Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians in real life. The aim of the study is to define characteristics of a biologic-treated T2-driven-SA population and to evaluate the effectiveness of biologic treatments in a real-world setting by variation in intra/inter-biologic parameters in an up to 4-year follow-up. Methods: Demographic, clinical, functional, and biological characteristics were evaluated retrospectively in 104 patients recruited until July 2022 at baseline (T0) and over a maximum of 4 years (T4) of biologic therapy (omalizumab/OmaG = 41, from T0 to T4, mepolizumab/MepoG = 26, from T0 to T4, benralizumab/BenraG = 18, from T0 to T2, and dupilumab/DupiG = 19, from T0 to T1). Variations of parameters using means of paired Delta were assessed. Results: At baseline, patients had high prevalence of T2-driven comorbidities, low asthma control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV₁ 65 ± 18 %pred), frequent exacerbations/year (AEs 3.5 ± 3), and OCS dependence (60%). DupiG had lower T2 biomarkers/comorbidities and AEs, and worse FEV₁ (57 ± 19 %pred) compared to other biologics (p < 0.05). All biologics improved ACT, FEV₁%, FVC%, AEs rate, and OCS use. FEV₁% improved in MepoG and BenraG over the minimal clinically important difference and was sustained over 4 years in OmaG and MepoG. A significant RV reduction in OmaG (T4) and DupiG (T1), and BenraG normalization (T2) of airflow limitation were found. We observed through inter-biologic parameters pair delta variation comparison a significant nocturnal awakenings reduction in BenraG vs. OmaG/MepoG, and neutrophils reduction in BenraG/DupiG vs. OmaG. Conclusions: Indirect comparison among biologics unveils clinical and functional improvements that may mark a different effectiveness. These results may highlight the preference of a single biologic compared to another with regard to specific treatable traits.

Introduction: Dietary Inflammatory Index (DII) assesses the role of diet in relation to its inflammatory potential. Positive values indicate a proinflammatory diet while negative anti-inflammatory. International Physical Activity Questionnaire (IPAQ) measures physical activity (PA) in populations. Aim of the study: In this pilot study we evaluated a cohort of mild-moderate-to severe asthmatic patients to define potential clusters based on DII, IPAQ and age. Methods: K-means cluster analysis was performed in 60 mild-moderate to severe asthmatics recruited until January 2024: n=30 GINA STEP from 1 to 3, n=30 GINA STEP 4-5. DII and IPAQ were calculated for each subject. 5 groups were identified: inactive young with negative DII (IY, N=8), active young with positive DII (AY, N=7), inactive elderly with negative DII (IEN, N=18), very active elderly with positive DII (VAE, N=7), inactive elderly with positive DII (IEP, N=20). Results: AY had lower BMI, ICS equivalent dose, LTRAs treatment, SNOT-22, ER accesses, total IgE, peripheral neutrophil/eosinophils count, LDL/cholesterol levels, less obesity, dyslipidemia, higher ACT, FEV1 abs, FVC abs compared to IY. IEN showed a T2 profile with more exacerbations/year, nasal polyposis, sinusitis, higher doses of daily ICS, LDL/cholesterol levels and lower ACT. VAE had a T2 profile too, with more atopy, rhinitis, less obesity, hypertension, dyslipidemia, LDL/cholesterol levels and A1AT values. IEP showed a non-T2 profile with higher parameters correlated to metabolic syndrome. Conclusions: PA seems to have a greater impact than diet on asthma outcomes, in both young and elderly patients. Extensive studies are needed to better define the mutual role of PA and diet in asthma.