Research has established that persistent airflow limitation and dyspnea may diminish exercise capacity and physical activity in patients with COPD. According to a recent publication in the journal, Respiratory Research, in patients with COPD, the use of long-acting muscarinic antagonist (LAMA) and long-acting beta-2 agonist (LABA) combinations are more effective than monotherapy or placebo for most exercise capacity and physical activity outcomes.

Due to the significance of exercise capacity and physical activity on the quality of life (QoL) of patients with COPD, researchers conducted a systematic review and meta-analysis of double-blind, randomized, controlled trials to assess the effect of the combination of LAMA/LABA bronchodilators compared with placebo or LAMA or LABA monotherapy on the exercise capacity and physical activity outcomes.

The literature search was performed in the MEDLINE, Central, and Embase databases for articles published between January 1, 2012, and December 31, 2021. Eligible trials included patients aged 40 years or older who were diagnosed with COPD with a postbronchodilator forced expiratory volume at 1 second/forced vital capacity of less than 0.7.

Seventeen randomized, controlled, double-blind trials with 4,041 patients were included. Of those patients, 2,964 were treated with the LAMA/LABA combination, 1,901 with placebo, 1,070 with LAMA, and 755 with LABA.

Examination of these articles revealed that in an endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results compared with placebo, but not monotherapy, while in a 6-minute walking test, results favored LAMA/LABA over monotherapy in four studies but not over placebo in one study.

Additionally, LAMA/LABA combinations obtained better results than placebo in number of steps per day, decrease in percentage of inactive patients and daily activity–related energy expenditure, and better than monotherapy when measuring time spent on ≥1.0-1.5, ≥2.0, and ≥3.0 metabolic equivalents of task activities.

Limitations noted by the authors included differences among the studies on variables employed to measure physical activity. Additionally, in some analyses different LAMA/LABA combinations were compared with different LAMA or LABA monotherapies  and outcome evaluation times were different, ranging from 3 to 12 weeks. Moreover, statistical heterogeneity was elevated in some comparisons, which limited the validity and the generalizability of the findings.

“Despite these limitations, the use of LAMA/LABA consistently improves exercise capacity and physical activity compared with placebo or monotherapy in most outcomes and combinations analyzed. On the other hand, our study has the following strengths: a reasonable number of studies and patients available and their rigorous methodological quality, as none of the studies included showed high risk of bias in any item,” wrote the authors.

The authors concluded that their findings demonstrated LAMA/LABA combination therapy was superior to placebo and monotherapy with regard to evaluating exercise capacity and physical activity in patients with COPD in almost every comparison. The authors also indicated that enhancing physical activity and exercise capacity in patients with COPD might result in an improvement in QoL and diminish the burden of disease in this patient population.

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