Chest
Volume 139, Issue 6, June 2011, Pages 1380-1387
Journal home page for Chest

Original Research
COPD
Persistent Airway Inflammation and Emphysema Progression on CT Scan in Ex-Smokers Observed for 4 Years

https://doi.org/10.1378/chest.10-0705Get rights and content

Background

Tobacco smoking is a principal cause of COPD-emphysema (COPD-E). Whether discontinuing smoking for at least 4 years halts airway inflammation and progression of COPD-E in prior smokers is unknown. In this study we investigated whether discontinuing smoking for approximately 4 years in ex-smokers with GOLD (Global Initiative for Chronic Lung Disease) stage IIb (moderately severe) COPD-E stopped airway inflammation (ie, sputum biomarkers) and halted the progression of COPD-E on chest CT scan.

Methods

Ten ex-smokers with COPD-E who had quit smoking underwent chest CT scans to document the extent of COPD-E, assessment of lung function (FEV1 and diffusing capacity of lung for carbon monoxide), sputum induction for biomarkers of inflammation (measured by enzyme-linked immunosorbent assay), and blood cotinine levels at baseline and approximately 4 years later. Normal healthy subjects (n = 7) and normal current smokers with no CT scan evidence of COPD-E (n = 8) served as sputum biomarker comparison groups.

Results

After approximately 4 years of not smoking (documented by cotinine levels), ex-smokers with COPD-E had persistent increased levels of mediators of inflammation in sputum (myeloperoxidase, leukotriene B4, IL-8, monocyte chemoattractant protein-1, matrix metalloprotease-9), which was associated with significant progression of COPD-E on chest CT scan.

Conclusions

Cessation of tobacco smoking in heavy smokers with moderately severe COPD-E is associated with evidence of persistent airway inflammation and progression of COPD-E on CT scan 4 years later. Discontinuing smoking may slow the rate of progression of moderate severity COPD-E, but it does not prevent persistent airway inflammation and significant progression of COPD-E on CT scan.

Section snippets

Baseline Visits

Study and control subjects were recruited as part of a National Institutes of Health Biomarker study, and their clinical characteristics, pulmonary function, and selected biomarkers have previously been described in detail.16, 17 In brief, subjects with COPD-E were recruited based on clinical evaluation and chest CT scan evidence of emphysema, which had to be present to be included in the study, whereas control subjects were required to have no clinical evidence of COPD and a normal chest CT

Baseline COPD-E Study Subject CT Scan, Pulmonary Function

At the baseline visit, the subjects with COPD-E (n = 10) had a mean age of 69 ± 2 years, were clinically stable, and had a St. George Questionnaire mean score of 37 ± 10. Based on the GOLD criteria, the subjects with COPD-E had GOLD stage IIb moderate severity COPD (GOLD stage IIb; FEV1/FVC ratio < 0.70, and FEV1 ≤ 50% and ≥ 30% predicted).21

The subjects with COPD-E at the baseline visit all had evidence of significant emphysema based on their chest CT scan (Table 1). Subjects with COPD-E had

Discussion

This study demonstrated that ex-smokers with GOLD Stage IIb COPD-E who were followed for 4 years while not smoking have persistent airway inflammation detectable in sputum and progression of emphysema on chest CT scan. The mediators of inflammation that persisted at elevated levels in sputum included mediators associated with neutrophil-mediated inflammation (MPO, LTB4, IL-8), mediators associated with recruitment of mononuclear cells (MCP-1), and mediators associated with extracellular matrix

Acknowledgments

Author contributions: Dr Miller: contributed to processing and analyzing sputum samples, performing statistical analysis of results, and editing the manuscript.

Dr Cho: contributed to processing and analyzing sputum samples, performing statistical analysis of results, and editing the manuscript.

Ms Pham: contributed to processing and analyzing sputum samples, performing statistical analysis of results, and editing the manuscript.

Dr Friedman: contributed to interpreting and scoring of chest CT

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    Funding/Support: This work was supported by the National Institutes of Health [Grants HL72342, and GCRC MO1RR000827].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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