{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:07:06Z","timestamp":1775560026651,"version":"3.50.1"},"reference-count":42,"publisher":"European Respiratory Society (ERS)","issue":"2","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2025,10,3]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe asthma encompasses heterogeneous inflammatory phenotypes and airway bacteriome diversity but the state of its airway resistome remains understudied. We therefore evaluated the link between the airway microbiome and the antibiotic-resistant genes by determining the clusters from a bacteriome\u2013resistome integration from sputum samples of patients with severe asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Induced sputum samples from severe asthma (SA; n=96), mild\u2013moderate asthma (MMA; n=23) and healthy controls (HCs; n=23) in the European U-BIOPRED asthma cohort were metagenomically sequenced. Respiratory bacteriome was evaluated by taxonomical and functional classification. The comprehensive antibiotic resistance database was used to determine airway resistome and Similarity Network Fusion to cluster integratively the bacteriome\u2013resistome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      More multidrug-resistance genes were present in SA compared with MMA and HCs with the\n                      <jats:italic>hmrM<\/jats:italic>\n                      , encoded in\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      chromosome, being highest. Two of the three defined clusters were dominated by commensals with resistance genes from different classes but different in \u03b1- and \u03b2-diversities. The third cluster was dominated by multidrug-resistant\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      , with SA characteristics of increased asthma duration, reduced pulmonary macrophages and decreased lung function. It had the highest signature expression of neutrophil activation, NETosis and of interleukin (IL)-5, IL-6, IL-13, IL-17 and IL-33 signalling pathways. These clusters were reproduced in an Asian-Singapore SA cohort including the multidrug-resistant\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      cluster, but with an additional cluster of multidrug-resistant\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The demonstration of U-BIOPRED multiresistant\n                      <jats:italic>H. Influenzae<\/jats:italic>\n                      and of Asian-Singapore multiresistant\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      clusters highlights the potential importance of antibiotic-resistant genes in driving severe asthma.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.01298-2025","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T16:50:17Z","timestamp":1761843017000},"page":"01298-2025","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidrug-resistant\n                    <i>Haemophilus influenzae<\/i>\n                    cluster of severe asthma from sputum bacteriome\u2013resistome"],"prefix":"10.1183","volume":"12","author":[{"given":"Fransiskus Xaverius","family":"Ivan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Versi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei Yee","family":"Tiew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-7137","authenticated-orcid":false,"given":"Mahmoud I.","family":"Abdel-Aziz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazanin Zounemat","family":"Kermani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke H.","family":"Maitland-Van Der Zee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0619-7927","authenticated-orcid":false,"given":"Peter","family":"Howarth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-0129","authenticated-orcid":false,"given":"Mariko Siyue","family":"Koh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-8843","authenticated-orcid":false,"given":"Ian M.","family":"Adcock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7607","authenticated-orcid":false,"given":"Sanjay H.","family":"Chotirmall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-1426","authenticated-orcid":false,"given":"Kian Fan","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"2026040703150842000_12.2.01298-2025.1","doi-asserted-by":"crossref","first-page":"e70007","DOI":"10.1002\/ctm2.70007","article-title":"A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia","volume":"14","author":"Versi","year":"2024","journal-title":"Clin Transl Med"},{"key":"2026040703150842000_12.2.01298-2025.2","doi-asserted-by":"publisher","DOI":"10.3390\/epidemiologia6020021"},{"key":"2026040703150842000_12.2.01298-2025.3","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12866-020-01785-9","article-title":"Extensively drug-resistant Haemophilus influenzae \u2013 emergence, epidemiology, risk factors, and regimen","volume":"20","author":"Su","year":"2020","journal-title":"BMC Microbiol"},{"key":"2026040703150842000_12.2.01298-2025.4","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-023-08930-5"},{"key":"2026040703150842000_12.2.01298-2025.5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201302-0289PP"},{"key":"2026040703150842000_12.2.01298-2025.6","doi-asserted-by":"crossref","unstructured":"Kwok WC , Pates K , Shah A , et al. 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