Successful clinical remission of severe asthma with small airway dysfunction and eosinophilic gastrointestinal disease using dupilumab after benralizumab failure.

Background: Small airway dysfunction (SAD) is an underrecognized but important feature of severe asthma, contributing to persistent symptoms and treatment resistance. Biologics targeting type 2 inflammation vary in their efficacy for SAD, and comorbid eosinophilic gastrointestinal disease (EGID) may further complicate management. Case presentation: A 65-year-old woman with severe, type 2-high asthma and eosinophilic esophagitis had uncontrollable symptoms despite inhaled triple therapy and benralizumab. She exhibited impaired ventilatory parameters, with markedly reduced maximum mid-expiratory flow (%MMF), elevated difference in respiratory resistance between 5 Hz and 20 Hz (R5-R20), and area of reactance (AX), and mucus plugs on chest CT, along with gastrointestinal symptoms that required long-term corticosteroid therapy. Intervention and outcomes: Given her insufficient response and comorbid gastrointestinal symptoms, therapy was switched to dupilumab. Following treatment initiation, the patient demonstrated marked improvements in SAD parameters with markedly elevated %MMF (50 to 79%), reduced R5-R20 (1.20 to 0.53 kPa/L/s), AX (4.06 to 0.81 kPa/L) and resolution of mucus plugging. Her dyspnea and gastrointestinal symptoms also improved, allowing discontinuation of oral corticosteroids within one year. Conclusions: Dupilumab effectively improved both SAD and EGID in a patient with severe asthma refractory to benralizumab likely due to its effects on IL-4/IL-13 signaling, leading to reduction of mucus hypersecretion and eosinophilic mucosal inflammation. This case highlights the importance of considering small airway involvement and comorbid EGID when selecting biologics, and supports the use of dupilumab in type 2-high, SAD-dominant asthma with concomitant EGID.