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Review
. 2018 Jan 24;19(1):18.
doi: 10.1186/s12931-018-0721-3.

Long-acting Bronchodilators Improve Exercise Capacity in COPD Patients: A Systematic Review and Meta-Analysis

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Free PMC article
Review

Long-acting Bronchodilators Improve Exercise Capacity in COPD Patients: A Systematic Review and Meta-Analysis

Fabiano Di Marco et al. Respir Res. .
Free PMC article

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Abstract

Background: We carried out a systematic review and meta-analysis with the aim to evaluate the efficacy of longacting bronchodilators on exercise capacity in COPD patients.

Methods: The endpoints were the efficacy of long-acting bronchodilators (altogether, and by single classes) vs. placebo in modifying endurance time (ET), inspiratory capacity (IC) and dyspnea during exercise, taking into consideration the outcomes according to different patients’ inclusion criteria and exercise methodology.

Results: Twenty-two studies were deemed eligible for analysis. Weighted mean increase in ET resulted of 67 s (95% CI ranges from 55 to 79). For isotime IC and dyspnea during exercise, weighted improvements were 195 ml (162–229), and − 0.41 units (− 0.56 to − 0.27), respectively. The increase in trough IC was 157 ml (138–175). We found a trend in favour of LAMA compared to LABA in terms of ET. In the 11 studies which reported a value of functional residual capacity > 120% as inclusion criterion, weighted mean increase in endurance time was 94 s (65 to 123); however we did not find any significant correlation between ET and mean trough IC (P: 0.593). The improvement of ET in the 5 studies using walking as exercise methodology resulted of 58 s (− 4 to 121).

Conclusions: Long-acting bronchodilators improve exercise capacity in COPD. The main effect of long-acting bronchodilators seems to be a increase of basal IC rather than a modification of dynamic hyperinflation during exercise. The efficacy in terms of endurance time seems higher in studies which enrolled patients with hyperinflation, with a similar efficacy on walking or cycling.

Background: We carried out a systematic review and meta-analysis with the aim to evaluate the efficacy of long-acting bronchodilators on exercise capacity in COPD patients.

Methods: The endpoints were the efficacy of long-acting bronchodilators (altogether, and by single classes) vs. placebo in modifying endurance time (ET), inspiratory capacity (IC) and dyspnea during exercise, taking into consideration the outcomes according to different patients’ inclusion criteria and exercise methodology.

Results: Twenty-two studies were deemed eligible for analysis. Weighted mean increase in ET resulted of 67 s (95% CI ranges from 55 to 79). For isotime IC and dyspnea during exercise, weighted improvements were 195 ml (162–229), and − 0.41 units (− 0.56 to − 0.27), respectively. The increase in trough IC was 157 ml (138–175). We found a trend in favour of LAMA compared to LABA in terms of ET. In the 11 studies which reported a value of functional residual capacity > 120% as inclusion criterion, weighted mean increase in endurance time was 94 s (65 to 123); however we did not find any significant correlation between ET and mean trough IC (P: 0.593). The improvement of ET in the 5 studies using walking as exercise methodology resulted of 58 s (− 4 to 121).

Conclusions: Long-acting bronchodilators improve exercise capacity in COPD. The main effect of long-acting bronchodilators seems to be a decrease of basal IC rather than a modification of dynamic hyperinflation during exercise. The efficacy in terms of endurance time seems higher in studies which enrolled patients with hyperinflation, with a similar efficacy on walking or cycling.

Keywords: Bronchodilator; COPD; Exercise.

Conflict of interest statement

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Competing interests

Fabiano Di Marco has received honoraria for lectures at national and international meetings from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Dompe, Guidotti/Malesci, GlaxoSmithKline, Menarini, Novartis, and Zambon. He has served as consultant for AstraZeneca, Chiesi Farmaceutici, Novartis, and Zambon. He has received financial support for research from Novartis, and Boehringer Ingelheim.

Pierachille Santus participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, Malesci, Guidotti, Mundipharma, Novartis, Zambon. He has received financial support for research from Chiesi, Boehringer Ingelheim and Almirall.

Denis O’Donnell has received research funding via Queen’s University from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline; and has served on speakers bureaus, consultation panels and advisory boards for Almirall, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Pfizer.

Kai-Michael Beeh declares no personal payments were received from any pharmaceutical entity in the past 5 years. The institution he represents has received compensation: 1) for services on advisory boards or consulting for Ablynx, Almirall, AstraZeneca, Berlin Chemie, Boehringer, Chiesi, Cytos, Mundipharma, Novartis, Pohl Boskamp, Zentiva; 2) for speaker activities in scientific meetings supported by Almirall, AstraZeneca, Berlin Chemie, Boehringer, Cytos, ERT, GSK, Novartis, Pfizer, Pohl Boskamp, Takeda; 3) for design and performance of clinical trials from Almirall, Altana/Nycomed, AstraZeneca, Boehringer, Cytos, GSK, Infinity, Medapharma, MSD, Mundipharma, Novartis, Parexel, Pearl Therapeutics, Pfizer, Revotar, Teva, Sterna, and Zentiva.

Francesco Blasi has received research grants from Bayer, Chiesi, Zambon, and Pfizer, congress lecture fees from AstraZeneca, Guidotti, Menarini, GSK, Chiesi, Pfizer, and Novartis, and consultancy fees from AstraZeneca, Menarini,Novartis, GSK, Zambon,Teva and Pfizer.

Stefano Centanni has received financial support for research from Novartis and Pfizer. He has served as a consultant for AstraZeneca, Novartis, Chiesi Farmaceutici, Boehringer Ingelheim, GlaxoSmithKline, Mundipharma, and Almirall.

Giovanni Sotgiu, Simone Dore, Maria Adelaide Roggi, and Lisa Giuliani declare no conflicts of interest.

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Figures

Fig. 1
Fig. 1
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram
Fig. 2
Fig. 2
Efficacy of long-acting bronchodilators on endurance time. I2 21.1% (95% CI 0–48.8%). Error bars represent 95% confidence intervals. †: study n. 1222.37; *: study n. 1222.38
Fig. 3
Fig. 3
Efficacy of long-acting bronchodilators on isotime inspiratory capacity. I2 1.2% (95% CI 0–42.8%). Error bars represent 95% confidence intervals. *: study n. 417
Fig. 4
Fig. 4
Efficacy of long-acting bronchodilators on dyspnea. I2 55.1% (95% CI 26.8–69.4%). Error bars represent 95% confidence intervals. For Ume/Vil †: study n. 1222.37; *: study n. 1222.38. For Olo †: study n. 418; *: study n. 417
Fig. 5
Fig. 5
Efficacy of different classes of long-acting bronchodilators tested at the approved dose for COPD treatment. Error bars represent 95% confidence intervals

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