In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting bronchodilators improved exercise capacity, according to the results of a systematic review and meta-analysis published in Respiratory Research.
The primary end point was an assessment of the efficacy of all long-acting bronchodilators (long-acting beta-2 agonists [LABA], long-acting muscarinic antagonists [LAMA], LABA/inhaled corticosteroids [ICS] fixed-dose combinations [FDCs], and LABA/LAMA FDCs) vs placebo in modifying exercise endurance time. Secondary end points included the role played by the above-mentioned agents in inspiratory capacity and dyspnea, as well as a comparison among the various drug classes used to treat COPD with respect to endurance time, dyspnea, and inspiratory capacity.
Of 88 possibly relevant studies, a total of 22 were eligible for qualitative and quantitative analysis. Six studies assessed the efficacy of LABAs, 10 studies assessed LAMAs, 3 studies assessed LABA/ICS FDCs, and 3 studies assessed LABA/LAMA FDCs. Meanwhile, 5 of the 22 studies used another active drug as a control in the experimental arm.
The mean duration of treatment was 8.9±15.9 weeks. The total sample size comprised 2898 participants, approximately 65% of whom were men. Mean patient age was 62.9 years.
A weighted mean increase in endurance time of 67 seconds (95% CI, 55-79 s) was observed in participants following exposure to long-acting bronchodilators. Regarding the role played by long-acting bronchodilators on isotime inspiratory capacity and dyspnea during exercise, weighted mean improvements were 195 mL (95% CI, 162-229 mL) and –0.41 units (95% CI, –0.56 to –0.27 units), respectively. The increase in trough inspiratory capacity was 157 mL (95% CI, 138-175 mL).
A trend in favor of LAMA vs LABA was shown with respect to endurance time. Among the 11 studies reporting a value of functional residual capacity >120% as an inclusion criterion, the weighted mean increase in endurance time was 94 seconds (95% CI, 65-123 s). No significant link between endurance time and mean trough inspiratory capacity was observed (P =.593).
In the subgroup of 5 studies that used walking as exercise methodology, the weighted mean change in endurance time following long-acting bronchodilator exposure was 58 seconds (95% CI, –4 to 121 s, computed on 5 treatment arms), compared with 68 seconds (95% CI, 56-79 s, computed on 29 treatment arms) in the studies that used a cycle ergometry.
The investigators concluded that the mean effect of long-acting bronchodilators in patients with COPD appears to be a decrease in basal inspiratory capacity rather than a modification of dynamic hyperinflation during exercise. Efficacy in terms of endurance time appeared higher in studies that enrolled patients with hyperinflation, with a similar efficacy on walking or cycling. The ongoing challenge for clinicians is to convert this benefit into increased habitual physical activity in patients with COPD.
Di Marco F, Sotgiu G, Santus P, et al. Long-acting bronchodilators improve exercise capacity in COPD patients: a systematic review and meta-analysis. Respir Res. 2018;19:18.