Is there hope for persistent airflow obstruction? From trial to practice: real-world efficacy of Tezepelumab in severe asthma with persistent airflow obstruction

Abstract

Persistent airflow obstruction (PAO) is a challenging phenotype of severe asthma, characterized by accelerated lung function decline, increased morbidity, and poor response to conventional therapies.

Background: Persistent airflow obstruction (PAO) is a challenging phenotype of severe asthma, characterized by accelerated lung function decline, increased morbidity, and poor response to conventional therapies. Tezepelumab, a human monoclonal antibody targeting thymic stro-mal lymphopoietin (TSLP), has demonstrated efficacy in reducing airway inflammation and improving lung function.

Objective: We report a real-world case of a 72-year-old male with long-standing severe allergic and eosinophilic T2 asthma, PAO, and multiple comorbidities, uncontrolled despite optimized therapy.

Material and Methods: Correlating with post hoc analyses of the PATHWAY and NAVIGATOR trials, Tezepelumab treatment resulted in significant clinical lessening of the condition.
In two trials, Tezepelumab reduced annualized asthma exacerbations by 61% in patients with PAO and improved lung function, with some patients no longer meeting PAO criteria. In our patient, 24 weeks of Tezepelumab therapy yielded a 370 mL increase in FEV1, only one mild exacerbation without hospitalization, decreased sputum production, and recovery of olfactory function.

Conclusion: These outcomes highlight the potential of Tezepelumab to address both lower and upper airway disease, likely through TSLP blockade and modulation of airway remodeling. Early intervention may be critical to maximize benefit, emphasizing the importance of indi-vidualized, multidisciplinary management and precision medicine in severe asthma with PAO.