Additional file 1: Supplementary Table 1. Patients with FEV1 decline or SGRQ increase 6, 12, 18, 24, 30, 36, 42, and 48 months after the first confirmed FEV1 decline or SGRQ increase by GOLD 2, GOLD 3, and GOLD 4. Supplementary Table 2. Patients with FEV1 decline or SGRQ deterioration in the total UPLIFT population 6, 12, 18, 24, 30, 36, 42, and 48 months after the initial unconfirmed FEV1 decline or SGRQ deterioration. Supplementary Table 3. Risk of exacerbation or death by unconfirmed clinically important deterioration status at Months 6 and 12. Supplementary Table 4. Risk of exacerbation or death by confirmed clinically important deterioration status at Month 6 in the tiotropium and placebo arms, and at Month 12 in the tiotropium and placebo arms and total population. Supplementary Table 5. Risk of exacerbation or death by confirmed clinically important deterioration status calculated using clinically important deterioration event as a time-varying covariate. Supplementary Table 6. Patients with FEV1 decline or SGRQ deterioration in the total UPLIFT population 6, 12, 18, 24, 30, 36, and 42 months after the initial confirmed FEV1 decline or SGRQ deterioration: Tiotropium and placebo. Supplementary Table 7. Timing of FEV1 decline and SGRQ deterioration relative to each other in the tiotropium and placebo arms. Supplementary Figure 1. Time to first event for (A) trough FEV1 decline ≥100 mL, (B) SGRQ increase ≥4 units and (C) moderate/severe exacerbation.