Preschool wheeze endotypes and their association with asthma attacks and ICS response

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 Ninety-five preschool children (aged 12–59 months) 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 eight-to-nine 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 had higher wheeze attack odds over nine months [N=60, Odds ratio (OR):4.27, 95%CI:1.7–11.38]. Odds were greatest in those with BEC ≥300 cells/μL and FeNO ≥10 ppb (N=12, OR:60.74, 95%CI:2.98–1238.9). ICS prescription was associated with reduced three-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 odd reduction in children with elevated BEC or allergic sensitisation. These findings provide rationale for future randomised controlled trials comparing biomarker-guided and symptom-based treatment strategies.