Changes in Small Airway Dysfunction in Patients With Severe Asthma 6 Months After Initiating Tezepelumab – Initial Observations

Abstract Background: SAD is frequent in asthma patients. It is closely related to symptoms and exacerbation risk. We evaluated changes in SAD parameters 6 months after initiating Tezepelumab in patients with severe asthma. Methods: Patients were included prior to initiation and followed-up at 6-month intervals. We assessed lung function (spirometry, body plethysmography, oscillometry), disease control (ACT) and QoL (miniAQLQ). SAD improvement was defined as decrease in reactance area (AX, 1.05 kPa/L) or peripheral obstruction (R5-20, 0.08 kPa/L/s, Abdo et al. ERJ 2023). Clinical responders were defined as increase in both ACT (3 pts) and miniAQLQ (0.5pts). Results: 17 patients (54±17 years, m/f 5/12) were included in this preliminary analysis. T2 inflammation was found in 15 patients (88%). Ten patients (59%) were on prior antibody and 6 (35%) on OCS maintenance therapy. Improvements in ACT (11±4 vs. 16±6, p<0.01) and miniAQLQ (2.9±1.0 vs. 3.9±1.6, p<0.05) but no changes in FEV1 (2.0±1.0 vs. 1.95±0.8L, p=0.7) and sRtot (1.8±1.3 vs. 1.8±1 kPa/s, p=0.99) were observed. In contrast, numeric changes of SAD were found in 11 patients (65%). AX and R5-20 numerically decreased from 4.1±4.6 to 2.6±2.2 kPa/L (p=0.07, Cohen's d=0.47) and 0.13±0.13 to 0.10±0.11 kPa/L/s (p=0.31, d=0.25). Clinical responders had greater reduction in AX (-2.5±3.9 vs. -1.6±3.3 kPa/L, p=0.7, d=-0.24), R5-20 (-0.07±0.09 vs. 0±0.11 kPa/L/s, p=0.2, d=-0.7) and sRtot (-19±29 vs. 22±44%, p<0.05, d=-1.1). Conclusion: Lung function parameters of SAD might improve in response to anti-TSLP antibody therapy. More data are needed to confirm our initial observation and yield statistically robust results.