{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:54:34Z","timestamp":1790906074101,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL162570"],"award-info":[{"award-number":["R01 HL162570"]}],"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 HL127332"],"award-info":[{"award-number":["R01 HL127332"]}],"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 HL129935"],"award-info":[{"award-number":["R01 HL129935"]}],"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 HL161362"],"award-info":[{"award-number":["R01 HL161362"]}],"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 HL139634"],"award-info":[{"award-number":["R01 HL139634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570048"],"award-info":[{"award-number":["82570048"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20230807110302006"],"award-info":[{"award-number":["JCYJ20230807110302006"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20240813150456074"],"award-info":[{"award-number":["JCYJ20240813150456074"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20250604143521027"],"award-info":[{"award-number":["JCYJ20250604143521027"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["A2024136"],"award-info":[{"award-number":["A2024136"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202411013"],"award-info":[{"award-number":["SZSM202411013"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Piwi\u2010interacting RNAs (piRNAs) have been linked to type 2\u2010high asthma phenotypes. Although vitamin D modulates inhaled corticosteroid (ICS) response via microRNAs, its potential role through piRNAs remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Baseline plasma piRNA expression was profiled by small RNA sequencing in 492 participants from the Childhood Asthma Management Program (CAMP), with 187 children randomised to the ICS arm. Serum vitamin D levels were classified as insufficient (\u2264\u200930\u2009ng\/mL) or sufficient (&gt;\u200930\u2009ng\/mL). Linear regression was used to assess associations between piRNA expression and changes in prebronchodilator percent predicted forced expiratory volume in 1 s (FEV\n                      <jats:sub>1<\/jats:sub>\n                      %) over 4\u2009years, including interaction analyses with vitamin D status. Replication was performed in 375 ICS\u2010treated participants from the Genetics of Asthma in Costa Rica Study (GACRS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fourteen piRNAs were significantly associated with FEV\n                      <jats:sub>1<\/jats:sub>\n                      % changes among vitamin D\u2013insufficient children, six showing significant interactions with vitamin D status (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Four piRNAs were replicated in GACRS, with piR\u201036241 also confirmed in interaction analyses. Predicted targets of piR\u201036241 were enriched in immune\u2010 and respiratory\u2010related pathways. piR\u201036241 demonstrated strong predictive performance for ICS response in vitamin D\u2013insufficient children (AUROC\u2009=\u20090.84) and was detected in bronchial epithelial cells, where it was differentially expressed in asthma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating piRNAs are associated with ICS response in childhood asthma, with vitamin D acting as an effect modifier, which may serve as non\u2010invasive biomarkers for ICS responsiveness, particularly in vitamin D\u2013insufficient patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      Identifier: NCT00000575 and\u00a0NCT00021840\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cea.70314","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:20:23Z","timestamp":1776741623000},"page":"1215-1223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Piwi\u2010Interacting RNAs Associate With Childhood Asthma ICS Response With Vitamin D Effect Modification"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9226-0536","authenticated-orcid":false,"given":"Jiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"},{"name":"Department of Otolaryngology, The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"},{"name":"Institute of Cell and Gene Technology Shenzhen University of Advanced Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"},{"name":"Department of Otolaryngology, The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengshi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin T.","family":"Kho","sequence":"additional","affiliation":[{"name":"The Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Computational Health Informatics Program Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2197-5563","authenticated-orcid":false,"given":"Zhongxu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Biomics Center, Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences The Hong Kong Polytechnic University  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, Joint International Research Laboratory of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Allergy and Clinical Immunology Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"McGeachie","sequence":"additional","affiliation":[{"name":"The Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Celed\u00f3n","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Weiss","sequence":"additional","affiliation":[{"name":"The Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelan G.","family":"Tantisira","sequence":"additional","affiliation":[{"name":"The Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Pediatrics, Division of Respiratory Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"},{"name":"Department of Otolaryngology, The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"},{"name":"The Channing Division of Network Medicine, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01037-2"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00367-2"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00757-8"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02730-2021"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.05.034"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(23)00128-1"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.122635"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh149"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201907-1454OC"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-022-00732-z"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2017.09.001"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.954768"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00029011"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201202-0351OC"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.03.043"},{"issue":"2","key":"e_1_2_13_17_1","article-title":"Vitamin D for the Management of Asthma","volume":"2","author":"Williamson A.","year":"2023","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1586\/ers.12.85"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21759"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax\u20102024\u2010222618"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30306-5"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0073-3"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.09.003"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01724-5"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-023-02367-9"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.10.032"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200010123431501"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-61495-0"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v028.i05"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139019"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1012"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl243"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(98)00044-0"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.067934"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bay059"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.664044"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/14.5.513"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adf4699"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45854-3"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-021-00145-5"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00782-8"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2493-4"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.70314","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cea.70314","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.70314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:17:45Z","timestamp":1790903865000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.70314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/cea.70314"],"URL":"https:\/\/doi.org\/10.1111\/cea.70314","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}