Transcriptomic profiling of the airway epithelium in COPD links airway eosinophilia to type 2 inflammation and corticosteroid response

Eur Respir J. 2025 May 6;65(5):2401875. doi: 10.1183/13993003.01875-2024. Print 2025 May.

Abstract

Background: A subset of COPD patients have high levels of eosinophils in the distal airways ("airway eosinophilia").

Objectives: To compare the gene expression of type 2 inflammation in airway epithelial brushings of COPD patients with and without airway eosinophilia and to investigate the changes after inhaled corticosteroids (ICS).

Methods: Post hoc analyses of the DISARM randomised controlled trial investigated the expression of airway inflammation (type 1, 2 and 17), interleukin (IL)-13 and mast cell gene signatures at baseline and after 12-week ICS treatment. Gene signatures were generated from RNA sequencing of airway epithelial brushings. Airway eosinophilia was defined as eosinophils >1% of the total leukocyte count in bronchoalveolar lavage. Gene set enrichment analyses identified upregulated canonical pathways in airway eosinophilia.

Results: Among 58 COPD patients, 38% had airway eosinophilia at baseline. Patients with airway eosinophilia had more severe airflow obstruction and more radiographic emphysema than the non-eosinophilia group. Patients with airway eosinophilia showed a higher epithelial expression of type 2 airway inflammation and IL-13 and mast cell activation at baseline, but the expression of type 1 and type 17 airway inflammation was similar to patients without airway eosinophilia. The airway eosinophilia group showed an upregulation of canonical pathways related to type 2 immune response and asthma. Treatment with ICS for 12 weeks reduced the epithelial expression of type 2 inflammation and mast cell gene signatures in patients with airway eosinophilia, while this change was not significant in patients without airway eosinophilia.

Conclusions: Airway eosinophilia marks a subset of COPD patients with increased airway epithelial expression of type 2 inflammation and a response to ICS treatment.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones* / administration & dosage
  • Adrenal Cortex Hormones* / therapeutic use
  • Aged
  • Eosinophilia* / genetics
  • Eosinophils
  • Female
  • Gene Expression Profiling
  • Humans
  • Inflammation / genetics
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism
  • Male
  • Mast Cells / metabolism
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive* / complications
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Respiratory Mucosa* / metabolism
  • Transcriptome

Substances

  • Adrenal Cortex Hormones
  • Interleukin-13