Severe asthma (SA) is a complex condition often involving small airway dysfunction (SAD). Tezepelumab has demonstrated efficacy in clinical trials, but real-world evidence is scarce, and its impact on SAD remains unexplored.

This prospective study evaluated the effectiveness of tezepelumab in patients with SA, stratified by the SAD presence and asthma phenotype (type 2-high vs type 2-low).

Seventeen SA patients received tezepelumab. A range of clinical and laboratory outcomes were assessed, including annualized asthma exacerbation rate (AAER), lung function, and oral corticosteroids (OCS) use. Respiratory parameters were assessed using spirometry, body plethysmography, and forced oscillation technique (FOT).

After 6 months of treatment, tezepelumab significantly reduced median AAER (from 5.0 to 0.0, p = 0.001) and OCS dose (from 14.6 mg/day to 0.0 mg/day, p < 0.001), alongside a marked reduction in median blood eosinophil count (from 130 to 60 cells/mm³, p = 0.032). Among respiratory parameters, total resistance, measured by body plethysmography, improved significantly in the overall population (median values from 0.49 to 0.37 KPa L s⁻¹, p = 0.005). Spirometry and FOT measures, including total reactance (p = 0.018) and tidal expiratory flow limitation (p = 0.043), improved only in patients with SAD.

Tezepelumab significantly reduced exacerbations and improved asthma control, positively impacting respiratory parameters and small airway function in patients with SAD. These findings support SAD as a treatable trait, highlighting the importance of integrating advanced diagnostic tools, such as body plethysmography and FOT, into routine clinical practice.