Improvements in small airway dysfunction and respiratory symptoms following tezepelumab for severe asthma

Small airway dysfunction (SAD) is a key feature of severe asthma, contributing to poor symptom control and exacerbations. Tezepelumab has demonstrated efficacy in reducing exacerbations and improving lung function, but its specific effects on SAD remain underexplored. We aimed to assess changes in SAD among patients initiating tezepelumab.

A prospective observational study was carried out among patients with severe asthma treated with tezepelumab in a tertiary centre. SAD was assessed at baseline and 6 months using impulse oscillometry (IOS) and spirometry. We focused on frequency dependence of resistance (R _5-20) and the area under the reactance curve (AX) to define SAD, with pathological cut-offs >0.1 kPa·L^-1·s^-1 and >1.0 kPa·L^-1, respectively. Paired analyses were used to compare changes over time.

34 patients were included (median age 60 years, 74% females, 21% biologic-experienced) with a median follow-up of 183 days. There were significant improvements from baseline to follow-up in forced expiratory volume in 1 s (FEV₁) (median 1.73 versus 1.97 L, p=0.001), mid-expiratory flow at 25-75% of forced vital capacity (FVC) (median 1.26 versus 1.73 L·s^-1, p=0.002), R _5-20 (median 0.16 versus 0.08 kPa·L^-1·s^-1, p<0.001) and AX (median 1.62 versus 0.80 kPa·L^-1, p<0.001). Improvements in IOS parameters were larger in patients with increased Asthma Control Test (ACT) scores ≥3 points. Prevalence of SAD decreased from 76% to 44% at follow-up (p=0.003). SAD at follow-up was associated with smoking, lower FEV₁ and FVC, and smaller improvements in ACT score.

Tezepelumab significantly improved small airway function, which was associated with better asthma control. Our findings highlight SAD as a treatable trait in patients with severe asthma.