Relationship between exercise endurance and static hyperinflation in a post hoc analysis of two clinical trials in patients with COPD

Abstract

Sally Singh,1 François Maltais,2 Lee Tombs,3 William A Fahy,4 Mitra Vahdati-Bolouri,4 Nicholas Locantore,5 John H Riley4 1Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK; 2Centre de Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, QC, Canada; 3Precise Approach Ltd, London, UK; 4GSK, Stockley Park West, Uxbridge, UK; 5GSK, King of Prussia, PA, USA Background: Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD). However, their relationship remains uncertain. A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (Umec) and long-acting β2-agonist vilanterol (Vi) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD. Methods: Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to Umec/Vi 62.5/25 µg, Umec 62.5 µg, Vi 25 µg, or placebo for 12 weeks. Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured. In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers. Results: After 12 weeks, Umec/Vi and Umec and Vi showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]). Umec/Vi showed significant improvements versus Umec and Vi in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]). Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC. Umec/Vi showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005). There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point. Conclusion: Although the dual bronchodilator Umec/Vi demonstrated greater improvements in static hyperinflation markers than Umec or Vi and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance. Keywords: bronchodilators, COPD, exercise, hyperinflation

Keywords

• bronchodilators
• COPD
• exercise
• hyperinflation