Mucoactive agents in bronchiectasis: a systematic review and meta-analysis
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Background Mucoactive agents aim to improve mucociliary clearance in bronchiectasis, disrupting the cycle of impaired clearance, infection and inflammation. Registry data show 28% of patients use these agents, but prescribing varies due to limited evidence. We aimed to update evidence on mucoactive agents’ effects in adults with bronchiectasis. Methods We conducted a systematic review and meta-analysis, searching Medline, Embase, CENTRAL and trial registries to 1 October 2025. Eligible studies included adults with bronchiectasis, evaluating any mucoactive agentplacebo or control. Cystic fibrosis and paediatric studies were excluded. The primary outcome was exacerbation frequency; secondary outcomes included lung function, quality of life and adverse events. Findings From 1512 records, 24 studies (20 randomised, four observational: n=7051) evaluated eight mucoactive agents (ambroxol, bromhexine, carbocisteine, erdosteine, hypertonic saline, mannitol, N-acetylcysteine, rhDNase). Most trials had high or some risk of bias. Seven randomised studies (n=1259) reported exacerbations; pooled analysis did not demonstrate a statistically significant difference in annualised exacerbation incidence (mean difference −0.40 per patient per year, 95% CI –1.04–0.24; p=0.22; I=91%; very low certainty). Nine studies (n=767) reported percent predicted forced expiratory volume in 1 s (FEV% pred), showing a small mean increase of 3.23% (95% CI 0.31–6.15; p=0.03; I=69.9%; very low certainty). Pooled
Abstract
Background Mucoactive agents aim to improve mucociliary clearance in bronchiectasis, disrupting the cycle of impaired clearance, infection and inflammation. Registry data show 28% of patients use these agents, but prescribing varies due to limited evidence. We aimed to update evidence on mucoactive agents’ effects in adults with bronchiectasis. Methods We conducted a systematic review and meta-analysis, searching Medline, Embase, CENTRAL and trial registries to 1 October 2025. Eligible studies included adults with bronchiectasis, evaluating any mucoactive agentplacebo or control. Cystic fibrosis and paediatric studies were excluded. The primary outcome was exacerbation frequency; secondary outcomes included lung function, quality of life and adverse events. Findings From 1512 records, 24 studies (20 randomised, four observational: n=7051) evaluated eight mucoactive agents (ambroxol, bromhexine, carbocisteine, erdosteine, hypertonic saline, mannitol, N-acetylcysteine, rhDNase). Most trials had high or some risk of bias. Seven randomised studies (n=1259) reported exacerbations; pooled analysis did not demonstrate a statistically significant difference in annualised exacerbation incidence (mean difference −0.40 per patient per year, 95% CI –1.04–0.24; p=0.22; I=91%; very low certainty). Nine studies (n=767) reported percent predicted forced expiratory volume in 1 s (FEV% pred), showing a small mean increase of 3.23% (95% CI 0.31–6.15; p=0.03; I=69.9%; very low certainty). Pooled analyses did not demonstrate significant differences for other spirometry measures, quality of life or adverse events. Interpretation Pooled evidence did not show a reduction in exacerbations and FEV% pred improvements were small. Evidence certainty was low/very low, meaning overall clinical benefit remains uncertain, highlighting the need for targeted trials of specific agents and subgroups. Shareable abstract Mucoactive agents were not associated with significant reductions in exacerbations or improved quality of life in bronchiectasis. Evidence certainty was very low, highlighting further trials are needed to identify which patients, if any, may benefit. https://bit.ly/4msQS5G short abstract-1