Dupilumab Treatment is Associated with Improvement in Small Airway Dysfunction in Children with Moderate to Severe Asthma: A Retrospective Analysis

BACKGROUND: Small airway dysfunction (SAD) is common in pediatric asthma and is associated with poor disease control and frequent exacerbations. Current therapies show limited efficacy in improving small airway function. Dupilumab suppresses type 2 inflammation and may provide benefit; however, real-world evidence in Chinese children is limited. This study evaluated the association between dupilumab and improvements in SAD in children with uncontrolled moderate-to-severe asthma. METHODS: This retrospective cohort study without a concurrent comparator group included 106 children (aged 6-14 years) with uncontrolled moderate-to-severe asthma treated with dupilumab between January 2022 and March 2025. Dupilumab was generally administered at a dose of 300 mg every 4 weeks. The primary outcome was the proportion of patients with SAD at 6 months, defined as ≥2 of maximal mid-expiratory flow (MMEF₂₅₋₇₅), MEF₂₅, or MEF₅₀ <65% predicted. Secondary outcomes included changes in small airway function, type 2 inflammatory biomarkers, lung function, and exacerbation rates. Longitudinal changes were assessed using paired analyses, with mixed-effects models as sensitivity analyses. RESULTS: Among the 106 children included in the study, the proportion of patients with SAD decreased from 63.2% at baseline to 27.0% at 6 months. Small airway indices improved significantly, including MMEF₂₅₋₇₅% predicted (57.2% to 75.8%), MEF₂₅% predicted (48.3% to 66.4%), and MEF₅₀% predicted (58.7% to 76.1%) (all p<0.01). Type 2 inflammatory biomarkers were reduced, including fractional exhaled nitric oxide and serum IgE. Annualized exacerbation rates declined, accompanied by improved lung function and symptom control. Improvement in SAD was associated with greater increases in FEV₁/FVC and larger reductions in FeNO. CONCLUSION: Dupilumab treatment is associated with amelioration of SAD in children with moderate-to-severe asthma, accompanied by reductions in type 2 inflammatory biomarkers.