Predictive determinants of response to biological therapy in children and adults with severe asthma

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Background: The introduction of biological therapies in severe asthma (SA) has revolutionized its management. However, predictors of clinical response and treatable traits in children and adults are still poorly investigated. Aim: To identify determinants of clinical response in pediatric and adult patients with SA undergoing biological therapy. Methods: This retrospective observational study included 50 adults and 9 pediatric patients between 2017 and 2024, performed at Sacco and Buzzi Hospital in Milan. Clinical response was defined as the absence of asthma symptoms, no exacerbations, stable lung function, and no need of oral corticosteroids (OCS) for at least 12 months; treatable traits (TT) were defined as therapeutic target identified by phenotypes or endotypes through a validated biomarker. Results: We evaluated 50 adults (30 males, 39.2±20.7 years), and 9 pediatric (3 males, 5.9±4.5 years) patients with SA. On multivariate analysis, no smoking history (p = 0.043), no bronchiectasis (p = 0.027), and normal baseline FeNO values (p = 0.006) are independent predictors of clinical response (R= 0.702, R2=0.492). Adults exhibited improvements in clinical scores, functional parameters, and inflammatory markers. In contrast, pediatric patients, despite a higher prevalence of T2 phenotypes, did not show any changes, likely due to differences in disease natural history or limited sample size. TT including obesity, emphysema, and bronchiectasis were associated with exacerbations and hospitalizations, while anxiety, diabetes, and high ACQ scores contributed to the persistence OCS. Conclusions: Early identification of TT and their targeted management are crucial for severe asthma treatment.

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