This study evaluated whether the effect of tiotropium on the change in trough forced expiratory Volume in 1 s (FEV(1)), vs. placebo, is affected by smoking status. In a 3-month, double-blind Study in 31 centres in Portugal, 311 (289 completed) patients were randomised to tiotropium 18 mu g once daily or placebo. Baseline mean (standard deviation (SD)) FEV(1) was 1.11 (0.39) 1 in the tiotropium group and 1.13 (0.39) 1 in the placebo group. Patients had an average smoking history of 55 (25.7) pack-years; 80 (26%) were smokers and 224 (74%) were ex-smokers. The primary end-point was change in morning pre-dose (i.e. trough) FEV(1) after 12 weeks. Trough FEV(1) at 12 weeks was significantly improved with tiotropium vs. placebo: the difference in means was 102 ml, P = 0.0011 95% confidence interval (0) (41, 164). The difference in means in smokers was 138 ml, P = 0.0105, CI (32, 244); in ex-smokers it was 66 ml, P = 0.0375, Cl (3, 129). The difference between smokers and ex-smokers was not statistically significant (P = 0.6982) and may be due to greater variability and differences in disease severity. The significant improvement in lung function in patients treated with tiotropium vs. placebo in both smokers and ex-smokers suggests that tiotropium is an effective and well-tolerated therapy in chronic obstructive Pulmonary disease (COPD), regardless of smoking status. (C) 2007 Elsevier Ltd. All rights reserved.