Dominance of IL-5 and CCL17 in nasal cytokine profiles of children with type 2 inflammation

BACKGROUND: Type 2 (T2) inflammation, driven by TH2 cells and associated cytokines, has been linked with asthma and allergic rhinitis. Early detection and immunophenotyping of T2-related diseases in childhood are crucial for effective targeted therapies.

OBJECTIVE: We evaluated the usefulness of a noninvasive method to measure nasal cytokine profiles for airway-specific immunophenotyping of T2 inflammation in children.

METHODS: Nasal epithelial lining fluid was analyzed for levels of 24 cytokines in 612 children at age 6 years from the Danish COPSAC2010 mother-child cohort with prospective diagnoses of T2 diseases (T2-high asthma, allergic rhinitis, allergic conjunctivitis, and atopic dermatitis), non-T2 diseases (T2-low asthma, nonallergic rhinitis) and assessment of T2 biomarkers (blood eosinophils, fractional exhaled nitric oxide, specific IgE and skin prick test for aeroallergens). Associations between nasal cytokine levels, T2 diseases, and biomarkers were analyzed by Spearman correlation, linear regression models, and sparse partial least squares models.

RESULTS: Children with T2-high asthma and allergic rhinitis had increased nasal IL-5/chemokine C-C motif ligand (CCL) 17 levels, while children with allergic conjunctivitis showed elevated CCL17. No associations were observed for atopic dermatitis, T2-low asthma, or nonallergic rhinitis. Positive correlations were also observed between nasal IL-5/CCL17 levels and all T2 biomarkers. A sparse partial least squares-derived nasal cytokine T2 inflammation score performed equally to blood eosinophils in cross-sectional and predictive analyses of T2 diseases.

CONCLUSION: Nasal epithelial lining fluid sampling is a valuable, noninvasive, and airway-specific tool for immunophenotyping T2 inflammation in 6-year-old children. Nasal IL-5 and CCL17 are consistent biomarkers of T2 inflammation and disease.