Endotyping Chronic Obstructive Pulmonary Disease, Bronchiectasis, and the "Chronic Obstructive Pulmonary Disease-Bronchiectasis Association"

• Published in: American journal of respiratory and critical care medicine 2022-08, Vol.206 (4), p.417-426
• Main Authors: Huang, Jeffrey T-J, Cant, Erin, Keir, Holly R, Barton, Alun K, Kuzmanova, Elena, Shuttleworth, Morven, Pollock, Jennifer, Finch, Simon, Polverino, Eva, Bottier, Mathieu, Dicker, Alison J, Shoemark, Amelia, Chalmers, James D
• Format: Article
• Language: English
• Subjects: Bacteria; Bronchiectasis; Chronic obstructive pulmonary disease; Comorbidity; Critical care; Humans; Microbiota; Neutrophils; Principal components analysis; Proteomics; Pulmonary Disease, Chronic Obstructive - genetics; RNA, Ribosomal, 16S; Sputum - microbiology
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.202108-1943OC

Bronchiectasis and chronic obstructive pulmonary disease (COPD) are two disease entities with overlapped clinical features, and codiagnosis frequently occurs (termed the "COPD-bronchiectasis association"). To investigate the sputum microbiome and proteome in patients with bronchiectasis, COPD, and the COPD-bronchiectasis association with the aim of identifying endotypes that may inform treatment. Sputum microbiome and protein profiling were carried out using 16S rRNA amplicon sequencing and a label-free proteomics workflow, respectively, in a cohort comprising patients with COPD (  = 43), bronchiectasis (  = 30), and the COPD-bronchiectasis association (  = 48). Results were validated in an independent cohort of 91 patients (  = 28-31 each group) using targeted measurements of inflammatory markers, mucins, and bacterial culture. Principal component analysis of sputum microbiome and protein profiles showed a partial separation between the COPD and the "COPD-bronchiectasis association" group. Further analyses revealed that patients with the "COPD-bronchiectasis association" had a higher abundance of proteobacteria, higher expression of mucin-5AC and proteins from the "neutrophil degranulation" pathway compared to those with COPD. In contrast, patients with COPD had an elevated expression of mucin-5B and several peptidase inhibitors, higher abundance of common commensal taxa, and a greater microbiome diversity. The profiles of "COPD-bronchiectasis association" and bronchiectasis groups were largely overlapping. Five endotypes were proposed with differential inflammatory, mucin, and microbiological features. The key features related to the "COPD-bronchiectasis association" were validated in an independent cohort. Neutrophilic inflammation, differential mucin expression, and Gram-negative infection are dominant traits in patients with the "COPD-bronchiectasis association."