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

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          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 β 2-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.

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          Most cited references 29

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          The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease.

          The purpose of this study was to develop an externally controlled, constant paced field walking test to assess endurance capacity in patients with chronic obstructive pulmonary disease (COPD). There were four objectives: (1) to develop a protocol; (2) to compare treadmill and shuttle walk tests of endurance capacity; (3) to examine the repeatability of the endurance shuttle walk test; and (4) to compare the sensitivity to pulmonary rehabilitation of endurance and incremental shuttle walk tests. The test was designed to complement the incremental shuttle walk test (ISWT) using the same 10 m shuttle course and an audio signal to control pace. The intensity of the field endurance test was related to a percentage of each patient's maximum field exercise performance assessed by the ISWT. A number of cassette tapes were pre-recorded with a range of audio signal frequencies to dictate walking speeds between 1.80 and 6.00 km/h. In the first limb of the study 10 patients with COPD (mean (SD) forced expiratory volume in one second (FEV1) 1.0 (0.36) 1, 35% predicted) performed three endurance shuttle walk tests (ESWTs) and three treadmill endurance tests. The walking speeds were calculated to elicit 75%, 85%, and 95% of each patient's maximum ISWT performance for the field tests and measured peak oxygen consumption for the treadmill tests. In a separate group of patients the repeatability of the ESWT at an intensity of 85% of the ISWT performance was evaluated. Finally, the ESWT (at the 85% intensity) and the ISWT were performed at the start of a five week control period and at the start and end of a seven week pulmonary rehabilitation programme in 21 patients with COPD (mean FEV1 0.80 (0.18) 1). The mean (SE) times achieved during the ESWT were 13.1 (2.3), 10.2 (2.5), and 5.3 (1.7) min for the walks at 75%, 85%, and 95% intensities, respectively. Patients tended to walk for longer on the treadmill than during the field tests at all intensities, but there were no significant differences between the end of test heart rates or Borg ratings of breathlessness or perceived exertion. Following one practice ESWT at the 85% intensity, the mean difference and limits of agreement (2SD) between tests 2 and 3 was +15 (42) s (p > 0.05). There was no significant change in performance on either test following the five week control period prior to rehabilitation. Following rehabilitation the ESWT duration increased by 160 (24)% and the ISWT distance increased by 32 (11)% (effect sizes 2.90 and 0.41, respectively). The ESWT was simple to perform, acceptable to all patients, and exhibited good repeatability after one practice walk. The test showed major improvement following rehabilitation and was more sensitive to change than the field test of maximal capacity.
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            Reference values for residual volume, functional residual capacity and total lung capacity. ATS Workshop on Lung Volume Measurements. Official Statement of The European Respiratory Society.

             P Quanjer,  J Stocks (1995)
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              Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation.

              Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation, little is known about its relation to daily physical activity. To analyze the contribution of dynamic hyperinflation, exercise tolerance, and airway oxidative stress to physical activity in patients with COPD. In a cross-sectional study, we included 110 patients with moderate to very severe COPD. Daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients performed the 6-minute walk test, incremental exercise test with measurement of breathing pattern and operating lung volumes, and constant-work rate test at 75% of maximal work rate. Using the GOLD stage and BODE index, we determined arterial blood gases, lung volumes, diffusing capacity, and biomarkers in exhaled breath condensate. Daily physical activity was lower in the 89 patients who developed dynamic hyperinflation than in the 21 who did not (n =161 [SD 70] vs. n = 288 [SD 85] VMU; P = 0.001). Physical activity was mainly related to distance walked in 6 minutes (r = 0.72; P = 0.001), Vo(2) (r = 0.63; P = 0.001), change in end-expiratory lung volume during exercise (r = -0.73; P = 0.001), endurance time (r = 0.61; P = 0.001), and 8-isoprostane in exhaled breath condensate (r = -0.67; P = 0.001). In a multivariate linear regression analysis using VMU as a dependent variable, dynamic hyperinflation, change in end-expiratory lung volume, and distance walked in 6 minutes were retained in the prediction model (r(2) = 0.84; P = 0.001). Daily physical activity of patients with COPD is mainly associated with dynamic hyperinflation, regardless of severity classification.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2018
                08 January 2018
                : 13
                : 203-215
                Affiliations
                [1 ]Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK
                [2 ]Centre de Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, QC, Canada
                [3 ]Precise Approach Ltd, London, UK;
                [4 ]GSK, Stockley Park West, Uxbridge, UK;
                [5 ]GSK, King of Prussia, PA, USA
                Author notes
                Correspondence: Sally Singh, Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK, Tel +44 116 250 2350, Email sally.singh@ 123456uhl-tr.nhs.uk
                Article
                copd-13-203
                10.2147/COPD.S145285
                5764300
                © 2018 Singh et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                hyperinflation, bronchodilators, exercise, copd

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