Chronic Bacterial Airways Infection in Severe Asthma

Introduction: Corticosteroid-resistant severe asthma is associated with significant morbidity and lacks targeted therapies. Emerging evidence implicates chronic airways infection, particularly with Haemophilus influenzae, and innate immune dysregulation during stable disease as drivers of this phenotype. Previous asthma metagenomic studies lack adequate phenotyping and sequencing depth for bacterial species-level identification. We hypothesise chronic airways infection is a ‘treatable-trait’ but its prevalence, clinical phenotype and biomarkers need definition. Methods: We performed Oxford Nanopore sequencing, and RT-qPCR of total DNA extracts on induced sputum samples (n=52) from the Wessex Severe Asthma Cohort and identified sputum cytokines associated with airways infection. Results: A dominant pathogenic airway organism (H.influenzae, Streptococcus pneumoniae or Moraxella catarrhalis, Figure 1) was identified in 21%of patients with severe asthma by metagenomic sequencing and PCR. Infection was associated with sputum neutrophilia and elevated sputum pro-inflammatory cytokines (including IL-1, IL-6, IL-8, TNF; p<0.01, unpaired t-test, Benjamini-Hochberg correction). Conclusions: Airways infection in asthma is reliably identified using molecular microbiological methods and associated with neutrophilic inflammation. Ongoing analyses will fully characterise this phenotype including mucosal immune responses within the airway.