Preschool wheeze endotypes and their association with asthma attacks and inhaled corticosteroid response

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.

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.

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).

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.