First-Line Treatment with Tiotropium/Olodaterol Improves Physical Activity in Patients with Treatment-Naïve Chronic Obstructive Pulmonary Disease

Background: Comparative effects on physical activity of mono and dual bronchodilators remain unclear in patients with treatment-naïve chronic obstructive pulmonary disease (COPD). We sought to compare the changes in physical activity before and after tiotropium and tiotropium/olodaterol treatment in treatment-naïve COPD patients. Methods: A prospective, multicenter, randomized, open-labeled, and parallel interventional study was conducted. Eighty Japanese patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks. Spirometry and dyspnea index were assessed, and COPD assessment test (CAT) and the 6-minute walk distance (6MWD) were conducted before and after treatment. Evaluation of physical activity was assessed by a triaxle accelerometer over a 2-week period before and after treatment. Results: There were no differences in the mean age (69.8 vs 70.4 years), body mass index (BMI) (22.5 vs 22.6 kg/m2) and mean % forced expiratory volume in 1 second (%FEV1) at baseline (61.5 vs 62.6%) between the two groups. Changes in FEV1 (mean±standard error, 242.8± 28.8 mL) and transient dyspnea index (TDI) (2.4± 0.3 points) before and after tiotropium/olodaterol treatment were greater than with tiotropium treatment (104.1± 31.9 mL, p< 0.01 and 1.5± 0.3, p=0.02, respectively). Changes in the duration of physical activity with 1.0– 1.5 metabolic equivalents (METs) estimated in the sedentary position following tiotropium/olodaterol treatment (− 38.7± 14.7 min) tended to be reduced more than with tiotropium treatment (− 4.6± 10.6 min) (p=0.06), although those with ≥ 2.0 METs numerically increased with both treatments (+10.8± 7.6 min for tiotropium/olodaterol vs +8.3± 7.6 min for tiotropium, p=0.82). Tiotropium/olodaterol treatment reduced the duration of physical activity with 1.0– 1.5 METs (regression coefficient, − 43.6 [95% CI − 84.1, − 3.1], p=0.04) in a multiple regression model adjusted for cofounding factors such as age, FEV1, total CAT scores, 6MWD, and TDI. Conclusion: This is the first study to report the impact of dual bronchodilator on physical activity in treatment-naïve COPD patients of Japanese with low BMI.