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

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), 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.