Characterisation of Eosinophilic Bronchiectasis: A European Multicohort Study

Rationale: Bronchiectasis is classically considered a neutrophilic disorder but eosinophilic subtypes have recently been described. Objectives: To use multiple datasets available through the EMBARC consortium to characterise eosinophilic bronchiectasis as a clinical entity focussing on the impact of eosinophils on bronchiectasis exacerbations. Methods: Patients were included from 5 countries to examine the relationships between blood eosinophil counts and clinical phenotypes after excluded co-existing asthma. 16S rRNA sequencing was used to examine relationships between eosinophil counts and the sputum microbiome. A posthoc analysis of the PROMIS phase-2 trial was used to examine the impact of blood eosinophil counts on exacerbations in patients with P.aeruginosa infection. Measurements and main results: A relationship between sputum and blood eosinophil counts was demonstrated in 2 cohorts. In analysis of 1007 patients from 5 countries, 22.6% of patients had blood eosinophil counts >300cells/ul. Counts<100cells/ul were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts >300cells/ul were associated with both Streptococcus and Pseudomonas dominated microbiome profiles. To investigate the relationship of eosinophil counts with exacerbations after controlling for the confounding effects of infection, 144 patients were studied in a clinical trial following treatment with antipseudomonal antibiotics. Compared to patients with blood eosinophil counts<100cells(reference), elevated eosinophil counts 100-300cells/ul (HR 2.38 95%CI 1.33-4.25,p=0.003) and >300cells/ul (HR 3.99 95%CI 2.20-7.85,p<0.0001) were associated with shorter time to exacerbation. Conclusion: Eosinophilic bronchiectasis affects approximately 20% of patients. After accounting for infection status, raised blood eosinophil counts are associated with shortened time to exacerbation.