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Randomized Controlled Trial
. 2018 Jan 8:13:203-215.
doi: 10.2147/COPD.S145285. eCollection 2018.

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

Sally Singh  1 , François Maltais  2 , Lee Tombs  3 , William A Fahy  4 , Mitra Vahdati-Bolouri  4 , Nicholas Locantore  5 , John H Riley  4
Affiliations
Randomized Controlled Trial

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

Sally Singh et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

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: COPD; bronchodilators; exercise; hyperinflation.

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Conflict of interest statement

Disclosure SS was supported by the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East Midlands and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre. The views expressed are those of the author(s), and not necessarily those of the National Health Service (NHS), NIHR, or Department of Health. SS was also involved in the development of the endurance shuttle-walk test, and has served on advisory boards for AstraZeneca, GSK, and Novartis. FM has received fees for speaking at conferences sponsored by Boehringer Ingelheim, Grifols, and Novartis, research grants for participating in multicenter trials sponsored by AstraZeneca, Boehringer Ingelheim, GSK, and Novartis, and unrestricted research grants from Boehringer Ingelheim and Novartis. FM holds a Canadian Institutes of Health Research (CIHR)/GSK research chair on COPD. LT is a contingent worker on assignment at GSK. WAF, MVB, NL, and JHR are employees of GSK and hold stock/shares in GSK. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
LS mean absolute changes from baseline in trough IC/TLC ratio versus placebo at each clinic visit. Note: Error bars represent 95% CIs. Abbreviations: CI, confidence interval; IC, inspiratory capacity; LS, least squares; TLC, total lung capacity; UMEC, umeclidinium; VI, vilanterol.
Figure 2
Figure 2
Effect of UMEC/VI versus comparators on percentage change from baseline in IC/TLC ratio in different subpopulations at week 12. Notes: Error bars represent 95% CIs. Differences between UMEC/VI and comparators are statistically significant when these lines do not extend below 0. Abbreviations: CI, confidence interval; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IC, inspiratory capacity; ICS, inhaled corticosteroid; PBO, placebo; TLC, total lung capacity; UMEC, umeclidinium; VI, vilanterol.
Figure 3
Figure 3
Scatterplots of changes in hyperinflation parameters against changes in exercise endurance (A–C) and lung volume measurements (D–F) at Week 12. Abbreviations: EET, exercise endurance time; FEV1, forced expiratory volume in 1 second; IC, inspiratory capacity; RV, residual volume; TLC, total lung capacity.
See this image and copyright information in PMC

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