AbstractBackground and ObjectiveWhile the lung microbiome in severe asthma has been studied, work has employed targeted amplicon‐based sequencing approaches without functional assessment with none focused on multi‐ethnic Asian populations. Here we investigate the clinical relevance of microbial phenotypes of severe asthma in Asians using metagenomics.MethodsProspective assessment of clinical, radiological, and immunological measures were performed in a multi‐ethnic Asian severe asthma cohort (N = 70) recruited across two centres in Singapore. Sputum was subjected to shotgun metagenomic sequencing and patients followed up for a 2‐year period. Metagenomic assessment of sputum microbiomes, resistomes and virulomes were related to clinical outcomes.ResultsThe lung microbiome in a multi‐ethnic Asian cohort with severe asthma demonstrates an increased abundance of Pseudomonas species. Unsupervised clustering of sputum metagenomes identified two patient clusters: C1 (n = 52) characterized by upper airway commensals and C2 (n = 18) dominated by established respiratory pathogens including M. catarrhalis, S. aureus and most significantly P. aeruginosa. C2 patients demonstrated a significantly increased exacerbation frequency on 2‐year follow up and an antimicrobial resistome characterized by multidrug resistance. Virulomes appear indistinguishable between severe asthmatics with or without co‐existing bronchiectasis, and C2 patients exhibit increased gene expression related to biofilm formation, effector delivery systems and microbial motility. Independent comparison of the C2 cluster to a non‐asthmatic bronchiectasis cohort demonstrates analogous airway microbial virulence patterns.ConclusionSputum metagenomics demonstrates a multidrug‐resistant Pseudomonas‐dominant severe asthma phenotype in Asians, characterized by poor clinical outcome including increased exacerbations which is independent of co‐existing bronchiectasis.
Read full abstract