Inflammatory Endotypes, Microbiome and Exacerbation Risk in Bronchiectasis: A European Multicentre Study

Introduction: Inflammation is believed to be central to the pathophysiology of bronchiectasis. This study aimed to perform inflammatory endotyping in bronchiectasis and examine the validity of identified inflammatory clusters by comparing the microbiome profiles and exacerbation risk among endotypes of bronchiectasis.
Methods: Patients with stable bronchiectasis were enrolled at three European centres. K-means cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Sputum microbiome composition was determined through 16S rRNA amplicon sequencing. Endotypes were compared for their risk of exacerbations over 12 months follow-up.
Results: 199 patients were enrolled, and using cluster analysis, four endotypes were defined according to their inflammatory profiles: cluster 1 (milder neutrophilic inflammation), cluster 2 (mixed-neutrophilic and type 2 inflammation), cluster 3 (most severe neutrophilic), and cluster 4 (mixed-epithelial and type 2). In the sputum microbiome, Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more dominant in clusters 2 and 3 than in clusters 1 and 4. Although the four clusters were indistinguishable by clinical characteristics at baseline, patients in clusters 2 (rate ratio [RR] 1.53, 95% CI 1.19–1.97) and 3 (RR 1.46, 95% CI 1.02–2.09) were at higher risk of exacerbation and severe exacerbation over 12 months follow-up compared to cluster 1.
Conclusion: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.