COPD in Oxidative Stress, and Airway Inflammation ...

Sputum Dysplasia, Related to Bacterial Load, Oxidative Stress, and Airway Inflammation in COPD * Philip E. Silkoff, Ashley Busacker, John Trudeau, Mary Jackson and Wilbur Franklin Chest 2004;125;151S DOI 10.1378/chest.125.5_suppl.151S 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/125/5_suppl/151S.full.html

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invasion and metastatic disease. Immunofluorescence has revealed greater membrane staining for ALCAM in MVECs than in PAECs (cultured rat cells). Immunohistochemistry for N-cadherin in human and rat lung sections exhibited strong staining in large and intermediate-size vessels. Capillary endothelial cells occasionally exhibit staining that is less intense. It has been proposed by other investigators that metastatic tumor preferentially goes to specific organs or parts of organs. Human lung carcinoma (ie, non-small cell carcinoma) is strongly positive for ALCAM (4⫹) and exhibits occasional staining for N-cadherin (0 to 1⫹). The human breast carcinoma cell line is positive for ALCAM by flow cytometry. Human breast carcinoma (tissue section) has strong immunohistochemical staining with ALCAM (3⫹ to 4⫹) and with N-cadherin (0 to 2⫹). These findings collectively suggest that ALCAM and/or N-cadherin may fulfill a role in the homing of metastatic carcinoma to the lung or, possibly, in the vascular proliferation that is associated with metastatic disease.

Sputum Dysplasia, Related to Bacterial Load, Oxidative Stress, and Airway Inflammation in COPD*

2-deoxy-8OH-guanosine), and bacterial load. Finally, lung volumes, spirometry, and the CO transfer coefficient were measured. Ten subjects with normal sputum were compared to 25 subjects with dysplasia for all outcomes.

Results There were no significant differences (Table 1) in lung function, markers of airway inflammation (including interleukin-8, leukotriene B4, leukotriene E4, prostaglandin E2, and 15-hydroxyeicosatetraenoic acid), and oxidative stress between subjects with and without dysplasia. There was, however, a significant reduction in the bacterial load of normal flora for subjects with dysplasia, who had a significantly increased incidence of Staphylococcus aureus (isolates, 6 vs 1, respectively) and Haemophilus influenzae (isolates, 5 vs 0, respectively).

Conclusion The airway milieu in dysplasia is characterized by the replacement of normal flora by different organisms, but by no significant differences in markers of airway inflammation, oxidative stress, or lung function. The change in flora could be pathogenic for dysplasia or secondary to other factors that are operative in dysplasia.

Philip E. Silkoff, MD, FCCP; Ashley Busacker, BS; John Trudeau, BS; Mary Jackson; and Wilbur Franklin, MD

(CHEST 2004; 125:151S) putum dysplasia on light microscopy in subjects with S COPD may be related to the degree of airway inflammation, oxidative stress, and bacterial colonization, all of which may lead to DNA damage.

Materials and Methods We recruited subjects aged ⱖ 45 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage 2A) and a ⬎ 30 pack-year smoking history. Pooled home-collected sputum stored in Saccomanno preservative was mailed to the Department of Pathology. The presence of sputum dysplasia on light microscopy was graded by two independent readers. We examined airway inflammation (ie, induced-sputum inflammatory cells, exhaled nitric oxide, and sputum mediators), oxidative stress (ie, exhaled breath condensate hydrogen peroxide, and sputum *From the National Jewish Medical and Research Center (Dr. Silkoff, Ms. Busacker, and Mr. Trudeau), Denver, CO; and the University of Colorado Health Sciences Center (Dr. Franklin and Ms. Jackson), Denver CO. This research was supported by the Colorado Tobacco Research Program grant No. IR 021. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Philip E. Silkoff, MD, FCCP, The National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206; e-mail: [email protected] www.chestjournal.org

Table 1—Comparison of Outcomes Between Select Groups* Variables Age, yr Male gender Current smokers Smoking history, pack-yr FEV1, % predicted FVC, % predicted FEV1/FVC ratio RV, % Dlco, % Exhaled NO, ppb Sputum cell distribution, % Neutrophils Lymphocytes Eosinophils Macrophages Exhaled H2O2, nmol/L 2D8HG ratio Normal flora, CFU/mL sputum

No Dysplasia (n ⫽ 10) 59.3 (5.7) 8 3 61.5 (7.9) 39.8 (6.5) 67.5 (7.0) 44.7 (4.0) 229.4 (19.2) 46.7 (7.0) 25.3 (8.3) 51.8 (7.6) 3.2 (0.7) 2.3 (0.9) 36.7 (6.0) 43.5 (65.4) 1,243 (547.6)† 1,001.3 (195.9)§

Dysplasia (n ⫽ 25) 64.2 (3.4) 14 11 57.8 (5.0) 48.8 (4.2) 72.8 (4.2) 47.6 (2.6) 254.0 (12.2) 50.1 (4.4) 25.3 (5.4) 51.9 (4.8) 2.8 (0.5) 1.6 (0.5) 30.6 (3.8) 90.4 (33.5) 175.7 (296)‡ 269.4 (123.9)㛳

*Values given as mean (SEM) or No. RV ⫽ residual volume; Dlco ⫽ diffusing capacity of the lung for carbon monoxide; H2O2 ⫽ hydrogen peroxide; 2D8HG ⫽ 2-deoxy-8OH-guanosine. †n ⫽ 5. ‡n ⫽ 17. §n ⫽ 8. 㛳n ⫽ 20; p ⬍ 0.004. CHEST / 125 / 5 / MAY, 2004 SUPPLEMENT


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Sputum Dysplasia, Related to Bacterial Load, Oxidative Stress, and Airway Inflammation in COPD * Philip E. Silkoff, Ashley Busacker, John Trudeau, Mary Jackson and Wilbur Franklin Chest 2004;125; 151S DOI 10.1378/chest.125.5_suppl.151S This information is current as of October 17, 2011 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/125/5_suppl/151S.full.html 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.
