{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:00:03Z","timestamp":1781686803079,"version":"3.54.5"},"reference-count":47,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005639","name":"Universidade de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005639","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.jaci.2025.12.1015","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T07:42:22Z","timestamp":1769758942000},"page":"1061-1070","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-dependent differences in airway inflammation and function in severe uncontrolled asthma"],"prefix":"10.1016","volume":"157","author":[{"given":"J\u00f4se M\u00e1ra","family":"de Brito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia","family":"de Souza Xavier Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogenes Seraphim","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Pierantozzi","family":"Vergani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina Maria","family":"de Carvalho-Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Vicente Ribeiro Ferreira","family":"da Silva-Filho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Abensur","family":"Athanazio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim Carlos","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais","family":"Mauad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-5480","authenticated-orcid":false,"given":"Miriam Cardoso Neves","family":"Eller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaci.2025.12.1015_bib1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1183\/09031936.00202013","article-title":"International ERS\/ATS guidelines on definition, evaluation and treatment of severe asthma","volume":"43","author":"Chung","year":"2014","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2025.12.1015_bib3","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jaci.2014.08.042","article-title":"The prevalence of severe refractory asthma","volume":"135","author":"Hekking","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib4","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.2147\/JAA.S327659","article-title":"Severe asthma in a general population study: prevalence and clinical characteristics","volume":"14","author":"R\u00f6nnebjerg","year":"2021","journal-title":"J Asthma Allergy"},{"key":"10.1016\/j.jaci.2025.12.1015_bib5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2147\/JAA.S129159","article-title":"Managing the pediatric patient with refractory asthma: a multidisciplinary approach","volume":"10","author":"Cook","year":"2017","journal-title":"J Asthma Allergy"},{"key":"10.1016\/j.jaci.2025.12.1015_bib6","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1183\/13993003.00780-2015","article-title":"The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts","volume":"46","author":"Fleming","year":"2015","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2025.12.1015_bib7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0091-6749(00)90184-2","article-title":"Basophils, eosinophils, and mast cells in atopic and nonatopic asthma and in late-phase allergic reactions in the lung and skin","volume":"105","author":"Macfarlane","year":"2000","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib8","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/all.13323","article-title":"Airway pathology in severe asthma is related to airflow obstruction but not symptom control","volume":"73","author":"Ferreira","year":"2018","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2025.12.1015_bib9","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3389\/fped.2017.00154","article-title":"Mechanisms mediating pediatric severe asthma and potential novel therapies","volume":"5","author":"Martin Alonso","year":"2017","journal-title":"Front Pediatr"},{"key":"10.1016\/j.jaci.2025.12.1015_bib10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jaci.2011.08.011","article-title":"Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma","volume":"129","author":"Tsitsiou","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib11","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1164\/ajrccm.164.4.2102018","article-title":"Activated, cytotoxic CD8+ T lymphocytes contribute to the pathology of asthma death","volume":"164","author":"O\u2019Sullivan","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib12","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1164\/rccm.200504-619OC","article-title":"Bronchial CD8 cell infiltrate and lung function decline in asthma","volume":"172","author":"van Rensen","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib13","doi-asserted-by":"crossref","DOI":"10.1177\/03946320221114194","article-title":"Identification of potential biomarkers and immune infiltration characteristics in severe asthma","volume":"36","author":"Jiang","year":"2022","journal-title":"Int J Immunopathol Pharmacol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib14","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1183\/13993003.00947-2016","article-title":"Mast cells are associated with exacerbations and eosinophilia in children with severe asthma","volume":"48","author":"Lezmi","year":"2016","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2025.12.1015_bib16","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1002\/ppul.24075","article-title":"Can inflammatory markers in induced sputum be used to detect phenotypes and endotypes of pediatric severe therapy-resistant asthma?","volume":"53","author":"Eller","year":"2018","journal-title":"Pediatr Pulmonol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib17","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/s12931-022-02259-4","article-title":"Bronchial eosinophils, neutrophils, and CD8+ T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma","volume":"23","author":"Eller","year":"2022","journal-title":"Respir Res"},{"key":"10.1016\/j.jaci.2025.12.1015_bib18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.rmed.2011.08.013","article-title":"Clinical characteristics and possible phenotypes of an adult severe asthma population","volume":"106","author":"de Carvalho-Pinto","year":"2012","journal-title":"Respir Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib19","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1183\/09031936.01.17203020","article-title":"Plethysmographic measurements of lung volume and airway resistance","volume":"17","author":"Stocks","year":"2001","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2025.12.1015_bib20","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2025.12.1015_bib21","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1164\/rccm.9120-11ST","article-title":"An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FeNO) for clinical applications","volume":"184","author":"Dweik","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib22","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1164\/rccm.200406-710ST","article-title":"ATS\/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005","volume":"171","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib23","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1164\/ajrccm.154.2.8756799","article-title":"Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements","volume":"154","author":"Pizzichini","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib24","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.aanat.2013.05.003","article-title":"Immune cell profile in infants\u2019 lung tissue","volume":"195","author":"dos Santos","year":"2013","journal-title":"Ann Anat"},{"key":"10.1016\/j.jaci.2025.12.1015_bib25","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3109\/08958371003621633","article-title":"Subchronic effects of nasally instilled diesel exhaust particulates on the nasal and airway epithelia in mice","volume":"22","author":"Yoshizaki","year":"2010","journal-title":"Inhal Toxicol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib26","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.jaip.2022.02.002","article-title":"Personalized treatment of asthma: the importance of sex and gender differences","volume":"10","author":"Jenkins","year":"2022","journal-title":"J Allergy Clin Immunol Pract"},{"key":"10.1016\/j.jaci.2025.12.1015_bib27","series-title":"Sex-based differences in lung physiology","first-page":"13","article-title":"Sex differences in the anatomy of the airways and the lungs: impact on dysanapsis across the lifespan","author":"LoMauro","year":"2021"},{"key":"10.1016\/j.jaci.2025.12.1015_bib28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1136\/thorax-2023-220512","article-title":"Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care","volume":"79","author":"Loewenthal","year":"2024","journal-title":"Thorax"},{"key":"10.1016\/j.jaci.2025.12.1015_bib29","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3390\/cells13050384","article-title":"Eosinophilic asthma: pathophysiology and therapeutic horizons","volume":"13","author":"Hussain","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.jaci.2025.12.1015_bib30","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1183\/13993003.00779-2015","article-title":"Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort","volume":"46","author":"Shaw","year":"2015","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2025.12.1015_bib31","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.4049\/jimmunol.1202790","article-title":"Cutting edge: rapid boosting of cross-reactive memory CD8 T cells broadens the protective capacity of the Flumist vaccine","volume":"190","author":"Sl\u00fctter","year":"2013","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib32","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.3389\/fimmu.2018.02692","article-title":"Defining memory CD8 T cell","volume":"9","author":"Martin","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib33","doi-asserted-by":"crossref","DOI":"10.3389\/falgy.2021.692841","article-title":"Respiratory viral and bacterial factors that influence early childhood asthma","volume":"2","author":"Mthembu","year":"2021","journal-title":"Front Allergy"},{"key":"10.1016\/j.jaci.2025.12.1015_bib34","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1164\/ajrccm.154.3.8810601","article-title":"The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis","volume":"154","author":"Johnston","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib35","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1164\/ajrccm.162.supplement_1.maic-14","article-title":"Developmental airway cell biology","volume":"162","author":"Grigg","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib36","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1056\/NEJMoa053614","article-title":"CD4+ invariant T-cell\u2013receptor+ natural killer T cells in bronchial asthma","volume":"354","author":"Akbari","year":"2006","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib37","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1056\/NEJM199010113231505","article-title":"Eosinophilic inflammation in asthma","volume":"323","author":"Bousquet","year":"1990","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib38","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.jaci.2012.01.059","article-title":"Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines","volume":"129","author":"Bossley","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib39","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.ccm.2012.05.002","article-title":"Airway smooth muscle in asthma","volume":"33","author":"Black","year":"2012","journal-title":"Clin Chest Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib40","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1183\/09031936.00130008","article-title":"Monitoring sputum eosinophils in mucosal inflammation and remodelling: a pilot study","volume":"35","author":"Chakir","year":"2010","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2025.12.1015_bib41","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1111\/all.13666","article-title":"Mast cell chymase impairs bronchial epithelium integrity by degrading cell junction molecules of epithelial cells","volume":"74","author":"Zhou","year":"2019","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2025.12.1015_bib42","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.jaci.2021.07.020","article-title":"Mast cell chymase affects the functional properties of primary human airway fibroblasts: implications for asthma","volume":"149","author":"Zhao","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib43","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.pupt.2004.09.032","article-title":"Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and inflammatory disorders","volume":"18","author":"Cairns","year":"2005","journal-title":"Pulm Pharmacol Ther"},{"key":"10.1016\/j.jaci.2025.12.1015_bib44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1067\/mai.2000.107396","article-title":"Mast cell tryptase release and asthmatic responses to allergen increase with regular use of salbutamol","volume":"106","author":"Swystun","year":"2000","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2025.12.1015_bib45","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1164\/rccm.200205-414OC","article-title":"Early thickening of the reticular basement membrane in children with difficult asthma","volume":"167","author":"Payne","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2025.12.1015_bib46","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1042\/CS20191309","article-title":"Bidirectional interaction of airway epithelial remodeling and inflammation in asthma","volume":"134","author":"Banno","year":"2020","journal-title":"Clin Sci"},{"key":"10.1016\/j.jaci.2025.12.1015_bib47","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1398-9995.2008.01656.x","article-title":"Airway remodeling is correlated with obstruction in children with severe asthma","volume":"63","author":"Tillie-Leblond","year":"2008","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2025.12.1015_bib48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jaip.2025.08.013","article-title":"Detecting small airways dysfunction in asthma: rationale, findings, and future of ATLANTIS","volume":"14","author":"Siddiqui","year":"2026","journal-title":"J Allergy Clin Immunol Pract"},{"key":"10.1016\/j.jaci.2025.12.1015_bib49","first-page":"404","article-title":"Offline exhaled nitric oxide in children: chemiluminescence vs electrochemical devices","volume":"78","author":"Madrid","year":"2021","journal-title":"Bol Med Hosp Infant Mex"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674926000680?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674926000680?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:40:13Z","timestamp":1781685613000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091674926000680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["S0091674926000680"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2025.12.1015","relation":{},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Age-dependent differences in airway inflammation and function in severe uncontrolled asthma","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2025.12.1015","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 American Academy of Allergy, Asthma & Immunology","name":"copyright","label":"Copyright"}]}}