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Macrolides for asthma: A systematic review and meta-analysis of randomized trials
Leonardo M Ologundudu1, Melanie M Wong2, Nazmul Islam3
1Evidence in Allergy Group, McMaster University, Hamilton, Ontario, Canada; Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Background:
The benefits and harms of using macrolides for asthma remain unclear.
Objective:
As part of upcoming Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters guidelines addressing severe asthma, we systematically reviewed the efficacy and safety of macrolides for asthma.
Methods:
We systematically searched MEDLINE, Embase, and CENTRAL to April 12, 2025, for randomized trials comparing macrolides with placebo or standard care for asthma. Paired reviewers independently screened records and extracted data. Individual patient-level data in random effects analysis of covariance models addressed asthma control and asthma-related quality of life. Random effects meta-analyses addressed severe exacerbations and harms. We used the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate certainty of evidence. Our study protocol is registered in PROSPERO (CRD42023408677).
Results:
Our meta-analysis comprised 19 trials enrolling 1825 participants. Compared with placebo, macrolides improve asthma control (6-item Asthma Control Questionnaire; score range 0-6, lower better; between-group mean difference: -0.23 [95% CI -0.32 to -0.13]; 40.6% vs 21.6% improving by minimally important difference of 0.5 point; high certainty), likely reduce severe exacerbations (incidence rate ratio: 0.75 [95% CI 0.57 to 0.98]; rate difference: 0.26 fewer events per patient-year [95% CI 0.45 to 0.02 fewer events]; moderate certainty), and likely modestly improve quality of life (Asthma Quality of Life Questionnaire; score range 1-7, higher better; mean difference: 0.11 [95% CI -0.06 to 0.29]; 47.6% vs 42.4% improving by minimally important difference of 0.5 points; moderate certainty) with little to no effect on serious adverse events and mortality (high certainty). Relative effects were similar among patients with type 2 high inflammation versus type 2 low inflammation asthma.
Conclusions:
Macrolides likely reduce severe exacerbations and improve asthma control and quality of life with little to no difference in serious harms among patients with type 2 high inflammation or type 2 low inflammation asthma.
Insights
Macrolides improve asthma control and quality of life while reducing severe exacerbations. This systematic review found these benefits with little to no increase in serious harms for asthma patients.
Area of Science:
- Pulmonology
- Pharmacology
- Clinical Medicine
Background:
- The efficacy and safety of macrolide use in asthma management are not well-established.
- Uncertainty exists regarding the net benefit-risk profile of macrolides for asthma patients.
Purpose of the Study:
- To systematically review the efficacy and safety of macrolides for asthma as part of upcoming severe asthma guidelines.
- To synthesize evidence on macrolide treatment for asthma control, exacerbations, quality of life, and adverse events.
Main Methods:
- Systematic search of MEDLINE, EMBASE, and CENTRAL databases up to April 12, 2025.
- Inclusion of randomized trials comparing macrolides to placebo or standard care for asthma.
- Analysis of individual patient-level data and random effects meta-analyses, with GRADE certainty assessment.
Main Results:
- Nineteen trials with 1825 participants showed macrolides improve asthma control (MD: -0.23) and quality of life (MD: 0.11) with high certainty.
- Macrolides likely reduce severe exacerbations (IRR: 0.75) with moderate certainty.
- No significant increase in serious adverse events or mortality was observed (high certainty).
Conclusions:
- Macrolides likely improve asthma control and quality of life.
- Macrolides are associated with a reduction in severe asthma exacerbations.
- The benefits of macrolides in asthma occur with minimal to no increase in serious harms, irrespective of T2-inflammation status.
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