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

Koichiro Takahashi,1 Masaru Uchida,2 Go Kato,3 Ayako Takamori,4 Takashi Kinoshita,5 Makoto Yoshida,6 Ryo Tajiri,4 Keisuke Kojima,7 Hiroshi Inoue,8 Hiromi Kobayashi,9 Hironori Sadamatsu,1 Hiroki Tashiro,1 Masahide Tanaka,1 Shinichiro Hayashi,10 Atsushi Kawaguchi,4,11 Shinya Kimura,1 Naoko Sueoka-Aragane,1 Tomotaka Kawayama5 Saga-naïve COPD Physical Activity Evaluation (SCOPE) Study Investigator Group1Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan; 2Division of Internal Medicine, Japan Community Health Care Organization Saga Central Hospital, Saga, Japan; 3Division of Respiratory Medicine, Saga Prefectural Medical Center Koseikan, Saga, Japan; 4Clinical Research Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan; 5Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka, Japan; 7Division of Internal Medicine, Imari Arita Kyouritsu Hospital, Saga, Japan; 8Division of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan; 9Division of Respiratory Medicine, National Hospital Organization East Saga Hospital, Saga, Japan; 10Division of Internal Medicine, Kouhoukai Takagi Hospital, Fukuoka, Japan; 11Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, JapanCorrespondence: Koichiro TakahashiDivision of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, JapanEmail takahak@cc.saga-u.ac.jpBackground: 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.Keywords: chronic obstructive pulmonary disease, physical activity, long-acting muscarinic antagonist, long-acting beta 2 agonist