Effects of hypertonic saline and/or carbocisteine on sputum rheology in bronchiectasis (CLEAR-EME)

Background Mucoactives such as hypertonic saline (HTS) and carbocisteine are widely used in the treatment of bronchiectasis, though there is insufficient evidence to support their use. The aim of this mechanistic sub-study, embedded within the CLEAR trial, was to characterise the properties of sputum from patients with bronchiectasis and to assess whether treatment with HTS and/or carbocisteine altered these properties. Methods In CLEAR, patients were randomised to receive HTS, carbocisteine, HTS plus carbocisteine or standard care, and sputum samples were collected at randomisation (baseline) and at 2 and 8 weeks post-randomisation. Sputum viscoelasticity was determined by rotational plate rheometry. Biomarkers were quantified by ELISA and microbiome composition was assessed by next-generation sequencing. The primary outcome was differences in sputum viscoelasticity between groups at 2 weeks following the commencement of treatment. Results Sputum viscoelastic properties were not reduced by 2 or 8 weeks of treatment with HTS and/or carbocisteine (n=6–15 per group). Sputum biomarker levels and bacterial community composition were similar across groups at 2 or 8 weeks. At baseline, viscoelasticity (crossover point σc) was positively correlated with IL-8 (r=0.49, p=0.012) and greater relative bacterial dominance (r=0.35, p=0.041). Conclusions These data do not support the use of HTS or carbocisteine to alter sputum viscoelasticity, inflammatory marker levels or bacterial community composition in patients with bronchiectasis.

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Journal
ERJ Open Research
Published
2026-04-16
DOI
https://doi.org/10.1183/23120541.00202-2026
Primary Topic
Cystic Fibrosis Research Advances
Type
article
Field-Weighted Citation Impact
0.00

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article

Effects of hypertonic saline and/or carbocisteine on sputum rheology in bronchiectasis (CLEAR-EME)

Adam T. Hill, Clíona McDowell, Ryan Brown, Timothy Gatheral et al.
ERJ Open Research
Cystic Fibrosis Research Advances
article

Effects of hypertonic saline and/or carbocisteine on sputum rheology in bronchiectasis (CLEAR-EME)

Adam T. Hill, Clíona McDowell, Ryan Brown, Timothy Gatheral, Clifford C. Taggart, Daniel Francis McAuley, Rebecca H. McLeese, Michael M. Tunney, Jack Carson, Mike J Clarke, Anthony De Soyza, Aram Kadoom, J. Duckers, G.G. Einarsson, Michael C. McKelvey, Martin Kelly, Andrew Jackson, Mary Carroll, Mitra Shahidi, Damian G Downey, J Stuart Elborn, Muhammed Anwar, Anita L. Sullivan, Brenda O'Neill, James D. Chalmers, Kathryn Ferguson, A Alina Ionescu, Rory Convery, Judy M. Bradley, William Flight, Christina Campbell, Michael R. Loebinger, John R. Hurst, Fiona Copeland
article en

Abstract

Background Mucoactives such as hypertonic saline (HTS) and carbocisteine are widely used in the treatment of bronchiectasis, though there is insufficient evidence to support their use. The aim of this mechanistic sub-study, embedded within the CLEAR trial, was to characterise the properties of sputum from patients with bronchiectasis and to assess whether treatment with HTS and/or carbocisteine altered these properties. Methods In CLEAR, patients were randomised to receive HTS, carbocisteine, HTS plus carbocisteine or standard care, and sputum samples were collected at randomisation (baseline) and at 2 and 8 weeks post-randomisation. Sputum viscoelasticity was determined by rotational plate rheometry. Biomarkers were quantified by ELISA and microbiome composition was assessed by next-generation sequencing. The primary outcome was differences in sputum viscoelasticity between groups at 2 weeks following the commencement of treatment. Results Sputum viscoelastic properties were not reduced by 2 or 8 weeks of treatment with HTS and/or carbocisteine (n=6–15 per group). Sputum biomarker levels and bacterial community composition were similar across groups at 2 or 8 weeks. At baseline, viscoelasticity (crossover point σc) was positively correlated with IL-8 (r=0.49, p=0.012) and greater relative bacterial dominance (r=0.35, p=0.041). Conclusions These data do not support the use of HTS or carbocisteine to alter sputum viscoelasticity, inflammatory marker levels or bacterial community composition in patients with bronchiectasis.

ERJ Open Research
Queen's University Belfast (GB), Belfast Health and Social Care Trust (GB), Cardiff and Vale University Health Board (GB), University of Ulster (GB), University Hospitals of Morecambe Bay NHS Foundation Trust (GB), Royal Gwent Hospital (GB), Princess Alexandra Hospital NHS Trust (GB), Chartered Institute of Library and Information Professionals (GB), Buckinghamshire Healthcare NHS Trust (GB), Ninewells Hospital (GB), University Hospital Southampton NHS Foundation Trust (GB), Western Health and Social Care Trust (GB), Royal Brompton Hospital (GB), Alexandra Hospital (GB), Southern Health and Social Care Trust (GB), NIHR Surgical Reconstruction and Microbiology Research Centre (GB), Princess Alexandra Hospital (GB), Oxford University Hospitals NHS Trust (GB), Centre for Inflammation Research (GB), University College London (GB), Newcastle University (GB)
Efficacy and Mechanism Evaluation Programme
Openalex Percentile: Top 17%
Cystic Fibrosis Research Advances
DOIOpen Access PDFOpenAlex
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