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

  • 2026-04
  • European respiratory review : an official journal of the European Respiratory Society 35(180)
    • Benjamin McCullough
    • John Busby
    • Brenda O'Neill
    • Bronwen Connolly
    • Rebecca H McLeese
    • Dermot Linden
    • Daniel F McAuley
    • J Stuart Elborn
    • Anthony De Soyza
    • James D Chalmers
    • Mike Clarke
    • Judy M Bradley

Study Design

Type
Meta-Analysis
Sample size
n = 7,051
Population
adults with bronchiectasis
Methods
systematic review and meta-analysis, searching Medline, Embase, CENTRAL and trial registries to 1 October 2025

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 agent versus placebo 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; I2=91%; very low certainty). Nine studies (n=767) reported percent predicted forced expiratory volume in 1 s (FEV1 % pred), showing a small mean increase of 3.23% (95% CI 0.31-6.15; p=0.03; I2=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 FEV1 % 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.

Research Insights

  • N-Acetyl Cysteine→Improved Lung Function

    Nine studies (n=767) reported percent predicted forced expiratory volume in 1 s (FEV₁ % pred), showing a small mean increase of 3.23% (95% CI 0.31-6.15; p=0.03; I²=69.9%; very low certainty).

    Effect
    Beneficial
    Effect size
    Small
  • N-Acetyl Cysteine→Improved Quality of Life

    Pooled analyses did not demonstrate significant differences for ... quality of life ...

    Effect
    Neutral
    Effect size
    Small
  • N-Acetyl Cysteine→Reduced Exacerbation Frequency

    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; I²=91%; very low certainty).

    Effect
    Neutral
    Effect size
    Small

Adverse Events Reported

  • N-Acetyl Cysteine→Overall tolerability

    Pooled analyses did not demonstrate significant differences for... adverse events.

    Finding
    Reported
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