Tiotropium and exercise training in COPD patients: Effects on dyspnea and exercise tolerance

Nicolino Ambrosino1, Katia Foglio2, Gianni Balzano2, Pier Luigi Paggiaro1, Patrizia Lessi3, Steven Kesten3 On behalf of the Tiotropium Multicentric Italian Study Group1Cardio-Thoracic Department, University Hospital, Pisa, Italy; 2S Maugeri Foundation IRCCS, Italy; 3Boehringer Ingelheim, GmbH, Milan, ItalyBackground: Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD). Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients.Aim: To determine whether tiotropium enhances the effects of exercise training in patients with COPD.Design: Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study.Setting: Twelve Italian Pulmonary Units practicing pulmonary rehabilitation.Patients and intervention: Two hundred thirty four COPD patients (196 males; mean age: 67.4 ± 7.6; forced expiratory volume at 1 second (FEV1): 41.4 ± 13.0% predicted) were randomised to tiotropium 18 μg or placebo inhalation capsules taken once daily. Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week.Measurements: Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St. George’s Respiratory Questionnaire (SGRQ).Results: Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days. At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo. Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort. Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p