{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:00:02Z","timestamp":1780066802507,"version":"3.54.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although respiratory pathology is known to develop in young children with cystic fibrosis (CF), the determinants of early\u2010onset lung disease have not been elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to determine the impact of potential intrinsic and extrinsic risk factors during the first 3 years of life, testing the hypothesis that both contribute significantly to early\u2010onset CF lung disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We studied 104 infants born during 2012\u20132017, diagnosed through newborn screening by age 3 months, and evaluated comprehensively to 36 months of age. Lung disease manifestations were quantified with a new scoring system known as CFELD for Cystic Fibrosis Early\u2010onset Lung Disease. The variants in the cystic fibrosis transmembrane conductance regulator (<jats:italic>CFTR<\/jats:italic>) gene were determined and categorized. Whole genome sequencing was performed on each subject and the data transformed to polygenic risk scores (PRS) that aggregate variants associated with lung function. Extrinsic factors included socioeconomic status (SES) indicators and environmental experiences such as exposures to smoking, pets, and daycare.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found by univariate analysis that <jats:italic>CFTR<\/jats:italic> genotype and genetic modifiers aggregated by the PRS method were significantly associated with early\u2010onset CF lung disease. Ordinal logistic regression analysis demonstrated that high and stable SES (maternal education \u2265community college, stable 2\u2010parent home, and not receiving Medicaid) and better growth (weight\u2010for\u2010age and height\u2010for\u2010age <jats:italic>z<\/jats:italic>\u2010scores) reduced risks, while exposure to smoking and daycare \u226520\u2009h\/week increased the risk of CFELD severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Extrinsic, modifiable determinants are influential early and potentially as important as the intrinsic risk factors in the onset of CF lung disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.26625","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T11:41:15Z","timestamp":1691149275000},"page":"3071-3082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of intrinsic and extrinsic risk factors on early\u2010onset lung disease in cystic fibrosis"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9778-8102","authenticated-orcid":false,"given":"Leslie","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-3988","authenticated-orcid":false,"given":"HuiChuan J.","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA"},{"name":"Department of Nutritional Sciences University of Wisconsin College of Agriculture and Life Sciences Madison Wisconsin USA"},{"name":"Department of Population Health Sciences University of Wisconsin School of Medicine of Public Health Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Statistics University of Wisconsin College of Letters and Sciences Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Statistics University of Wisconsin College of Letters and Sciences Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongshi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Statistics University of Wisconsin College of Letters and Sciences Madison Wisconsin USA"},{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangita G.","family":"Murali","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Wisconsin College of Agriculture and Life Sciences Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Genetics Center for Computational Genomics and Data Science at the UAB Marnix E. Heersink School of Medicine Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Worthey","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Genetics Center for Computational Genomics and Data Science at the UAB Marnix E. Heersink School of Medicine Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0036-7016","authenticated-orcid":false,"given":"Philip M.","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA"},{"name":"Department of Population Health Sciences University of Wisconsin School of Medicine of Public Health Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30337-6"},{"key":"e_1_2_10_3_1","first-page":"94","article-title":"Observations in cystic fibrosis of the pancreas. 3. Pulmonary lesions","volume":"122","author":"Esterly JR","year":"1968","journal-title":"Johns Hopkins Med J"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(76)80023-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200901-0069OC"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.05.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301725"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26040"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2020.06.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201610-2158OC"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199011293232203"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05879.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2005.09.008"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2016.1196140"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-0345"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2019-213179"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.05.018"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202102-0509OC"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25825"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnesp.2022.07.018"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00742-5"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0321-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1605086"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.09.001"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-1784"},{"issue":"9","key":"e_1_2_10_26_1","first-page":"1","article-title":"Use of world health organization and CDC growth charts for children aged 0\u201059 months in the United States","volume":"59","author":"Grummer\u2010Strawn LM","year":"2010","journal-title":"Morb Mortality Weekly Report. Recommend Reports"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-3552"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp589"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09718-5"},{"key":"e_1_2_10_30_1","unstructured":"Cystic Fibrosis Foundation. Patient Registry 2021 Annual Data Report.Bethesda Maryland:2021.https:\/\/www.cff.org\/sites\/default\/files\/2021-11\/Patient-Registry-Annual-Data-Report.pdf"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.130.5.1441"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202209-1653OC"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23317"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-0496(199808)26:2<81::AID-PPUL2>3.0.CO;2-K"},{"key":"e_1_2_10_35_1","first-page":"1170","article-title":"Early childhood risk factors for decreased FEV1 at age six to seven years in young children with cystic fibrosis","volume":"12","author":"Sanders DB","year":"2015","journal-title":"Ann Am Thorac Soc"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2012.04.003"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-199302000-00006"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770903.2011.604884"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-014635"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2004.11.007"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200010001-00004"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202010-1274ED"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2020.0029"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/0890334415618668"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051469"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9382"},{"key":"e_1_2_10_47_1","first-page":"1040","article-title":"Complex two\u2010gene modulation of lung disease severity in children with cystic fibrosis","volume":"118","author":"Dorfman R","year":"2008","journal-title":"J Clin Invest"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.26625","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:50:39Z","timestamp":1740617439000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.26625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/ppul.26625"],"URL":"https:\/\/doi.org\/10.1002\/ppul.26625","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]},"assertion":[{"value":"2023-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}