Late Breaking Abstract - Rheological, inflammatory and bacterial analysis of sputum samples from patients with bronchiectasis in the CLEAR trial

In the CLEAR trial, the effectiveness of hypertonic saline (HTS) and/or carbocisteine (CS) were compared to usual care in patients with bronchiectasis. The aim of this embedded mechanistic study was to characterise the baseline rheological, inflammatory and microbiological properties of sputum from patients enrolled in the CLEAR trial. Sputum viscoelastic properties were measured by rheometry to generate values for elastic (G’) and viscous (G’’) moduli, and yield stress (σc) (n=63). Sputum supernatants were assayed for IL-8 and 8-isoprostane by ELISA (n=42). NGS was performed for the assessment of sputum bacterial composition, and Shannon diversity and relative dominance were calculated (n=51). Spearman’s r test was performed to assess the correlations between these measures. All rheological measures (G’, G’’ and σc) were significantly positively correlated with IL-8 (p<0.05), with the strongest correlation between σc and IL-8 (Spearman r=0.48, p=0.0015). G’’ and σc were also positively correlated with the marker of oxidative stress 8-isoprostane and relative bacterial dominance (p<0.05). G’’ and σc were significantly negatively correlated with Shannon diversity (p<0.05). These findings indicate that, in patients with bronchiectasis, higher sputum yield stress (the shear-stress at which sputum transitions to fluid-like behaviour) is associated with increased pulmonary inflammation, oxidative stress and a less diverse bacterial microbiome, with greater species dominance. Subsequent analysis of sputum samples collected at 2 and 8 weeks will address whether treatment with mucoactives alters sputum properties.