Small airway dysfunction may mediate the association between body mass index and severe asthma exacerbations

Background Obesity is associated with poorer asthma outcomes and an increased risk of exacerbations, but the underlying mechanisms remain incompletely understood. Small airway dysfunction (SAD) may represent a key mechanistic link between excess body weight and adverse asthma outcomes. Methods In this multicentre observational study, adult patients with asthma underwent clinical characterisation, spirometry and impulse oscillometry (IOS). SAD was defined using a composite criterion based on small airway resistance (frequency dependence of resistance between 5 and 20 Hz ( R 5–20 )), reactance area (A X ) and ratio of peripheral airway to total airway resistance (( R 5–20 )/ R 5 ). Associations between body mass index (BMI), SAD and severe asthma exacerbations were assessed using multivariable regression models. Non-linear relationships were explored using generalised additive models, and mediation analyses quantified the contribution of SAD to the obesity–exacerbation association. Results Among 1169 patients, IOS-defined SAD was significantly more prevalent in individuals with BMI ≥30 kg·m −2 . Increasing BMI was associated with worse IOS parameters (p<0.0001), following a non-linear pattern with steeper deterioration beyond BMI values of ∼28–30 kg·m −2 . SAD was independently associated with obesity (adjusted OR 2.11, 95% CI 1.56–2.86) and with severe asthma exacerbations in the previous year (adjusted OR 2.01, 95% CI 1.53–2.65) (both p<0.0001). Mediation analyses showed that SAD accounted for 26–41% of the association between obesity and exacerbation risk (p=0.004 and p=0.03). Spirometry indices provided limited additional information. Conclusion Oscillometry-defined SAD represents a non-linear functional trait underlying the association between obesity and severe asthma exacerbations, supporting its clinical relevance in obese patients with asthma and identifying SAD as a potential treatable trait.