Long-acting bronchodilators improve exercise capacity in COPD patients: a systematic review and meta-analysis

Fabiano Di Marco,Francesco Blasi,Lisa Giuliani,Simone Dore,Kai-Michael Beeh,Denis E O'Donnell,Giovanni Sotgiu,Pierachille Santus,Maria Adelaide Roggi,Stefano Centanni

doi:10.1186/s12931-018-0721-3

Abstract

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. 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. 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). 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.

Highlights

We carried out a systematic review and meta-analysis with the aim to evaluate the efficacy of longacting bronchodilators on exercise capacity in chronic obstructive pulmonary disease (COPD) patients
Despite the availability of studies on LABA, Long-acting muscarinic antagonists (LAMA), and Inhaled steroids (ICS)/LABA or LABA/LAMA Fixed-dose combinations (FDC) on exercise capacity, evidence for the efficacy of bronchodilators in enhancing the exercise capacity of patients with COPD is sometimes contradictory [20], with, for instance, a recent trial which failed to demonstrate the superiority of a LABA/LAMA FDC vs. placebo [21]; current literature is characterized by a large heterogeneity of studies, due to differences in terms of inclusion criteria, and/or exercise methodology
Search strategy We selected randomized controlled studies (RCTs) focused on the efficacy of long-acting bronchodilators (i.e.: LABA, LAMA, LABA/ICS, and LABA/LAMA FDCs) on exercise capacity in COPD patients based on endurance time with high-intensity constant-load performed on a cycle or treadmill and whose duration was longer than one week

Summary

Introduction

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. Di Marco et al Respiratory Research (2018) 19:18 bodies, e.g. the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), no label claim for improvements in exercise capacity has been granted this far [10, 11]. This approach allows an evaluation of symptoms intensity (e.g., dyspnea and leg effort), or physiological variables (e.g., inspiratory capacity, IC, assessment of dynamic hyperinflation) at a standardized time (isotime), which has been proved very useful in identifying the underlying physiological mechanisms responsible for modifications in exercise tolerance induced by a particular intervention [12]. Despite the availability of studies on LABA, LAMA, and ICS/LABA or LABA/LAMA FDCs on exercise capacity, evidence for the efficacy of bronchodilators in enhancing the exercise capacity of patients with COPD is sometimes contradictory [20], with, for instance, a recent trial which failed to demonstrate the superiority of a LABA/LAMA FDC vs. placebo [21]; current literature is characterized by a large heterogeneity of studies, due to differences in terms of inclusion criteria (unselected patients vs. COPD patients with evidence of hyperinflation), and/or exercise methodology (cycling vs. walking, cycle or treadmill ergometer vs. shuttle walking test)

Methods

Results

Conclusion