Endotyping bronchiectasis through multi-omic profiling

Introduction: Neutrophil extracellular traps (NETs) are a form of antimicrobial defence composed of DNA, histones and over 30 granular proteins. This study investigated the role of NETs in bronchiectasis. Method: Endotyping of bronchiectasis (BE) was performed in 6 independent UK and European cohorts. LC/MS proteomics was used to compare profiles between severe and mild BE (20 vs 20 patients). Microbiome changes, using 16S rRNA sequencing, and clinical characteristics were analysed (n=172). Results were validated in the European BRIDGE cohort (n=226). Antibiotic response was addressed in 3 cohorts (2 cohorts receiving IV antibiotics and one treated with long-term macrolides). Method: Using proteomics, a cluster of patients with severe disease characterised by elevated azurocidin1, resistin, elastase, lipocalin 2 and myeloperoxidase was identified. Relationships between NETs and associated proteins (resistin/azurocidin1) were validated in two independent cohorts (p Conclusion: We identified novel endotypes of bronchiectasis which may be used for future personalised therapy.