Efficacy of tiotropium and indacaterol monotherapy and their combination on dynamic lung hyperinflation in COPD: a random open-label crossover study

Abstract

Background and objective: The difference in efficacy of long-acting muscarinic antagonists (LAMAs) and long-acting β₂-agonists (LABAs) for dynamic lung hyperinflation (DLH) in COPD is unclear. The purpose of this study was to elucidate the difference in efficacy of LAMA and LABA alone and the combination thereof for DLH.

Subjects and methods: Thirty stable patients were enrolled and randomly divided into two groups following baseline measurements. One group was treated with 5 μg tiotropium (Respimat inhaler) for 4 weeks following a 4-week treatment with 150 μg indacaterol, while the other group was treated with indacaterol for 4 weeks following a 4-week treatment with tiotropium. For both groups, these treatments were followed by a combination of the two drugs for 4 weeks. Pulmonary function tests, including DLH evaluated by metronome-paced incremental hyperventilation and exercise tolerance evaluated by the shuttle-walk test, were performed at the end of each treatment period.

Results: In total, 23 patients completed this study. Both tiotropium and indacaterol alone significantly increased forced expiratory volume in 1 second, exercise tolerance, and improved health status. Tiotropium significantly improved DLH, but indacaterol did not. The combination therapy resulted in further improvements in lung function and exercise tolerance, but not in DLH.

Conclusion: The efficacy of tiotropium in inhibiting DLH following metronome-paced incremental hyperventilation may be superior to that of 150 μg indacaterol, although the effects on airflow obstruction were the same, and the combination therapy showed further improvement in airflow obstruction, but not in DLH.

Keywords: COPD; bronchodilator agents; clinical respiratory medicine; quality of life; respiratory function tests.

Figure 1

Effects of tiotropium (Tio) and indacaterol (Ind) alone and the combination thereof. Notes: Effect on inspiratory capacity (IC) at rest (IC_rest) and IC following metronome-paced incremental hyperventilation at rates of 20, 30, and 40 breaths/min (IC₂₀, IC₃₀, and IC₄₀, respectively). Data expressed as mean ± standard error of mean. *P<0.05, **P<0.01 vs baseline; ^#P<0.05, ^##P<0.01 vs Ind.

Figure 2

Effects of tiotropium (Tio) and indacaterol (Ind) alone and the combination of thereof. Notes: Effect on changes in IC following metronome-paced incremental hyperventilation at rates of 20, 30, and 40 breaths/min (%Ch. ΔIC₂₀, IC₃₀, and IC₄₀, respectively) from IC at rest. Data expressed as mean ± standard error of mean. *P<0.05 vs baseline, ^#P<0.05 vs Ind. Abbreviations: IC, inspiratory capacity; IC_rest, resting IC; IC₂₀, IC at 20 breaths/min; ΔIC₂₀, change in IC from IC_rest to IC₂₀; IC₃₀, IC at 30 breaths/min; ΔIC₃₀, change in IC from IC_rest to IC₃₀; IC₄₀, IC at 40 breaths/min; ΔIC₄₀, change in IC from IC_rest to IC₄₀.