Mucoactive agents in bronchiectasis: a systematic review and meta-analysis

Background: Mucoactive agents in bronchiectasis aim to improve mucociliary clearance, disrupting the cycle of impaired clearance, infection, inflammation, and structural lung damage. Registry data show 28% of patients use these agents, but prescribing varies due to limited evidence and conditional <br/>guideline recommendations. We aimed to update evidence on mucoactive agents’ effects in adults with bronchiectasis, including recent randomised trials and observational studies.<br/>Methods: We conducted a systematic review and meta-analysis (PROSPERO: CRD42024545050). MEDLINE, Embase, CENTRAL, EU Clinical Trials Register, ClinicalTrials.gov, and WHO trial registry portals were searched to April 14, 2025. Eligible studies included adults with bronchiectasis, evaluating <br/>any mucoactive agent versus placebo, standard care, or control; cystic fibrosis and paediatric studies were excluded. Reviewers independently screened studies, extracted data, and assessed risk of bias. The primary outcome was exacerbation frequency; secondary outcomes included lung function, quality of life, and adverse events. Random-effects meta-analyses were performed.<br/>Findings: From 1,424 records, 25 studies (21 randomised, 4 observational: n=7,075) evaluated eight mucoactive agents (ambroxol, bromhexine, carbocisteine, erdosteine, hypertonic saline, mannitol, Nacetylcysteine, rhDNase). Most trials had high or some risk of bias, with one low; non-randomised studies ranged from serious to unassessable. Nine studies (n=3,729) reported exacerbations; pooled analysis estimated a mean reduction of 0.56 per patient per year (95% CI –1.30 to 0.19; p=0.14; I²=97.3%; very low certainty). Eight studies (n=767) reported FEV₁% predicted, showing a mean increase of 3.3% (95% CI 0.2 to 6.4; p=0.04; I²=73.4%; very low certainty). Pooled analyses did not demonstrate significant differences for other spirometric measures, quality of life, or adverse events, though certainty was low.<br/>Interpretation: Pooled evidence did not show a reduction in exacerbations, and FEV₁% improvements were small. The certainty of evidence was very low with high heterogeneity, so overall clinical benefit remains uncertain, highlighting the need for targeted trials of specific agents and subgroups.<br/>