Asthma-COPD Overlap: Effectiveness of Long-Acting Muscarinic Antagonists

How effective are long-acting muscarinic antagonists in treating patients with asthma-COPD overlap? A systematic review and meta-analysis examined the research.

A long-acting muscarinic antagonist (LAMA) significantly enhances lung function and lowers rescue medicine use in patients with overlapping asthma and chronic obstructive pulmonary disease (COPD), according to findings of a recent systemic review and meta-analysis published in Clinical Immunology.

LAMA is the foundation of COPD treatment and has been shown to play a role in the treatment of asthma. Because the symptoms of asthma-COPD overlap (ACO) are more severe than those of asthma or COPD alone, LAMA sometimes is prescribed. But the therapeutic benefit of LAMA in ACO has not yet been confirmed.

Researchers based in Shaanxi, China, conducted a systematic search of PubMed, Embase, the Cochrane Library, and for studies conducted up to November 2021 on treatment of ACO. Of 1833 trials identified in the initial search, 39 were reserved for more detailed assessment, with 6 randomized controlled trials (RCTs) involving 1151 participants met the inclusion criteria. In all, data from 669 patients were allocated to the LAMA treatment groups and 518 to control groups.

Overall, the review found that use of LAMA by those with ACO was associated with significant improvements in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) as well as significant reductions in daily rescue medicine use.

A total of 5 RCTs (1101 patients) yielded data on changes in FEV1. Compared with the control group, patients receiving LAMA treatment had significantly increased FEV1 (weighted mean difference [WMD], 98.31 mL; 95% CI, 94.32-102.30 mL; P <.00001).

Changes in FVC were assessed in 4 RCTs (847 patients). Compared with the control cohort, LAMA therapy users saw significant improvement in FVC (WMD, 128.00 mL; 95% CI, 121.89-134.12 mL; P <.00001).

Data on PEF were pulled from 3 RCTs (764 patients). LAMA use was linked to a significant increase in PEF (WMD, 20.60 L/min; 95% CI, 19.90-21.29 L/min; P <.00001), compared with lung function data from the control groups.

Data from 2 trials (715 patients) showed that LAMA treatment cut rescue medicine use significantly compared with controls (WMD, −0.67 puffs/day; 95% CI, −1.11 to −0.23 puffs/day; P =.003).

No statistically significant difference was observed between the 2 groups in risk of exacerbation (relative risk, 0.79; 95% CI, 0.48-1.30; P =.34), change in Asthma Control Test scores (WMD, 1.90; 95% CI, −1.61-5.41; P =.29), or change in COPD Assessment Test scores (WMD, −1.84; 95% CI, −4.97-1.30; P =.25).

Limitations of the analysis included some trials with small sample sizes, potential confounding between study variables that could have affected outcomes and results, and a patient-level meta-analysis producing results that should be deemed provisional.

“Since clinical studies have traditionally excluded patients with ACO, there is a lack of knowledge about the best evidence-based management of this population,” the authors noted. “This meta-analysis establishes that the LAMA treatment may be critical in patients with overlapping asthma and COPD,” they asserted.


Qin J, Wang G, Han D. Benefits of LAMA in patients with asthma-COPD overlap: a systematic review and meta-analysis. Clin Immunol. Published online March 25, 2022. doi:10.1016/j.clim.2022.108986