Exploring chronic obstructive pulmonary disease (COPD) phenotypes: evaluating associations between molecular profile, airway microbiome and impact of anti-eosinophil treatment

Background: Chronic obstructive pulmonary disease (COPD) is characterised by persistent symptoms and airflow obstruction. In COPD there is heterogeneity in the airway inflammation and microbiome. Neutrophilic inflammation is the commonest pattern of airway inflammation in COPD but in some patients, there is eosinophilic inflammation. Biological drugs targeting cytokines associated with type 2-mediated immunity have had limited benefit in COPD in contrast to the substantial benefit in severe asthma suggesting that different mechanisms drive eosinophilic COPD and asthma.Methods: In sputum samples the airway microbiome in COPD was compared with healthy controls. The stability and strain change of an important pathogen was explored in stable state and exacerbations of COPD. Post hoc the effect on the airway microbiome in a randomised placebo-controlled trial of anti-interleukin-5 receptor monoclonal therapy (Benralizumab) was examined. Gene expression RNAseq of bronchial epithelial brushes was examined in COPD compared to asthma subjects with and without eosinophilic inflammation.Results: The microbiome in COPD was distinct from healthy controls and was independent of smoking history. At the phyla level there was a predominance of Proteobacteria in COPD in association with neutrophilic inflammation and Firmicutes in health. The airway pathogen, Moraxella catarrhalis, demonstrated substantial strain diversity with no specific strain associated with exacerbations. Benralizumab reduced total bacterial load and Streptococcus pneumoniae. Bronchial epithelial gene expression showed 12 genes were associated with eosinophilic inflammation in COPD in contrast to 1197 genes in asthma with only CST1 common to both.Conclusion: Microbial dysbiosis mediated by increased Proteobacteria is a feature of COPD, which was not promoted by anti-eosinophil therapy. Strain change of the respiratory pathogen Moraxella catarrhalis was not associated with exacerbations. Bronchial epithelial gene expression profiling suggests the molecular mechanisms of eosinophilic COPD and asthma are distinct.