An Observational and Translational Pilot Study Phenotyping the Responses to Systemic Corticosteroids in the Management Asthma Attacks (PRISMA): interim translational results.

<bold>Rationale:</bold> Asthma attacks are heterogeneous. The response to oral corticosteroids (OCS) may vary with the inflammatory phenotype. <bold>Aim:</bold> To assess the response to OCS in asthma attacks according to the presence or absence of type (T)2 inflammation (blood eosinophils ≥0.15x10⁹/L and/or exhaled nitric oxide (FeNO) ≥25ppb). <bold>Methods:</bold> An observational longitudinal pilot study in asthma attacks evaluated before/after prednisone (2 visits: days 0 vs 7) and healthy controls (1 visit). Alarmins, T2 cytokines and chemokines levels were quantified by 9-plex electrochemiluminescent assays in 3 compartments (nasal epithelium, induced sputum, and serum). <bold>Results:</bold> We report interim results at 50% of target recruitment (n=25 adults, 68% women, 80% GINA steps 4-5, 60% T2-high). Compared to n=13 controls, 12 analytes were abnormal (p<0.05) at visit 1 (Table). In T2-high attacks, prednisone suppressed blood eosinophils (Eos); sputum Eos, interleukin (IL)-4, IL-5 and eotaxin-3; and serum IL-5, IFN and tumour necrosis factor. Suppression of sputum interferon-γ (IFN) occurred significantly more in T2-low than T2-high attacks (Figure). <bold>Conclusions:</bold> We found a differential effect of OCS in T2-high vs T2-low asthma attacks. Prednisone may blunt airway IFN response in T2-low asthma attacks. <bold>Registration:</bold> <ext-link>NCT05870215</ext-link> <bold>Funding:</bold> APQ, FRQS, Sanofi-Regeneron, bioMérieux <fig><object-id>erj;64/suppl_68/OA3762/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>