Effects of tiotropium on hyperinflation and treadmill exercise tolerance in mild to moderate chronic obstructive pulmonary disease.

Abstract

Bronchodilator therapy represents a potentially valuable therapeutic option to increase exercise tolerance and enhance lung function in mild to moderate chronic obstructive pulmonary disease (COPD). To determine effects of tiotropium on pulmonary hyperinflation and exercise tolerance in patients with symptomatic Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and 2 COPD who experienced inspiratory capacity decrease greater than or equal to 100 ml during incremental and constant work rate treadmill exercise. This 22-week, randomized, double-blind, two-period crossover study evaluated the efficacy of once-daily tiotropium bromide (18 μg) versus placebo in patients with GOLD 1 and 2 COPD. Primary endpoint was between-group (tiotropium vs. placebo) difference in inspiratory capacity at isotime (i.e., at the time the shortest test ended) during constant work rate treadmill exercise from baseline to the end of a 6-week treatment period. Key secondary endpoints included differences in exercise duration and exertional dyspnea. Safety was assessed by recording adverse events. Study population comprised 48 patients with GOLD 1 COPD and 78 patients with GOLD 2 COPD. Resting inspiratory capacity significantly improved with tiotropium versus placebo in the overall (P < 0.0001), GOLD 1 (P = 0.0183), and GOLD 2 (P < 0.0001) groups. Isotime inspiratory capacity was significantly enhanced during exercise in the overall (P = 0.0087) and GOLD 2 (P = 0.0494) groups after tiotropium versus placebo. Tiotropium versus placebo significantly enhanced exercise duration in the GOLD 2 group (P = 0.0070) but not in the GOLD 1 or overall patient groups. In the overall group, increase in exercise duration seen with tiotropium was well correlated with the increase in isotime inspiratory capacity (r = 0.463, P < 0.0001). Resting and exercise hyperinflation were ameliorated by bronchodilator therapy with tiotropium in the overall GOLD 1 plus 2 COPD group. Exercise tolerance was enhanced in GOLD 2, but not GOLD 1, COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01072396).