Miriam C N Eller1, Karina P Vergani1, Beatriz M Saraiva-Romanholo2, Leila Antonangelo3, Claudio Leone4, Joaquim C Rodrigues5. 1. Instituto da Criança, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil. 2. School of Medicine, University of São Paulo (FMUSP) and University of City of São Paulo (UNICID), São Paulo, Brazil. 3. Clinical Laboratory, Pathology Department, Hospital das Clínicas, University of Sao Paulo, São Paulo, Brazil. 4. Maternal and Child Health Department, School of Public Health, University of São Paulo, São Paulo, Brazil. 5. Department of Pediatric, Pediatric Pulmonology Unit, Instituto da Criança, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.
Abstract
BACKGROUND: The 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. METHODS: A 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. RESULTS: 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-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-γ, and TNF-α were significantly higher in the STRA group (P < 0.05). GM-CSF and TNF-α levels showed inverse correlations with ACT scores. CONCLUSION: The presence of neutrophils, the cytokines IL-10, and IFN-γ and, more particularly, TNF-α, 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.
BACKGROUND: The 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. METHODS: A 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. RESULTS: 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-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-γ, and TNF-α were significantly higher in the STRA group (P < 0.05). GM-CSF and TNF-α levels showed inverse correlations with ACT scores. CONCLUSION: The presence of neutrophils, the cytokines IL-10, and IFN-γ and, more particularly, TNF-α, 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.
Authors: Emma S Campisi; Myrtha E Reyna; May Brydges; Aimee Dubeau; Theo J Moraes; Paolo Campisi; Padmaja Subbarao Journal: Eur Arch Otorhinolaryngol Date: 2021-09-20 Impact factor: 2.503
Authors: Helena Crisford; Elizabeth Sapey; Geraint B Rogers; Steven Taylor; Prasad Nagakumar; Ravi Lokwani; Jodie L Simpson Journal: Thorax Date: 2021-02-25 Impact factor: 9.139