Table 2 Changes in respiratory parameters after treatment with tiotropium Group A B Baseline mean FEV1 (mL) 1191 ± 185 1249 ± 373 Mean FEV1 after tiotropium 1236 ± 201 1423 ± 411 Baseline mean FVC (mL) 2212 ± 803 2433 ± 649 Mean FVC after tiotropium 2284 ± 780 2587 ± 671 Baseline FEF25–75 (mL) 624 ± 418 865 ± 372 FEF25–75 after tiotropium 892 ± 497 1012 ± 438 A signiﬁcant advance in the knowledge of the kind of damage in COPD was achieved by the study of Hogg et al. These authors investigated the progression of the disease in different COPD stages by means of lung biopsies. They found that the grade of wall thickness of the small airways, resulting from inﬁltration of inﬂammatory cells and structural changes, was correlated with disease severity, as assessed by FEV1 values (Hogg et al 2004). It is somewhat surprising that, following such observation, measurement of small airway parameters in COPD patients has been almost overlooked. We designed the present study to investigate the changes in small airway obstruction in patients with COPD with frequent or infrequent exacerbations undergoing treatment with tiotropium. We chose tiotropium because of its effec- tiveness, which was clearly demonstrated by a Cochrane meta-analysis (Barr et al 2005), by its ability to reduce the number of exacerbations (Brusasco et al 2003), and by its capacity to improve pulmonary function (Casaburi et al 2000; Cazzola et al 2005; Incorvaia et al 2007) including small airway parameters (Incorvaia et al 2007). In particular, such effects had already been detected after short-term treatment and are likely to be linked to the ability of the drug to reach the deeper airways and to interact with muscarinic receptors, particularly with those positioned in the smooth muscle of small airways (Barnes 1993). The efﬁciency of the speciﬁc dry powder inhaler device may possibly help patient perfor- mance in such effects (Dahl et al 2003). Our ﬁndings indicate that frequent exacerbators have signiﬁcantly lower FEF25–75 (the main functional parameter of small airways) values compared to infrequent exacerbatiors. The mean number of exacerbations was 3.6 ± 0.64/year in frequent and 1.38 ± 0.59/year in infrequent exacerbators, data comparable to those reported by Donaldson et al in the study on association between lung function decline and frequent exacerbations (Donaldson et al 2002). Treatment with tiotro- pium improved pulmonary function parameters, including FEV1, FVC, and FEF25–75, but only the increase in FEF25– 75 mean value in frequent exacerbators was statistically International Journal of COPD 2008:3(1) COPD exacerbations and small airways signiﬁcant. Otherwise these subjects had a signiﬁcantly lower mean baseline value, indicating a more severe impairment in small airways, compared with infrequent exacerbators. Both groups showed a decrease in rate of exacerbations during the 3-month study period. We planned such a trial duration because as our patients were undergoing pulmonary rehabilita- tion we needed to avoid possible bias on exacerbations by this treatment, as observed in a previous study (Riario-Sforza et al 2005). On the other hand, the ability of tiotropium to reduce the rate of COPD exacerbations has already been reported in a 6-month, multicenter, controlled study, which detected a signiﬁcantly lower number of exacerbations in tiotropium than in placebo-treated patients (Brusasco et al 2003). The nature of such an effect is not easy to explain, since tiotro- pium is a bronchodilating and not a antinﬂammatory agent, as are IC, which is known to reduce exacerbations (Phua and Macintyre 2007). A recent study evaluated the effect of tiotro- pium on inﬂammatory markers in sputum and in serum and on exacerbations in COPD: a 52% reduction in exacerbation frequency was observed, compared with no signiﬁcant change in inﬂammatory markers (Powrie et al 2007). 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