day s on treatment ** p<0.001 vs. placebo Figure 1a Mean trough FEV1 response of active treatment groups above placebo (patients concurrently using ICS). Tiotropium or salmeterol plus treatment with ICS for COPD Tiotrop ium Salmeterol Tiotrop ium Salmeterol 140 120 mL 100 80 60 mL 250 200 150 100 ** ** 15 + ** ** 1 ++ ** ** 15 ** ** 57 ++ ** ** 57 ** ** 113 ++ ** ** 113 ** ** 169 ++ ** ** 169 day s on treatment ** p<0.001 vs. placebo + p<0.05,++ p<0.001, tiotropium vs. salmeterol Figure 1b Mean peak FEV1 response of active treatment groups above placebo (patients concurrently using ICS). Health status responses Patients treated with ICS Health status, as quantified by the change in SGRQ total score after 169 days on treatment, improved sig- nificantly in patients on ICS treated with tiotropium (–3.27 + 1.22 vs placebo; p < 0.01), but not in patients receiving salmeterol (–1.12 + 1.21; p > 0.05 vs placebo) (Table 4a). Although only patients receiving tiotropium experienced a statistically significant improvement in SGRQ vs placebo, there was no significant difference in SGRQ total score after 6 months between the tiotropium and salmeterol groups. When the change in SGRQ total score from baseline is considered, only the tiotropium group showed an improvement equal to or greater than the accepted minimally important clinical difference of 4 units (Figure 3). Patients not treated with ICS In patients without concurrent ICS treatment, the improvement in health status achieved by active study drugs after 169 days of treatment did not reach the level of signiﬁcance (Table 4a). International Journal of COPD 2007:2(2) Exacerbations Patients treated with ICS In patients concurrently treated with ICS there was a trend towards reduced exacerbation frequency and number of exacerbation days experienced by the tiotropium and salme- terol groups compared with the placebo group (Table 3b). Fewer patients in both the tiotropium and salmeterol groups experienced 1 or more exacerbations during the 6 months treatment period compared with placebo (40% receiving tiotropium or salmeterol, 45% receiving placebo), although the differences were not statistically signiﬁcant (Table 3b). Patients not treated with ICS In patients not receiving concurrent treatment with ICS (Table 4b), only tiotropium use was associated with a signiﬁcant reduction in the number of COPD exacerbations (p < 0.05) and in the number of exacerbation days (p < 0.05). The reduction in the proportion of patients experiencing an exacerbation of COPD approached statistical signiﬁcance (p = 0.08). Salmeterol use was associated with a signiﬁcant numerical reduction in exacerbations in this subgroup of patients (p = 0.81). 161