Although our study demonstrates that airway inflammation persists in ex-smokers and is associated with increased extent of COPD-E 4 years later, there are several limitations in the study design, including the small number of subjects studied, the duration of having quit smoking before entering the study, the limited number of time-points studied, and the absence of a control group of study subjects with COPD-E who continued to smoke to compare the extent of airway inflammation and rate of decline in COPD-E in persistent vs ex-smokers. Although no sputum bacterial counts were assessed, subjects Viagra in Canada had no history of recent infection. Levels of mediators of inflammation may also be influenced by whether the sputum was spontaneous in subjects with chronic sputum production or induced as in this study, as well as by day to day variability in sputum mediator levels and the stability of mediators stored in a — 80°C freezer.
Because some mediator levels were lower at the first visit compared with the second visit, it is possible that either the stability of mediators in the freezer or bacterial colonization of sputum were the cause of changes in sputum mediator levels with time. An alternative explanation is that the day-to-day variability of sputum mediator levels in an individual subject contributed to the change in levels of sputum mediators noted. However, despite these limitations, in contrast to previous studies a significant strength of this study is the phenotyping of all subjects as having COPD-E based on chest CT scan at entry into the study and documenting changes in extent of COPD-E following 4 years of tobacco smoke cessation (documented by cotinine levels). This longitudinal biomarker study design differs from previous biomarker studies in COPD-E in which serial CT scans, biomarkers, and cotinine levels to verify smoking status were not obtained. In addition, prior studies have predominantly examined the effect of discontinuing smoking on end points other than emphysema (such as symptoms associated Viagra Australia Pharmacy with chronic bronchitis, lung function, and airway hyperresponsiveness).
In summary, in this study we have demonstrated that in subjects with GOLD stage IIb COPD-E, even after at least 4 years of not smoking, airway inflammation persists and that this is associated with continued airspace destruction as revealed by increased emphysema on CT scan.