Can inflammatory markers in induced sputum be used to detect phenotypes and endotypes of pediatric severe therapy-resistant asthma?

Autor(es)

Eller, Miriam C. N. ^[1] ; Vergani, Karina P. ^[1] ; Saraiva-Romanholo, Beatriz M. ^{[2, 3]} ; Antonangelo, Leila ^[4] ; Leone, Claudio ^[5] ; Rodrigues, Joaquim C. ^[6]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Crianca, Hosp Clin, Sch Med, Rua Muniz de Souza 1020, Apt 132, BR-01534000 Sao Paulo, SP - Brazil

^[2] Univ City Sao Paulo UNICID, Sao Paulo - Brazil

^[3] Univ Sao Paulo FMUSP, Sch Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Clin Lab, Dept Pathol, Hosp Clin, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Maternal & Child Hlth Dept, Sch Publ Hlth, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Dept Pediat, Pediat Pulmonol Unit, Inst Crianca, Hosp Clin, Sch Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PEDIATRIC PULMONOLOGY; v. 53, n. 9, p. 1208-1217, SEP 2018.
• Citações Web of Science: 5

Resumo

BackgroundThe phenotypes and endotypes of severe therapy-resistant 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. MethodsA prospective cohort of children (6-18 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. ResultsForty 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-up. 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 (P<0.05). The median sputum levels of the cytokines IL-10, GM-CSF, IFN-, and TNF- were significantly higher in the STRA group (P<0.05). GM-CSF and TNF- levels showed inverse correlations with ACT scores. ConclusionThe presence of neutrophils, the cytokines IL-10, and IFN- and, more particularly, TNF-, and GM-CSF 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. (AU)

• Processo FAPESP: 12/20532-4 - Fatores clínicos e laboratoriais associados com a asma grave de difícil controle em crianças e adolescentes
• Beneficiário: Joaquim Carlos Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Regular