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Randomized Controlled Trial
. 2025 Jan;167(1):98-111.
doi: 10.1016/j.chest.2024.05.051. Epub 2024 Aug 21.

The Responsiveness of Exercise Tests in COPD: A Randomized Controlled Trial

Theresa C Harvey-Dunstan  1 , Molly M Baldwin  2 , Ruth Tal-Singer  3 , Matthew Allinder  3 , Michael I Polkey  4 , Alan Hamilton  5 , Matthew Richardson  1 , Sarah A Edwards  1 , Michael C Steiner  2 , Mike D Morgan  2 , Sally J Singh  6 ; COPD/MAP Consortium
Affiliations
Randomized Controlled Trial

The Responsiveness of Exercise Tests in COPD: A Randomized Controlled Trial

Theresa C Harvey-Dunstan et al. Chest. 2025 Jan.

Abstract

Background: COPD is characterized by reduced exercise tolerance, and improving physical performance is an important therapeutic goal. A variety of exercise tests are commonly used to assess exercise tolerance, including laboratory and field-based tests. The responsiveness of these various tests to common COPD interventions is yet to be compared, but the results may inform test selection in clinical and research settings.

Research question: What exercise test possesses the greatest sensitivity to change from before to after intervention in patients with COPD?

Study design and methods: One hundred fifty-four patients with symptomatic COPD were recruited and randomized (2:1:1) to 6 weeks of long-acting muscarinic antagonist, pulmonary rehabilitation (PR), or usual care. Before and after intervention, participants performed an incremental cycle exercise test and constant work rate cycle test (CWRCT), incremental shuttle walk test and endurance shuttle walk test (ESWT), 6-min walk test, and 4-m gait speed test.

Results: One hundred three participants (mean ± SD age, 67 ± 8 years; 75 male participants [73%]; FEV1, 50.6 ± 16.8% predicted) completed the study. Significant improvements in the incremental cycle exercise test, CWRCT, incremental cycle exercise test, ESWT, and 6-min walk test results were observed after PR (P < .05), with the greatest improvements seen in the constant work rate protocols (percentages change: CWRCT, 42%; ESWT, 41%).

Interpretation: The ESWT and CWRCT seemed to be the most responsive exercise test protocols to long-acting muscarinic antagonist and PR therapy. The magnitude of change was much greater after a program of rehabilitation compared with bronchodilator therapy.

Clinical trial registry: International Standard Randomised Controlled Trial Number (ISRCTN): No. 64759523; URL: https://www.isrctn.com/ISRCTN64759523.

Keywords: COPD; exercise testing; outcome measure; pulmonary rehabilitation; responsiveness.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: R. T.-S. is a retiree and shareholder of GlaxoSmithKline since 2019. M. A. is a former employee of GlaxoSmithKline. A.H is a former employee of Boehringer Ingelheim (Canada) Ltd. M. C. S reports personal fees and non-financial support from Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work. None declared (T. C.H.-D., M. M. B, M. I. P, M. R, S. A. E, M. D. M, S. J. S).

Figures

Figure 1
Figure 1
Diagram showing visit and testing schedule. 4MGS = 4-m gait speed; 6MWT = 6-min walk test; CWRCT = constant work rate cycle test; ESWT = endurance shuttle walk test; ICET = incremental cycle exercise test; ISWT = incremental shuttle walk test; LAMA = long-acting muscarinic antagonist; PR = pulmonary rehabilitation; SAMA = short-acting muscarinic antagonist; UC = usual care.
Figure 2
Figure 2
Flow diagram showing progress of participants through the trial. AECOPD = acute exacerbation of COPD; CVS = cardiovascular system; DNA = did not attend; EID = exercise-induced desaturation; LAMA = long-acting muscarinic antagonist; MSK = musculoskeletal; PFT = pulmonary function test; PR = pulmonary rehabilitation; UC = usual care; V = visit.
Figure 3
Figure 3
A-D, Graphs showing the repeatability of the ICET (A), ISWT (B), 6-min walk test (C), and 4MGS test (D). Solid blue line represents mean change in test performance between the first and second test. Dashed blue lines represent upper and lower (95% CI) limits, with gray dotted lines representing the precision of these limits (95% CI of limits). 4MGS = 4-m gait speed; 6MWT = 6-min walk test; ICET = incremental cycle exercise test; ISWT = incremental shuttle walk test; PPO = peak power output; Tlim = time to limitation.
Figure 4
Figure 4
A, B, Bar graphs showing the percentage improvement (A) and Cohen d effect size (B) for exercise tests after bronchodilation (LAMA), PR, and UC. 4MGS = 4-m gait speed; 6MWT = 6-min walk test; CWRCT = constant work rate cycle test; ESWT = endurance shuttle walk test; ICET = incremental cycle exercise test; ISWT = incremental shuttle walk test; LAMA = long-acting muscarinic antagonist; PPO = peak power output; PR = pulmonary rehabilitation; Tlim = time to limitation; UC = usual care; V˙O2peak = peak oxygen uptake.
Figure 5
Figure 5
A, B, Graphs showing sample size (parallel group) and power plots using individual exercise test effect sizes for LAMA (A) and PR (B). The square points represent the actual power of the exercise tests in the study based on the given sample size and calculated effect size, Cohen d. aThe 4MGS, 6MWT, and ISWT points in the LAMA plot overlap, and only the ISWT point is seen. b4MGS, 6MWT, and ISWT curves are missing in the LAMA plot because of the extremely high sample sizes needed for power. c4MGS curve is missing in the PR plot because of extremely high sample sizes needed for power. 4MGS = 4-m gait speed; 6MWT = 6-min walk test; CWRCT = constant work rate cycle test; ESWT = endurance shuttle walk test; ICET = incremental cycle exercise test; ISWT = incremental shuttle walk test; LAMA = long-acting muscarinic antagonist; PR = pulmonary rehabilitation.
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