It seems logical that repeated episodes of COPD exacerbations may potentially impair lung tissues and lead to an accelerated rate of decline in pulmonary function. This concept is supported by a number of experimental observations. 1) Exacerbations are associated with transient decreases in pulmonary function that, in some cases, take weeks to return to baseline levels [36, 37]. 2) Patients suffering from recurrent exacerbations have been shown to have increased concentrations of inflammatory markers in sputum, even in stable phase, which suggests persistent inflammation and potential lung damage [38]. 3) Neutrophils are attracted into the airway lumen during exacerbations [39]. In fact, increased levels of neutrophils in sputum correlated with rapid decline in FEV1 in a 15-yr follow-up study [40]. There are recent reports that have identified a significantly increased number of eosinophils in patients with COPD exacerbation [41, 42]. The significance of these findings is not fully understood. 4) In cross-sectional studies, higher bacterial load in respiratory secretions have been associated with increased inflammation and decreased lung function [43]. 5) The urinary excretion of desmosine and isodesmosine, products of degradation of lung elastine, are significantly increased during exacerbations of COPD compared with stable phase [44], coinciding with an increase in free elastase during exacerbations [38, 45]; furthermore, higher urinary concentrations of desmosine have been associated with faster decline in FEV1 in COPD [46]. 6) A correlation has been found between the number of previous exacerbations and the extent of emphysematous changes seen by computed tomography scan [17].