{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T09:46:09Z","timestamp":1792835169599,"version":"4.5.0"},"reference-count":60,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"funder":[{"DOI":"10.13039\/100002590","name":"American Lung Association","doi-asserted-by":"publisher","award":["INALA2023"],"award-info":[{"award-number":["INALA2023"]}],"id":[{"id":"10.13039\/100002590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007229","name":"Harvard University","doi-asserted-by":"publisher","award":["Eleanor and Miles Shore Faculty Development Award"],"award-info":[{"award-number":["Eleanor and Miles Shore Faculty Development Award"]}],"id":[{"id":"10.13039\/100007229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007229","name":"Harvard University","doi-asserted-by":"publisher","award":["William F. Milton Fund"],"award-info":[{"award-number":["William F. Milton Fund"]}],"id":[{"id":"10.13039\/100007229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01 AI-153558"],"award-info":[{"award-number":["K01 AI-153558"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI-114552"],"award-info":[{"award-number":["R01 AI-114552"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI-127507"],"award-info":[{"award-number":["R01 AI-127507"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI-134940"],"award-info":[{"award-number":["R01 AI-134940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI-137091"],"award-info":[{"award-number":["R01 AI-137091"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI-148338"],"award-info":[{"award-number":["R01 AI-148338"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI-087881"],"award-info":[{"award-number":["U01 AI-087881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UG3\/UH3 OD-023253"],"award-info":[{"award-number":["UG3\/UH3 OD-023253"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2024,9,8]]},"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Infants with bronchiolitis are at increased risk of developing asthma. Growing evidence suggests bronchiolitis is a heterogeneous condition. However, little is known about its biologically distinct subgroups based on the integrated metagenome and asthma genetic risk signature and their longitudinal relationships with asthma development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a multicentre prospective cohort study of infants with severe bronchiolitis (<jats:italic>i.e.<\/jats:italic>bronchiolitis requiring hospitalisation), we profiled nasopharyngeal airway metagenome and virus at hospitalisation, and calculated the polygenic risk score of asthma. Using similarity network fusion clustering approach, we identified integrated metagenome\u2013asthma genetic risk endotypes. In addition, we examined their longitudinal association with the risk of developing asthma by the age of 6\u2005years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Out of 450 infants with bronchiolitis (median age 3\u2005months), we identified five distinct endotypes, characterised by their nasopharyngeal metagenome, virus and asthma genetic risk profiles. Compared with endotype A infants (who clinically resembled \u201cclassic\u201d bronchiolitis), endotype E infants (characterised by a high abundance of<jats:italic>Haemophilus influenzae<\/jats:italic>, high proportion of rhinovirus (RV)-A and RV-C infections and high asthma genetic risk) had a significantly higher risk of developing asthma (16.7%<jats:italic>versus<\/jats:italic>35.9%; adjusted OR 2.24, 95% CI 1.02\u20134.97; p=0.046). The pathway analysis showed that endotype E had enriched microbial pathways (<jats:italic>e.g.<\/jats:italic>glycolysis,<jats:sc>l<\/jats:sc>-lysine, arginine metabolism) and host pathways (<jats:italic>e.g.<\/jats:italic>interferons, interleukin-6\/Janus kinase\/signal transducers and activators of transcription-3, fatty acids, major histocompatibility complex and immunoglobin-related) (false discovery rate (FDR)&lt;0.05). Additionally, endotype E had a significantly higher proportion of neutrophils (FDR&lt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this multicentre prospective cohort study of infant bronchiolitis, the clustering analysis of integrated-omics data identified biologically distinct endotypes with differential risks of developing asthma.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.01130-2024","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T15:41:18Z","timestamp":1727365278000},"page":"2401130","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Integrated nasopharyngeal airway metagenome and asthma genetic risk endotyping of severe bronchiolitis in infancy and risk of childhood asthma"],"prefix":"10.1183","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5662-1541","authenticated-orcid":false,"given":"Zhaozhong","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6195-441X","authenticated-orcid":false,"given":"Ryohei","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi L.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juwan","family":"Cormier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Mansbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5071-7654","authenticated-orcid":false,"suffix":"Jr","given":"Carlos A.","family":"Camargo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"2024123106451270000_64.6.2401130.1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-2614"},{"key":"2024123106451270000_64.6.2401130.2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-043956"},{"key":"2024123106451270000_64.6.2401130.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101257"},{"key":"2024123106451270000_64.6.2401130.4","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad093"},{"key":"2024123106451270000_64.6.2401130.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00811-5"},{"key":"2024123106451270000_64.6.2401130.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.01.020"},{"key":"2024123106451270000_64.6.2401130.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.08.035"},{"key":"2024123106451270000_64.6.2401130.8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1187065"},{"key":"2024123106451270000_64.6.2401130.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.04.017"},{"key":"2024123106451270000_64.6.2401130.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32323-y"},{"key":"2024123106451270000_64.6.2401130.11","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00502-2023"},{"key":"2024123106451270000_64.6.2401130.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41300-y"},{"key":"2024123106451270000_64.6.2401130.13","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02187-2023"},{"key":"2024123106451270000_64.6.2401130.14","doi-asserted-by":"publisher","DOI":"10.1111\/all.15390"},{"key":"2024123106451270000_64.6.2401130.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.05.036"},{"key":"2024123106451270000_64.6.2401130.16","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02293-2021"},{"key":"2024123106451270000_64.6.2401130.17","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz021"},{"key":"2024123106451270000_64.6.2401130.18","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201701-0071OC"},{"key":"2024123106451270000_64.6.2401130.19","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-2742"},{"key":"2024123106451270000_64.6.2401130.20","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65088"},{"key":"2024123106451270000_64.6.2401130.21","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3176"},{"key":"2024123106451270000_64.6.2401130.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"2024123106451270000_64.6.2401130.23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"2024123106451270000_64.6.2401130.24","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad156"},{"key":"2024123106451270000_64.6.2401130.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104742"},{"key":"2024123106451270000_64.6.2401130.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2020.10.001"},{"key":"2024123106451270000_64.6.2401130.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.09.029"},{"key":"2024123106451270000_64.6.2401130.28","doi-asserted-by":"publisher","DOI":"10.1186\/2045-7022-2-24"},{"key":"2024123106451270000_64.6.2401130.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100212"},{"key":"2024123106451270000_64.6.2401130.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100241"},{"key":"2024123106451270000_64.6.2401130.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09718-5"},{"key":"2024123106451270000_64.6.2401130.32","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02224"},{"key":"2024123106451270000_64.6.2401130.33","doi-asserted-by":"crossref","unstructured":"Satopaa V , Albrecht J , Irwin D , et al. Finding a \u201ckneedle\u201d in a haystack: detecting knee points in system behavior. 31st International Conference on Distributed Computing Systems Workshops; 20\u201324 June 2011. Minneapolis, IEEE, 2011. pp. 166\u2013171. DOI:10.1109\/ICDCSW.2011.20","DOI":"10.1109\/ICDCSW.2011.20"},{"key":"2024123106451270000_64.6.2401130.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23859-6"},{"key":"2024123106451270000_64.6.2401130.35","doi-asserted-by":"crossref","unstructured":"Korotkevich G , Sukhov V , Budin N , et al. Fast gene set enrichment analysis. bioRxiv 2021; preprint [https:\/\/doi.org\/10.1101\/060012].","DOI":"10.1101\/060012"},{"key":"2024123106451270000_64.6.2401130.36","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"2024123106451270000_64.6.2401130.37","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"2024123106451270000_64.6.2401130.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.08.043"},{"key":"2024123106451270000_64.6.2401130.39","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00832-2023"},{"key":"2024123106451270000_64.6.2401130.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42309-z"},{"key":"2024123106451270000_64.6.2401130.41","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00471-2023"},{"key":"2024123106451270000_64.6.2401130.42","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202211-2107OC"},{"key":"2024123106451270000_64.6.2401130.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.08.026"},{"key":"2024123106451270000_64.6.2401130.44","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211592"},{"key":"2024123106451270000_64.6.2401130.45","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2830"},{"key":"2024123106451270000_64.6.2401130.46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01746.x"},{"key":"2024123106451270000_64.6.2401130.47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1028209"},{"key":"2024123106451270000_64.6.2401130.48","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03312-2020"},{"key":"2024123106451270000_64.6.2401130.49","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2193"},{"key":"2024123106451270000_64.6.2401130.50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.649520"},{"key":"2024123106451270000_64.6.2401130.51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005913"},{"key":"2024123106451270000_64.6.2401130.52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.637948"},{"key":"2024123106451270000_64.6.2401130.53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01029.x"},{"key":"2024123106451270000_64.6.2401130.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.07.004"},{"key":"2024123106451270000_64.6.2401130.55","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110711-155532"},{"key":"2024123106451270000_64.6.2401130.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0121-0"},{"key":"2024123106451270000_64.6.2401130.57","doi-asserted-by":"publisher","DOI":"10.2217\/fvl.15.55"},{"key":"2024123106451270000_64.6.2401130.58","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12642"},{"key":"2024123106451270000_64.6.2401130.59","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.16852"},{"key":"2024123106451270000_64.6.2401130.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.11.025"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.01130-2024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T07:23:10Z","timestamp":1740381790000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.01130-2024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,12,19]]},"published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1183\/13993003.01130-2024"],"URL":"https:\/\/doi.org\/10.1183\/13993003.01130-2024","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,26]]}}}