Amelia Shoemark1,2, Michal Shteinberg3, Anthony De Soyza4,5, Charles S Haworth6,7, Hollian Richardson1, Yonghua Gao8, Lidia Perea9, Alison J Dicker1, Pieter C Goeminne10, Erin Cant1, Eva Polverino11,12, Josje Altenburg13, Holly R Keir1, Michael R Loebinger2, Francesco Blasi14,15, Tobias Welte16, Oriol Sibila9, Stefano Aliberti17,18, James D Chalmers1. 1. Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom. 2. Royal Brompton Hospital and Imperial College London, London, United Kingdom. 3. Pulmonology Institute and Cystic Fibrosis Center, Carmel Medical Center, Haifa, Israel. 4. Population and Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom. 5. National Institute for Health Research Biomedical Research Centre for Ageing, Freeman Hospital, Newcastle, United Kingdom. 6. Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, United Kingdom. 7. Department of Medicine, University of Cambridge, Cambridge, United Kingdom. 8. Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 9. Hospital Clinic of Barcelona, University of Barcelona, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. 10. Department of Respiratory Disease, AZ Nikolaas, Sint-Niklaas, Belgium. 11. Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 12. Thorax Institute, Institute of Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain. 13. Department of Respiratory Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. 14. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy. 15. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. 16. Department of Pulmonary Medicine and Infectious Diseases, Hannover University School of Medicine, Hannover, Germany. 17. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. 18. Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Abstract
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/μl. Counts of <100 cells/μl were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts of ⩾300 cells/μl 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/μl (reference), elevated eosinophil counts of 100-299 cells/μl (hazard ratio, 2.38; 95% confidence interval, 1.33-4.25; P = 0.003) and ⩾300 cells/μl (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.
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/μl. Counts of <100 cells/μl were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts of ⩾300 cells/μl 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/μl (reference), elevated eosinophil counts of 100-299 cells/μl (hazard ratio, 2.38; 95% confidence interval, 1.33-4.25; P = 0.003) and ⩾300 cells/μl (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.