{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:41:21Z","timestamp":1787611281202,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI\u2010114552"],"award-info":[{"award-number":["R01 AI\u2010114552"]}],"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\u2010127507"],"award-info":[{"award-number":["R01 AI\u2010127507"]}],"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\u2010134940"],"award-info":[{"award-number":["R01 AI\u2010134940"]}],"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\u2010137091"],"award-info":[{"award-number":["R01 AI\u2010137091"]}],"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\u2010023253"],"award-info":[{"award-number":["UG3\/UH3 OD\u2010023253"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While infant bronchiolitis contributes to substantial acute (eg, severity) and chronic (eg, asthma development) morbidities, its pathobiology remains uncertain. We examined the integrated relationships of local (nasopharyngeal) and systemic (serum) responses with bronchiolitis morbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we applied a network analysis approach to identify distinct networks (modules)\u2014clusters of densely interconnected metabolites\u2014of the nasopharyngeal and serum metabolome. We examined their\n                      <jats:italic>individual<\/jats:italic>\n                      and\n                      <jats:italic>integrated<\/jats:italic>\n                      relationships with acute severity (defined by positive pressure ventilation [PPV] use) and asthma development by age 5\u00a0years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 140 infants, we identified 285 nasopharyngeal and 639 serum metabolites. Network analysis revealed 7 nasopharyngeal and 8 serum modules. At the\n                      <jats:italic>individual<\/jats:italic>\n                      module level, nasopharyngeal\u2010amino acid, tricarboxylic acid (TCA) cycle, and carnitine modules were associated with higher risk of PPV use (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0&gt;\u00a0.20;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001), while serum\u2010carnitine, amino acid, and glycerophosphorylcholine (GPC)\/glycerophosphorylethanolamine (GPE) modules were associated with lower risk (all\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0&lt;\u00a0\u2212.20;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). The\n                      <jats:italic>integrated<\/jats:italic>\n                      analysis for PPV use revealed consistent findings\u2014for example, nasopharyngeal\u2010TCA (adjOR: 2.87, 95% CI: 1.68\u201012.2) and serum\u2010GPC\/GPE (adjOR: 0.54, 95% CI: 0.38\u20100.80) modules\u2014and an additional module\u2014serum\u2010glucose\u2010alanine cycle module (adjOR: 0.69, 95% CI: 0.56\u20100.86). With asthma risk, there were no\n                      <jats:italic>individual<\/jats:italic>\n                      associations, but there were\n                      <jats:italic>integrated<\/jats:italic>\n                      associations (eg, nasopharyngeal\u2010carnitine module; adjOR: 1.48, 95% CI: 1.11\u20101.99).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In infants with bronchiolitis, we found integrated relationships of local and systemic metabolome networks with acute and chronic morbidity. Our findings advance research into the complex interplay among respiratory viruses, local and systemic response, and disease pathobiology in infants with bronchiolitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.13466","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T22:57:23Z","timestamp":1612911443000},"page":"905-916","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Integrated associations of nasopharyngeal and serum metabolome with bronchiolitis severity and asthma: A multicenter prospective cohort study"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4179-3612","authenticated-orcid":false,"given":"Michimasa","family":"Fujiogi","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Carlos A.","family":"Camargo","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-9369","authenticated-orcid":false,"given":"Yoshihiko","family":"Raita","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozhong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Celed\u00f3n","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Pediatrics UPMC Children's Hospital of Pittsburgh University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Mansbach","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Boston Children\u2019s Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4658-5353","authenticated-orcid":false,"given":"Jonathan M.","family":"Spergel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Perelman School of Medicine and Division of Allergy and Immunology Children's Hospital of Philadelphia Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2014.906901"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13624"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-2614"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.33"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.02.010"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.121582"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.02.021"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2012.01283.x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00152-2016"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw456"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.309"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0742-8"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13723"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix680"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13101"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz021"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201701-0071OC"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-2742"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-0442"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2018.05.038"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1128"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2016.09.016"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000021478"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.86"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq329"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/00401706.2000.10485983"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_12_30_1","unstructured":"KuhnM.Caret: classification and regression training.2020. https:\/\/cran.r\u2010project.org\/package=caret.https:\/\/cran.r\u2010project.org\/package=caret."},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511802843"},{"key":"e_1_2_12_32_1","unstructured":"CantyA RipleyBD.Boot: bootstrap R (S\u2010Plus) functions.2020."},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2016.1190647"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.12.1004"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14326"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13296"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.01.014"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3704"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/19768354.2017.1405072"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.05.008"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0921"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0354"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111227"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00011"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09619-x"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2895-8_5"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-951305"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-200X.1997.tb03606.x"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-009-0011-8"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/509730"},{"issue":"6","key":"e_1_2_12_51_1","first-page":"295","article-title":"The role of L\u2010carnitine in treatment of a murine model of asthma","volume":"56","author":"Uzuner N","year":"2002","journal-title":"Acta Med Okayama"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32833489c3"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.11.025"}],"container-title":["Pediatric Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pai.13466","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pai.13466","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pai.13466","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T14:59:58Z","timestamp":1693407598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pai.13466"}},"subtitle":[],"editor":[{"given":"\u00d6mer","family":"Kalayc\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/pai.13466"],"URL":"https:\/\/doi.org\/10.1111\/pai.13466","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/PAI.13466\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/PAI.13466\/v1\/review1","asserted-by":"object"}]},"ISSN":["0905-6157","1399-3038"],"issn-type":[{"value":"0905-6157","type":"print"},{"value":"1399-3038","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]},"assertion":[{"value":"2020-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}