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

Int J Chron Obstruct Pulmon Dis. 2020 Sep 14:15:2115-2126. doi: 10.2147/COPD.S268905. eCollection 2020.

Abstract

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.

Keywords: chronic obstructive pulmonary disease; long-acting beta 2 agonist; long-acting muscarinic antagonist; physical activity.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-2 Receptor Agonists* / therapeutic use
  • Aged
  • Benzoxazines* / therapeutic use
  • Bronchodilator Agents / therapeutic use
  • Double-Blind Method
  • Drug Combinations
  • Exercise
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Tiotropium Bromide* / therapeutic use
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Benzoxazines
  • Bronchodilator Agents
  • Drug Combinations
  • olodaterol
  • Tiotropium Bromide

Grants and funding

This study was financially supported by Nippon Boehringer Ingelheim Co., Ltd. as an independent investigator study.