{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:08:52Z","timestamp":1771924132001,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2012\/20532\u20104"],"award-info":[{"award-number":["2012\/20532\u20104"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The phenotypes and endotypes of severe therapy\u2010resistant asthma (STRA) have not been fully elucidated in children. The aim of the present study was to investigate inflammatory markers in the induced sputum of children with STRA and to compare them with those present in a group of children who achieved control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective cohort of children (6\u201018 years of age) diagnosed with severe asthma (GINA criteria) who had undergone treatment for at least 6 months was comprehensively followed for 3 months. Inhalation technique, adherence to treatment, ACT score, and main comorbidities were assessed. Induced sputum samples were collected for cytology analysis and quantitative assessment of cytokines; the participants also underwent spirometry, plethysmography, and fractional exhaled nitric oxide (FeNO) measurement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty patients were included (average age 12.8 years; 62.5% male); of these, 13 (32.5%) were classified as STRA at the end of follow\u2010up. There were no significant differences between the STRA and control groups in demographic data, functional test results, or FeNO levels. The eosinophilic inflammatory pattern predominated in both groups; however, the STRA group showed a proportionally higher percentage of sputum neutrophils (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The median sputum levels of the cytokines IL\u201010, GM\u2010CSF, IFN\u2010\u03b3, and TNF\u2010\u03b1 were significantly higher in the STRA group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). GM\u2010CSF and TNF\u2010\u03b1 levels showed inverse correlations with ACT scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The presence of neutrophils, the cytokines IL\u201010, and IFN\u2010\u03b3 and, more particularly, TNF\u2010\u03b1, and GM\u2010CSF in the sputum may play an important role in the pathophysiological mechanism of STRA in children and adolescents. Specific antagonists for these cytokines may represent a future therapeutic strategy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.24075","type":"journal-article","created":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T13:49:48Z","timestamp":1528206588000},"page":"1208-1217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Can inflammatory markers in induced sputum be used to detect phenotypes and endotypes of pediatric severe therapy\u2010resistant asthma?"],"prefix":"10.1002","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-5480","authenticated-orcid":false,"given":"Miriam C. N.","family":"Eller","sequence":"first","affiliation":[{"name":"Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, School of Medicine University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina P.","family":"Vergani","sequence":"additional","affiliation":[{"name":"Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, School of Medicine University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz M.","family":"Saraiva\u2010Romanholo","sequence":"additional","affiliation":[{"name":"School of Medicine University of S\u00e3o Paulo (FMUSP) and University of City of S\u00e3o Paulo (UNICID) S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Antonangelo","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Pathology Department Hospital das Cl\u00ednicas University of Sao Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Leone","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department School of Public Health University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquim C.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pediatric Pulmonology Unit, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, School of Medicine University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200906-0896OC"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00202013"},{"key":"e_1_2_7_4_1","first-page":"274","article-title":"Severe asthma: how can we differentiate phenotypes","volume":"139","author":"Louis R","year":"2009","journal-title":"Swiss Med Wkly"},{"key":"e_1_2_7_5_1","first-page":"1198","article-title":"Difficult\/therapy\u2010resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. 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