Molecular markers of type 2 airway inflammation are similar between eosinophilic severe asthma and eosinophilic chronic obstructive pulmonary disease

Abstract

Airway and systemic eosinophilia are important treatable traits in both severe asthma and COPD. The molecular basis of eosinophilia in COPD is poorly understood but could involve type 2 cytokines (IL5, IL13) and prostaglandin D2 (PGD2 ). This study included non-obstructive airways disease (OAD) controls (n=19), a COPD cohort (n=96) and a severe asthma cohort (n=84). Demographics, exacerbation history, disease impact (SGRQ) and spirometry were assessed. Participants were categorized as eosinophilic using either sputum eosinophil proportion (≥3%) or blood eosinophil count (≥300/μL). Sputum type 2 inflammatory measures included PGD2 by ELISA and gene expression (qPCR) of IL5, IL13 and the haematopoietic PGD2 synthase (HPGDS). Type 2 markers did not differ across groups except HPGDS mRNA which was highest in non-OAD controls and lowest in COPD. IL5 and IL13 mRNA and PGD2 levels were significantly increased in eosinophilic vs non-eosinophilic severe asthma but did not differ between eosinophilic COPD and eosinophilic severe asthma or non-eosinophilic COPD. HPGDS expression was higher in eosinophilic severe asthma compared with eosinophilic COPD. Results were similar using sputum or blood eosinophil cut-offs. Sputum IL5 and IL13 were highly intercorrelated in severe asthma (r=0.907, p<0.001) and COPD (r=0.824, p<0.001), were moderately correlated with sputum eosinophils in severe asthma (IL5 r=0.440, p<0.001; IL13 r=0.428, p<0.001) and were weakly correlated in COPD (IL5 r=0.245, p<0.05; IL13 r=0.317, p<0.05). Molecular markers of type 2 airway inflammation do not differ between eosinophilic asthma and eosinophilic COPD; however, the relationship between eosinophilia and type 2 airway markers appears weaker in COPD than in severe asthma.