Small Airways Disease (SAD) in Severe Asthma (SA) negatively affects the response to biologic therapy

<bold>Introduction:</bold> SA often involves the small airways. Patients with SA could respond less to maximal inhalation therapy or biologic drugs. The prevalence of SAD in SA has not yet been defined both because of difficulties in measurement of the endobronchial district and for the lack of a gold standard. Few studies correlate small airway involvement in SA with response to biological drugs. <bold>Objectives:</bold> The aim of our study is to define among 160 outpatients referred to the SA Unit the non responders to biological therapy; to determine the prevalence of SAD and to predict the response to biologics. <bold>Methods:</bold> Responders were defined by both the following 2 criteria: complete suspension of systemic corticosteroids and <2 asthma flare-ups 1 year after treatment. Patients treated with omalizumab (n= 60), benralizumab (n=23), mepolizumab (n=32) and dupilumab (n=41) underwent complete functional spirometric and FOT evaluation to establish SAD involvement. Differences between groups were investigated through ANOVA (with Bonferroni post test). A multivariate linear logistic regression was used to predict non-response to therapy. Significance was set at p< 0,05. <bold>Results:</bold> After 1 year of treatment, patients in Omalizumab showed significantly impaired lung function and lower response to therapy. The prevalence of SAD is higher in non responders (> 50%) according to the parameter X5%< lower limit of normality (LLN) and R5-R20 kPa/L/s>0,03. Logistic regression analysis shows that X5%<LLN is a negative predictor variable of response to biological therapy. <bold>Conclusions:</bold> The SAD phenotype, particularly characterized by X5%<LLN parameter, is associated with lower response to biological therapy.