Characterisation of eosinophilic bronchiectasis: A European multicohort study

<b>Introduction:</b> Bronchiectasis is historically regarded as a neutrophilic disorder but eosinophilic subtypes have recently been described. We investigated whether sputum or blood eosinophilia was associated with clinical outcomes across multiple datasets held by the EMBARC bronchiectasis network. <b>Methods:</b> 1007 patients were included from 5 countries to examine the relationships between blood eosinophil counts and clinical phenotypes. 16s rRNA sequencing was used to examine relationships between eosinophil counts and the microbiome. A posthoc analysis of the PROMIS trial was used to examine the impact of eosinophil counts on exacerbations in patients with P. aeruginosa infection. <b>Results:</b> Across 2 cohorts, blood and sputum eosinophils were significantly correlated. 22.6% of patients had blood eosinophil counts &gt;300cells/ul. Counts &lt;100cells/ul were associated with higher bronchiectasis severity index, (median 8 IQR 5-11 vs 6 IQR 4-9,p&lt;0.0001),worse FEV1 and increased mortality. Proteobacteria dominance was associated with &lt;100cells/ul, while eosinophilic profiles were associated with firmicutes dominance (p&lt;0.0001 by PERMANOVA). To investigate the relationship between eosinophil counts and exacerbations after controlling for the effects of infection, 144 patients were studied in PROMIS. Time to first exacerbation was significantly decreased with increasing blood eosinophil counts. Compared to patients with blood eosinophil counts &lt;100cells (reference) 100-300cells/ul (HR 2.38 95% CI 1.33-4.25,p=0.003) and &gt;300cells/ul (HR 3.99 95% CI 2.20-7.85,p&lt;0.0001) were associated with shorter time to exacerbation. <b>Conclusion:</b> Eosinophilic inflammation is associated with increased exacerbations in bronchiectasis.