Repeat visit cotinine assays confirmed that all the subjects with COPD-E were not smoking (cotinine levels at year 4 visit <10 ng/mL), and that the current smokers without COPD-E continued to be smokers (cotinine level at 2 years, 315 ± 84 ng/mL vs cotinine level at baseline, 224 ± 51 ng/mL).
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 Propecia in Canada detectable in sputum and progression of emphysema. 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 remodeling (MMP-9), all of which have been implicated in the pathogenesis of COPD. Interestingly, the subjects with COPD-E entered into this study were all ex-smokers who by history had not smoked for at least 2 years and had a history of not smoking for 15 ± 7 years. Although their past history of quitting smoking prior to entering the study was not verified by cotinine levels, we were able to verify by cotinine levels that they were not smoking at the baseline and 4-year follow-up visit. Thus, the persistent inflammation in sputum of subjects with moderate to severe COPD-E who have quit smoking is likely to be of even longer duration than the 4 years we have followed these subjects.
Although these mediators of inflammation have been detected at increased levels in sputum in several past cross-sectional studies of COPD, the majority of cross-sectional studies have not examined levels of these mediators in subjects phenotyped as having emphysema based on was done in this study. In addition, previous studies have not examined whether levels of mediators of inflammation persist in subjects with COPD-E phenotyped by repeat CT scans over a 4-year period. We are aware of a limited number of cross-sectional studies of biomarkers in BAL or sputum in subjects with COPD-E phenotyped by CT scan, including studies from our group and others, but none of these studies has evaluated changes in biomarkers of inflammation over time in relation to changes in the extent of COPD-E on chest CT scan in subjects with COPD-E who have quit smoking.