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Analyses included longitudinal differential gene expression, weighted gene co-expression network analysis, and cis-expression quantitative trait loci analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and main results<\/jats:title>\n                    <jats:p>At age 1 year, 42 genes, mostly upregulated in future asthmatics, were associated with neutrophilic inflammation and NLRP3 inflammasome-markers. By 4.5\u2009years, this shifted to a novel eosinophil-related signature (40 genes), remaining increased in asthmatics until 10.5\u2009years. Co-expression analysis confirmed a neutrophilic module at 1\u2009year and eosinophilic modules at 4.5, 6, and 10.5\u2009years, all associated with asthma. Fractional exhaled nitric oxide was associated with the eosinophilic module at age 6 years (P\u2009=\u2009.003). A total of 86 SNPs were identified modulating the expression of 10 eosinophil-associated genes and GSDMB from this eosinophilic signature. A variant-based genetic risk score was associated with asthma diagnosis (adjusted odds ratio [aOR], 1.47; 95% CI, 1.13-1.93).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified a shift from a neutrophil-driven gene signature at age\u202f1 year to a persistent eosinophilic signature at 4.5-10.5\u2009years in asthmatic children, highlighting the 1- to 4.5-year period as the most vulnerable period. Genetic variants strongly influenced the persistent eosinophilic gene signature, comprising potential novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag142","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:36:43Z","timestamp":1774355803000},"page":"1214-1226","source":"Crossref","is-referenced-by-count":1,"title":["Early neutrophil and persistent eosinophil-associated gene signature in childhood asthma"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5650-9984","authenticated-orcid":false,"given":"Francesco","family":"Foppiano","sequence":"first","affiliation":[{"name":"Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children\u2019s Hospital, LMU Munich , Munich,","place":["Germany"]},{"name":"Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Faculty of Medicine, LMU Munich, Pettenkofer School of Public Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4511-7769","authenticated-orcid":false,"given":"Andreas","family":"B\u00f6ck","sequence":"additional","affiliation":[{"name":"Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children\u2019s Hospital, LMU Munich , Munich,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), LMU Munich , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-4659","authenticated-orcid":false,"given":"Claudia","family":"Beerweiler","sequence":"additional","affiliation":[{"name":"Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children\u2019s Hospital, LMU Munich , Munich,","place":["Germany"]},{"name":"German Center for Lung Research (DZL), Comprehensive Pneumology Center (CPC-M), University of Munich, LMU Munich , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3832-3896","authenticated-orcid":false,"given":"Kathrin","family":"Urner","sequence":"additional","affiliation":[{"name":"Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children\u2019s Hospital, LMU Munich , Munich,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), LMU Munich , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6643-3923","authenticated-orcid":false,"given":"Markus","family":"Ege","sequence":"additional","affiliation":[{"name":"Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children\u2019s Hospital, LMU Munich , Munich,","place":["Germany"]},{"name":"German Center for Lung Research (DZL), Comprehensive Pneumology Center (CPC-M), University of Munich, LMU Munich , 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