Dupilumab improves the small airway dysfunction in children with moderate to severe asthma: A retrospective analysis

Background: In children with asthma, airway wall inflammation and mucus secretion can obstruct the lumen, causing small airway dysfunction (SAD) which correlates with poor asthma control and frequent acute exacerbations. However, current medications show limited efficacy in improving small-airway function in pediatric patients. Dupilumab effectively suppresses type 2 inflammation in asthma and may represent a novel, effective therapy for children with asthma, although real-world evidence is still lacking in China. This study evaluated the effectiveness of dupilumab on SAD in children with uncontrolled moderate-to-severe asthma. Methods: This retrospective cohort study analyzed 106 children (aged 6-14 years) with moderate-to-severe asthma treated with dupilumab at the Guangzhou Institute of Respiratory Health (January 2022 and March 2025). All participants had uncontrolled asthma despite the treatment with medium-to-high-dose inhaled corticosteroid (ICS) plus long-acting β₂-agonist (LABA) or leukotriene receptor antagonists (LTRA), with type 2 inflammation characteristics. The primary endpoint was the change of the percentage of patients with SAD (defined as at least two of MMEF _25/75 , MEF ₂₅ or MEF ₅₀ below 65% of predicted values) at 6 months after dupilumab initiation. The secondary endpoints included changes of the percentage of patients with SAD at 3, 9, 12 months and changes in small-airway function indicators at 3, 6, 9, 12 months; changes in type 2 inflammation biomarkers (FeNO, serum total IgE, blood eosinophil count and sputum eosinophil percentage) at 3, 6, 9, 12 months; changes in annualized asthma exacerbation, pulmonary function tests, asthma symptom scores and rescue medication use at 6 months; a multivariable logistic regression model was constructed to identify factors associated with improvement in SAD and baseline characteristics were compared between patients with and without improvement in SAD. Results: In children with asthma (mean age 8.71±2.5), 75.5% had allergic rhinitis and 15.1% had atopic dermatitis, with mean pre-treatment exacerbations of 2.0±1.1 annually. Post-dupilumab, the proportion of SAD patients significantly decreased from 63.2% to 16.0% at 6 months. All small airway indicators improved significantly ( p < 0.001). MMEF _25/75 % predicted increased from 57.2±21.3% to 75.8±20.3%, MEF ₂₅ % predicted from 48.3±21.1% to 66.4±20.0%, and MEF ₅₀ % predicted from 58.7±21.7% to 76.1±20.2% at 6 months. All type 2 inflammation biomarkers declined significantly: FeNO from 26.00 (13.00, 46.5) to 10.00 (8.00, 16.25) ppb, serum total IgE from 721.34 (294.75, 1330.94) to 162.81 (90.33, 297.70) IU/mL, blood eosinophil count from 610.00 (400.00, 840.00)×10 ⁶ /L to 385.00 (260.00, 675.00)×10 ⁶ /L, and sputum eosinophil percentage from 6.00 (2.50, 21.50)% to 0.50 (0.00, 1.50)% at 6 months. Dupilumab also significantly reduced asthma exacerbation rates, improved pre-BD FEV ₁ and asthma symptom scores, and decreased the medication requirement. Multivariable logistic regression model showed that SAD improvement was independently associated with greater increases in pre-BD FEV₁/FVC% predicted (OR 1.27, 95% CI 1.09–1.51) and larger reductions in FeNO (OR 1.02, 95% CI 1.00–1.06). Children who improved in SAD had better baseline asthma control and less impaired lung function. Conclusion: Dupilumab effectively ameliorates SAD in children with moderate-to-severe asthma, probably through suppression of type 2 inflammation.