Impact of Dupilumab on Small Airway Disease in Severe Asthma: A 12-Month Retrospective Real-World Study

TL;DR

Dupilumab improves small airway function and asthma control in severe asthma patients over 12 months in real-world settings.

Contribution

This study provides real-world evidence that dupilumab effectively targets small-airway disease in severe asthma.

Findings

Dupilumab significantly reduced R5–R20 and increased FEF25–75% predicted over 12 months.

Improvements in small-airway function correlated with better asthma control and reduced FeNO.

Treatment led to fewer exacerbations, reduced OCS use, and lower type 2 inflammation.

Abstract

What are the main findings?
Dupilumab significantly and sustainably improved small-airway disease (SAD) over 12 months, as demonstrated by reductions in R5–R20 and increases in FEF25–75% predicted in a real-world severe asthma cohort.Improvements in small-airway function were associated with better clinical control and reduced FeNO.

Dupilumab significantly and sustainably improved small-airway disease (SAD) over 12 months, as demonstrated by reductions in R5–R20 and increases in FEF25–75% predicted in a real-world severe asthma cohort.

Improvements in small-airway function were associated with better clinical control and reduced FeNO.

What are the implications of the main findings?
SAD is a relevant and modifiable treatment target in severe asthma, and dupilumab may effectively address this under-recognized component of airflow limitation.Assessment of small-airway function may improve phenotyping, and impulse oscillometry (IOS) may represent a valuable tool for monitoring biologic treatment response.

SAD is a relevant and modifiable treatment target in severe asthma, and dupilumab may effectively address this under-recognized component of airflow limitation.

Assessment of small-airway function may improve phenotyping, and impulse oscillometry (IOS) may represent a valuable tool for monitoring biologic treatment response.

Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5–R20) and spirometry FEF25–75% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV1, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5–R20 > 0.07 kPa/L/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5–R20 decreased from 0.18 ± 0.17 kPa/L/s to 0.09 ± 0.07 at T12 (p = 0.04), while predicted FEF25–75% increased from 29.5 ± 20.8% to 47.0 ± 21.1% (p < 0.001). ACT scores improved from 13.1 ± 4.9 to 19.6 ± 3.8 (p < 0.001). FeNO levels declined from 64.1 ± 50.7 ppb to 24.8 ± 20.9 ppb (p = 0.01). Improvements in R5–R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months.

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