{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:09:43Z","timestamp":1788844183244,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["K01HL166436"],"award-info":[{"award-number":["K01HL166436"]}],"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":["R03HS029088"],"award-info":[{"award-number":["R03HS029088"]}],"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":[[2026,6]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Evidence supporting inhaled corticosteroid plus long\u2010acting \u03b2\n 2<\/jats:sub>\n \u2010agonist (ICS\u2009+\u2009LABA) therapy in preschool children with asthma remains limited, and guideline recommendations remain cautious. However, real\u2010world effectiveness in high\u2010risk young children has not been adequately characterized.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate short\u2010 and long\u2010term effectiveness of ICS\u2009+\u2009LABA initiation on severe asthma exacerbations (SAEs) and determine whether early\u2010life asthma risk burden modifies treatment response.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a retrospective longitudinal cohort study using electronic health record data from the Indiana Network for Patient Care (2010\u20132024). Children aged \u226411\u2009years with asthma who initiated ICS\u2009+\u2009LABA between 2010 and 2023 and had \u226512\u2009months of pre\u2010 and post\u2010initiation follow\u2010up were included. The primary outcome was \u22651 SAE per year, defined per ATS\/ERS criteria as asthma\u2010related hospitalization or emergency department admission. Piecewise generalized linear mixed\u2010effects models estimated annualized changes in SAE odds before versus after ICS\u2009+\u2009LABA initiation. Recurrent events were analyzed using Andersen\u2013Gill models. Effect modification by age at diagnosis, age at prior ICS initiation, and early\u2010life asthma risk burden (passive digital marker [PDM] score) was assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 249 children (mean age at asthma diagnosis 2\u2009years; at ICS\u2009+\u2009LABA initiation 5\u2009years), annualized SAE incidence increased before initiation and declined thereafter. Adjusted SAE odds decreased by 15% per year following ICS\u2009+\u2009LABA initiation (aOR 0.85; 95% CI 0.58\u20130.98). Recurrent\u2010event modeling demonstrated a 68% reduction in SAE hazard after ICS\u2009+\u2009LABA initiation (aHR 0.32; 95% CI 0.26\u20130.38), exceeding reductions observed with ICS alone (aHR 0.49). Treatment benefit was greatest among children initiating ICS before age 5\u2009years (aOR 0.77; 95% CI 0.65\u20130.92) and those with high early\u2010life asthma risk burden (aOR 0.80; 95% CI 0.67\u20100.97). No significant heterogeneity was observed by sex, race, or formulation.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n ICS\u2009+\u2009LABA initiation was associated with sustained reductions in severe exacerbations, including among preschool children, in real\u2010world clinical practice. These findings suggest that strict age\u2010based treatment restrictions may not fully capture heterogeneity in exacerbation risk and support further prospective evaluation of risk\u2010stratified escalation strategies.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/pai.70411","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T03:51:09Z","timestamp":1781495469000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early initiation of inhaled corticosteroid\u2013long\u2010acting \u03b2\n 2<\/sub>\n \u2010agonist therapy and reduction of severe asthma exacerbations in high\u2010risk preschool children: A longitudinal real\u2010world cohort study"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4580-7428","authenticated-orcid":false,"given":"Arthur H.","family":"Owora","sequence":"first","affiliation":[{"name":"Division of Pediatric Pulmonology, Allergy\/Immunology and Sleep Medicine, Department of Pediatrics Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Center for Biomedical Informatics, Regenstrief Institute Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Allergy\/Immunology and Sleep Medicine, Department of Pediatrics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Allergy\/Immunology and Sleep Medicine, Department of Pediatrics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2024.09.002"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005535.pub2"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005533.pub2"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta12200"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-108852"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2012.05.006"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13010"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/02770903.2018.1474923"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1081\/JAS-120033986"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.562843"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.146845"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.12.1033"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022363"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2010.12.007"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.11.042"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.11.014"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201702-101OC"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24782"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02241-2018"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00339-2019"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13403"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000338"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200801-060ST"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2025.103254"},{"key":"e_1_2_13_26_1","unstructured":"HussonF JosseJ PagesJ.Principal component methods\u2014hierarchical clustering\u2014partitional clustering: why would we need to choose for visualizing data? 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