Preschool wheeze endotypes and their association with asthma attacks and ICS response
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Eosinophilic airway inflammation predicts asthma attacks and inhaled corticosteroid (ICS) response in adults; similar mechanisms may apply to preschool wheeze. This study assessed whether blood eosinophil count (BEC) alone or combined with allergic sensitisation and fractional exhaled nitric oxide (FENO) was associated with future wheeze attacks.
Methods
95 preschool children (12–59 months old) with clinician-confirmed wheeze were recruited from primary and secondary care. At baseline, finger-prick BEC, skin-prick testing for allergic sensitisation and offline FENO were performed. Children were followed for 8–9 months. The primary outcome was the number of acute wheeze attacks diagnosed during unscheduled visits to an emergency department or general practitioner, documented by parental reports, medical records or oral corticosteroid prescriptions. Exploratory analyses examined ICS association with wheeze attack odds across different biomarker subgroups.
Results
Children with BEC ≥300 cells·μL−1 had higher wheeze attack odds over 9 months (n=60, odds ratio (OR) 4.27, 95% confidence interval (CI) 1.7–11.38). Odds were greatest in those with BEC ≥300 cells·μL−1 and FENO ≥10 ppb (n=12, OR 60.74, 95% CI 2.98–1238.9). ICS prescription was associated with reduced 3-month wheeze attack odds among children with elevated BEC (n=21, OR 0.11, 95% CI 0.02–0.49) or allergic sensitisation (n=19, OR 0.11, 95% CI 0.01–0.65), with further reduction when both were combined (n=10, OR 0.06, 95% CI 0.002–0.59).
Conclusion
Elevated BEC may identify preschool children at increased wheeze attack odds, particularly when combined with FENO. ICS treatment was associated with odds reduction in children with elevated BEC or allergic sensitisation. These findings provide a rationale for future randomised controlled trials comparing biomarker-guided and symptom-based treatment strategies.
Eosinophilic airway inflammation predicts asthma attacks and inhaled corticosteroid (ICS) response in adults; similar mechanisms may apply to preschool wheeze. This study assessed whether blood eosinophil count (BEC) alone or combined with allergic sensitisation and fractional exhaled nitric oxide (FENO) was associated with future wheeze attacks.
Methods
95 preschool children (12–59 months old) with clinician-confirmed wheeze were recruited from primary and secondary care. At baseline, finger-prick BEC, skin-prick testing for allergic sensitisation and offline FENO were performed. Children were followed for 8–9 months. The primary outcome was the number of acute wheeze attacks diagnosed during unscheduled visits to an emergency department or general practitioner, documented by parental reports, medical records or oral corticosteroid prescriptions. Exploratory analyses examined ICS association with wheeze attack odds across different biomarker subgroups.
Results
Children with BEC ≥300 cells·μL−1 had higher wheeze attack odds over 9 months (n=60, odds ratio (OR) 4.27, 95% confidence interval (CI) 1.7–11.38). Odds were greatest in those with BEC ≥300 cells·μL−1 and FENO ≥10 ppb (n=12, OR 60.74, 95% CI 2.98–1238.9). ICS prescription was associated with reduced 3-month wheeze attack odds among children with elevated BEC (n=21, OR 0.11, 95% CI 0.02–0.49) or allergic sensitisation (n=19, OR 0.11, 95% CI 0.01–0.65), with further reduction when both were combined (n=10, OR 0.06, 95% CI 0.002–0.59).
Conclusion
Elevated BEC may identify preschool children at increased wheeze attack odds, particularly when combined with FENO. ICS treatment was associated with odds reduction in children with elevated BEC or allergic sensitisation. These findings provide a rationale for future randomised controlled trials comparing biomarker-guided and symptom-based treatment strategies.
Date Issued
2026-05-11
Date Acceptance
2025-11-12
Citation
ERJ Open Research, 2026, 12 (3)
ISSN
2312-0541
Publisher
European Respiratory Society
Journal / Book Title
ERJ Open Research
Volume
12
Issue
3
Copyright Statement
©The authors 2026 This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org
License URL
Publication Status
Published
Article Number
01183
Date Publish Online
2026-05-11