{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:58:13Z","timestamp":1791590293941,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL155095"],"award-info":[{"award-number":["R01 HL155095"]}],"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":["F32 HL154062"],"award-info":[{"award-number":["F32 HL154062"]}],"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":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Little is known about the immune responses during acute asthma exacerbation. In this study, we examined immune responses in children following an acute asthma exacerbation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated pro\u2010inflammatory cytokine levels and gene expression profiles in blood samples from pediatric patients admitted for acute asthma exacerbation. Viral PCR was performed to differentiate between viral or non\u2010viral\u2010associated exacerbations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following informed consent, clinical data were obtained from 20 children with asthma (median [interquartile range, IQR]: age 11.5 [8.0, 14.2]) years and 14 healthy age\u2010matched controls (10.5 [7.0, 13.0]). Twelve had positive nasopharyngeal Polymerase chain reaction (PCR) for viral infection (11 rhinoviruses and 1 respiratory syncytial virus (RSV)). Nine were in the pediatric intensive care unit (PICU) and among them five required continuous positive airway pressure (CPAP). Mean (\u00b1SD) days on systemic steroids before drawing blood sample were 2.5\u2009\u00b1\u20091.6. Twelve had history of environmental allergies with 917 (274, 1396) IU\/mL total IgE (median (IQR)). Compared with controls, IL\u20101RA and IL\u201010 levels were significantly increased and TNF\u2010\u03b1 significantly decreased in asthma subjects (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05 for all). RNA\u2010seq analysis revealed 852 differentially expressed genes in subjects with asthma. Pathway analysis found upregulated genes and pathways involved in innate immune responses in subjects with asthma. Significantly reduced genes included pathways associated with T helper cell differentiation and activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In acute asthma exacerbation, innate immune pathways remained increased while adaptive immune responses related to T helper cells are blunted and are independent of trigger or asthma severity. Our novel findings highlight the need to identify new therapies to target persistent innate immune responses to improve outcomes in acute asthma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.14173","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T06:21:30Z","timestamp":1718346090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Innate immune responses are increased in children with acute asthma exacerbation"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-5076","authenticated-orcid":false,"given":"Shahid","family":"Sheikh","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Ohio State University College of Medicine  Columbus Ohio USA"},{"name":"Division of Pulmonary Medicine Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"Abigail Wexner Research Institute Nationwide Children's Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4703-4342","authenticated-orcid":false,"given":"Mariah","family":"Eisner","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"Biostatistics Resource Nationwide Children's Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Walum","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Heyob","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiman Q.","family":"Khan","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Lewis","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Grayson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Ohio State University College of Medicine  Columbus Ohio USA"},{"name":"Abigail Wexner Research Institute Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"Division of Allergy &amp; Immunology Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"Center for Clinical and Translational Research  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kopp","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"McCoy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Ohio State University College of Medicine  Columbus Ohio USA"},{"name":"Division of Pulmonary Medicine Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"Abigail Wexner Research Institute Nationwide Children's Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0027-9545","authenticated-orcid":false,"suffix":"Jr","given":"Rodney","family":"Britt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Ohio State University College of Medicine  Columbus Ohio USA"},{"name":"Center for Perinatal Research  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69283-0"},{"key":"e_1_2_12_3_1","unstructured":"Prevention CfDCa.Asthma's Impact on the Nation. Data Statistics and Surveillance. Accessed March 25 2013.http:\/\/www.cdc.gov\/asthma\/asthmadata.htm"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2019"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2020.1860755"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab3142"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.08.020"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.16186"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2018.10.1.12"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060516680439"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9375967"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2016.11.006"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26261"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185056"},{"key":"e_1_2_12_15_1","unstructured":"AndrewsS.FastQC.2015.https:\/\/qubeshub.org\/resources\/fastqc"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.275193.120"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.213611.116"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky955"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts356"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-07304-4"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62801-6"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac166"},{"key":"e_1_2_12_24_1","volume-title":"Python 3 Reference Manual","author":"Van Rossum G","year":"2009"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3252"},{"key":"e_1_2_12_27_1","unstructured":"WickhamH.ggplot2: Elegant Graphics for Data Analysis.2016.https:\/\/ggplot2.tidyverse.org"},{"key":"e_1_2_12_28_1","unstructured":"BligheK RanaS LewisM.EnhancedVolcano: Publication\u2010ready volcano plots with enhanced colouring and labeling.2022.https:\/\/github.com\/kevinblighe\/EnhancedVolcano"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_2_12_30_1","unstructured":"BligheK LunA.PCAtools: Everything Principal Components Analysis.2022.https:\/\/github.com\/kevinblighe\/PCAtools"},{"key":"e_1_2_12_31_1","unstructured":"TeamRC.R: A Language and Environment for Statistical Computing.2022.https:\/\/www.R\u2010project.org\/"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.012"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.01.015"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacig.2023.100135"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.155.5.9154849"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(95)70128-1"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.3.9809071"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.13"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-019-0906-7"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101615"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02586.x"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.109925"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02743-z"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13388"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.129055"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.07.039"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.07.022"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00938-2018"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12345"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12093312"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021902"}],"container-title":["Pediatric Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pai.14173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T03:46:45Z","timestamp":1724125605000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pai.14173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/pai.14173"],"URL":"https:\/\/doi.org\/10.1111\/pai.14173","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/PAI.14173\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/PAI.14173\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/PAI.14173\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/PAI.14173\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/PAI.14173\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/PAI.14173\/v2\/response1","asserted-by":"object"}]},"ISSN":["0905-6157","1399-3038"],"issn-type":[{"value":"0905-6157","type":"print"},{"value":"1399-3038","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2024-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14173"}}