Sputum metagenomics reveals a multidrug resistant Pseudomonas-dominant severe asthma phenotype in an Asian population.

IF 6.6 2区 医学 Q1 RESPIRATORY SYSTEM
Respirology Pub Date : 2024-12-02 DOI:10.1111/resp.14863
Fransiskus Xaverius Ivan, Pei Yee Tiew, Tavleen Kaur Jaggi, Kai Xian Thng, Pee Hwee Pang, Thun How Ong, John Arputhan Abisheganaden, Mariko Siyue Koh, Sanjay H Chotirmall
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引用次数: 0

Abstract

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.

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来源期刊
Respirology
Respirology 医学-呼吸系统
CiteScore
10.60
自引率
5.80%
发文量
225
审稿时长
1 months
期刊介绍: Respirology is a journal of international standing, publishing peer-reviewed articles of scientific excellence in clinical and clinically-relevant experimental respiratory biology and disease. Fields of research include immunology, intensive and critical care, epidemiology, cell and molecular biology, pathology, pharmacology, physiology, paediatric respiratory medicine, clinical trials, interventional pulmonology and thoracic surgery. The Journal aims to encourage the international exchange of results and publishes papers in the following categories: Original Articles, Editorials, Reviews, and Correspondences. Respirology is the preferred journal of the Thoracic Society of Australia and New Zealand, has been adopted as the preferred English journal of the Japanese Respiratory Society and the Taiwan Society of Pulmonary and Critical Care Medicine and is an official journal of the World Association for Bronchology and Interventional Pulmonology.
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