Abstract

BACKGROUNDS Childhood asthma is a heterogeneous disease wherein systemic inflammation, particularly involving nontype 2 cytokines such as interleukin-6 (IL-6), is not universally present and its clinical significance remains unclear. This cross-sectional observational study aimed to elucidate the association between circulating IL-6 levels and the phenotypic characteristics of pediatric asthma, and to explore the potential value of IL-6 as a predictive biomarker for asthma phenotypic risk stratification. METHODS Plasma IL-6 levels were quantified in 105 newly diagnosed pediatric asthma patients (≤15 years old) and 104 age-matched healthy controls to establish a normal reference range. Asthma patients were stratified into two subgroups based on a predefined threshold: "IL-6-normal" (<3.1 pg/mL) and "IL-6-high" (≥3.1 pg/mL, the 95th percentile of IL-6 levels in the healthy control group). Clinical, inflammatory, and lung function characteristics were compared between the two subgroups. Spearman's rank correlation analysis was conducted to explore the associations between cytokine levels and lung function/airway inflammation indices. Multivariate logistic regression analysis was performed to identify variables associated with asthma phenotypic characteristics, and subsequent feature selection was carried out using Least Absolute Shrinkage and Selection Operator (LASSO) regression with fivefold cross-validation. A priori sample size estimation and sex-stratified analyses were conducted, and all methods followed STROBE reporting guidelines. RESULTS Compared with healthy controls, pediatric asthma patients had significantly elevated serum IgE levels, peripheral blood eosinophil counts, and plasma concentrations of IL-4, IL-6, and IL-12 (all p < 0.05). Among the asthma cohort, the "IL-6-high" subgroup (n = 20, 19.0%) had significantly higher body mass index (BMI) and plasma IL-12 levels relative to the "IL-6-normal" subgroup (n = 85).