Effect of Bronchodilation, Exercise Training, and Behavior Modification on Symptoms and Physical Activity in Chronic Obstructive Pulmonary Disease.

RATIONALE: Bronchodilation and exercise training (ExT) improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD); however, behavior modification is required to impact daily physical activity (PA).

OBJECTIVES

To assess whether tiotropium/olodaterol, with or without ExT, would improve exercise endurance time (EET) and PA compared with placebo in patients participating in a self-management behavior-modification (SMBM) program.

METHODS

This was a 12-week, randomized, partially double-blind, placebo-controlled, parallel-group trial in patients with COPD (PHYSACTO; NCT02085161). All patients were enrolled into SMBM and randomized 1:1:1:1 to once-daily placebo, tiotropium 5 μg, tiotropium/olodaterol 5/5 μg, or tiotropium/olodaterol 5/5 μg plus 8 weeks ExT. EET, measured by endurance shuttle walk test after 8 weeks, was the primary endpoint. Additional endpoints assessed downstream effects on PA (measured via accelerometry), and activity-related dyspnea and difficulty (using validated patient-reported questionnaires).

MEASUREMENTS AND MAIN

RESULTS

SMBM plus tiotropium/olodaterol, with or without ExT, significantly improved EET at Week 8 versus SMBM plus placebo (treatment ratio vs. placebo: with ExT, 1.46; 95% confidence interval, 1.20-1.78; P = 0.0002; without ExT, 1.29; 95% confidence interval, 1.06-1.57; P = 0.0109). No significant increases in steps per day from baseline were observed over SMBM plus placebo at Week 12 (increase of 1,098) when other therapies were added. Adding tiotropium/olodaterol, with or without ExT, to SMBM reduced activity-related dyspnea versus placebo, whereas adding tiotropium/olodaterol plus ExT reduced activity-related difficulty.

CONCLUSIONS

Tiotropium/olodaterol, with or without ExT, improved EET in patients with COPD taking part in an SMBM program. Combination bronchodilation, with or without ExT, did not provide additional increases in objective PA compared with SMBM alone but did reduce PA-related dyspnea and difficulty. Clinical trial registered with www.clinicaltrials.gov (NCT02085161).