In this section
@article{Ivan:2024:10.1111/resp.14863,
author = {Ivan, FX and Tiew, PY and Jaggi, TK and Thng, KX and Pang, PH and Ong, TH and Abisheganaden, JA and Koh, MS and Chotirmall, SH},
doi = {10.1111/resp.14863},
journal = {Respirology},
title = {Sputum metagenomics reveals a multidrug resistant Pseudomonas-dominant severe asthma phenotype in an Asian population.},
url = {http://dx.doi.org/10.1111/resp.14863},
year = {2024}
}
TY - JOUR
AB - BACKGROUND AND OBJECTIVE: While 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. METHODS: Prospective 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. RESULTS: The 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. CONCLUSION: Sputum 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.
AU - Ivan,FX
AU - Tiew,PY
AU - Jaggi,TK
AU - Thng,KX
AU - Pang,PH
AU - Ong,TH
AU - Abisheganaden,JA
AU - Koh,MS
AU - Chotirmall,SH
DO - 10.1111/resp.14863
PY - 2024///
TI - Sputum metagenomics reveals a multidrug resistant Pseudomonas-dominant severe asthma phenotype in an Asian population.
T2 - Respirology
UR - http://dx.doi.org/10.1111/resp.14863
UR - https://www.ncbi.nlm.nih.gov/pubmed/39622769
ER -
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