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 fractional exhaled nitric oxide (F _ENO). We aimed 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 change in forced expiratory volume in 1 s (FEV₁) according to ordinal BEC-F _ENO three-group categories (T2-Low/Low: BEC <0.15×10⁹ cells·L^-1 and F _ENO <25 ppb; T2-High/High: BEC ≥0.30×10⁹ cells·L^-1 and F _ENO ≥35 ppb; T2-Mid: not meeting Low/Low or High/High criteria). A key secondary outcome was the change in Asthma Control Questionnaire-5 score. Exploratory outcomes included OCS-attributable adverse events.

Results: 53 people were enrolled, with 16 (30%) T2-Low/Low, 27 (51%) T2-Mid and 10 (19%) T2-High/High asthma attacks. Post-bronchodilator FEV₁ changes increased with combined BEC-F _ENO elevation (p for interaction=0.007), peaking in the T2-High/High phenotype (0.390±0.512 L, p for trend<0.0001). Conversely, T2-Low/Low attacks showed nonsignificant FEV₁ changes (0.017±0.153 L). In univariable and multivariable analyses, only ordinal BEC-F _ENO stratification, not symptoms nor FEV₁, predicted subsequent post-bronchodilator FEV₁ improvement. All patients had improved Asthma Control Questionnaire-5 score, 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 33 patients (62%) reporting at least one event.

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