O R I G I N A L R E S E A R C H Impairment of small airways in COPD patients with frequent exacerbations and effects of treatment with tiotropium Cristoforo Incor vaia1 Gian Galeazzo Riario- Sforza1 Chiara Pravettoni1 Mona-Rita Yacoub2 Franco Frati3 1Pulmonary 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, Italy Correspondence: Cristoforo Incorvaia Viale Molise 69, 20137 Milano, Italy Tel/Fax +39 2 5513852 Email cristoforo.incorvaia@fastwebnet.it Abstract: 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 effective- ness 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 ver- sus 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 Introduction Chronic obstructive pulmonary disease (COPD) is a major health problem. It is char- acterized by a progressive impairment of lung function (Barnes 2000) and leads to inability and mortality, which are projected to increase their burden in future (Murray and Lopez 1997). This makes the treatment strategies for COPD very important, cur- rently stated as mainly smoking cessation, drug therapy, and pulmonary rehabilitation (Sutherland and Cherniak 2004). An important aspect of COPD is the exacerbations, which occur regardless of the stage of disease according to GOLD classiﬁcation (Pauwels et al 2004; Rabe et al 2007), and is currently deﬁned as “... a sustained worsening of the patient’s symptoms from his or her usual stable state that is beyond normal day to day variations, and is acute in onset. Commonly reported symptoms are worsening breathlessness, cough, increased sputum production and change in sputum color. The change in these symptoms often necessitates a change in medication.” (The National Collaborating Centre for Chronic Conditions 2004). Exacerbations clearly affect the course of the disease, since their frequency is related to lung function decline (Donaldson et al 2002). In particular, data obtained by biopsies demonstrated that the progression of COPD is associated with an increasing impairment of small airways which is strongly related to inﬁltration of inﬂammatory cells in airways walls and accumulation of exudate in the lumen (Hogg et al 2004). International Journal of COPD 2008:3(1) 123–126 © 2008 Incorvaia et al, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 123