Endotyping Chronic Obstructive Pulmonary Disease, Bronchiectasis, and the “Chronic Obstructive Pulmonary Disease–Bronchiectasis Association”

Jeffrey T.-J. Huang, Erin Cant, Holly R. Keir, Alun K. Barton, Elena Kuzmanova, Morven Shuttleworth, Jennifer Pollock, Simon Finch, Eva Polverino, Mathieu Bottier, Alison J. Dicker, Amelia Shoemark, James D. Chalmers (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)
224 Downloads (Pure)

Abstract

Rationale: Bronchiectasis and chronic obstructive pulmonary disease (COPD) are two disease entities with overlapped clinical features, and codiagnosis frequently occurs (termed the "COPD-bronchiectasis association"). Objectives: 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. Methods: 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 (n = 43), bronchiectasis (n = 30), and the COPD-bronchiectasis association (n = 48). Results were validated in an independent cohort of 91 patients (n = 28-31 each group) using targeted measurements of inflammatory markers, mucins, and bacterial culture. Measurements and Main Results: 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. Conclusions: Neutrophilic inflammation, differential mucin expression, and Gram-negative infection are dominant traits in patients with the "COPD-bronchiectasis association."

Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume206
Issue number4
Early online date19 Apr 2022
DOIs
Publication statusPublished - 15 Aug 2022

Keywords

  • COPD
  • bronchiectasis
  • endotype
  • microbiome
  • proteome
  • sputum
  • the “COPD–bronchiectasis association”

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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