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).

Objectives: To determine effects of tiotropium on pulmonary hyperinflation and exercise tolerance in symptomatic Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and 2 COPD patients who experienced inspiratory capacity decrease ≥100 mL during incremental and constant work rate treadmill exercise.

Methods: 22-week, randomized, double-blind, two-period cross-over study evaluated efficacy of once-daily tiotropium bromide (18 µg) versus placebo in GOLD 1 and 2 COPD patients. 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.

Measurements and Main Results: Study population comprised 48 GOLD 1 and 78 GOLD 2 patients. 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 following 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).

Conclusions: Resting and exercise hyperinflation was 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.