Phenotype Overlap and Lung Function in Childhood Asthma: The Interaction Between T2 and Non-T2 Responses

This study aimed to investigate the association between asthma severity, lung function and serum levels of cytokines associated with T-helper type 2 (T2) and non-T2 responses in children and adolescents.

We conducted a cross-sectional study and recruited children and adolescents (7-17 years old) with asthma. Asthma severity was classified by daily corticosteroid dosage and pulmonary function, while asthma control was assessed using the Asthma Control Test and the Child Asthma Control Test. Spirometry, blood collection for cytokine analysis (IL-4, IL-5, IL-10, IL-13, IL-17, IFNγ, TNF-α), and induced sputum collection for cellularity evaluation were performed.

A total of 80 participants were included, with a mean age of 11.9 years, and 60% were male. Severe asthma was observed in 17.5%, and 15% had uncontrolled asthma. No differences in sputum cellularity were found (p = 0.509). Cytokine levels of TNF-α (p = 0.043) and IL-5 (p = 0.010) differed by asthma severity. Negative correlations were observed between cytokines (IL-4, IL-5, IL-10, IL-17) and spirometric parameters. IL-17 (p = 0.001) and IL-5 (p = 0.045) levels varied with airway obstruction, and IL-17 levels differed with bronchodilator response in FEV1 (p = 0.041).

Our findings highlight the heterogeneity of immune responses in childhood asthma. Cytokines from both T2 and non-T2 pathways were associated with lung function impairment, underscoring the interplay of diverse immune responses in the complexity of asthma pathophysiology.