Cristoforo Incorvaia1, Gian Galeazzo Riario-Sforza1, Chiara Pravettoni1, Mona-Rita Yacoub2, Franco Frati31Pulmonary Rehabilitation Unit, ICP Hospital, Milan, Italy; 2Allergy and Rheumatology Unit, IRCCS San Raffaele Hospital, Milan, Italy; 3Institute of Pediatrics, Department of Medical and Surgical specialty and Public Health, University of Perugia, Policlinico Monteluce, Perugia, ItalyAbstract: Disease exacerbations are an important aspect of COPD, because they affect its course and are associated with higher lung function decline. On the other hand, data obtained by biopsies have demonstrated that the progression of COPD is related to an increasing impairment of small airways. We sought to evaluate the small airway impairment (FEF25–75) in two groups of COPD patients (each group had 37 subjects) in relation to the frequency of exacerbations and the effectiveness of treatment with tiotropium bromide on the small airway impairment. The mean number of exacerbations was 3.6/year and 1.38/year in frequent and in infrequent exacerbators, respectively (p < 0.001). The mean value of FEF25–75 at baseline was 624 mL and 865 mL in frequent and in infrequent exacerbators respectively (p = 0.002). The changes in respiratory parameters versus baseline showed increases in mean FEV1, FVC, and FEF25–75 in both groups but only the increase in FEF25–75 in frequent exacerbators was statistically significantly (p = 0.013). During the 3-month period of the study the mean number of exacerbations was 0.66 in frequent and 0.12 in infrequent exacerbators. These findings indicate that COPD patients with frequent exacerbations have a higher impairment of small airways. Treatment with tiotropium in COPD subjects with frequent exacerbations proved to be effective in improving small airway impairment.Keywords: COPD, exacerbations, small airways, FEF25–75, tiotropium