Inhaled Corticosteroids for Recurrent Wheezing in Preschool Children: Predictors of Response

Abstract

Introduction: Recurrent wheezing in preschool children (1–5 years) is common, but response to inhaled corticosteroids (ICS) is highly variable. Identifying clinical or biomarkers predicting ICS response could prevent unnecessary treatment and side effects.

Methods: Systematic review with individual participant data (IPD) meta-analysis of RCTs of ICS (≥6 weeks) versus placebo for recurrent wheezing in preschool children. Databases: MEDLINE, Embase, Web of Science. Primary outcome: wheezing exacerbation rate. We examined effect modifiers: atopic dermatitis, blood eosinophils ≥300/μL, aeroallergen sensitization, viral etiology (rhinovirus vs. RSV). IPD requested from trial authors.

Results: Eight RCTs (n=1,678 children) provided IPD. Overall ICS reduced exacerbations (IRR 0.68, 95% CI 0.57–0.81). Effect was large in children with blood eosinophils ≥300/μL (IRR 0.41, 95% CI 0.29–0.58) and atopic dermatitis (IRR 0.45, 0.33–0.61). In contrast, children with neither had no benefit (IRR 0.97, 0.78–1.21). Viral etiology did not modify response. Growth velocity (height z-score change) decreased modestly with ICS (–0.10 SD/year), limited to children receiving high-dose ICS (>200 μg fluticasone equivalent).

Discussion: Blood eosinophil count and atopic dermatitis are strong predictors of ICS response in preschool wheezing, likely reflecting eosinophilic airway inflammation. Children without these features have episodic viral wheezing that does not respond to ICS. Growth suppression is minimal at low-medium doses.

Conclusions: ICS should be reserved for preschool children with recurrent wheezing plus blood eosinophils ≥300/μL or atopic dermatitis. Others should avoid ICS and use as-needed bronchodilators only.