As far as we are aware, this is the first prospective study to examine how smoking cessation is reflected in the levels of sputum MMPs. Most previous smoking cessation studies have been cross-sectional and the real effects of smoking cessation on airway remodelling processes/tissue destruction have remained unclear. Based on this study, it seems that sputum MMP levels generally decline slowly after smoking cessation. However, the elevated levels of MMP-9 in smokers are sustained for many months after giving up smoking for reasons that remain unclear.
Smoking cessation reduces COPD morbidity, hospital admissions  and COPD progression . It has also been shown that symptoms decrease significantly after a month of quitting of smoking . The decline of lung function is attenuated slowly, only after 2-3 years from smoking cessation [26, 27]. Smoking evokes very similar airway pathology in asthma and COPD, with the typical features being the recruitment of increased numbers of neutrophils to the airways and elevated oxidative stress [4, 8]. In this study, smoking resulted in neutrophil predominance and elevation of several MMPs in the IS of smokers with or without mild airway disease as compared to the situation in non-smokers. The fact that MMP-9 increased from the baseline during the 3-6 months after smoking cessation suggests that extracellular matrix breakdown continue in the airways for several months after an individual stops smoking. Since neutrophils are an important source of MMP-9, it could be argued that the elevated level of this MMP is simply a marker of neutrophilic inflammation. However, the finding of the persistently elevated MMP-9 levels after 6 months at a time when the neutrophil counts had returned to those encountered in non-smokers suggests that the rise in MMP-9 is not dependent on the numbers of neutrophils per se but instead reflects increased MMP-9 release. Our recent studies have shown that the elevated levels of MMP-9 are associated with increased MMP-9 activity [16, 28]. However, Lowrey et al.  have reported that MMP-9 protein but not MMP activity is higher in sputum of smokers with COPD when compared to smokers without COPD. The significance of MMP-9 in the airways needs further investigations, since it has also been suggested that MMP-9 may have protective role at least against ozone induced airway inflammation . It needs to be emphasized also that our results are preliminary and final conclusions about the significance of sputum MMP-9 after smoking cessation remain unclear.
All of the other markers studied had returned to the levels of non-smokers by 6 months after cessation, which suggests that significant repair of tissue damage elicited by smoking has been initiated. A previous study noted that inflammatory markers such as macrophages and IL-8 declined significantly in asymptomatic smokers one year after smoking cessation . This is in agreement with our results showing that MMP-7, -8 and TIMP-1 though its' variability can return to normal levels within 6 months after the patients successfully quits smoking. Baseline proportion of neutrophils and the levels of MMPs and TIMP-1 were significantly higher in smokers compared to those of non-smokers. These findings are in full agreement with the studies reporting that MMP-8, -9 and TIMP-1 are elevated in COPD and that the increased levels are related to smoking [10, 16, 32] and also that the disease itself, not only smoking, results in MMP elevation [33–35]. MMP-7 is induced by hypoxia  but, as far as we are aware, this is the first study showing that MMP-7 elevation is provoked by smoking. MMP-7 is expressed by macrophages and expression is upregulated also in pulmonary epithelial cells in the presence of chronic infection, which might support the hypothesis that MMP-7 contributes to pulmonary immunity  and that smoking cessation decreases the chronic inflammation in the airways.
One weakness of this study was the high number of dropouts, despite our best efforts, only 15% of our subjects were still non-smoking six months later. This considerable numbers of the dropouts was to be anticipated taking into account the well-known difficulties associated with smoking cessation. In the study of Kaper et al. , for example, subjects receiving reimbursed smoking cessation treatment had an abstinence rate of 5.5% half a year after the interventions. In the present study, the cases from different subgroups were combined, which was also justified for several reasons i.e. the subjects were smokers who had no airway disease or the disease was mild. Smoking asthmatics also develop airway neutrophilia in a similar manner as smokers and subjects with COPD, and the same phenomenon was found in this study. Moreover, the differentiation of symptomatic smokers from mild COPD, and smoking asthmatics from COPD is a demanding task since there is a clear overlap in the cell profiles and diseases [4, 8]. In our study, also the MMP levels were overlapping in these subgroups of smokers as expected. The high number of dropouts diminishes the power of this study, why these results, though important, require further investigations with larger numbers of patients with various phenotypes of asthma and COPD.