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

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 σ_c) was positively correlated with interleukin-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.