Queen’s University Belfast-led research reports on a multicenter trial finding no significant reduction in pulmonary exacerbations with hypertonic saline or carbocisteine over 52 weeks among adults with non–cystic fibrosis bronchiectasis.
Bronchiectasis brings chronic cough, sputum production, chest pain, shortness of breath, and recurrent pulmonary exacerbations that diminish quality of life and survival.
Guideline recommendations for mucoactive agents vary, with earlier evidence graded as low quality and real-world use inconsistent across countries. Large, well-controlled trials have been sought to clarify safety and effectiveness.
In the study, “Hypertonic Saline or Carbocisteine in Bronchiectasis,” published in The New England Journal of Medicine, researchers conducted an open-label, randomized, two-by-two factorial trial to test whether 6% hypertonic saline or carbocisteine reduce adjudicated pulmonary exacerbations over 52 weeks.
Enrollment included 288 participants across 20 hospitals in the United Kingdom.
Participants received standard care plus assignment to one of four paths; hypertonic saline, carbocisteine, both agents, or standard care alone. Hypertonic saline was delivered via an eFlow rapid nebulizer. Carbocisteine was dosed at 750 mg three times daily for eight weeks, then 750 mg twice daily. Current smokers and those with recent mucoactive use were excluded.
The primary outcome was the number of fully qualifying pulmonary exacerbations over 52 weeks using EMBARC criteria adjudicated by an independent panel. Analyses followed a modified intention-to-treat approach with negative binomial regression adjusted for site, prior antibiotic use for exacerbations, and baseline macrolide therapy.
Results showed no significant difference between hypertonic saline versus no hypertonic saline, with an adjusted difference of ?0.25, 95% CI ?0.57 to 0.07, P=0.12.
Carbocisteine also failed to make a significant impact versus without carbocisteine, with an adjusted difference ?0.04, 95% CI ?0.36 to 0.28, P=0.81.
Secondary outcomes, including disease-specific quality-of-life scores, time to next exacerbation, antibiotic days, and lung function, appeared similar across comparisons.
Authors conclude that adding hypertonic saline or carbocisteine to standard care did not significantly reduce exacerbations over 52 weeks in this population. Findings may guide clinicians and patients who weigh treatment burden, costs, and side-effect profiles when considering mucoactive therapy in bronchiectasis.
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More information:
Judy M. Bradley et al, Hypertonic Saline or Carbocisteine in Bronchiectasis, New England Journal of Medicine (2025). DOI: 10.1056/nejmoa2510095
John Hansen-Flaschen et al, Time to Reconsider Mucoactive Agents for Airway Clearance, New England Journal of Medicine (2025). DOI: 10.1056/nejme2512146
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