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Published on: May 10, 2024
Preschool wheeze endotypes and their association with asthma attacks and inhaled corticosteroid response
Andreas Perikleous1, Sarah-Jane Bowen2, Chris Griffiths3
1National Heart and Lung Institute, Imperial College London, London, UK.
Insights
Elevated blood eosinophil counts (BEC) in preschoolers may predict wheeze attacks, especially when combined with fractional exhaled nitric oxide (Feno). Inhaled corticosteroid (ICS) treatment reduced attack odds in children with elevated BEC or allergic sensitization.
Area of Science:
- Pediatric Pulmonology
- Allergy and Immunology
- Biomarkers in Respiratory Disease
Background:
- Eosinophilic airway inflammation is a known predictor of asthma attacks and treatment response in adults.
- Similar inflammatory mechanisms may be involved in preschool wheeze, suggesting potential biomarker utility.
- This study investigated the association of blood eosinophil count (BEC), allergic sensitization, and fractional exhaled nitric oxide (Feno) with future wheeze attacks in preschoolers.
Purpose of the Study:
- To assess the predictive value of blood eosinophil count (BEC) alone and in combination with allergic sensitization and fractional exhaled nitric oxide (Feno) for wheeze attacks in preschool children.
- To explore the association between inhaled corticosteroid (ICS) treatment and wheeze attack risk across different biomarker subgroups.
Main Methods:
- Recruitment of 95 preschool children (12-59 months) with clinician-confirmed wheeze.
- Baseline measurements included finger-prick BEC, skin-prick testing for allergic sensitization, and offline Feno.
- Children were followed for 8-9 months, with wheeze attacks documented through unscheduled healthcare visits, parental reports, or oral corticosteroid prescriptions.
Main Results:
- Children with BEC ≥300 cells/μL had significantly higher odds of wheeze attacks over 9 months (OR 4.27).
- The highest odds of wheeze attacks were observed in children with BEC ≥300 cells/μL and Feno ≥10 ppb (OR 60.74).
- ICS treatment was associated with reduced wheeze attack odds in children with elevated BEC (OR 0.11) or allergic sensitization (OR 0.11), with further reduction when both biomarkers were elevated (OR 0.06).
Conclusions:
- Elevated BEC, particularly when combined with elevated Feno, may identify preschool children at increased risk of wheeze attacks.
- ICS treatment demonstrated a significant reduction in wheeze attack odds for children with elevated BEC or allergic sensitization.
- These findings support the potential for biomarker-guided treatment strategies in preschool wheeze and warrant further investigation in randomized controlled trials.
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 (F ENO) 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 F ENO 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 F ENO ≥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 F ENO. 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.
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