Phenotyping the Responses to Systemic Corticosteroids in the Management of Asthma Attacks (PRISMA).

Abstract

Background: Asthma attacks are heterogeneous. It is not known whether the response to oral corticosteroids (OCS) in acute asthma varies according to type-2 (T2) inflammatory biomarkers, blood eosinophil count (BEC) and exhaled nitric oxide (FeNO). We aim to explore the relationship between T2 biomarkers and response to OCS in acute asthma.

Methods: We conducted a longitudinal observational study of people experiencing an asthma attack evaluated before and after a 7-day OCS course. The primary outcome was post-bronchodilator (BD) FEV₁ change according to ordinal BEC-FeNO 3-group categories (T2-Low/Low, BEC <0.15×10⁹ cells·L^-1 and FeNO <25 ppb; T2-High/High, BEC ≥0.30×10⁹ cells·L^-1 and FeNO ≥35 ppb and T2-Mid, not meeting Low/Low-High/High criteria). A key secondary outcome was the Asthma Control Questionnaire (ACQ-5) change. Exploratory outcomes included OCS-attributable adverse events.

Results: Fifty-three people were enrolled with 16 (30%) T2-Low/Low, 27 (51%) T2-Mid and 10 (19%) T2-High/High asthma attacks. Post-BD FEV₁ changes increased with combined BEC-FeNO elevation (p-for-interaction=0.007), peaking in the T2-High/High phenotype (0.390±0.512L, p-for-trend<0.0001). Conversely, T2-Low/Low attacked achieved nonsignificant FEV₁ changes (0.017±0.153L). In univariable and multivariable analyses, only ordinal BEC-FeNO stratification - not symptoms nor FEV₁ - was a predictor of subsequent post-BD FEV₁ improvement. All patients improved ACQ-5, numerically peaking in the T2-High/High phenotype (-1.58±0.60, p-for-trend=0.08). All groups experienced similar OCS-attributable adverse events, with n=33 (62%) participants reporting ≥1 event.

Conclusions: We found that objective improvement following OCS is confined to T2-High/High events. As in chronic asthma, greater T2 burden identifies a distinct clinical and therapeutic trajectory, whereas OCS-related adverse events are uniformly distributed.