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

• Published in: Pediatric pulmonology Vol. 53; no. 9; pp. 1208 - 1217
• Main Authors: Eller, Miriam C. N., Vergani, Karina P., Saraiva‐Romanholo, Beatriz M., Antonangelo, Leila, Leone, Claudio, Rodrigues, Joaquim C.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2018
• Subjects: ACT assessment; Adolescent; Age of Onset; Asthma; Asthma - diagnosis; Asthma - therapy; Biomarkers; Child; children; Cohort Studies; Cytokines; Drug Resistance; endotypes; Eosinophils - metabolism; Exhalation; Female; Follow-Up Studies; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; induced sputum; Inflammation; inflammatory markers; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Male; Neutrophils; Neutrophils - metabolism; Nitric Oxide - analysis; Phenotype; Prospective Studies; Respiratory Function Tests; severe asthma; Severity of Illness Index; Spirometry; Sputum - metabolism; Treatment Outcome; Tumor Necrosis Factor-alpha - metabolism; endotypes; induced sputum; severe asthma; inflammatory markers; cytokines; children
• ISSN: 8755-6863; 1099-0496
• DOI: 10.1002/ppul.24075

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.