UPLIFT (Understanding Potential Long-Term Improvements in Function with Tiotropium), a 4-yr trial of tiotropium in chronic obstructive pulmonary disease, allowed for assessment of smoking status on long-term responses to maintenance bronchodilator therapy.

5,993 patients were randomised (tiotropium/placebo). Lung function, St George's Respiratory Questionnaire, exacerbations and adverse events were followed. Patients were characterised as continuing smokers (CS), continuing ex-smokers (CE), or intermittent smokers (IS) based on self-reporting smoking behaviour.

60%, 14% and 26% of patients were CE, CS and IS, respectively. The rate of forced expiratory volume in 1 s (FEV₁) decline for placebo patients was most rapid in CS (-51±4, -36±2 and -23±2 mL·yr⁻¹ in CS, IS, and CE, respectively). Tiotropium did not alter FEV₁ decline, but was associated with significant improvements in pre- and post-bronchodilator FEV₁ over placebo that persisted throughout the 4-yr trial for each smoking status (pre-bronchodilator: 125, 55 and 97 mL at 48 months in CS, IS and CE, respectively; p≤0.0003). Tiotropium reduced exacerbation risk in CS (HR (95%CI) 0.81 (0.68–0.97)), in CE (0.86 (0.79–0.93)) and trended towards significance in IS (0.89 (0.80–1.01)). At 4 yrs, St George’s Respiratory Questionnaire for tiotropium patients improved the most in CS (-4.62 units, p = 0.0006) and the least in IS (-0.54 units, p = 0.55), compared with control.

Tiotropium provided long-term benefits irrespective of smoking status, although differences among categories were observed.