{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:55:53Z","timestamp":1782996953568,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>While the lung microbiome in severe asthma has been studied, work has employed targeted amplicon\u2010based sequencing approaches without functional assessment with none focused on multi\u2010ethnic Asian populations. Here we investigate the clinical relevance of microbial phenotypes of severe asthma in Asians using metagenomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Prospective assessment of clinical, radiological, and immunological measures were performed in a multi\u2010ethnic Asian severe asthma cohort (<jats:italic>N<\/jats:italic>\u2009=\u200970) recruited across two centres in Singapore. Sputum was subjected to shotgun metagenomic sequencing and patients followed up for a 2\u2010year period. Metagenomic assessment of sputum microbiomes, resistomes and virulomes were related to clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The lung microbiome in a multi\u2010ethnic Asian cohort with severe asthma demonstrates an increased abundance of <jats:italic>Pseudomonas<\/jats:italic> species. Unsupervised clustering of sputum metagenomes identified two patient clusters: C1 (<jats:italic>n<\/jats:italic>\u2009=\u200952) characterized by upper airway commensals and C2 (<jats:italic>n<\/jats:italic>\u2009=\u200918) dominated by established respiratory pathogens including <jats:italic>M. catarrhalis<\/jats:italic>, <jats:italic>S. aureus<\/jats:italic> and most significantly <jats:italic>P. aeruginosa.<\/jats:italic> C2 patients demonstrated a significantly increased exacerbation frequency on 2\u2010year follow up and an antimicrobial resistome characterized by multidrug resistance. Virulomes appear indistinguishable between severe asthmatics with or without co\u2010existing 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\u2010asthmatic bronchiectasis cohort demonstrates analogous airway microbial virulence patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sputum metagenomics demonstrates a multidrug\u2010resistant <jats:italic>Pseudomonas<\/jats:italic>\u2010dominant severe asthma phenotype in Asians, characterized by poor clinical outcome including increased exacerbations which is independent of co\u2010existing bronchiectasis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.14863","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T02:54:38Z","timestamp":1733194478000},"page":"217-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sputum metagenomics reveals a multidrug resistant <i>Pseudomonas<\/i>\u2010dominant severe asthma phenotype in an Asian population"],"prefix":"10.1111","volume":"30","author":[{"given":"Fransiskus Xaverius","family":"Ivan","sequence":"first","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6346-2072","authenticated-orcid":false,"given":"Pei Yee","family":"Tiew","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"},{"name":"Department of Respiratory and Critical Care Medicine Singapore General Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tavleen Kaur","family":"Jaggi","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Xian","family":"Thng","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"},{"name":"Collaborative Institute, Interdisciplinary Graduate Programme Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0027-5026","authenticated-orcid":false,"given":"Pee Hwee","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Tan Tock Seng Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thun How","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Singapore General Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Arputhan","family":"Abisheganaden","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"},{"name":"Department of Respiratory and Critical Care Medicine Tan Tock Seng Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-0129","authenticated-orcid":false,"given":"Mariko Siyue","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Singapore General Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7607","authenticated-orcid":false,"given":"Sanjay H.","family":"Chotirmall","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"},{"name":"Department of Respiratory and Critical Care Medicine Tan Tock Seng Hospital  Singapore 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