Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 205, Issue 8, Pages 894-902Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.202108-1889OC
Keywords
eosinophil; bronchiectasis; microbiome; exacerbations
Categories
Funding
- European Respiratory Society through the European Multicentre Bronchiectasis Audit and Research Collaboration 2 (EMBARC2 Consortium)
- AstraZeneca
- Chiesi
- Insmed
- Zambon
- GSK/British Lung Foundation Chair of Respiratory Research
- Scottish Senior Fellowship from the Chief Scientist Office
- Grifols
- Janssen
- Novartis
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Eosinophilic bronchiectasis is a common clinical entity that affects approximately 20% of patients. Blood eosinophil counts are associated with bronchiectasis severity, mortality, and time to exacerbation.
Rationale: Bronchiectasis is classically considered a neutrophilic disorder, but eosinophilic subtypes have recently been described. Objectives: To use multiple datasets available through the European Multicentre Bronchiectasis Audit and Research Collaboration to characterize eosinophilic bronchiectasis as a clinical entity focusing on the impact of eosinophils on bronchiectasis exacerbations. Methods: Patients were included from five countries to examine the relationships between blood eosinophil counts and clinical phenotypes after excluding coexisting asthma. 16S rRNA sequencing was used to examine relationships between eosinophil counts and the sputum microbiome. A post hoc analysis of the PROMIS (Inhaled Promixin in the Treatment of Non-Cystic Fibrosis Bronchiectasis) phase 2 trial was used to examine the impact of blood eosinophil counts on exacerbations in patients with Pseudomonas aeruginosa infection. Measurements and Main Results: A relationship between sputum and blood eosinophil counts was demonstrated in two cohorts. In analysis of 1,007 patients from five countries, 22.6% of patients had blood eosinophil counts of >= 300 cells/mu l. Counts of <100 cells/mu l were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts of >= 300 cells/mu l 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 after treatment with antipseudomonal antibiotics. Compared with patients with blood eosinophil counts of <100 cells/mu l (reference), elevated eosinophil counts of 100-299 cells/mu l (hazard ratio, 2.38; 95% confidence interval, 1.33-4.25; P = 0.003) and >= 300 cells/mu l (hazard ratio, 3.99; 95% confidence interval, 2.20-7.85; P < 0.0001) were associated with shorter time to exacerbation. Conclusions: Eosinophilic bronchiectasis affects approximately 20% of patients. After accounting for infection status, raised blood eosinophil counts are associated with shortened time to exacerbation.
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