with PS but not with DE and type of response to treatment. PS was the only predictor of type of response to treatment in multivariate analysis. DE, PS and sCEA⬎3 ng/ml were found to be a negative prognostic factors in multivariate analysis. sCyfra 21-1⬎10 ng/ml was a prognostic indicator in univariate analysis only. CONCLUSION: sCEA but not sCyfra 21-1 is an independent prognostic factor in advanced NSCLC.

FACTORS INFLUENCING THE RATE OF LUNG CANCER RESECTION IN A VETERAN POPULATION Brion J. Lock, MD*; Mark T. Dransfield, MD; The Birmingham VA Medical Center and the University of Alabama, Birmingham, AL PURPOSE: Lung cancer is the leading cause of cancer death in the United States. Although optimal treatment for non-small cell lung cancer (NSCLC) is surgical resection, most patients are ineligible as they present with advanced disease. A resection rate of 25% has been reported in the US while in the United Kingdom rates may be as low as 5%. Pre-operative delays may contribute to this discrepancy and in 1999 the Birmingham VA established a specialized Lung Mass Clinic (LMC) to streamline care. We hypothesized that since then, the resection rate would be comparable to US standards. METHODS: We examined the medical records of all veterans seen in the LMC between October 1999 and October 2003 and identified those subsequently diagnosed with NSCLC. Baseline demographics and pulmonary function were recorded as were diagnostic methods, times to diagnosis and resection, and post-operative survival. Reasons for nonresection were tabulated. Differences between those resected and nonresected were examined using Chi Square or t-tests as appropriate. RESULTS: 157 patients were diagnosed with NSCLC and 31 (19.7%) underwent resection. There were no differences in age, race, or sex between the two groups although resected patients had better pulmonary function (Table 1). Patients diagnosed by bronchoscopy were less likely to undergo resection. The median time to diagnosis was 70 days in those resected and 8 days in the non-resected group (P⬍0.001). The median time to resection was 104 days. To date, time to resection does not correlate with post-operative survival. 106 (84%) of those not resected had evidence of advanced disease, poor pulmonary function, or refused therapy (Table 2). CONCLUSION: Since the inception of the LMC, the resection rate appears comparable to that observed nationally. Those whose disease was amenable to bronchoscopic diagnosis had faster tissue confirmation but were unlikely to undergo resection. The primary determinant of the resection rate was advanced stage at presentation and not pre-operative delays. CLINICAL IMPLICATIONS: The VA performs as well as other health systems in the surgical treatment of lung cancer.

TABLE 1 Resected (N⫽31) Age (years) Race (% Caucasian) Sex (% Male) FEV1 (mean % predicted) FVC (mean % predicted) Method of diagnosis Bronchoscopy (% total)

Not Resected (N⫽126)

64.8 84 97 67

66.8 74 99 55

71

62

10/31

p Value 0.28 0.35 NS 0.002 0.02

97/126 (77)

⬍0.001

9/126 (7)

⬍0.001

19/126 (15) 8

NS ⬍0.001

(32) Surgery (% total) TTNA (% total) Median time to diagnosis (days)

19/31 (61) 2/31 (6) 70


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PURPOSE: The aim of our work was to evaluate the role of VATS in mediastinal lymph nodal biopsies for staging lung cancer. When preoperatively staging lung cancer, it is very difficult to evaluate sure lymph node involvement, but lymph node invasion and the degree of infiltration are factors conditioning the therapy choice. VATS permits to effect mediastinal nodes biopsies unlikely accessible at mediastinoscopy such as subaortic nodes, paraaortic, subcarinal posterior, paraesophageal and pulmonary ligament nodes. METHODS: From 1995 to 2004, 78 patients were submitted to VATS for mediastinal lymphonodal biopsy. The goal of biopsy was staging lung cancer. Seventy-six patients underwent lymph nodal thoracoscopic biopsy (97%), while in 2 histology was done by pleural metastatic nodule thoracoscopic biopsy (3%). We performed 27 lymph nodal biopsies in level 5 (34%), 22 in level 6 (28%), 20 in level 7 (26%) and 7 in level 8 (9%). In 63 cases lymph nodal biopsy was ipsilateral (81%) while in 13 contralateral (16%). RESULTS: No post-operative complications were observed and 26 subjects (33%), whose lymph node specimens showed no evidence of neoplastic cells at extemporary analysis, underwent to open lung resection in one time. Histology was adenocarcinoma in 38 cases (49%), squamous carcinoma in 21 (27%), microcitoma in 11 (14%) and giant-cell lung carcinoma in 8 (10%). Fifteen patients were at stage I (19%), 11 at stage II (14%) and 50 at stage III (64%). These last subjects received neoadjuvant chemotherapy or chemotherapy and/or radiotherapy. Two patients at stage IV (3%) underwent to definitive chemotherapy. CONCLUSION: VATS seems to be a safe and effective technique for diagnosis, staging and treatment of lung cancer patients. Our results indicate that it allows adequately sized lymphonodal specimens to be taken for histological typing and treatment decision making. It is not very invasive and led to a low incidence of complications. CLINICAL IMPLICATIONS: Vats permits to obtain a surely diagnosis in lung cancer linfonodal biopsies in all the station difficulty to reach by mediastinoscopy. DISCLOSURE: P.P. Brega-Massone, None.

Wednesday, October 27, 2004 Thoracic Oncology, continued TABLE 2 Primary Reason for Non-Resection (N⫽126)

# (%Total)

Advanced disease by imaging IIIA/IIIB disease - transbronchial needle aspiration Biopsy proven distant metastases IIIA/IIIB disease – mediastinoscopy Pulmonary function Refused treatment Comorbidities/poor functional status Died during evaluation Lost to follow-up/unknown

53(42) 29(23) 7(6) 6(5) 6(5) 5(4) 5(4) 4(3) 11(9)

DISCLOSURE: B.J. Lock, None. HIGH-RESOLUTION CT FINDINGS OF PRIMARY SITE IN SMALL PERIPHERAL LUNG CANCER WITH MEDIASTINAL METASTASES TO NORMAL-SIZED LYMPH NODES Hitomi Awaya, MD; Nobuyuki Tanaka, MD; Nobuyuki Matsunaga, MD; Tsuneo Matsumoto, MD*; Yamaguchi University School of Medicine, Ube, Japan PURPOSE: To preserve pulmonary function in lung cancer patients, the video assistant thoracic surgery and conformal radiotherapy are developing. The accurate nodal staging is essential in these treatments. Although FDG-PET is the most accurate diagnostic procedure, there are some false-positive and false–negative diagnoses. We hypothesized that some pathological features of lymphatics are revealed on HRCT in patients with mediastinal metastases to normal-size lymph nodes. The purpose of this study is to evaluate whether it is useful to assess CT appearances of the primary site of lung cancer in the nodal staging. METHODS: Two chest radiologists reviewed thoracic CT images of 91 non-small-cell lung cancer patients diagnosed as clinical T1N0 by nodal size criterion. The nodal staging of all patients was pathologically proven by thoracotomy within four weeks after CT examinations (pN0⫽72, pN1⫽7, pN2⫽12). Radiologists assessed HRCT findings of the primary site including the size, density, and marginal characteristics of the nodule and the appearances around the nodule. These HRCT findings were compared between patients with and without nodal metastases. RESULTS: The patients with the primary lesion of ground-glass attenuation alone had no nodal metastasis. Irregular and long pleural tags (more than 1 cm in length) were seen in all patients with N2 and 10 patients with N0 (p⬍0.01). Irregular thickening of proximal vessels running toward primary tumor were seen in eight patients with N2 and one with N0 (p⬍0.01). This CT feature was pathologically correlated with the dilatation of lymph channels accompanied by the vessels. Areas of GGA around the primary lesion were present in eight patients with N2 and one with N0 (p⬍0.01). CONCLUSION: Some HRCT features of primary sites indicated mediastinal nodal metastasis in T1 lung cancer. The assessment of HRCT appearances of the primary site may be useful in the nodal staging of lung cancer. CLINICAL IMPLICATIONS: HRCT may be useful in the nodal staging of the lung cancer as well as the differnetial diagnosis of the small nodule. DISCLOSURE: T. Matsumoto, None.

or nonresponsive to standard treatments of radio- and chemotherapy, and their prognosis is very poor. Because chemotherapy and irradiation induce programmed cell death or apoptosis in vitro and in vivo, efforts are now being made to define the molecular events underlying or opposing the apoptotic process in NSCLC. Recent findings indicate that multiple human NSCLC cell lines (including A549 lung adenocarcinoma cells) have constitutively active levels of the transcription factor STAT3 that are linked to cell survival. Since STAT1 opposes the actions of STAT3 in many cell types, we tested the hypothesis that STAT1 has antigrowth effects in A549 cells. METHODS: A549 cell were obtained from ATCC and grown in medium supplemented with antibiotics and serum. Before an experiment, cells were serum-starved overnight. Western immunoblotting of whole cell lysates was used to assess STAT1 activation. Cell number was determined with a hemocytometer. RESULTS: Treatment of A549 cells with IFN-␥ (10 ng/ml) induced robust STAT1 activation as indicated by increased Tyr701 phosphorylation. Activation was rapid and sustained out to 90 min (62 ⫾ 12-fold increase over control). We next assessed the effect of IFN-␥ on cell growth. Treatment of A549 cells for 72 h with IFN-␥ (10 ng/ml) resulted in a 75% decrease in cell number. However, prior infection of A549 cells with adenovirus expressing the naturally occurring STAT1 inhibitor PIASy relieved this inhibition. Over 72 h, cell number increased by 150% compared to IFN-␥-treated cells infected with control adenovirus. CONCLUSION: IFN-␥ opposes proliferative growth of A549 nonsmall cell lung cancer cells by activating the STAT1 transcription factor. CLINICAL IMPLICATIONS: Our findings support the idea that STAT1 signaling could be a novel therapeutic target in the treatment of non-small cell lung cancer. DISCLOSURE: N. Salamat, None.

ROBOTIC BRACHYTHERAPY TECHNIQUES FOR LUNG CANCER Scott J. Belsley, MD*; Cliff P. Connery, MD; Julianna Pisch, MD; Karen McGinnis, MD; Andrew J. Evans, MD; Joesph J. DeRose, MD; Robert C. Ashton, MD; St Luke’s Roosevelt Hospital, Columbia University, New York, NY

PURPOSE: Lung cancer is the most lethal form of cancer for both men and women in the United States. On the basis of histopathological criteria, over 75% of lung cancer cases are classified as non-small cell. In general, patients with non-small cell lung cancer (NSCLC) are poorly responsive

PURPOSE: Novel approaches combining limited surgical resection and radiation therapy for lung cancer continue to evolve. Brachytherapy techniques are applicable in a subset of patients with non-small cell lung cancer and limited cardiopulmonary reserve who are not able to tolerate a lobectomy. Robotic surgical techniques now offer the ability to deliver precise brachytherapy through a minimally invasive surgical approach. METHODS: Using the da Vinci Surgical System and our previously reported research developed in animal models, two patients underwent robotic brachytherapy. A thoracoscopic wedge resection, followed by robotic intracorporeal suturing of I125 radiation seeds was performed in two patients. Patients had a tissue diagnosis prior to surgery and no evidence of metastatic disease. Patients were not candidates for lobectomy due to severe interstitial lung disease, decreased performance status, cardiac dysfunction, previous contralateral lobectomy and significant co-morbidities. RESULTS: Patients underwent uncomplicated wedge resections of their primary tumor. Radiation seeds were sutured in place using one of two geometric configurations; longitudinal technique and spiral technique. The seed activity is designed to give a dose of 14,400 cGy at 1 cm from the plane of the implant. Radiation seed activity is delivered over nine months [5 half-lives]. There were no complications and postoperative courses were eventful. CONCLUSION: The goal of therapy for patients with lung cancer who have significant risk factors and/or poor perfromance status is two-fold: 1. Complete resection of the primary lesion through a minimally invasive approach. 2. Deliver radiation that would achieve the highest tumoricidal dose with the least collateral damage to the surrounding lung parenchyma. Intracorporeal dexterity of the robotic system allows accurate and specific configurations of seed placement limiting excessive collateral damage to healthy tissue. CLINICAL IMPLICATIONS: For selected patients with limited pulmonary reserve and significant comorbidities, tailored application of brachytherapy geometric patterns is now part of the treatment armentarium for high risk lung cancer patients. The use of robotic technology is

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ACTIVATION OF STAT1 BY IFN-⌫ INHIBITS GROWTH OF HUMAN NON-SMALL CELL LUNG CANCER CELLS Nikhat Salamat, MD*; Steve A. Maxwell, PhD; J. R. Brewer, BS; Jonathan N. Day, BS; Richard E. Winn, MD; George W. Booz, PhD; Scott and White Hospital, Temple, TX

Wednesday, October 27, 2004 Thoracic Oncology, continued now an integral part of the evolution in the treatment of lung cancer at our institution. DISCLOSURE: S.J. Belsley, None.

HOXB4 INDUCES APOPTOSIS IN ACUTE LYMPHOBLASTIC LEUKEMIA REH CELLS Robert J. Pauley, PhD; Yanni Zhuang; Amro Aboukameel; Kamal K. Mubarak, MD*; Larry R. Tait, PhD; Ramzi M. Mohammad, PhD; Wayne State University, Detroit, MI

TYPICAL CARCINOIDS OF THE LUNG: MULTICENTRIC FORMS, LYMPH-NODE METASTASES AND LONG-TERM SURVIVAL IN 83 PATIENTS Piero Ferolla, MD*; Niccolo Daddi, MD, PhD; Moira Urbani, MD; Costanzo Fedeli, MD; Mark Ragusa, MD; Rodolfo Ribacchi, MD; Giovanni Battista Bolis, MD; Francesco Puma, MD; Gabriella Angeletti, MD; Fausto Santeusanio, MD; Giuliano Daddi, MD; DIMISEM University of Perugia, Perugia, Italy PURPOSE: Typical carcinoids (TC) are still considered by many authors as associated with a fairly benign behaviour and therefore at times treated with a more or less conservative surgical approach. Furthermore long term clinical follow-up is often judged as not strictly necessary. Purpose of this study is to retrospectively analyse the features and behaviour of 83 patients with typical bronchial carcinoids, treated surgically and followed-up in our Department from February 1983 to March 2004. METHODS: Diagnostic work-up included CT scan, bronchoscopy, bronchial biopsy or fine needle aspiration biopsy, 111In-pentetreotide scan (OctreoScan), and mediastinoscopy in selected patients. Neuroendocrine (NE) differentiation was assessed on the basis of morphology and immunohistochemical reactivity for the pan-neuroendocrine markers NSE, CGA, Synaptophysin, PGP 9.5 and Leu-7. Multiple forms and tumorlets were carefully researched performing serial sections of lung parenchyma. Histological subtypes were diagnosed according to Travis WHO Classification (1999) criteria. Staging was established according to the International System for Staging of Lung Cancer (2002). Survival data were analysed using Kaplan-Meyer method by Log-Rank test (MantelCox) at 5,10 and 15 years.

OUTCOME OF LUNG CANCER PATIENTS ADMITTED TO INTENSIVE CARE UNIT Jerry M. Maniate, MD*; Sat Sharma, MD, FCCP; University of Manitoba, Winnipeg, MB, Canada PURPOSE: Patients diagnosed with bronchogenic carcinoma are increasingly getting admitted to the medical intensive care units (ICU). Epidemiology and outcome of these patients is not well delineated in medical literature. The aim of our study was to investigate the outcome of these patients and to examine the predictors of mortality. METHODS: Retrospective study of all patients admitted to the ICUs at the 2 local tertiary care university hospitals in Winnipeg, from May 30, 1999 to July 31, 2003. A computerized search of the database identified 28 patients who were admitted with a previously known or a new diagnosis of primary lung cancer. 11 patients were excluded for non-primary lung cancer diagnoses (lymphoma, metastatic rectal carcinoma, bronchiectasis, and bronchiolitis obliterans). A total of 17 patients were included in this study. Data on demographics (age, sex, geographic data, admitting diagnosis, length of stay, outcome, treatment, TISS and APACHE II day 1 scores, admission bloodwork, co-morbid diseases and cancer related data (histology, metastases, staging, treatment options) were extracted. RESULTS: 47% of the 17 patients were female; the median age was 64 (42 -81). 29.4% were small cell lung cancer (SCLC), 52.9% were non-small cell lung cancer (NSCLC) and 17.7% of unknown type. The mean ICU length of stay was 5.5 days (0 – 16 days) and the mean ICU mortality rate was 47.1%. Mean hospital length of stay 15.7 days (1 – 53 days) and mean hospital mortality rate 52.9%. A small number (5.8%) were transferred to the palliative care unit. CONCLUSION: Patients admitted to ICU with previously or newly diagnosed primary lung cancer has high mortality rates. However, their outcome is similar to the patients admitted with other common ICU diagnoses such as pneumonia and septic shock. A successful discharge from the ICU was associated with a successful discharge from the hospital. CLINICAL IMPLICATIONS: Patients with a new or a previous diagnosis of primary lung cancer have favourable prognosis when admitted to an intensive care unit with a life threatening problem. DISCLOSURE: J.M. Maniate, None.

THE USEFULNESS OF ULTRASOUND-GUIDED FINE NEEDLE ASPIRATION CYTOLOGY OF IMPALPABLE NECK NODES IN PATIENTS WITH LUNG CANCER Chulho Oak, MD*; Kosin University Gospel Hospital, Pusan, South Korea PURPOSE: In lung cancer patients, the presence of metastatic neck nodes is a crucial indicator of inoperabilty. Ultrasonography is a useful diagnostic method in detection of small impalpable lymph nodes and in guidance of fine needle aspiration biopsy. In this study we evaluated the clinical usefulness of ultrasonography and ultrasound-guided fine needle aspiration cytology(US-FNA) in lung cancer patients without palpable neck nodes. METHODS: From Sep 2002 to Sep 2003, 36 non-small cell lung cancer patients (20 adenocarcinoma, 16 squamous cell cancer) without palpable neck nodes were enrolled. patients who had contralateral mediastinal nodal enlargement(⬎1cm) on chest CT were excluded. After the routine check of USG on the neck, US-FNA was done in cases with enlarged neck nodes (⬎5 mm in the short axis). The presence of enlarged CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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PURPOSE: Pathogenesis of primary pulmonary mucosa-associated lymphoid tumors (MALT) and lymphomas remains unknown, but is thought to involve antigen stimulation leading to immortalization, and then subsequent transformation into a more aggressive phenotype. HoxB4 is a homeobox transcription factor that is known to clonally expand hematopoietic stem cells. We hypothesized that HoxB4 was responsible for transformation and proliferation of lymphoma cells and therefore transfected a pre-B ALL cell line (Reh) with this gene, anticipating increased resistance to chemotherapy. The results were entirely unexpected. METHODS: The HoxB4 cDNA was ligated into the mammalian expression vector pLNCX2 and Reh cells were transfected with the plasmid construct using lipofection. Constitutive expression was confirmed by immunocytochemistry. RESULTS: The Reh cells transfected with control plasmid began to grow exponentially 4 weeks after transfection. Cells transfected with pLNCX2-HoxB4 declined in number and died. TdT-mediated dUTP nick-end labeling (TUNEL) assay confirmed the presence of DNA disintegration, a hallmark of apoptosis. Immunocytochemistry for caspase-3 confirmed the activation of this enzyme in HoxB4 transfected cells compared to control transfected cells. RT-PCR confirmed the upregulation of FLASH, an activator of the intrinsic apoptosis pathway via caspase-8, compared to controls. Transfection of HoxB4 into other hematopoietic malignant cells has shown that the effect is not limited to just one cell line, but may be present across the entire spectrum of hematological malignancies. CONCLUSION: HoxB4 induces apoptosis in hematopoietic malignancies and is known to cause clonal expansion in hematopoietic stem cells. CLINICAL IMPLICATIONS: Targeting the HoxB4 gene may have therapeutic benefit in hematological malignancies. Such therapy would most likely enhance host immunity. These effects could be achieved without the side effects of conventional cytotoxic chemotherapy. DISCLOSURE: K.K. Mubarak, None.

RESULTS: Presenting symptoms were invariably respiratory-related in central forms. History of tobacco abuse was 52%. Lymph-node involvement was present in 12%. Overall survival was 97.5% at five years, 95% at 10 years, and 92% at 15 years. Synchronous multicentric forms were found performing serial sections of the pulmonary parenchyma specimens in 13% of cases (4 multicentric carcinoids and 7 cases with multiple tumorlets). Multiple bronchiectases were associated in 19% of cases. CONCLUSION: The high frequency of multicentric forms, associated bronchiectasis and lymph-node involvement reinforce the statement that well-differentiated NE tumors require major surgical procedures with radical node dissection. CLINICAL IMPLICATIONS: Due to the finding of tumor recurrence (not infrequently more than 10 years following surgery), careful search for multifocal lesions should always be performed and follow-up in these cases must be accurate and protracted. DISCLOSURE: P. Ferolla, None.

Wednesday, October 27, 2004 Thoracic Oncology, continued lymph node on USG, and of malignant cells on cytology were evaluated by the histological type and the patients’ clinical stage of lung cancer. RESULTS: Among 36 non-small lung cell cancer patients, 14 (38.8%) had enlarged neck nodes on USG, and 5 of 10 small cell lung carcinoma patients. The mean diameter of the neck nodes was 9.8 mm (range, 7-12 mm). US-FNA of 14 non-small cell lung cancer patients revealed tumor cells in eight patients (57.1%). In 5 small cell lung cancer pateints, tumor cells were found in all cases. By the result of US-FNA, the clinical stage of 8 out of 36 (22.2%) non-small cell lung cancer patients had changed, including two cases of shift from the operable IIIa to the inoperable IIIb. CONCLUSION: USG and US-FNA of neck node seem to be safe, sensitive and cost-effective diagnostic tools in the evaluation of lung cancer patients without palpable neck nodes. CLINICAL IMPLICATIONS: US-FNA seem to have clinical value for evaluation of lung cancer patients with N2 disease who are candidates for operation and concurrent chemoradiotherapy. DISCLOSURE: C. Oak, None. INCREASED TNF-〈 AND INTERLEUKIN-6 IN BREATH CONDENSATE, BAL AND BLOOD OF PATIENTS WITH NONSMALL CELL LUNG CANCER Giuseppe Di Gioia*; Giovanna Elisiana Carpagnano; Onofrio Resta; Institute of Respiratory Diseases, University of Bari, Bari, Italy PURPOSE: Recent studies suggest that IL-6 and TNF-␣ are directly produced by the tumoral cells and involved in thedevelopment of lung cancer.The aim of this study was to investigate the concentration of TNF-␣and interleukin (IL)-6 in the breath condensate, bronchoalveolar lavage (BAL) and blood of non-small cell lung cancer (NSCLC) patients before treatment. METHODS: We enrolled 13 patients with histological evidence of NSCLC (8 men and 5 women, age 61⫾7 years) and 15 controls with non-malignant lung disease (9 men and 6 women, age 49⫾8 years). IL6 and TNF-␣ were measured, in patients and controls, using a specific enzyme immunoassay kit. RESULTS: Higher concentrations of TNF-␣ (10.1⫾3.6 vs 4.2⫾0.6 pg/ml, 13.4⫾5.9 vs 5.3⫾0.9 pg/ml and 11.5⫾4.8 vs 4.5⫾0.5 pg/ml) and IL6 (11.2⫾2.9 vs 2.6⫾0.6 pg/ml, 11.5⫾3.1 vs 3.0⫾0.7 pg/ml and 8.3⫾1.7 vs 2.5⫾0.4 pg/ml) were found respectively in exhaled condensate, BAL and plasma of NSCLC patients compared to healthy subjects. CONCLUSION: A positive correlation was observed between concentrations of these two markers in the breath condensate, BAL and plasma. CLINICAL IMPLICATIONS: These findings suggest that the measurement of TNF-␣ and IL-6 in exhaled breath condensate of NSCLC patients could be used for the diagnosis and the monitoring of evolution of this disease. DISCLOSURE: G. Di Gioia, None. IDENTIFICATION OF TUMOR SUPPRESSOR LOCI ON THE LONG ARM OF CHROMOSOME 5 IN PULMONARY LARGE CELL NEUROENDOCRINE CARCINOMA Shin-Myung Kang, MD*; Ju Hye Shin; Jin Wook Moon, MD; Moo Suk Park, MD; Young Sam Kim, MD; Se Kyu Kim, MD; Joon Chang, MD; Sung Kyu Kim, MD; Yonsei University College of Medicine, Seoul, South Korea

between D5S107 and D5S409, region of 5q11.2-13.3 and 5q14-15, were 91.7%. The frequencies of LOH between IL-9 and D5S210, region of 5q22.3-32 and 5q31.3-33.3, were 84.6%. The frequencies of LOH at D5S209, D5S400 and D5S429, each located in the region of 5q31.1-33.3, 5q34-35 and 5q34-qter, were 53.8%, 85.7%, and 63.6% respectively. CONCLUSION: Our data suggest the presence of at least 5 tumor suppressor loci on 5q in LCNEC. CLINICAL IMPLICATIONS: We think that more effort is needed to find tumor suppressor genes through the 5 putative tumor suppressor loci in LCNEC. It may contribute to understanding the pathogenesis of LCNEC. DISCLOSURE: S. Kang, None.

HIV Related Lung Disease 12:30 PM - 2:00 PM ROENTGENORGRAPHIC PRESENTATION OF COMMUNITYACQUIRED PNEUMONIA (CAP) IN AIDS PATIENTS M. A. Khan, MBBS; Hany Aziz, MD*; Suleiman Momany, MD; Ghassan Wardeh, MD; Amal Al-Shrouf, MD; St. Joseph’s Regional Medical Center and Seton Hall University, Paterson, NJ PURPOSE: To evaluate roentgenographic severity of CAP in AIDS. METHODS: We retrospectively reviewed medical records and chest roentgenograms of 30 consecutive patients with AIDS (17 males, 13 females, age range: 25-63 years; mean age: 44 years) hospitalized with the diagnosis of CAP. Diagnosis of CAP was based on symptoms of cough, sputum production and a chest x-ray showing an infiltrate. All patients underwent sputum Gram-stains and cultures and blood cultures before the initiation of antibiotics. RESULTS: Twenty-one of 30 (70%) patients presented with an infiltrate involving a single lobe, while 9 (30%) patients had multi-lobar disease (P: .005). Sputum Gram-stains and cultures showed normal flora in all patients. Blood cultures were positive in 6 (20%) patients: Strept Pneumoniae in 4, Klebsiella Pneumoniae in 1, and Staph Aureus in 1. Five of 6 (83%) patients with positive blood cultures had multi-lobar pneumonia and one (5%) patient with single-lobe disease (P: .005). CONCLUSION: Majority of AIDS patients with CAP present with single-lobe disease. Multi-lobar pneumonia is predictive of a positive blood culture, which is infrequent in single-lobe disease. Sputum Gramstains and cultures tend to have little value in etiologic diagnosis of CAP in AIDS. CLINICAL IMPLICATIONS: Blood cultures are useful in the etiologic diagnosis of multilobar pneumonia in AIDS patients. DISCLOSURE: H. Aziz, None.

PREDICTORS OF IRREVERSIBLE OBSTRUCTIVE LUNG DISEASE IN HIV PATIENTS M. A. Khan, MD, FCCP; Ghassan Wardeh, MD*; Iqbal Mohsin, MD; Hany Aziz, MD; Suleiman Momany, MD; Vincent DeBari, PhD; St. Joseph’s Regional Medical Center and Seton Hall University, Paterson, NJ

PURPOSE: A number of genetic and molecular alterations have been identified in lung cancer cells and thought to be important during the process of carcinogenesis. Several allelotyping studies of lung carcinoma indicate frequent losses at chromosome 5q, suggesting the presence of tumor suppressor genes in its place. Pulmonary large cell neuroendocrine carcinoma (LCNEC) is high-grade malignant neuroendocrine tumor. But the data on genetic changes of LCNEC are so limited. Therefore, to map the precise tumor suppressor loci on the chromosome 5q for further positional cloning efforts, we tested 13 surgically resected LCNEC specimens. METHODS: The DNAs extracted from paraffin-embedded tissue blocks with LCNEC and corresponding normal tissues were investigated. Nineteen polymorphic microsatellite markers located in chromosome 5q were used for analysis. Polymerase chain reaction was performed and loss of heterozygosity (LOH) was evaluated by the gel electrophoresis. RESULTS: We found that all of 13 tumors exhibited LOH in at least one of tested microsatellite markers from D5S118 to D5S498. LOH was observed in five common deleted regions at 5q. The frequencies of LOH

PURPOSE: Respiratory insufficiency is a common problem in AIDS patients. To assess the frequency of obstructive lung disease as the cause of shortness of breath we retrospectively reviewed our experience with this disorder in AIDS patients. METHODS: We retrospectively reviewed medical records of 40 patients with obstructive lung disease and HIV (13 males, 27 females; age-range: 21-58 yrs; mean age: 41.9 yrs) hospitalized during the past two years. Patients with the diagnosis of obstructive lung disease before HIV infection were excluded. Criteria for reversibility included 12% and ⬎200 cc increase in FEV1 or FVC after bronchodilator. Patients were divided into two groups: one with a history of drug-abuse, and the other without it. Reversibility of obstructive lung disease was then assessed in the two groups. Fisher’s exact test was used for statistical analysis. RESULTS: Table 1 compares reversibility of obstructive lung disease in the two groups. Data was tested by Lillefors-KS test for normality. All sets passed, so t-test was used for comparison of data. In the second part of the study, Table 2 we looked at the relationship between the following

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Wednesday, October 27, 2004 HIV Related Lung Disease, continued independent variables and the risk of irreversible obstructive lung disease, using Fisher’s exact test for statistical analysis. CONCLUSION: 1. Irreversible obstructive lung disease is more common in HIV patients with history of drug-abuse (both IVDA and sniffing). 2. Independent predictors of irreversible obstructive lung disease in HIV patients in order of significance include: a) Duration of HIV b) IVDA and sniffing c) Smoking 3. Duration of HIV is the most significant predictor of irreversible obstructive lung disease in HIV patients. CLINICAL IMPLICATIONS: Assessment of pulmonary function is an important part of the work-up in a patient with HIV infection.

Table 1

Reversible obstructive lung disease Irreversible obstructive lung disease

Drug Abuse (IVDA and Sniffing

No Drug Abuse

8/22(36.3%)

14/18(73.7%)

14/22(63.6%)

4/18(22.2%)

Table 2 Risk Factor

Relative Risk

P Value

Duration of HIV⬎10 yrs IVDA and sniffing Smoking

⬎20 5.25 8.75

⬍0.0001 0.008 0.011

DISCLOSURE: G. Wardeh, None.

PNEUMOCYSTIS CARINII 〉-GLUCAN-INDUCED INFLAMMATORY SIGNALING IN ALVEOLAR EPITHELIAL CELLS IS PROTEIN KINASE C-DEPENDENT Scott E. Evans, MD*; Peter Y. Hahn, MD; Theodore J. Kottom, MS; Andrew H. Limper, MD; Mayo Clinic and Foundation, Rochester, MN PURPOSE: Robust inflammatory responses are observed in respiratory failure associated with Pneumocystis carinii (PC) pneumonia. Increasing evidence indicates that alveolar epithelial cells (AECs) not only promote PC attachment, but also contribute substantially to PC-induced inflammatory responses. Our laboratory has demonstrated that N␬B is essential to PC ␤-glucan (PCBG)-induced inflammatory signaling. Herein, we assess the role of protein kinase C (PKC) in these responses. METHODS: For each experiment, primary rat AECs were isolated and cultured. AECs were exposed to PCBG in the presence or absence of PKC inhibitors, then the media was assayed for production of inflammatory cytokines. AEC nuclear translocation of N␬B p50 subunit was assessed after PCBG stimulation, with or without PKC, MEK-1 and p38 inhibition. AEC PKC activation was also assayed by demonstration of PKC phosphorylation after PCBG challenge by Western blotting technique, with attention to the various PKC isoforms. RESULTS: While little was noted from unstimulated AECs, PCBG induced MIP-2 and TNF-␣ production from AECs. This response was blocked by both inhibition of N␬B and PKC. PCBG-induced N␬B activation was similarly blocked by PKC inhibition, though inhibition of MEK-1 and p38 had little effect. PCBG induced phosphorylation of PKC isoform theta, and to a lesser extent alpha. CONCLUSION: PCBG induces PKC activation in AECs, the inhibition of which significantly attenuates the expression of inflammatory mediators. PKC activation likely precedes N␬B activation following PCBG challenge. CLINICAL IMPLICATIONS: Clinical outcomes in PC pneumonia are more closely linked to lung inflammation than organism burden. These data provide insight into novel therapeutic targets to manage exuberant host inflammatory responses. DISCLOSURE: S.E. Evans, None.

PURPOSE: In a study conducted prior to the widespread availability of highly active antiretroviral therapy (HAART), HIV positive (HIV⫹) patients were reported to have accelerated emphysema compared to HIV negative (HIV-) patients. In the current HAART era, we asked whether HIV infection was independently associated with chronic obstructive lung disease (OLD). METHODS: We studied veterans enrolled in the 5-site Veterans Aging Cohort Study, a prospective longitudinal study of 1042 HIV⫹ and 750 HIV- patients. Smoking status, pack years of smoking, and patientreported physician diagnosis of OLD (chronic obstructive pulmonary disease, chronic bronchitis, emphysema or asthma) were obtained at baseline from patient survey. Patients were also asked if they had trouble with cough or dyspnea, and to what degree this symptom was bothersome. RESULTS: 895 HIV⫹ and 653 HIV- veterans with known smoking status were included in this analysis. HIV⫹ veterans were more likely to be current smokers (45% HIV⫹ vs 36% HIV-, p⬍0.001), whereas HIVveterans were more likely to be former smokers (27% HIV⫹ vs 37% HIV-, p⬍0.001). HIV⫹ veterans had fewer pack years of smoking compared to HIV- veterans (median of 16 pack years vs 20 pack years, p⫽0.003). Dyspnea that was bothersome was equally prevalent in both populations (43% HIV⫹ vs 40% HIV-, p⫽0.2). HIV⫹ veterans were younger and more likely to be African American, both of which were associated with a decreased likelihood of OLD. However, after adjusting for age, race, and pack years of smoking, HIV⫹ veterans were 59% more likely to have OLD (OR⫽1.59, 95% CI⫽1.15-2.19). CONCLUSION: HIV⫹ veterans were more likely to be diagnosed with OLD than HIV- veterans. These results are consistent with the possibility that HIV⫹ patients on effective antiretroviral therapy have an increased susceptibility to OLD. CLINICAL IMPLICATIONS: As HIV⫹ patients are living longer on HAART, non-infectious complications such as OLD may contribute substantially to the morbidity and mortality of these patients. The possibility that HIV accelerates OLD deserves further investigation. DISCLOSURE: K.A. Crothers, None. SPECTRUM OF PULMONARY INFECTIONS IN HIV POSITIVE PATIENTS: INDIAN SCENARIO Sanjeev Sinha, MD*; Randeep Guleria, MD, DM; AIIMS, New Delhi, India PURPOSE: The aims of the present study was to see the radiological, clinical and bacteriological profile of pulmonary infection in human immunodeficiency virus (HIV) positive patients in India. METHODS: All consecutive HIV positive patients with clinical and/or radiological evidence of pulmonary infection have been included in the study. Sputum samples were sending for AFB smear and culture, Pneumocystis carinii infection, bacterial Gram staining and culture and fungus smear and culture was done in all patients. Also sample or biopsy was taken from other sites i.e. pleural fluid and lymph nodes. CD4/CD8 count and viral load was also done as a part of initial evaluation. RESULTS: 85 (69 males and 16 females) HIV positive patients have been enrolled in the study. The mean value of age was 33.4⫾9.1 (range; 20-65 years. Radiological findings were as follows; Pleural effusion in 21, military mottling in 16, hilar lymph nodes in 19, consolidation in 11, alveolar shadows in 10 and calcified lesions in 8 patients. CD4 cells were less than 400 in 60 patients and more than 400 in 16 patients. HIV viral load (copies/ml) was less than 50,000 in 18 patients and were more than 50,000 in 27 patients. Fiber optic bronchoscopy has been performed in three patients and found PCP positive in one patient. 5 patients were diagnosed as PCP on sputum examination. In 12 patients the sputum grew fungus (Candida albicans). Pleural effusion was present in 16 patients; 11 were tubercular, 3 were Klebsiella and 2 grew Pseudomonas on culture. The overall spectrum of pulmonary infections in HIV positive patients was as follows; pulmonary tuberculosis in 40, bacterial pneumonia in 16, fungal infections in 15, Pneumocystis carinii were positive in 5, tubercular meningitis in 2 and toxoplasmosis was seen in 1 patient. CONCLUSION: Tuberculosis was found the most common pulmonary infection in HIV positive patients followed by bacterial and fungal infection. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

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P⫽ 0.012

HIV INFECTION IS ASSOCIATED WITH INCREASED CHRONIC OBSTRUCTIVE LUNG DISEASE Kristina A. Crothers, MD*; Tephany A. Griffith, MPH; Adeel A. Butt, MD; Cynthia L. Gibert, MD; Stephen Crystal, PhD; Amy C. Justice, MD, PhD; Yale University School of Medicine, New Haven, CT

Wednesday, October 27, 2004 HIV Related Lung Disease, continued CLINICAL IMPLICATIONS: Tuberculosis is the commonly occurring pulmonary infection in HIV positive patients. DISCLOSURE: S. Sinha, None. BRONCHOSCOPY IN THE HIV-INFECTED PATIENT IN THE ERA OF ANTIRETROVIRAL THERAPY: ROLE OF BRONCHOALVEOLAR LAVAGE AND TRANSBRONCHIAL LUNG BIOPSY Steve H. Salzman, MD; Adam J. Posner, MD*; Rana Adawi, MD; Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY PURPOSE: Antiretroviral therapy has reduced the incidence of pulmonary complications of HIV. The use of high-volume, multilobe bronchoalveolar lavage (BAL) has improved the yield for Pneumocystis jiroveci pneumonia (PCP). This study evaluates the role of bronchoscopy in 2000-2002 in comparison to our same-institution data from 1992 (Salzman et al, JBronchology1996;3:88-95). METHODS: All HIV-infected inpatients who underwent bronchoscopy from 7/00-9/02 were enrolled. Data collected included results of sputum examination, BAL and trans-bronchial biopsy (TBB). Charts were reviewed to determine final diagnoses. RESULTS: In the 2000-2002 period 147 bronchoscopic procedures were performed in HIV-infected patients, including 27 in mechanically-ventilated patients. Bronchoscopy was diagnostic in 84/147(57%) cases; BAL in 69/ 147(47%) and TBB in 58/99(59%). TBB was the exclusive source of diagnostic material in 11/99(11%). In 1992, bronchoscopy was more frequently diagnostic, with 162/181(90%) positive (p⬍0.001). In 2000-2002 PCP was diagnosed in 60(41%) procedures; BAL was positive in 58/60(97%) and TBB was positive in in 45/48(94%). Only 2/48(5%) had PCP established only by TBB. In 1992, TBB was the exclusive positive specimen for PCP in 8/95(8%)(p⫽NS). For diagnoses other than PCP, in 2000-2002 TBB provided exclusive diagnosis in 9/24(38%). In 1992, TBB provided exclusive diagnosis in 34/55(62%) of non-PCP cases (p⬍0.05). In 2000-2002, there were 5(3.4%) complications (pneumothorax(2), massive hemoptysis requiring intubation(1), post-procedure intubation(2)). TBB was performed in 6 mechanically-ventilated patients without complication. Pneumothorax postbronchoscopy occurred only in PCP cases, 2/53 (3.7%). CONCLUSION: In comparison with 1992, bronchoscopy in HIVinfected patients was perfomed less frequently in 2000-2002 and was less likely to be diagnostic. This is likely due to the lower incidence of opportunistic pulmonary complications due to antiretroviral therapy. The use of large-volume bilobar BAL as standard technique in HIV-infected patients may account for the significanly lower additional yield of TBB in 2000-2002. CLINICAL IMPLICATIONS: Although the complication rate of bronchoscopy was relatively low (3.4%) in HIV-infected patients, some will choose to use BAL alone. TBB should also be done when non-PCP diagnoses are likely or when BAL is negative on an initial procedure. DISCLOSURE: A.J. Posner, None. ROLE OF TRANSBRONCHIAL LUNG BIOPSY IN HIVⴙ PATIENTS SUSPECTED TO HAVE PNEUMOCYSTIS CARINII PNEUMONIA Rakesh Patel, MD; Gilda Diaz-Fuentes, MD; Ernesto Sy, MD; Varadarajalu Lakshmi, MD*; Latha Menon, MD; Bronx Lebanon Hospital, Bronx, NY

inflammatory changes consistent with pneumonia (39) was found with the TBbx. BAL alone was done in 39 patients; PCP was identified in 8 of them. Only one patient who underwent biopsy had a complication namely bleeding, which was easily controlled. CONCLUSION: TBbx increases the diagnostic yield, in patients suspected to have PCP. BAL alone had a yield of 74% (29/39), whereas the yield from TBbx and BAL was 95% (37/39). In 10/39 (26%) of patients, the diagnosis of PCP was obtained only by TBbx. TBbx also provided alternative diagnosis such as tuberculosis and malignancy. CLINICAL IMPLICATIONS: We recommend that where possible, both BAL and TBbx be done in patients suspected to have PCP, as it improves the diagnostic yield and provides incremental diagnosis without significantly increasing the complications. Performing BAL alone carries the risk of missing the diagnosis in a significant number of patients.

Table 1 Yield of FOB for Pneumocystis carinii pneumonia FOB

TBbx ⫹ BAL ⫹

TBbx ⫹ BAL -

TBbx – BAL ⫹

PCP⫹ n⫽39

27(69%)

10(26%)

2(5)

DISCLOSURE: V. Lakshmi, None.

PNEUMOCYSTIS CARINII PNEUMONIA AND MYCOBACTERIUM TUBERCULOSIS CO-INFECTION IN AIDS IN AN INNER CITY HOSPITAL John Salazar-Schicchi, MD; Jeanine Damian, MD; Javed Iqbal, MD; Sami A. Nachman, MD; Vinette E. Coelho-D’Costa, MD*; Harlem Hospital Center/Columbia University College of Physicians, New York, NY PURPOSE: The significance of Pneumocystis carinii pneumonia(PCP) in AIDS is well established. However it has been reported to be simultaneously associated with other opportunistic infections. The aim of this study was to investigate the prevalence of Mycobacterium tuberculosis(MTB) in patients diagnosed by bronchoscopy with PCP in an inner city hospital with high prevalence rates of HIV infection and Tuberculosis. METHODS: Retrospective review of Bronchoscopy results obtained between 7/99 and 3/04.

Table 1.

VL

Clinical Suspicion

110

21.9K

⫹⫹⫹

MTB MTB

271 72

405K ⫹⫹⫹ ⬎100K ⫹/-

4

MTB

163

⬎750K ⫹/-

5

MTB

46

494K

-

6

Histoplasma

16

653K

⫹/-

Patient

Coinfection

CD4

1

MTB

2 3

Suggestive X Ray

Suggestive CT

Interstitial N/A infiltrate, R hilar calcified nodule Miliary N/A Diffuse Diffuse reticulonodules nodular Diffuse Diffuse reticuloNodules nodular Diff. Air N/A space consolidation Alveolar/ Alveolar/ nodular nodular infiltrate infiltrate

PURPOSE: Despite previous reports on the results of fiberoptic bronchoscopy (FOB) in patients suspected to have Pneumocystis carinii pneumonia (PCP), controversy still exists regarding the role of transbronchial biopsy (TBbx) in addition to bronchoalveolar lavage (BAL) in these patients.The goal of the study was to evaluate the role of TBbx in addition to BAL in the evaluation of patients suspected to have PCP. METHODS: A retrospective chart review of all the HIV positive patients, who were sputum negative for PCP, and who underwent FOB in 2002 and 2003 for suspicion of PCP. Results of TBbx and BAL and adequacy of specimen were reviewed. RESULTS: 164 patients underwent FOB. 125 had TBbx and BAL done; six of these patients were excluded from analysis due to poor specimens. In the 119 patients analyzed, 39 were PCP positive (Analysis in table 1); in the remaining 80 patients who underwent TBbx and BAL, the TBbx supported an alternative diagnosis in 47 (59%) patients; tuberculosis (4), malignancy (1), sarcoidosis (1), Cytomegalovirus (2) and

⫹ suspicious - not suspicious

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Wednesday, October 27, 2004 HIV Related Lung Disease, continued Table 2. BAL Fungal Culture

BAL AFB Smear/ Culture

1

-/-

-

-/-

2

-/⫹

-

-/⫹

3

-/⫹

Yeast

-/⫹

4

-/⫹

Candida

-/⫹

5 6

⫹/⫹ -/-

Histoplasma

-/⫹ -/-

Patient

Lung Biopsy AFB Stain/ Culture Caseating granuloma ⫹/not done Caseating granuloma -/⫹ Non-caseous granuloma -/⫹ Necrotizing pneumonia ⫹/Not done Histoplasmosis -/-

⫹ positive - negative RESULTS: A total of 500 bronchoscopies were performed during this period. PCP was detected in 75 patients (15%). All these patients were HIV infected. Five PCP patients were co-infected with MTB and 1 patient with histoplasma. Their clinical, radiological, microbiological and pathological characteristics are shown in Table 1 and Table 2. CONCLUSION: Patients with advanced AIDS may have an increased incidence of coexisting opportunistic lung infections. The presence of PCP in BAL can mask other opportunistic infections such as TB and fungal diseases. CLINICAL IMPLICATIONS: In AIDS patients presenting with pulmonary manifestations an aggressive diagnostic approach by bronchoscopy including transbronchial lung biopsy, as well as prompt initiation of empiric treatment is essential even when the suspicion for other comorbidities is low and diagnosis of PCP has been established. DISCLOSURE: V.E. Coelho-D’Costa, None. THORACIC SURGERY IN PATIENTS WITH HIV DISEASE Marc Margolis, MD*; Barbara Tempesta, CRNP; Matthew Facktor, MD; David Salter, MD; Nevin Katz, MD; Vicky Cole, CRNP; Farid Gharagozloo, MD; George Washington University Medical Center, Washington, DC PURPOSE: With the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection has become a more chronic disease with improved survival. Thoracic surgeons are increasingly involved in surgical procedures in this patient population. Surgical indications and outcomes are important variables in treating these patients. METHODS: A retrospective review of patients operated on at three institutions over a 3-year period (2002 - 2004) was performed. RESULTS: 21 patients with HIV underwent surgery during this time period. A total of 22 procedures were performed. There were 13 males and 8 females. Age ranged from 15 - 64 years. Patients with known HIV infection prior to hospital admission numbered 18/21. Eleven patients had previously been diagnosed with AIDS. 11/21 patients were using HAART prior to admission. CD4 counts ranged from 1 - 1079 /ul. Indications for surgery included respiratory failure of uncertain etiology in 6/21 undergoing lung biopsies, empyemas in 4/21 undergoing decortications, mediastinal adenopathy in 2/21 undergoing VATS biopsy or mediastinoscopy, bronchopleural fistula in 2/21 undergoing lung resection, pleural tents and muscle flaps, pericardial tamponade in 2/21 undergoing VATS pericardial windows, vertebral collapse in 1/21 undergoing a thoracoabdominal approach for corpectomy and stabilization, rib lesions in 1/21 undergoing bilateral rib biopsies, undiagnosed pleural effusion in 1/21 undergoing diagnostic VATS and pleurodesis, fibrothorax with restrictive lung disease in 1/21 undergoing decortication and pleurectomy and esophageal cancer in 1/21 undergoing Ivor Lewis esophagectomy and later a tracheostomy. 4/21 patients died and the remaining were discharged home (15/17) or to

COPD Evaluation/COPD and the Heart 12:30 PM - 2:00 PM COPD AND SPIROMETRY: CHF AND 2-D ECHO; THE GREAT DISCONNECT Mahendra Damarla, MD*; Victor M. Pinto-Plata, MD; Bartolome R. Celli, MD; Caritas St. Elizabeth’s Medical Center, Boston, MA PURPOSE: The diagnosis of COPD requires confirmation by spirometry. Likewise, the diagnosis of CHF requires the use of a 2-D echo. However in clinical practice there appears to be a discrepancy with which the frequencies of these confirmatory tests are being utilized. We compared the frequency with which spirometry is being used in confirming the diagnosis of COPD versus the frequency of 2-D echo in the diagnosis of CHF. METHODS: We retrospectively reviewed a six-month period of charts of patients with a discharge diagnosis of COPD and CHF, either primary or secondary, as defined by an ICD-9-CM code of 496, 491.21 and 428-428.9 respectively. We then searched the PFT and echocardiography lab databases to check if the patient had a spirometry or a 2-D echo performed. These two groups were also compared with each other looking for patients with both diagnoses. The chi-square test was used to test the differences between the two groups. The study was part of quality assurance protocol as such was not reviewed by the institutional review board. RESULTS: Out of the 553 individuals diagnosed with COPD, 169 patients (30%) had PFT’s performed within the past 7 years. In comparison, out of the 789 patients diagnosed with CHF, 619 patients (78%) had a 2-D echo performed within the past 7 years, (p⬍0.0001). There were a total of 219 patients with both diagnoses of COPD and CHF. One hundred and five patients (48%) had a 2-D echo only, 4 patients (2%) had spirometry only, 74 patients (34%) had both tests performed, and 36 patients (16%) had neither test performed. CONCLUSION: Patients diagnosed with COPD were statistically less likely to have a confirmatory test performed than were patients diagnosed with CHF. CLINICAL IMPLICATIONS: There appears to be a disconnect between the role of spirometry for confirming pulmonary diseases and that of echocardiography in CHF. To improve diagnosis and treatment of patients with COPD, effort must be made to close this gap.


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Sputum AFB Smear/ Culture

a rehabilitation unit (2/17). All four patients who died had initially undergone non-diagnostic bronchoscopies followed by surgical lung biopsies. There were no needle stick injuries. CONCLUSION: Despite the presence of HIV disease, thoracic surgical procedures appear safe in a select group of patients. Diagnostic lung biopsies for repiratory failure have an inherent poor outcome and this continues to be reflected in patients with underlying HIV disease. CLINICAL IMPLICATIONS: Thoracic surgery can be performed with adequate results in patients with HIV and AIDS. DISCLOSURE: M. Margolis, None.

Wednesday, October 27, 2004 COPD Evaluation/COPD and the Heart, continued

DISCLOSURE: M. Damarla, None.

CHANGES IN PULMONARY BLOOD FLOW DISTRIBUTION FOLLOWING HYPEROXIA IN ATS STAGE 1 TO 3 COPD PATIENTS Marc Zelter, MD; Andre´ Capderou, MD*; Malika Berkani, MD; Marie He´ le`ne Becquemin, MD; Universite´ Paris, Paris, France PURPOSE: We have shown that lung blood flow pulmonary transit time distribution (PTTD) in stage 1 COPD patients (ATS) fits three distinct patterns (patterns A, B, C), depending on the response to hyperoxic challenge. Pattern A distribution is normal and unchanged during hyperoxia, pattern B distribution is significantly enlarged but remains unchanged during hyperoxia, pattern C distribution is enlarged as in pattern B but returns to normal during hyperoxia (Am J Respir Crit Care Med 2002; 165, 8, part 2, A 654). METHODS: We studied 17 ATS stage 1, 9 stage 2 and 5 stage 3 COPD patients, non-responsive to salbutamol. A bolus of albumin 99mTc (3.5 MBq/kg) was injected in the external jugular vein in supine position, breathing air, and after administration of 3l/mn O2 with a mask. PTTD was computed by deconvolution from the first pass radioactivity curves reconstructed from the right and left ventricular region of interest. We computed microvascular and cardiopulmonary blood volumes from the global distributions, using the Z transform analysis suggested by Zierler (Ann Biomed Eng. 2000; 28:836-48). RESULTS: We observed an even repartition of patterns A, B, C in stage 1 patients; 1 A , 6 B and 2 C patterns in stage 2, and 4 B and 2 C patterns in stage 3 patients. CONCLUSION: We conclude that the distribution patterns tended to be limited to pattern B and C in stage 2 patients and then to pattern B in stage 3 patients. A longitudinal study is needed to understand the relationship over time between patterns and to determine if pattern B patients are better survivors or it correspond to the normal evolution of the disease. CLINICAL IMPLICATIONS: Distribution patterns may offer a quantitative approach to select COPD patients for oxygen therapy. DISCLOSURE: A. Capderou, None.

ventricular function; 2)to assess the correlation among TDI/SR parameters and respiratory function tests. METHODS: Twenty-nine patients with COPD were included in the study. 15 patients had pulmonary artery pressure ⬎35mmHg (group I), 14 patients had pulmonary artery pressure ⬍35mmHg (group II). Sixteen age- and gender-matched healthy subjects who had normal cardiac findings served as controls (group III). Right ventricular ejection fraction (EF), fractional shortening (FS), and tricuspid flow filling parameters (E/A ratio, DT) were determined. Offline analysis of the myocardial velocity data sets was performed using dedicated software (Aplio, Toshiba Corp.). Velocity and strain traces from right ventricular free wall at 3 levels (basal, mid cavity, and apical) were processed simultaneously in the same cineloop in the apical 4-chamber view. Diastolic TDI values (Ew, Aw), peak systolic strain and systolic and diastolic strain rate values were determined. Echocardiographic parameters were evaluated after the respiratory function tests were performed:FEV1;FEV1/VC;DLCO; DLCO/VA. RESULTS: Ew/Aw ratio at apical and mid level was lower in Group I and II than in Group III:p⬍0.005.Peak systolic strain and systolic and diastolic strain rate at apical and mid level were lower in Group I and II than in Group III:p⬍0.001.Right ventricular EF,FS,E/A ratio, and DT were not different among the three groups. No correlation was found between EF, FS, E/A ratio, DT, and respiratory function tests. A highly significant relationship was shown between peak systolic strain at mid level and DLCO/VA:r⫽0.67, p⬍0.001 and peak systolic strain at mid level and FEV1/VC:r⫽0.69,p⬍0.001. CONCLUSION: In COPD patients TDI/SR parameters can determine right ventricular dysfunction that is not shown by conventional echocardiographic indices and is correlated with respiratory function tests. CLINICAL IMPLICATIONS: FEV1/VC,DLCO/VA,TDI and SR will assist clinicians in making more accurate assessments of their COPD patients’ disease status. DISCLOSURE: C. Terzano, None.

DETECTION OF LOW ATTENUATION AREA WITH LOWDOSE SPIRAL CT ON THE HEALTH CHECK-UP – CORRELATION BETWEEN AUTOMATED ANALYSIS AND PULMONARY FUNCTION Suzushi Kusano, MD*; Toru Nakagawa, MD; Shuichiro Yamamoto, MD; Shuichiro Hosoda, MD; Masataka Irokawa, MD; Takeshi Nawa, MD; Kuniyoshi Nakashima; Yoshihiro Goto, PhD; Hitachi Health Care Center, Ibaraki, Japan

PURPOSE: The evaluation of right ventricular function is clinically useful in patients with COPD because the presence of right ventricular failure has prognostic implications. Our purpose was: 1)to compare tissue Doppler imaging, TDI, and the recently developed strain rate, SR, imaging technique parameters with conventional indices evaluating right

PURPOSE: According to diagnoses of pulmonary emphysema, many studies have suggested a relationship between the degree of low attenuation area (LAA) and pulmonary function. We developed an automated analysis system of LAA on Low-dose spiral CT (LDCT). The purpose of this study is to determine the correlation between LAA on LDCT and pulmonary function. METHODS: 80 participants (50 current smokers and 30 ex-smokers men, Brinkman index mean is 795.5 and mean age is 55.9) underwent LDCT. Those suspected of having LAA on LDCT were those who need high resolution CT for further examination. This automated system selects LAA as a candidate of pulmonary emphysema considering the threshold of pulmonary parenchyma. We established the threshold at –900HU in this study. We compared the area of LAA to the results of pulmonary function tests, including FEV1%(Gaensler) and FEV1%predicted to assess airway obstruction. RESULTS: The means of FEV1% and FEV1%predicted were 70.8% and 84.3% respectively. The mean of LAA was 14.14% (from 0.39 to 32.68%). The correlation coefficient between FEV1% and LAA was -0.57 and also between FEV1%predicted and LAA was -0.45. CONCLUSION: This system was effective to objectively estimate the degree of pulmonary function of the pulmonary emphysema. CLINICAL IMPLICATIONS: Our data suggest that LDCT on the health check-up is a useful tool in early detection of pulmonary emphysema when we use the appropriate analysis system of it. DISCLOSURE: S. Kusano, None.

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ASSESSMENT OF RIGHT VENTRICOLAR FUNCTION BY TISSUE DOPPLER IMAGING IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Angelo Petroianni, MD; Claudio Terzano, MD*; Antonio Vitarelli, MD; University “LA Sapienza” - Roma, Roma, Italy

Wednesday, October 27, 2004 COPD Evaluation/COPD and the Heart, continued USE OF BETA BLOCKERS IN CONGESTIVE HEART FAILURE(CHF) PATIENTS WITH COPD AND/OR ASTHMA Jay I. Peters, MD*; Patricia L. Gomez-Dinger, MD; Gregg L. Freeman, MD; Autumn D. Galbreath, MD; Paul B. Smith; University of Texas Health Science Center at San Antonio, San Antonio, TX

STUDY OF MICROBES RESPONSIBLE FOR ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IN DHAKA Mostafizur Rahman, MBBS, FRC*; A.K.M. R. Bari, MBBS, MCPS; S.M. Abdullah A. Mamun, MBBS, MD; NIDCH, Dhaka, Bangladesh PURPOSE: To assess the role of infection in the pathogenesis of acute exacerbation of COPD and to identify common agents causing infective acute exacerbation of COPD. METHODS: Microbiology sampling of sputum was performed in patient with diagnosis of COPD. Control consisted of 30 outpatients with stable COPD with no changes in volume/aspect of sputum or level of dyspnea in previous 15 days. Cases consisted of 60 exacerbated COPD patients. Fresh morning samples of sputum were processed on the day of collection. Each species was identified by standard methods. This study was approved by faculty of Medicine, Dhaka University, Dhaka. RESULTS: Positive cultures were obtained in 6(20%) out of 30controls. Pseudomonas spp. were cultured from 3samples. Klebsiella spp.1, Streptococcus pneumoniae1, Haemophilus influenzae 1 were cultured from another 3 samples. Positive cultures were obtained in 39(65%) out of 60 cases. Pseudomonas spp.15, Klebsiella spp.8, Acinetobacter spp.4, Streptococcus pneumoniae 4, Haemophilus influenzae 2, Moraxella catarrhalis 2, Enterobacter spp.1, mixed organisms (Pseudomonas spp.⫹ Klebsiella spp) 2, (Pseudomonas spp.⫹ Acinetobacter spp.) 1, were culture from 39 samples. There were statistically significant number of positive sputum culture among acute exacerbated than stable COPD patients (P ⬍ 0.001). Gram negative bacilli, Pseudomonas spp. and Klebsiella spp. were cultured in majority of sputum sample of culture positive stable and exacerbated COPD patient. CONCLUSION: The prevalence of lower airway bacterial colonization in outpatients with stable COPD is high and mainly due to Pseudomonas and Klebsiella and affect 20% of this population. The greater rate of isolation of pathogenic bacteria in exacerbated than in stable COPD in this study supports the pathogenic role of bacteria in a proportion of acute exacerbation of COPD. The organism commonly plays pathogenic role in acute exacerbation of COPD are Pseudomonas and Klebsiella. Acinetobacter, Moraxella catarrhalis and Enterobacter also contribute. CLINICAL IMPLICATIONS: Identification of common microbial agents causing infective acute exacerbation of COPD will ultimately facilitate prompt initiation of appropriate antimicrobial agents and thus will help rapid recovery from acute exacerbations of COPD. DISCLOSURE: M. Rahman, None. ELECTROCARDIOGRAPHY IN THE DETECTION OF EMPHYSEMA Anish J. Thomas, MD*; Sirin Apiyasawat, MD; David Spodick, MD, DSc; Saint Vincent Hospital @ Worcester Medical Center, Worcester, MA PURPOSE: The electrocardiogram (EKG) can sensitively reflect the presence of emphysema in patients with Chronic Obstructive Pulmonary (COPD). It is known that the presence of a vertical P wave axis can be used to detect emphysema. The QRS complexes in patients with emphysema seem to be of shorter duration than the QRS complexes of other patients. We observed the use of P wave vector and QRS duration in the detection of emphysema. METHODS: All EKGs done in the hospital on any particular day were randomly reviewed. Fifty consecutive EKGs with the P axis of 70° or more were selected (age 65.18 ⫾ 12.27, 36% male) and matched with a control (normal P axis) for age and sex (age 64.40 ⫾ 12.92, 34% male). The exclusion criteria were age less than 40 years, and presence of any intraventricular conduction delay (QRS duration of ⬎ 100 msec). The EKGs were reviewed by two independent observers. The diagnosis of emphysema was made by clinical presentation and findings on the chest X-ray. RESULTS: Patients with a vertical P wave axis had a strikingly higher incidence of emphysema than the control group (86% vs. 4%, P ⬍ 0.01). The sensitivity of P wave axis of 70° or more for emphysema was 95.6%, and the specificity was 87.3%. The mean QRS duration in patients with emphysema was significantly shorter (77.93 ⫾ 7.63 msec vs. 88.65 ⫾ 6.30 msec, P ⬍ 0.01). When using QRS duration of ⬍75 msec in conjunction with P wave axis of 70° or more, the specificity for emphysema was 100% but the sensitivity was down to 32.6%. CHEST / 126 / 4 / OCTOBER, 2004 SUPPLEMENT

921S


PURPOSE: Beta blockers have been shown to significantly reduce mortality in ischemic heart disease and CHF, yet are often avoided in patients with obstructive lung disease (OLD). We evaluated the prevalence of beta blocker use in patients with COPD and/or asthma and determined if respiratory events were more common in this subset of patients. METHODS: Retrospective analysis of prospectively collected data from 1067 patients with CHF followed over 18 months. Medications, non-routine office visits, ER visits, and hospitalizations for respiratory events were compared. RESULTS: In patients with CHF, 19.6% (209/1067)had OLD: 5.9% asthma, 11.2% COPD and 2.5% asthma/COPD. Only 35.9% of patients were on beta blockers. Cardioselective beta blockers were used in only 49% of patients with OLD on beta blockers. Patients with OLD had a 3 fold increase in respiratory encounters compared to patients with CHF alone. The use of beta blockers did not result in increased respiratory events. The rate of acute respiratory events (beta blocker vs. no beta blocker) in COPD was 1.13 vs. 1.44 events/yr (p⫽.42) and 1.20 vs. 1.40 events/yr (p⫽.57) in asthma. Patients with COPD and asthma (n⫽27) had a lower rate of acute respiratory events on beta blockers (.56 vs. 2.03 events/yr). Use of beta blockers was not associated with an increase in respiratory encounters, E.R. visits, or hospitalizations. The rates of respiratory events are shown below. CONCLUSION: Our study found that the long term use of beta blocking medication did not increase the risk of respiratory complications. We did not see any differences in outcomes with the use of cardioselective vs. noncardioselective agents. CLINICAL IMPLICATIONS: The proven mortality benefit of beta blockers after MI and in CHF mandates their use in patients with OLD whenever possible. Although our study was unable to show significant differences between different classes of beta blockers, cardioselective beta

blockers without intrinsic sympathomimetic activity are preferred until future studies resolve this issue. DISCLOSURE: J.I. Peters, None.

Wednesday, October 27, 2004 COPD Evaluation/COPD and the Heart, continued CONCLUSION: The QRS duration is significantly shorter in patients with emphysema. Vertical P axis and QRS duration can both sensitively and specifically reflect the presence of emphysema. CLINICAL IMPLICATIONS: P wave axis of 70° or more can be used independently with high sensitivity and specificity for detection of emphysema. When used in conjunction with the narrow QRS duration, the specificity increases. DISCLOSURE: A.J. Thomas, None.

PREDICTORS OF OBSTRUCTIVE AIRWAY DISEASE (OAD) IN POST ALLOGENIC BONE MARROW TRANSPLANT (BMT) Mohammad Khalid, MBBS; Sarfraz Saleemi, MD; Khaliq Agha Rehan, MD; Saleh Al Dammas, MD; Mohammed Zeitouni, MD; Ayman Kharaba, MD*; King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia PURPOSE: Establish the early predictors of development of OAD and its prevalence in post BMT patients and factors influencing its prognosis. METHODS: Review of 153-post (BMT) patients, pre and post BMT pulmonary function test (PFT’s) were reviewed, post BMT period ranged from 4 months to 2 years. Patients with existing OAD excluded from the study. Impact of treatment (immunosuppressive & steroid) and presence of GVHD on development of OAD recorded. RESULTS: 3 patients excluded for pre existing OAD, 20 patients developed OAD on their first (post BMT F/U PFTs) 15 patients had ⫺ FVC, 14 ⫺ FEV, 14 ⫺ MMEF, 10 - RV, - RV/TLC 14. FVC, FEV1, MMEF & RV/TLC showed changes in all 14 patient at the same time – all 20 patient then showed a progressive worsening in their OAD. All 20 patients with declining PFT’s had GVHD which is a strong predictor of development of future OAD syndrome. 8 patients received steroids/ immunosuppressive therapy but failed to show significant response. CONCLUSION: 13% patients developed OAD. An early decline in FVC, FEV, MMFF and RV/TLC are a strong predictor of future progressive OAD. Almost all patient with OAD had GVHD. A poor response to immunosuppressive therapy was noted. CLINICAL IMPLICATIONS: Early recognition and new treatment measures need to be explored for post BMT OAD.

GVHD

ImmunoSuppres- FVC sion

⫹ ⫹ ⫹ ⫹ ⫹

⫹ ⫹ ⫹ ⫹

⫹ ⫹ ⫹ ⫹

⫹

⫹ ⫹ ⫹ ⫹ ⫹

⫹

⫹ ⫹ ⫹

⫹ ⫹

FEV1

⫹ ⫹ ⫹

⫹ ⫹ ⫹

⫹ ⫹

⫹ ⫹

⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹

⫹ ⫹ ⫹ ⫹

⫹

⫹

⫹

DISCLOSURE: A. Kharaba, None.

⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹

⫹ ⫹ ⫹ ⫹

* Significant Changes : ⫹

922S

FEV1/ MMEF RV FVC 25-75

⫹

⫹ ⫹ ⫹ ⫹ ⫹ ⫹

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CYTOKINE PROFILE IN BAL OF COPD PATIENTS WITH OR WITHOUT REVERSIBILITY Napoleon Karagiannidis, MD, PhD; Koralia Paschalaki, MD; Emmanuel Kastanakis, MD; Elizabeth Passalidou, MD; Filia Diamantea, MD; Grigorios Tsonis, MD; Niki Karabella, MD; Kleopas Petronikolos, MD; Konstantina Tsakanika, MD, PhD; Vlasis Polychronopoulos, MD, PhD; Sismanogleion Hospital, Athens, Greece PURPOSE: Although the complex role of cytokines has not been fully established, it seems that the profile of cytokine expression in COPD differs from that in asthma. The aim of our study was to determine the cytokines’ levels in Bronchoalveolar Lavage (BAL) in COPD patients with and without reversibility during an exacerbation, in order to see if cytokines usually detected in asthma, are expressed in higher levels in COPD patients with asthmatic component. METHODS: 18 COPD patients ( 16 males and 2 females), admitted to our hospital because of an exacerbation, were included. Appropriate treatment for at least five days was provided, until stabilization was achieved. Bronchoscopy and assessment of cytokine levels (IL-1␤, IL-4, IL-8, IL-13, TNF⫾) using immunohistochemistry techniques, was performed in all patients. FEV1 reversibility test was performed according to ATS criteria, before bronchoscopy and after a 2-week course of oral steroids (20mg prednizolone). The patients were separated in two groups, Group A and Group B, with post-bronchodilator FEV1 reversibility ⱖ12% or ⬍ 12%, respectively. RESULTS: 11 patiens were included in Group A and 7 patients in Group B, according to the reversibility test. In Group A, all patients expressed high levels of IL-4 and IL-8, 8 of IL-13, 6 of IL-1␤ and 9 of TNF␣. In Group B, all patients expressed high levels of IL-4 and IL-8, 5 of IL-13 and 6 of IL-1␤ and TNF␣. CONCLUSION: Several studies have shown that IL-4 and IL-13 are increased in BAL of asthmatics, while IL-1␤, IL-8 and TNF␣ are increased in BAL of COPD patients. According to our results, the cytokine profile seen in patients with COPD, with or without FEV1 reversibility, was not different. IL-4 and IL-8 were elevated in both groups. Whether these inflammatory markers will be able to distinguish COPD patients with better response to treatment remains to be investigated in future clinical trials. CLINICAL IMPLICATIONS: Cytokine profile in BAL in COPD exacerbation, cannot predict reversibility, but may be related with the benefit from treatment. DISCLOSURE: V. Polychronopoulos, None.

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HEMODYNAMIC CHANGES TO EXERCISE IN PATIENTS WITH COPD AND NORMAL CONTROLS B. R. Celli, MD; Giri Hoskere, MD*; Jay B. Mehta, MD; Michael Ponder, MD; Mirle R. Girish, MD; Johnson City Medical Center, Johnson City, TN PURPOSE: To assess the hemodynamic changes to exercise in patients with COPD and normal control using impedance cardiography (ICG). METHODS: We studied 10 COPD patients (FEV1 ⫽ 36% predicted) and 5 controls (FEV1 ⫽ 90% predicted). Hemodynamic monitoring was done non invasively before and after 6 minute walking test using impedance cardiography byBioZ ® ICG Monitor (Cardio dynamics Inc, San Diego, CA). RESULTS: The increase in cardiac out put and cardiac index post exercise was only 7% and 8% respectively in COPD patients as compared to normal (34%, p⫽ 0.01). The systemic vascular resistance increased by 1% after exercise in COPD, whereas in normal controls it came down by 16 %. There was no difference in heart rate and blood pressure response. CONCLUSION: Ventilatory limitations and cardiac impairment seem to be the cause of limited exercise capacity in COPD. Possible explanations, such as dynamic hyperinflation with intra-thoracic pressures limiting cardiac contractility and stroke volume and/or decreased pulmonary vascular capacitance remain to be explored. CLINICAL IMPLICATIONS: Limitation of exercise capacity in COPD patients is thought to be due to a decreased ventilatory reserve. Based on our data, the role of the cardiovascular system may be more important in exercise limitation than previously thought. Abstracts of Original Investigations, CHEST 2004 —Poster Presentations

Wednesday, October 27, 2004 COPD Evaluation/COPD and the Heart, continued Pre p Post p Exercise COPD Control Value Exercise COPD Control Value CO CI SVR HR VAS MAP 6M walk

5.36 2.91 1499 83 3.9 97 976 ft

5.42 3.12 1313 78 0 93 2167 ft

.29 .07 .32 .89 .002* .47 .01*

CO CI SVR HR VAS MAP

5.72 3.15 1669 93 7.4 111

7.24 4.18 1107 108 3.8 102

.04* .01* .19 .29 .001* .89

DISCLOSURE: G. Hoskere, None. COMBINING ACTIGRAPHY WITH HOME OVERNIGHT OXIMETRY: A NEW APPROACH TO QUANTIFY NOCTURNAL OXYGEN DESATURATION Aislinn D. Black, BA; Michael V. Cutaia, MD; Miriam D. Cohen, NP*; NY Harbor Health Care System, VA Medical Center, Brooklyn, NY

COST-EFFECTIVENESS OF POPULATION SCREENING FOR ALPHA-1 ANTITRYPSIN DEFICIENCY: A DECISION ANALYSIS Thomas R. Gildea, MD*; Kenneth M. Shermock, PharmD; Mendel Singer, PhD; James K. Stoller, MD, MS; The Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder that may predispose to early-onset emphysema and to liver disease. The availability of effective interventions (such as primary avoidance of smoking, smoking cessation, and augmentation therapy) invites the question of whether early detection of alpha-1 antitrypsin deficiency is cost-effective, both through population-based screening or case-finding.

THE CORRELATIONS BETWEEN RIGHT HEART FAILURE AND THROMBIN-ANTITHROMBIN COMPLEX AND PLASMINOGEN ACTIVATOR INHIBITOR-1 IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Young Kim, MD*; Yongdong Severance, Seoul, Korea PURPOSE: Cardiac catheterization and echocardiography are used to measure right heart function. and first pass radionuclide (RI) angiography has been proven to be relatively accurate and simple and reproducible method for measuring right heart function compared with echocardiography. Now cardiac CT angiography, a new technique for measuring right heart function, is introduced and its usefulness has being investigated. In chronic obstructive pulmonary disease (COPD) patients right heart failure is developed from pulmonary hypertension and in situ thrombosis and activation of coagulation factors are well known to be cause of pulmonary hypertension. But, the correlations between coagulation factors and right heart failure is not yet studied enough. The aim of this study is to investigate the usefulness of cardiac CT angiography compared with first pass RI angiography and to evaluate the correlations between right heart failure and plasma TAT(Thrombin antithrombin complex) and PAI1(Plasminogen activator inhibitor-1) level. METHODS: First pass RI angiography and cardiac CT angiography were performed on 15 patients who were diagnosed COPD to measure right heart function and plasma TAT and PAI-1 level were measured. RESULTS: Right heart function measured by cardiac CT angiography showed excellent correlation with right heart function measured by first pass RI angiography in COPD patients. plasma TAT level showed significant inverted correlations with the right heart function measured by first pass RI angiography. CONCLUSION: The present study demonstrates that cardiac CT angiography is accurate and useful method to measure right heart function compared with first pass RI angiography. and plasma TAT level is a factor related with right heart failure in COPD patients. CLINICAL IMPLICATIONS: In the future further study should be done about TAT in diagnosis and follow-up with right heart failure in COPD patients. DISCLOSURE: Y. Kim, None.


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PURPOSE: Nocturnal oxygen desaturation (NOD) has long been recognized in chronic obstructive pulmonary disease (COPD), although its significance remains controversial. In patients with moderate daytime hypoxemia who are not on oxygen therapy, the reported prevalence of NOD is highly variable due, in part, to different definitions of NOD. In addition, oximetry studies in the hospital or sleep lab setting underestimate the duration of desaturation. Home studies demonstrate marked night-to-night variability that may be explained by the disrupted sleep patterns in patients with COPD. Therefore, we propose that measuring oxygen desaturation during the time patients are actually sleeping may be a more accurate method to detect NOD. METHODS: We evaluated 11 subjects with COPD and moderate daytime hypoxemia with 15 overnight home studies using a wearable pulse oximeter (WristOx, Nonin Medical Company) and a “sleep watch” (Actigraph, Ambulatory Monitoring, Inc). The actigraph software contained an algorithm that identifies sleep. Pulse oximetry data were then extracted from periods identified as sleep and compared to the oximetry data for the duration of the night study (total-night-study ⫽ time asleep ⫹ time in bed not sleeping). RESULTS: a. Subject cohort had variable sleep duration: percent of the total-night-study identified as sleep ranged from 44% to 99%. b. Using standard definitions of NOD: 3 patients desaturated below 90% for at least 30% of the night; 6 patients desaturated below 90% for at least 5 minutes with a nadir of 85% or lower. c. 89.2% of all desaturations occurred during the time identified as sleep. d. Subject cohort desaturated below 90% for 17.5⫾5.2% of their sleep time (range 0.1-59.3%). CONCLUSION: In this patient cohort, oxygen desaturated predominantly occurred during sleep. Actigraphy data enhanced these overnight home oximetry studies by distinguishing when subjects were asleep and when they were awake, thus allowing precise quantification of nocturnal hypoxemia. CLINICAL IMPLICATIONS: Accurate assessment and evaluation of the magnitude of NOD cannot be done with oximetry alone. DISCLOSURE: M.D. Cohen, Nonin Medical, Inc

Because no randomized controlled trials of population-based screening for alpha-1 antitrypsin deficiency is available or likely to be, the current study was undertaken to examine the cost-effectiveness of screening for AAT deficiency. METHODS: A Markov-based decision model was created to assess the cost-effectiveness of population screening for alpha-1 antitrypsin (AAT) deficiency, comparing strategies of: 1) screen all newborns, 2) screen all 10 year-old children, and 3) do not screen. Hypothetical cohorts were analyzed from birth and followed over time until death using Monte Carlo simulation. Screenees found to have PI*ZZ AAT deficiency received the benefits of lower smoking rates and were offered augmentation therapy. In keeping with reported experience, most (96%) non-screened AAT deficient individuals remained undiagnosed and, therefore, missed these benefits. RESULTS: Screening all newborns cost nearly $422,000 per qualityadjusted life-year (QALY) gained. Delaying screening until age 10 decreased the incremental cost-effectiveness ratio (ICER) to nearly $317,000. In sensitivity analysis, when the prevalence of PI*ZZ individuals increased from a baseline of 1.96 to 16 per 10,000, the ICER for newborn screening decreased below $100,000 per QALY. When the cost of screening and augmentation therapy were decreased simultaneously with increasing PI*ZZ prevalence, there were many scenarios in which the ICER decreased below $50,000. CONCLUSION: We conclude that while population-based screening for AAT deficiency is not cost-effective under current conditions, costeffectiveness criteria could be satisfied when case-finding in a high prevalence population is undertaken. CLINICAL IMPLICATIONS: The current study advances understanding of the advisability of population-based screening and can serve as a model for the broader consideration of screening for other genetic conditions. DISCLOSURE: T.R. Gildea, None.