Seasonal Variations in Type-2 Inflammation and Interferon Expression in Urban Children with Exacerbation-Prone Asthma

Document Type

Conference Proceeding

Publication Date

2-10-2026

Publication Title

J Allergy Clin Immunol

Keywords

mepolizumab, placebo, adult, asthma, child, conference abstract, controlled study, eosinophil, female, gene co-expression, gene expression, human, inflammation, lavage fluid, major clinical study, male, nasal lavage, randomized controlled trial, respiratory tract inflammation, return to school, RNA sequencing, scheduled visit, seasonal variation, secondary analysis

Abstract

Rationale: To evaluate the relationship of molecular pathways for T2 inflammation versus interferon response on the seasonal susceptibility for exacerbations in high-risk urban children, we evaluated gene expression in nasal samples in a secondary analysis of a clinical trial. Methods: Urban children (6-17 years) with exacerbation-prone asthma and blood eosinophils ≥150/microliter were randomized (1:1) to q4 week placebo or mepolizumab injections added to guideline-based care for 52 weeks. Nasal lavage samples were collected at scheduled visits (baseline, week08, week52) for RNA-sequencing. We assessed seasonal differences in expression of established gene co-expression modules and FeNO (log2-normalized) using linear mixed effects models. Results: 260 participants had 427 scheduled visits on placebo treatment (spring:129, summer:77, fall:81, winter:140). 110 participants had 163 scheduled visits on mepolizumab (spring:54, summer:35, fall:29, winter:45). Type-2 inflammation (T2) module expression was significantly inversely related to type-1 interferon response (IFN) module expression (placebo: β=-0.25, p=2.7E-14; mepolizumab: β=-0.21, p=0.0001). T2/IFN mean module expression was highest in summer and lowest in fall with a significant difference in means between summer and fall (placebo: p=0.036; mepolizumab: p=0.027). T2/IFN expression was significantly positively associated with FeNO (placebo: β=0.10, p=1.6E-13; mepolizumab: β=0.06, p=4.4E-5). For participants with repeated samples in the same season, there were no significant differences in mean module expression over time (T2, IFN, T2/IFN: p>0.05). Conclusions: Type-2 inflammation and interferon expression were strongly inversely related and T2/IFN expression was higher in summer compared to fall regardless of anti-IL5 treatment. These seasonal patterns of airway inflammation likely contribute to the risk for asthma exacerbations upon return to school.

Volume

157

Issue

2

First Page

AB259

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