Obstructive Sleep Apnea Treatment

Obstructive Sleep Apnea Treatment Chung-Ming Chu and Veronica L. Chan Chest 1999;116;1495-1496 DOI 10.1378/chest.116.5.1495 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/116/5/1495.full.html

Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1999by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

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communications to the editor Communications for this section will be published as space and priorities permit. The comments should not exceed 350 words in length, with a maximum of five references; one figure or table can be printed. Exceptions may occur under particular circumstances. Contributions may include comments on articles published in this periodical, or they may be reports of unique educational character. Please include a cover letter with a complete list of authors (including full first and last names and highest degree), corresponding author’s address, phone number, fax number, and email address (if applicable). An electronic version of the communication should be included on a 3.5-inch diskette. Specific permission to publish should be cited in the cover letter or appended as a postscript. CHEST reserves the right to edit letters for length and clarity.

Gemcitabine Toxicity To the Editor: We read with great interest the report by Vander Els and Miller (December 1998),1 regarding a patient with diffuse infiltrative lung disease during chemotherapy with gemcitabine that showed a favorable response to corticosteroids. Pavlakis et al2 described severe pulmonary toxicity in three patients treated with gemcitabine: two of them died, and autopsy revealed diffuse alveolar damage. In a third patient, the results of transbronchial biopsy showed a pattern of nonspecific interstitial pneumonia, and corticosteroids allowed a clinical improvement. We reported a similar case of a man who died due to progressive respiratory failure, despite the administration of high-dose IV corticosteroids.3 In our patient, autopsy revealed a pattern of diffuse alveolar damage. We suggest that different patterns of lung injury may be related to gemcitabine, as has been described for other drugs.4 In the case reported by Vander Els and Miller,1 the patient’s rapid response, following the administration of corticosteroids, makes it likely a hypersensitivity reaction. We think that BAL may be of value in elucidating mechanisms involved in drug toxicity, and that it should be used more extensively in clinical practice because it is safe for use in treating critical-care patients. A cellular profile suggestive of hypersensitivity reaction may help in excluding other causes and probably predicts a good response to corticosteroid therapy. Almerico Marruchella, MD Maurizio Tondini, MD Ospedale “E. Morelli” Sondalo, Italy Correspondence to: Almerico Marruchella, MD, Divisione di Broncopneumologia, Ospedale “E. Morelli,” 23039 Sondalo (SO), Italy

References 1 Vander Els NJ, Miller V. Successful treatment of gemcitabine toxicity with a brief course of oral corticosteroid therapy. Chest 1998; 114:1779 –1781

2 Pavlakis N, Bell DR, Millward MJ, et al. Fatal pulmonary toxicity resulting from treatment with gemcitabine. Cancer 1997; 80:286 –291 3 Maruchella A, Fiorenzano G, Merizzi A, et al. Diffuse alveolar damage in a patient treated with gemcitabine. Eur Respir J 1998; 11:504 –506 4 Foucher P, Biour M, Blayac JP, et al. Drugs that may injure the respiratory system. Eur Respir J 1997; 10:265–279 To the Editor: We thank Drs. Maruchella and Tondini for their comments on our study (December 1998).1 In addition to the reports cited, there have been several patient deaths in Japan that were attributable to gemcitabine pulmonary toxicity.2,3 The pathophysiology of gemcitabine pulmonary toxicity can be inferred only from the present data. We agree with Drs. Maruchella and Tondini on the importance of collecting BAL as well as biopsy material. Autopsies, although helpful, are limited in that they show the end stage of the injury rather than the path of progression. Nicholas Vander Els, MD, FCCP Vincent Miller, MD Memorial Sloan-Kettering Cancer Center New York, NY Correspondence to: Nicholas J. Vander Els, MD, FCCP, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: [email protected]

References 1 Vander Els NJ, Miller V. Successful treatment of gemcitabine toxicity with a brief course of oral corticosteroid therapy. Chest 1998; 114:1779 –1781 2 Takada M, Negoro S, Kudo S, et al. Activity of gemcitabine in non-small-cell lung cancer: results of the Japan gemcitabine group (A) phase II study. Cancer Chemother Pharmacol 1998; 41:217–222 3 Fukuoka M, Takada M, Yokoyama A, et al. Phase II studies of gemcitabine for non-small cell lung cancer in Japan. Semin Oncol 1997; 24(2 suppl 7):S7– 42–S7– 46

Pulse Oximetry for Assessment of Pulsus Paradoxus To the Editor: We read with interest the study of Hartert et al (February 1999)1 on the use of pulse oximetry for assessing pulsus paradoxus. We performed a very similar study in children,2 notably with the same brand of pulse oximeter, and gained the same results: there is a close association between pulsus paradoxus (in our study, measured by intra-arterial pressure monitoring) and the fluctuations of the plethysmographic respiratory wave (r 5 0.85; 95% confidence interval, 0.76 to 0.91). Hartert et al1 made an important contribution toward the routine application of pulse oximetry by working out the technical basis of the phenomCHEST / 116 / 5 / NOVEMBER, 1999


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enon. Obviously, this phenomenon is not restricted to a single device. The authors documented their observations in four different monitoring systems. After calibration of the device, which entails a specific association between the number of millimeters of change in the plethysmographic baseline and the number of millimeters of Hg recording pulsus paradoxus, electronic analysis of the plethysmographic fluctuations can show a continuous measurement of pulsus paradoxus. About half of the patients studied by Hartert et al1 were receiving mechanical ventilation. The authors did not mention that in patients receiving positive-pressure ventilation the lowest BP values are recorded during expiration (reversed pulsus paradoxus), whereas in spontaneous breathing they are recorded during inspiration. The correlation between pulsus paradoxus and pulse oximetry in tracing fluctuations might not be influenced by the state of respiration (spontaneous or mechanical ventilation). However, (reversed) pulsus paradoxus might not be a good parameter of disease severity in patients receiving mechanical ventilation, as the magnitude of pulsus paradoxus depends at least partly on the applied ventilator pressures.3 Bernhard Frey, MD Ostschweizer Kinderspital St. Gallen, Switzerland

disease: correlation with pulsus paradoxus. Chest 1999; 115: 475– 481 2 Frey B, Butt W. Pulse oximetry for assessment of pulsus paradoxus: a clinical study in children. Intensive Care Med 1998; 24:242–246

Treatment Descriptions Are Valuable to Clinicians To the Editor: I have read with interest the article by Yusen et al (April 1999)1 entitled “Criteria for Outpatient Management of Proximal Lower Extremity Deep Venous Thrombosis.” It appears to be a welldesigned study, but the results are difficult to evaluate because the authors have not defined their treatment protocol. Did they use the same medications and doses for all patients? Was the dose of heparin based on the patient’s weight? The authors are to be congratulated for their ability to point out the logic of outpatient treatment. For clinicians, however, such studies become far more relevant if the actual treatment methods are described.

Correspondence to: Bernhard Frey, MD, Intensivpflegestation, Ostschweizer Kinderspital, CH-9006 St. Gallen, Switzerland; e-mail: [email protected]

John Judson, MD, FCCP Hospital Albert Schweitzer Deschapelles, Haiti

References 1 Hartert TV, Wheeler AP, Sheller JR. Use of pulse oximetry to recognize severity of airflow obstruction in obstructive airway disease: correlation with pulsus paradoxus. Chest 1999; 115: 475– 481 2 Frey B, Butt W. Pulse oximetry for assessment of pulsus paradoxus: a clinical study in children. Intensive Care Med 1998; 24:242–246 3 Jardin F, Farcot JC, Gueret P, et al. Cyclic changes in arterial pulse during respiratory support. Circulation 1983; 68:266 – 274

Correspondence to: John P. Judson, MD, FCCP, Medical Director, Hospital Albert Schweitzer, Deschapelles, Haiti

Reference 1 Yusen R, Haraden B, Gage B, et al. Criteria for outpatient management of proximal lower extremity deep venous thrombosis. Chest 1999; 115:972–979

Outpatient Treatment of Deep Venous Thrombosis

To the Editor: I thank Dr. Frey for his thoughts and comments in regard to our study of the use of pulse oximetry in assessing pulsus paradoxus (February 1999).1 The confirmation of our study by his series2 in children is important in validating pulse oximetry as a useful tool in individuals who are critically ill. In regard to our utilization of the respiratory waveform variation in persons receiving mechanical ventilation, I concur that there are limitations. However, I feel that this finding is useful even in those patients receiving mechanical ventilation as it suggests that either the applied ventilator pressures or the work of breathing are such that they impact the inspiratory fall in systolic BP. I apologize for not having referenced the work of Frey and Butt2 in our manuscript, and thanks to Dr. Frey once again for his thoughtful comments. Tina V. Hartert, MD, MPH Vanderbilt University School of Medicine Nashville, TN Correspondence to: Tina V. Hartert, MD, MPH, Vanderbilt University School of Medicine, Center for Lung Research, T-1217 Medical Center North, Nashville, TN 37232-2650; e-mail: [email protected]

References 1 Hartert TV, Wheeler AP, Sheller JR. Use of pulse oximetry to recognize severity of airflow obstruction in obstructive airway

To the Editor: We read with interest the recent article by Yusen et al (April 1999)1 on the retrospective application of inclusion/exclusion criteria for the outpatient treatment of patients with proximal deep venous thrombosis (DVT). When we implemented a clinical pathway for treating patients with DVT, primarily as outpatients, we performed an investigation similar to that of Dr. Yusen and his colleagues. Our results differ significantly. Our retrospective review of patients admitted to our hospital between August 1997 and 1998 indicated that 24 of 75 patients (32%) treated for DVT (all sites inclusive) met the criteria for outpatient treatment. This rate is consistent with the rates given in previously published trials2– 4 and is considerably lower than that in Wells et al,5 who treated 83% of their patients using outpatient therapy. Our exclusion criteria differ from those of Yusen et al1 in that we do not have an upper limit to the age of the patient we are willing to treat and that we consider end-stage renal disease and pregnancy to be contraindications to outpatient therapy. Since implementing our pathway, we have treated 13 patients as outpatients (following a limited admission for teaching and initiation of therapy). This group comprises approximately 50% of the patients admitted to our hospital for DVT thus far. The majority of our patients are elderly, with an average age for our treated patients of 69 years (range, 38 to 98 years). Our patients

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have not experienced any major bleeding episodes. One patient suffered a pulmonary embolism while still in the hospital and was treated with IV unfractionated heparin and placement of an inferior vena cava filter. To date, 9 of 13 patients have been assisted with home health care following discharge, primarily for prothrombin time management and injection assistance. With the addition of home health care, most patients are “accessible” for follow-up, and we often use home health care to help follow our elderly patients after discharge. We feel that the estimate made by Yusen et al1 is very conservative with respect to the number of patients that may be successfully managed using outpatient therapy. The 100% sensitivity of their protocol for prediction of a negative outcome is commendable; however, the positive predictive value of 8% and the specificity of 20% are extremely low and omit a considerable number of patients who would do quite well with outpatient therapy. Teresa L. Carman, MD Bernardo B. Fernandez, MD Cleveland Clinic Florida Ft. Lauderdale, FL Correspondence to: Bernardo B. Fernandez, Jr., MD, Vascular Medicine, Cleveland Clinic Florida, 3000 W Cypress Creek Rd, Ft. Lauderdale, FL 33309-1710

References 1 Yusen, RD, Haraden BM, Gage BF, et al. Criteria for outpatient management of proximal lower extremity deep venous thrombosis. Chest 1999; 115:972–979 2 Koopman M, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996; 334:682– 687 3 Levine M, Gent M, Hirsch J, et al. A comparison of lowmolecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334: 677– 681 4 Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337:657– 662 5 Wells PS, Kovacs MJ, Bormanis J, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin. Arch Intern Med 1998; 158:1809 –1812 To the Editor: We appreciate the comments made by Dr. Judson. The purpose of our study (April 1999)1 was to evaluate the criteria for outpatient management of acute proximal lower extremity deep venous thrombosis (DVT). We attempted to assess the outcomes of patients undergoing “usual” care for DVT. One third of our cohort of patients had the diagnosis of DVT made in the outpatient setting, and two thirds of these outpatients were considered potentially eligible for outpatient DVT therapy. Of the combined cohort of outpatients and inpatients, 9% were classified as eligible and 9% were classified as possibly eligible for outpatient DVT therapy. During initial hospital-based therapy (heparin is converted to warfarin), no major complications occurred in these two groups. Of the 82% of patients not considered eligible for outpatient therapy, serious complications (recurrent thromboembolism, major bleeding, or death) occurred during initial therapy in 8%. These adverse outcomes were not associated with anticoagulation treatment intensity outside of the therapeutic window. Therefore, our eligibility criteria had a sensitivity of 100% and a negative predictive value of 100% for

predicting serious complications. We have applied and further prospectively validated our outpatient DVT treatment criteria in 50 consecutive patients who have undergone initial outpatient DVT therapy with low-molecular-weight heparin. In these patients, serious complications have not occurred during the initial DVT treatment period. We thank Drs. Carman and Fernandez for sharing their experience regarding outpatient DVT treatment. Though we are pleased to see that their patients did not have a significant rate of major bleeding, the literature suggests that elderly patients receiving anticoagulants are at higher risk for hemorrhage than younger patients.2,3 Further research on bleeding risks in the elderly will shed more light on this issue. Regarding outpatient treatment of acute DVT, we are not surprised to see the existence of heterogeneity of criteria and of patient eligibility.4,5 We agree that our criteria are quite conservative. When starting an outpatient DVT treatment program, health-care providers may wish to use conservative criteria. In addition, health-care providers and patients need to determine an acceptable level of risk that would accompany home therapy. We recommend that health-care providers do the following: (1) adapt and develop criteria to fit their local environment and patient population; (2) assess patient outcomes; and (3) revise criteria to improve outcomes. Continued discussion about the appropriateness of medical treatment regimens and the setting for their administration hopefully will lead to further research and improved patient outcomes. Roger D. Yusen, MD Brennan M. Haraden, MD Brian F. Gage, MD Brian G. Rubin, MD Mitchell D. Botney, MD Washington University School of Medicine St. Louis, MO Correpondence to: Roger D. Yusen, MD, Division of Pulmonary and Critical Care Medicine, and General Medical Sciences, Washington University School of Medicine, Campus Box 8052, 660 S Euclid Ave, St. Louis, MO 63110; e-mail: ryusen@ pulmonary.wustl.edu

References 1 Yusen R, Haraden B, Gage B, et al. Criteria for outpatient management of proximal lower extremity deep venous thrombosis. Chest 1999; 115:972–979 2 Landefeld S, Beyth R. Anticoagulant-related bleeding: clinical epidemiology, prediction and prevention. Am J Med 1993; 95:315–328 3 Kuijer P, Hutten B, Prins M, et al. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999; 159:457– 460 4 Koopman M, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996; 334:682– 687 5 Levine M, Gent M, Hirsh J, et al. A comparison of lowmolecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334: 677– 681

Stethoscope Haiku To the Editor: I read with interest the letter from Dr. Llamas published in CHEST / 116 / 5 / NOVEMBER, 1999


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CHEST (April 1999).1 The poem entitled “The Stethoscope” reminds me of my haiku. Haiku is a Japanese poem divided into three lines. I would like to present two haiku concerning the stethoscope: Stethoscope Between patient and me A smile

Correspondence to: Edward Carter, COL, MC, MD, Chief, Department of Pediatrics, Madigan Army Medical Center, Tacoma, WA 98431; e-mail: [email protected]

Reference 1 Block AJ. The results are not perfect [editorial]. Chest 1999; 115:1223

Through the stethoscope From a patient’s heart A spring song

Manipulation of Volume vs Osmolality in Cystic Fibrosis Lung Disease Hiroshi Kawane, MD, FCCP Kawasaki Medical School Kurashiki City, Japan

Correspondence to: Hiroshi Kawane, MD, FCCP, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama, 701-0192 Japan

Reference 1 Llamas R. The stethoscope. Chest 1999; 115:1218

Quality of Writing in Manuscripts To the Editor: I recently read the editorial concerning the quality of writing in manuscripts (May 1999).1 As a reviewer for CHEST and several other journals, I fully agree with your comments. While I review the manuscripts primarily for their scientific merit and clinical relevance, I am certainly influenced by the quality of the writing. I am frustrated by how poorly some authors use the English language. However, while one can usually guide authors to shorten and better organize their manuscripts, it seems much more difficult to get them to improve their grammar and sentence structure. My sister is a tenured Professor of English at an Ohio college, and I often have her review my manuscripts; most authors are not as fortunate to have a similar resource. To help the editors of CHEST determine how well we reviewers think the manuscript is written, I would suggest the following: include a section or question on the review sheet that asks the reviewer how well he/she thinks the paper was written from a technical, English language standpoint. Perhaps the reviewers should even be asked to comment specifically on whether the paper needs substantial rewriting with respect to grammar or sentence structure. Within this past year, I reviewed a paper for CHEST. The paper was significantly revised and then approved for publication. This paper deserves to be published because it adds important information concerning a rare disease to the medical literature. However, even though the revised manuscript was much improved, it still was not particularly well written from the standpoint of English grammar. Should we have sent it back to the authors for rewriting? I am not sure that would have helped. It is quite possible that the first author would not have known how to improve upon his writing and that the senior authors might not have had the time to rewrite it. Many papers are written by junior investigators who are just relearning how to write. Nevertheless, I think that we should specifically address the issue of “good writing” in our reviews. Edward Carter, COL, MC Madigan Army Medical Center Tacoma, WA

To the Editor: We appreciated the fine review article by Rubin et al (April 1999)1 concerning a therapeutic strategy for cystic fibrosis (CF) lung disease. Defensins are broad-spectrum antimicrobial peptide products of neutrophils (a-defensins)2 and epithelia (bdefensins).3,4 Because the chronic airway infection caused by Pseudomonas aeruginosa is the major source of pathogenesis of lung disease in CF, the killing of bacteria by human defensins produced by the airway epithelium in airway surface liquid (ASL) may be of clinical and pathologic importance in CF patients. It has been reported that healthy airway epithelia express two b-defensins, HBD-1 and HBD-2.3,4 Both HBDs can be detected in BAL fluid.5,6 However, the antimicrobial activities of both HBDs were known to be inhibited by NaCl. The key issue concerning the antimicrobial action of HBDs may be the composition and osmolality of ASL.7 Smith and coworkers8 demonstrated that normal airways reabsorb excessive salt in the water from the ASL, thus producing a sufficiently low level of NaCl (# 50 mM) to activate defensins; but that salt is poorly absorbed in CF airways, resulting in excessively salty ASL that disrupts the bacterial killing activities of HBDs. However, this “hypertonic ASL in CF airways” hypothesis recently has been challenged by a “low, but isotonic volume of ASL in CF airways” hypothesis.9 Matsui et al9 have demonstrated that airways absorb salt and water isotonically, adjusting the volume and height of the ASL components to maintain efficient mucous clearance. Several investigators also have reported that the ASL is isotonic rather than hypotonic in both normal subjects and in pediatric and adult patients with CF.10 –12 The “isotonic but low volume of ASL in CF airways” hypothesis may be in agreement with the earliest hypotheses to explain CF lung disease (the “thick mucous” hypothesis13,14; however, the major problem with it is that the layer of ASL is too thin to allow collection of a sufficient volume for reliable analysis of the composition.14 Further investigation of difference in regulation of the depth and composition of ASL between CF patients and healthy subjects may be important for the therapeutic strategy of CF lung disease. Shinji Teramoto, MD, FCCP Takeshi Mastsue, MD Yasuyoshi Ouchi, MD Tokyo University Hospital Tokyo, Japan Correspondence to: Shinji Teramoto, MD, FCCP, Department of Geriatric Medicine, Tokyo University Hospital, 7-3-1 Hongo Bunkyo-ku Tokyo 113-8655, Japan; e-mail: [email protected]

References 1. Rubin BK, Hiemstra PS, van Wetering S, et al. Emerging therapies for cystic fibrosis lung disease. Chest 1999; 115: 1120 –1126 2. Ashitani J, Mukae H, Nakazato M, et al. Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse

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panbronchiolitis. Eur Respir J 1998; 11:104 –111 3. Goldman MJ, Anderson GM, Stolzenberg ED, et al. Human b-defensin-1 is a salt sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 1997; 88:553–560 4. Bals R, Wang BR, Wu Z, et al. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 1998; 102:874 – 880 5. Singh PK, Jia HP, Wiles K, et al. Production of betadefensins by human airway epithelia. Proc Natl Acad Sci USA 1998; 95:14961–14966 6. Schnapp D, Harris A. Antibacterial peptides in bronchoalveolar lavage fluid. Am J Respir Mol Cell Biol 1998; 19:352– 356 7. Wine JJ. The genesis of cystic fibrosis lung disease. J Clin Invest 1999; 103:309 –312 8. Smith JJ, Travis SM, Greenberg EP, et al. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 1996; 85:229 –236 9. Matsui H, Grubb BR, Tarran R, et al. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airway disease. Cell 1998; 95:1005–1015 10. Farinas J, Kneen M, Moore M, et al. Plasma membrane water permeability of cultured cells and epithelia measured by light microscopy with spacial filtering. J Gen Physiol 1997; 110:283–296 11. Hull J, Skinner W, Robertson C, et al. Elemental content of airway surface liquid from infants with cystic fibrosis. Am J Respir Crit Care Med 1998; 157:10 –14 12. Knowles MR, Robinson JM, Wood RE, et al. Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and disease-control subjects. J Clin Invest 1997; 100:2588 –2595 13. Jiang C, Finkbeiner WE, Widdicombe JH, et al. Altered fluid transport across airway epithelium in cystic fibrosis. Science 1993; 262:424 – 427 14. Boucher RC. Human airway ion transport: part 2. Am J Respir Crit Care Med 1994; 150:581–593 To the Editor: Teramoto et al make some important points regarding my article (April 1999).1 It is tempting to hypothesize that chronic airway infection and inflammation and the abnormality in chloride transport resulting from mutations in the cystic fibrosis transmembrane (conductance) regulator protein are, in cystic fibrosis, related either through the inactivation of innate antimicrobial defense systems or by an alterion of the depth of the periciliary fluid layer, thus affecting the interaction between mucus and cilia. To date, there are few data to support either of these hypotheses. It has been established that the sputum of patients with cystic fibrosis has neither abnormal viscoelasticity nor abnormal salt content when compared to sputum from patients with other chronic lung diseases. Because of the difficulty in directly sampling the periciliary fluid layer, the volume and composition of this layer remain controversial. Although it is theoretically possible that hyperosmolar airway surface fluid could inactivate tracheal antibacterial peptides (defensins), it is unlikely that inactivation of this one part of the airway defense system would lead to such catastrophic and ongoing airway infection as is seen in patients with cystic fibrosis. Abnormalities in periciliary fluid depth would be expected to reduce mucociliary clearance. However, patients with primary ciliary dyskinesia who have congenitally dysfunctional mucociliary clearance do not develop the severe lung disease that is characteristic of those with cystic fibrosis. Understanding the regulation of the composition of the periciliary fluid layer in health and disease is certain to provide us with important insights. Unfortunately, this understanding may

not answer the vexing problem of the link between cystic fibrosis transmembrane (conductance) regulator dysfunction and lung disease in cystic fibrosis. Bruce K. Rubin, MD, FCCP Wake Forest University School of Medicine Winston-Salem, NC Correspondence to: Bruce K. Rubin, MD, FCCP, Wake Forest University Medical Center, Department of Pediatrics, Medical Center Blvd, Winston-Salem, NC 27157-1081; e-mail: rubin@ wfubmc.edu.

Reference 1 Rubin BK, Hiemstra PS, van Wetering S, et al. Emerging therapies for cystic fibrosis lung disease. Chest 1999; 115: 1120 –1126

Obstructive Sleep Apnea Treatment To the Editor: We read with interest the article “Indications for Positive Airway Pressure Treatment of Adult Obstructive Sleep Apnea Patients” by Loube and colleagues (March 1999),1 and we offer the following comments. They suggested that continuous positive airway pressure (CPAP) is indicated for all patients with obstructive sleep apnea (OSA) who have a respiratory disturbance index (RDI) of . 30 events per hour, and they cited Wisconsin sleep cohort data2 for support. However, the Wisconsin study used an apnea-hypopnea index (AHI) rather than an RDI. An RDI also takes respiratory effort-related arousal into account, and measurements using the RDI are usually larger than AHI. Using an RDI of . 30 events per hour seems unwarranted based on the evidence presented. Loube and colleagues1 also recommended that OSA of a lesser degree also is indicated for treatment if comorbidities, including hypertension, ischemic heart disease, or stroke, are present. However, coexisting COPD was not discussed. We suggest that patients with both OSA and COPD warrant special consideration. Pulmonary arterial pressure in patients with significant OSA (RDI, . 20 events per hour) has been shown to be correlated with FEV1.3 Patients with coexisting OSA and COPD also have been reported to have worse cardiopulmonary dysfunction than those with OSA alone, and tracheostomy improved right ventricular function significantly in these patients.4 Sampol and colleagues5 studied 10 male patients with AHIs of 15 to 74 events per hour and treated them with CPAP, oxygen, and suboptimal CPAP and effective CPAP with oxygen on successive nights. Effective CPAP corrected the OSA, but the mean level of arterial oxygen saturation (Sao2) remained at , 90% in all patients. The use of supplemental oxygen with suboptimal CPAP levels produced an increase in apnea frequency and duration. Only an effective CPAP level plus oxygen resulted in the elimination of OSA and produced a mean Sao2 level of . 90% in all patients. From the available evidence, it appears reasonable to offer CPAP with supplemental oxygen to patients with COPD who also have OSA and an AHI of . 15 events per hour. Notwithstanding these comments, we deeply appreciate the effort of Loube and colleagues in producing a much-needed consensus statement for the management of OSA. Chung-Ming Chu, MB, MSc Veronica L. Chan, MB United Christian Hospital Kowloon, Hong Kong SAR, China CHEST / 116 / 5 / NOVEMBER, 1999


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Correspondence to: Chung-Ming Chu, MB, MSC, Division of Respiratory Medicine, Department of Medicine and Geriatrics, United Christian Hospital, Kowloon, Hong Kong SAR, China; e-mail: [email protected]

References 1 Loube DI, Gay PC, Strohl KP, et al. Indications for positive airway pressure treatment of adult obstructive sleep apnea patients. Chest 1999; 115:863– 866 2 Young T, Peppard P, Palta M, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997; 157:1746 –1752 3 Laks L, Lehrhaft B, Grunstein RR, et al. Pulmonary hypertension in obstructive sleep apnoea. Eur Respir J 1995; 8:537–541 4 Fletcher EC, Schaff JW, Miller J, et al. Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease. Am Rev Respir Dis 1987; 135:525–533 5 Sampol G, Sagales MT, Roca A, et al. Nasal continuous positive airway pressure with supplemental oxygen in coexistent sleep apnoea-hypnoea syndrome and severe chronic obstructive pulmonary disease. Eur Respir J 1996; 9:111–116

itantly in individual patients.10,11 We purposely did not discuss the therapy of nocturnal breathing disorders in COPD patients as this is addressed in another recent consensus statement that was prepared with that specific objective.12 However, we did recommend that “a trial of bilevel positive airway pressure may be indicated for OSA patients with concomitant nocturnal breathing disorders including COPD.”1 Daniel I. Loube, MD, FCCP Virginia Mason Medical Center Seattle, WA Peter C. Gay, MD, FCCP Mayo Clinic Rochester, MN Kingman P. Strohl, MD, FCCP Case Western Reserve University Cleveland, OH Allan I. Pack MD, PhD University of Pennsylvania Philadelphia, PA David P. White, MD, FCCP Harvard University Boston, MA Nancy A. Collop, MD, FCCP University of Mississippi Oxford, MS

To the Editor: We thank Drs. Chu and Chan for their interest in and thoughtful comments on our consensus statement (March 1999).1 We agree that data from prior obstructive sleep apnea (OSA) syndrome outcome studies were based on nocturnal obstructive respiratory events for which airflow was measured by oronasal thermistor. However, the detection of airflow by these thermal sensors provides qualitative information that is not well correlated with breath amplitude. Thermistors have been shown to have poor accuracy in recording hypopneas in awake subjects under ideal conditions.2 Due to the inadequate nature of the signal, it is unlikely that any further research on thermal sensors would yield acceptable data on accuracy or precision. Hence, alternative techniques, including esophageal and pleural pressure (Pes) manometry,3 nasal pressure transduction,4 or quantitative respiratory inductive plethysmography,5 are advocated to aid in the detection of nocturnal obstructive respiratory events. Because of the decreased sensitivity of the oronasal thermistor in measuring airflow to detect events, compared to some of these other methods,6 the term respiratory effort-related arousal (RERA) was developed. A RERA is an event that is characterized by increasing respiratory effort for $ 10 s leading to an arousal from sleep, but that does not fulfill the criteria for a hypopnea or an apnea.7 At the present time, the recommendations are that there is no added clinical value in differentiating apneas from hypopneas, because they have similar pathophysiology and usually end in arousal, and often in desaturation.8 Similarly, with the exception of the number of apneas and hypopneas measured by thermistor, respiratory parameters evaluated by standard 12-channel polysomnography with the addition of Pes manometry recently were demonstrated to be the same for upper airway resistance syndrome patients and OSA patients when body mass index and gender were controlled for.9 These findings suggest that the inclusion of apneas, hypopneas, and RERAs in a single index is appropriate and that these events likely do not differ with respect to the potential for causing the consequences of untreated OSA. Thus, we still believe that positive airway pressure treatment is warranted for a patient with a respiratory disturbance index (RDI) of . 30 events per hour, with the inclusion of apneas, hypopneas, and RERAs in the RDI. We also agree with Drs. Chu and Chan that patients with both OSA and COPD warrant special consideration. It was an oversight not to state that some studies suggest that there is an additive risk for mortality when OSA and COPD occur concom-

Correspondence to: Daniel I. Loube, MD, FCCP, Director, Sleep Disorders Center, Virginia Mason Medical Center, 925 Seneca St (H10-SDC), Seattle, WA 98111

References 1 Loube DI, Gay P, Strohl KP, Pack A, White DP, Collop NJ. Indications for positive airway pressure treatment of adult obstructive sleep apnea syndrome. Chest 1999; 115:863– 866 2 Berg S, Haight JSJ, Yap V, et al. Comparison of direct and indirect measurements of respiratory airflow: implications for hypopneas. Sleep 1997; 20:60 – 64 3 Zamagni M, Sforza E, Boudewijns A, et al. Respiratory effort. A factor contributing to sleep propensity in patients with obstructive sleep apnea. Chest 1996; 109:651– 658 4 Hosselet JJ, Norman RG, Ayappa I, et al. Detection of flow limitation with a nasal cannula/pressure transducer system. Am J Respir Crit Care Med 1998; 157:1461–1467 5 Loube DI, Andrada TF. Upper airway resistance syndrome: detection with respiratory inductive plethysmography. Chest 1999; 115:1333–1337 6 Clark SA, Wilson CR, Satoh M, et al. Assessment of inspiratory flow limitation invasively and noninvasively during sleep. Am J Respir Crit Care Med 1999; 158:713–722 7 American Sleep Disorders Association Task Force. The Chicago criteria for measurements, definitions, and severity of sleep related breathing disorders in adults. Presented at: The Association of Professional Sleep Societies Conference; June 20, 1998; New Orleans, LA 8 Gould GA, Whyte KF, Rhind GB, et al. The sleep hypopnea syndrome. Am Rev Respir Dis 1988; 137:895– 898 9 Loube DI, Andrada TF. Comparison of nocturnal respiratory parameters in upper airway resistance and obstructive sleep apnea syndrome patients. Chest 1999; 115:1519 –1524 10 Lavie P, Herer P, Peled R, et al. Mortality in sleep apnea patients: a multivariate analysis of risk factors. Sleep 1995; 18:149 –157 11 Fletcher EC, Schaff JW, Miller J, et al. Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease. Am Rev Respir Dis 1987; 135: 525–533 12 Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation: a consensus conference report. Chest 1999; 116:521–534

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Salmeterol, Inhaled Corticosteroids, and Tolerance to Allergen Bronchoprotection To The Editor: We read with great interest the report by Giannini et al (March 1999)1 suggesting that regular use of inhaled beclomethasone dipropionate (BDP) might partially inhibit the development of tolerance to the bronchoprotective effect of salmeterol against allergen challenge. In 12 atopic asthmatic subjects, they initially confirm their previous observation2 that 7 days of salmeterol therapy, 50 mg bid, results in almost complete loss of the bronchoprotective effect of a single dose of salmeterol against allergen-induced early asthmatic response (EAR). Subjects then were entered into a double-blind parallel trial in which all subjects received BDP, 500 mg bid, for a week accompanied by either placebo or salmeterol, 50 mg bid. In the six subjects receiving salmeterol and BDP, the EAR at 1 week was improved compared to that after 1 week of salmeterol adminstration alone. The authors suggest that this was the result of BDP reducing the tolerance to salmeterol rather than a direct effect of BDP on baseline (ie, without salmeterol therapy) EAR. Their conclusions are based on the failure of BDP alone to significantly alter the EAR in the other six subjects; two references are cited in support of this conclusion.3,4 In contrast to their claims, several investigators have shown that a week of inhaled corticosteroid therapy, often at substantially lower doses than BDP, 500 mg bid, inhibits the allergeninduced EAR by $ 50%, which is equivalent to more than or equal to a doubling of a provocative concentration of allergen causing a 20% fall in FEV1.5–7 A careful look at the two studies cited by Giannini et al3,4 shows that the first involved a single dose of BDP,3 which is well recognized to have no influence on the EAR, and the second4 documented a 30% reduction in EAR evaluated by peak expiratory flow rate after 1 week of treatment with budesonide. There is marked interindividual variability in the effect of inhaled corticosteroids on allergen-induced EAR as documented by Burge et al5 and seen in the course of our own studies6,7; this supports the superiority of the cross-over design for this type of study. In summary, since most studies demonstrate that a week of inhaled corticosteroid therapy produces similar improvement in the EARs of patients as that demonstrated by Giannini et al1 in six subjects receiving BDP plus salmeterol, the conclusion that BDP partially reverses the tolerance produced by the regular use of salmeterol must be accepted with caution and requires confirmation by a study with a cross-over design. Donald W. Cockcroft, MD, FCCP Beth E. Davis, BSc Veronica A. Swystun, BSc University of Saskatchewan Saskatoon, Saskatchewan, Canada Correspondence to: Donald W. Cockroft, MD, FCCP, University of Saskatchewan, Division of Respiratory Medicine, 103 Hospital Dr, Ellis Hall, Saskatoon, SK, Canada S7N 0W0

References 1 Giannini D, Bacci E, Dente FL, et al. Inhaled beclomethasone dipropionate reverts tolerance to the protective effect of salmeterol on allergen challenge. Chest 1999; 115:629 – 634 2 Giannini D, Carletti A, Dente FL, et al. Tolerance to the protective effect of salmeterol on allergen challenges. Chest 1996; 110:1452– 457

3 Pizzichini MMM, Kidney JC, Wong BJO, et al. Effect of salmeterol compared with beclomethasone on allergeninduced asthmatic and inflammatory responses. Eur Respir J 1996; 9:449 – 455 4 Dahl R, Johansson S-A. Importance of duration of treatment with inhaled budesonide on the immediate and late bronchial reaction. Eur J Respir Dis 1982; 63(suppl 122):167–175 5 Burge PS, Efthimiou J, Turner-Warwick M, et al. Doubleblind trials of inhaled beclomethasone dipropionate and fluocortin butyl ester in allergen-induced immediate and late reactions. Clin Allergy 1982; 12:523–531 6 Cockcroft DW, Swystun VA, Bhagat R. Interaction of inhaled b2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine. Am J Respir Crit Care Med 1995; 152:1485–1489 7 Swystun VA, Bhagat R, Kalra S, et al. Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen. J Allergy Clin Immunol 1998; 102:363–367 To the Editor: The observations about our report (March 1999)1 are important and appropriate, and they particularly highlight the difficulty in finding the best design for this type of study. Actually, several studies have demonstrated that regular treatment with inhaled corticosteriods can reduce early asthmatic response (EAR) to allergens.2–5 All these studies considered patients with both EARs and late asthmatic responses (LARs) to allergens,2– 4 and in some studies the LAR was stopped immediately after the EAR by short-term treatment with corticosteroids.5 In all these studies, a large variability in the ability of corticosteroids to protect individual patients experiencing EARs was observed. In contrast to the subjects in these studies, those in our study had mild cases of asthma that did not require regular treatment and who did not experience LAR during the screening baseline allergen challenge. No studies evaluated the effect of inhaled corticosteroids on EAR in this particular subpopulation of patients. Our study was a double-blind placebo-controlled trial: the subjects were randomized to receive beclomethasone dipropionate (BDP) accompanied by placebo or salmeterol. After receiving BDP plus placebo, subjects showed a response to the allergen challenge similar to that observed during the screening provocative test, in terms of changes in FEV1 level at each time point of the EAR. The unequivocal positive response of the subjects to the allergen, in terms of area under curve and maximal percentage change in FEV1, after receiving BDP plus placebo, showed that the partial protection against EAR observed in the group treated with salmeterol plus BDP was not due to treatment with inhaled corticosteroid alone. Our study investigated a very select population of patients: those with mild forms of asthma who had never been regularly treated before the trial and who had positive EARs to the allergen. To determine the effect of different therapies against allergen challenge, it is mandatory to have subjects who have not been treated before. Our study population permitted evaluation of the baseline response to the protective effect of the study drug and the change obtained after regular treatment with it. A study with a cross-over design would not permit treatment of patients during the two randomized sequences of treatment, for the same time period as in our study. These limitations of the cross-over design are not present when regularly treated subjects are considered. In conclusion, even considering the limitations we have sugCHEST / 116 / 5 / NOVEMBER, 1999


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gested, the absolute absence of protection against EAR in the control group and the validity of the parallel-groups design make our study results reliable. Daniele Giannini, MD Pierluigi Paggiaro, MD Ospedale di Cisanello Pisa, Italy Correspondence to: Daniele Giannini, MD, U.O. Fisiopatologia Respiratoria, Ospedale di Cisanello, Via Paradisa 2, 56100 Pisa, Italy

References 1 Giannini D, Bacci E, Dente FL, et al. Inhaled beclomethasone dipropionate reverts tolerance to the protective effect of salmeterol on allergen challenge. Chest 1999; 115:629 – 634 2 Dahl R, Johansson S-A. Importance of duration of treatment with inhaled budesonide on the immediate and late bronchial reaction. Eur J Respir Dis 1982; 6(Suppl 122):167–175 3 Burge PS, Efthimiou J, Turner-Warwick et al. Double-blind trials of inhaled beclomethasone dipropionate and fluocortin butyl ester in allergen-induced immediate and late reactions. Clin Allergy 1982; 12:523–531 4 Cockcroft DW, Swystun VA, Bhagat R. Interaction of inhaled beta2-agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine. Am J Respir Crit Care Med 1995; 152:1485–1489 5 Swystun VA, Bhagat R, Kalra S, et al. Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen. J Allergy Clin Immunol 1998; 102:363–367

and stabilization is important. Also, as expressed in Dr. Ciaglia’s editorial,3 maintaining the noninserted end of each PDT dilator cephalad to the insertion end is likely to minimize trauma to the posterior tracheal wall. In combination with techniques to prevent guidewire misplacement, some experienced operators purposely do not withdraw the existing endotracheal tube above the tracheostomy insertion site prior to PDT. The presence of the distal endotracheal tube at the PDT insertion site prevents tracheal collapse, lessens inadvertent extubation, and may well protect the posterior tracheal wall from perforation. With appropriate PDT tube sizing, there is ample tracheal lumenal area to accommodate both the tapered dilators and the distal end of the endotracheal tube. Dean P. Sandifer, MD, FCCP Watson Clinic, LLP Lakeland, FL Correspondence to: Dean P. Sandifer, MD, FCCP, Department of Adult Critical Care Medicine, Watson Clinic, LLP, 1600 Lakeland Hills Blvd, Lakeland, FL 33804

References 1 Trottier ST, Hazard PB, Sakabu SA, et al. Posterior tracheal wall perforation during percutaneous dilational tracheostomy. Chest 1999; 115:1383–1389 2 Sandifer DP. Pathologic changes of the trachea after percutaneous dilational tracheostomy. Chest 1997; 111:255–256 3 Ciaglia P. Technique, complications, and improvements in percutaneous dilational tracheostomy. Chest 1999; 115:1229 – 1230

Percutaneous Dilational Tracheostomy Kits

Wean From the Tube Not Necessarily From the Ventilator

To the Editor:

To the Editor:

I read with interest the article by Trottier and colleagues (May 1999)1 concerning percutaneous dilational tracheostomy (PDT) using the PDT kit manufactured by Smith Industries (Keene, NH). In the 24 PDTs cases performed by Trottier et al, the development of three postprocedure tension pneumothoraces, two requiring thoracotomy, and two inadvertent extubations is unheard of and completely unacceptable. We have completed scores of PDTs using this kit without a single tension pneumothorax, mainstem tracheostomy tube placement, or tracheostomy tube obstruction, and certainly without any patients requiring post-PDT thoracotomy. If all medical centers had complications of this frequency and severity, PDT would not be a viable option. I have no affiliation, or relationship, with any PDT manufacturer. I have expressed that the tapered Portex PDT tube (Smith Industries) offers a distinct advantage over the kit manufactured by Cook Inc. (Bloomington, IN) regarding the final step of tracheostomy tube insertion over a dilator.2 Contrary to the protocol of this study, we do not routinely utilize neuromuscular blockade during PDT. Inhibiting the cough and respiratory reflexes of the patients may well increase the incidence of posterior tracheal perforation. Cough can be an early warning sign that posterior tracheal pressure is excessive when using any PDT kit. Neuromuscular blockade also exacerbates the urgency of rare inadvertent extubation. Although the use of adjunct of fiberoptic bronchoscopy (FOB) in the training for the performance of PDT is vital, many experienced operators perform PDT without FOB with far superior complication rates than in this study. The article’s focusing of attention on PDT catheter and guidewire positioning

The recent article by Price and Rizk (May 1999 supplement),1 entitled “Postoperative Ventilatory Management,” discusses many aspects of postoperative ventilatory care but fails to consider all of the options for one uncommon, but not rare, situation. Patients with neuromuscular ventilatory impairment for whom postoperative ventilator weaning difficulty may be anticipated can be trained prior to surgery to use noninvasive intermittent positive-pressure ventilation (IPPV) and expiratory muscle aids.2 This training permits the option of extubating such patients even when they are unable to autonomously ventilate the lungs. We come across this situation most commonly in patients with vital capacities of , 30% of the predicted normal rate who require scoliosis reduction surgery. However, it can occur in anyone with advanced neuromuscular disease who requires surgery. Once trained in mouthpiece and nasal IPPV3 and in manually and mechanically assisted coughing,2 the patients can usually be extubated when they meet the following criteria: 1. no requirement of supplemental oxygen to maintain arterial oxygen saturation at . 94%; 2. cleared or clearing chest radiograph abnormalities; 3. full alertness and discontinuation of any respiratory depressants; 4. extubation to continuous noninvasive IPPV without supplemental oxygen; and 5. ability to use oximetry feedback to guide the use of inspiratory and expiratory aids to augment cough flows and to reverse any desaturations due to airway mucus accumulation. Indeed, the “weaning” options are to wean from supplemental

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oxygen by clearing the airways and restoring normal pulmonary function, to remove any indwelling airway tubes whether the patient can breathe or not, and to let the patient wean from ventilator use by taking fewer and fewer assisted insufflations as needed to avoid dyspnea, oxyhemoglobin desaturation, and hypercapnia.3 Since many patients who require continuous longterm ventilatory support do not have tracheostomy tubes, one cannot expect them to wean from ventilator use before postoperative extubation. John R. Bach University of Medicine & Dentistry of New Jersey Newark, NJ Correspondence to: John R. Bach, MD, FCCP, Professor of Physical Medicine and Rehabilitation, University of Medicine & Dentistry of New Jersey, University Hospital B-403, 150 Bergen St, University Heights, Newark, NJ 07103-2406; e-mail: bachjr@ umdnj.edu

released or only partially released, although the device indicated that the dose had been delivered. With this in mind, patients unaware of the recommendations against the use of this device with ipratropium bromide MDIs may not receive accurate doses of ipratropium despite the readings of the Doser. The second observation about the Doser is related to problems using the device with longer MDI canisters, particularly those for albuterol. The 8-cm long albuterol canister extends to 10 cm with the counter in place. When holding this Doser-MDI combination between the thumb and forefinger, the distance may be too far for some patients to actuate comfortably. This may be difficult, especially for arthritic patients, children, or other persons with small hands. Although the Doser may be a useful external counting device, clinicians should be aware of these issues when recommending the product for patients. Dennis M. Williams, PharmD Andrea Wessell, PharmD(c) Tina Penick Brock, MS University of North Carolina School of Pharmacy Chapel Hill, NC

References 1 Price J, Rizk NW. Postoperative ventilatory management. Chest 1999; 115(suppl):130S–137S 2 Bach JR. Update and perspectives on noninvasive respiratory muscle aids: Part 2. The expiratory muscle aids. Chest 1994; 105:1538 –1544 3 Bach JR. Update and perspectives on noninvasive respiratory muscle aids: Part 1. The inspiratory muscle aids. Chest 1994; 105:1230 –1240 4 Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure: a different approach to weaning. Chest 1996; 110:1566 –1571

The Doser External Counting Device To the Editor: The Doser (Meditrack Products; Hudson, MA) is an external counting device for metered-dose inhalers (MDIs). It attaches to the top of an MDI canister and records actuations as the canister is depressed. The Doser tracks the number of actuations remaining in the canister and those used each day. Accuracy of the Doser was established in a study comparing it with a diary and the Nebulizer Chronolog, an established microelectronic monitoring device.1 We performed an evaluation of six Doser devices used with four fluticasone (Flovent; Glaxo Wellcome; Research Triangle Park, NC) and four albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) MDIs. Correlation between Doser results and manual actuation counts was good, with a Doser SE error rate of 6 4.5%. In seven of eight cases, however, the Doser overestimated actual actuations (102 to 107% of doses). In the remaining instance, the device registered 99% of doses actuated. We identified two potential concerns related to use of the Doser. While information from a published report1 and the Doser Web page2 indicated that the device should not be used with ipratropium, cromolyn, or nedocromil, the product labeling and accompanying package information did not include statements about these specific products. We were able to attach the Doser to the ipratropium bromide (Atrovent; Boehringer Ingelheim Pharmaceuticals, Inc; Ridgefield, CT) canister; however, the fit did not allow correct seating of the canister nozzle into the mouthpiece. Subsequently, when actuated, the dose was not

Dr. Williams is Assistant Professor and Clinical Specialist in Pulmonary Medicine and Ms. Brock is Clinical Assistant Professor. Correspondence to: Dennis M Williams, PharmD, University of North Carolina at Chapel Hill, School of Pharmacy, CB #7360, Beard Hall, Chapel Hill, NC 27599-7360

References 1 Simmons MS, Nides MA, Kleerup EC, et al. Validation of the Doser, a new device for monitoring metered-dose inhaler use. J Allergy Clin Immunol 1998; 102:409 – 413 2 Meditrack Products. Doser. Available at: http//www.doser.com. Accessed June 2, 1999

Erratum In the editorial “Steroids in Acute Exacerbation of Asthma: How Do We Grade Evidence?” by Paul E. Marik and Joseph Varon (Chest 1999; 116:273–274), there were errors in Table 1 and in the text. Several levels of evidence were listed in the table and in the text as “I,” “II,” or “III,” when they should have read, “2I”, “2II,” or “2III.” Below are the corrected versions of both Table 1 and the paragraph of text in which the errors occurred. Level I (and possibly level II) interventions should be regarded as the standard of care, and failure to offer eligible patients this intervention should be considered a serious breach of care. Similarly, it should be considered unethical to exclude level I and level II interventions in eligible patients in RCT studies that are testing new agents. Level III interventions are recommended, although they are not considered to be the standard of care. For interventions with level IV, level 2 III, and 0 grades of evidence, the clinician should base the intervention on the merits of the particular case. Furthermore, these interventions need to be tested in RCT studies. Grade 2 I and 2 II interventions should be regarded as harmful, and they should not be offered to patients (outside of a RCT). New or untested interventions (grade 0) should only be offered to patients in the RCT setting. This includes using a grade I, II, III, or IV intervention for an untested indication, patient subgroup, or treatment regimen.

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Table 1—Grades of Evidence* Level of Evidence and Grade Unequivocal benefit (level I) Three or more RCT studies all demonstrating significant clinical benefit; or one mega-RCT showing a significant clinical benefit. Strong benefit (level II) Two positive RCT studies; or a meta-analysis of RCT studies in which treatment effect exceeds the minimally clinically important benefit and none of the individual trials demonstrate a significant harmful effect. Moderate evidence for beneficial effect (level III) One positive RCT or a meta-analysis of RCT studies showing discordant results with the lower limit of the CI for the treatment effect that exceeds the minimally clinically important benefit. Weak evidence for beneficial effect (level IV) “Consensus” of expert opinion, cohort studies, or case series. Clinical equipoise (level 0) No data on beneficial or harmful effect, two or three RCT studies showing contradictory results, or meta-analysis of RCT studies or a mega-RCT in which the upper limit of the CI for the treatment effect is below the minimally clinically important benefit. Weak evidence for harmful effect (level 2 III) “Consensus” of expert opinion, cohort studies, or case series demonstrating a negative outcome. Moderate evidence for harmful effect (level 2 II) Results for a single RCT showing harmful outcome or a metaanalysis of RCT studies showing discordant results with the mean treatment effect , 1 (risk ratio). Strong/unequivocal evidence for harmful effect (level 2 I) Two or more RCT studies or a megatrial demonstrating a harmful outcome, or a meta-analysis of RCT studies in which the upper limit of the CI for the treatment effect is below the minimally acceptable adverse effect.

Examples b-blockers post AMI, antihypertensive Rx in preventing CVAs, thrombolytic Rx in AMI , 6 h, ACE inhibitors in CHF, statins in hypercholesterolemic patients Stress ulcer prophylaxis in preventing GI bleed

Steroids in the fibroproliferative ARDS, selective decontamination of digestive tract, once daily aminoglycoside Rx

CAVHD/CVVHD in ARF, vasopressors in sepsis Magnesium in AMI, anti-inflammatory Rx in sepsis, thrombolysis in stroke , 3 h, supranormal Do2 in sepsis

Pulmonary artery catheterization in ICU, long-term NMBA in patients on steroids, treatment of hypertension poststroke Flecainide for long-term arrhythmia suppression, steroids in sepsis (early)

Streptokinase in stroke . 3 h

*Grading system based on effect and RCT studies. ACE 5 angiotensin-converting enzyme; AMI 5 acute myocardial infarction; ARF 5 acute renal failure; CHF 5 congestive heart failure; NMBA 5 neuromuscular blocking agents; Rx 5 treatment; CAVHD 5 continuous arteriovenous hemodialysis; CVA 5 cerebrovascular accident; CVVHD 5 continuous veno-veno hemodialysis; Do2 5 oxygen delivery.

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Obstructive Sleep Apnea Treatment Chung-Ming Chu and Veronica L. Chan Chest 1999;116; 1495-1496 DOI 10.1378/chest.116.5.1495 This information is current as of January 4, 2012 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/116/5/1495.full.html References This article cites 15 articles, 8 of which can be accessed free at: http://chestjournal.chestpubs.org/content/116/5/1495.full.html#ref-list-1 Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.
