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Observational Study
. 2025 May 22;65(5):2402391.
doi: 10.1183/13993003.02391-2024. Print 2025 May.

Phenotyping the responses to systemic corticosteroids in the management of asthma attacks (PRISMA)

Carlos Celis-Preciado  1   2 , Simon Leclerc  1   3 , Martine Duval  1 , Dominic O Cliche  1 , Lucie Brazeau  1 , Félix-Antoine Vézina  1 , Marylène Dussault  3 , Pierre Larivée  1 , Samuel Lemaire-Paquette  3 , Simon Lévesque  1 , Philippe Lachapelle  1 , Simon Couillard  4
Affiliations
Observational Study

Phenotyping the responses to systemic corticosteroids in the management of asthma attacks (PRISMA)

Carlos Celis-Preciado et al. Eur Respir J. .

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.

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Conflict of interest statement

Conflict of interest: C. Celis-Preciado has received an education scholarship from the Université de Sherbrooke, within the current work; outside the current work, he has received speaker honoraria from AstraZeneca, GlaxoSmithKline and Sanofi-Regeneron, and consultancy fees from AstraZeneca, GlaxoSmithKline and Sanofi-Regeneron. S. Leclerc reports speaker honoraria from AstraZeneca, outside of the submitted work. F.A. Vézina reports speaker honoraria from AstraZeneca, Sanofi-Regeneron, GlaxoSmithKline, Boehringer Ingelheim and Novartis, outside of the submitted work. P. Lachapelle reports speaker honoraria from AstraZeneca, Sanofi-Regeneron, GlaxoSmithKline, Boehringer Ingelheim and Novartis, and has received consultancy fees from AstraZeneca, GlaxoSmithKline and Sanofi-Regeneron, outside the submitted work. S. Couillard reports he has received unrestricted research grants from Sanofi-Genyme-Regeneron, bioMérieux and the Québec Air-Intersectorialité-Respiratoire Network; he is the holder of the Association Pulmonaire du Québec's Research Chair in Respiratory Medicine; and he is a Clinical Research Scholar of the Fonds de Recherche du Québec, within the submitted work. Outside the submitted work, he reports unrestricted research grants from NIHR Oxford BRC, the Quebec Respiratory Health Research Network, the Fondation Québécoise en Santé Respiratoire, AstraZeneca, bioMérieux, Academy of Medical Sciences and the Association Pulmonaire du Québec; speaker honoraria from AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron and Valeo Pharma; consultancy fees from FirstThought, AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, Access Biotechnology and Access Industries; sponsorship to attend/speak at international scientific meetings from AstraZeneca and Sanofi-Regeneron; is an advisory board member and holds stock options for Biometry Inc., a company which is developing a FENO device (myBiometry); and he advised the Institut National d'Excellence en Santé et Services Sociaux (INESSS) for an update of the asthma general practice information booklet for general practitioners. The remaining authors report no potential conflicts of interest.

Figures

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Overview of PRISMA methods and findings. Type 2 (T2) inflammatory biomarkers (blood eosinophil count (BEC) and fractional exhaled nitric oxide (FENO)) can effectively stratify acute asthma patients, predicting better clinical responses to oral corticosteroids (OCS) and thus supporting a personalised approach to asthma management. ACQ-5: Asthma Control Questionnaire-5; BD: bronchodilator; Eos: eosinophil; CRP: C-reactive protein; POC: point of care; FEV1: forced expiratory volume in 1 s; MCID: minimal clinically important difference. #: FENO measurements taken using a NIOX VERO device (NIOX Group plc., Oxford, UK).
FIGURE 1
FIGURE 1
Change in a) post-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) in litres (primary outcome) and b) mean Asthma Control Questionnaire-5 (ACQ-5) score (key secondary outcome), according to ordinal biomarker stratification. Ordinal blood eosinophil count (BEC)-fractional exhaled nitric oxide (FENO) categories: T2-Low/Low, BEC <0.15×109 cells·L−1 and FENO <25 ppb (n=16); T2-Mid, not meeting Low/Low or High/High criteria (n=27); T2-High/High, BEC ≥0.30×109 cells·L−1 and FENO ≥35 ppb (n=10). Red dots represent patients with sputum eosinophils ≥3%, black dots represent patients with sputum eosinophils ≤2% and empty circles represent patients for whom sputum samples were unavailable or invalid. MCID: minimal clinically important difference.
FIGURE 2
FIGURE 2
Univariate and multivariable analysis of predictors of change in post-bronchodilator forced expiratory volume in 1 s (FEV1). Data are presented as the mean difference (MD) and error bars represent the 95% confidence intervals. Grey error bars indicate nonsignificant predictors. a) Forest plot presenting the univariable predictors for changes in post-bronchodilator FEV1 (litres). The predictors include various biomarkers, asthma-related metrics and demographic factors. b) Forest plot presenting the MD of a significant improvement in FEV1 for various predictors as determined by a multivariable regression model. BEC: blood eosinophil count; FENO: fractional exhaled nitric oxide; Eos: eosinophil; TCC: total cell count; Previously T2 high: defined as BEC ≥0.15×10⁹ cells·L−1 and/or FENO ≥25 ppb in the previous 12 months; FVC: forced vital capacity; ΔFEV1: change in FEV1 at visit 1 compared to best value in previous 12 months; ΔFVC: change in FVC at visit 1 compared to best value in previous 12 months; BMI: body mass index; ACQ-5: Asthma Control Questionnaire-5; MART: maintenance and reliever therapy; GINA: Global Initiative for Asthma. #: interaction term was included to assess the combined effect of biomarkers.
FIGURE 3
FIGURE 3
Peak expiratory flow (PEF) values and symptoms score trajectories analysis according to ordinal blood eosinophil count (BEC)-fractional exhaled nitric oxide (FENO) three-group categories. a) Mean PEF values and b) Asthma Control Questionnaire-5 (ACQ-5) and symptom scores measured over 7 days, stratified by ordinal BEC-FENO three-group categories. The T2-Low/Low group is shown in blue, the T2-Mid in grey and the T2-High/High group is shown in orange. *: p<0.05 for interaction between T2-High/High group and time on linear mixed effect modelling. PEF values are represented for both home device measurements (solid lines and squares) and spirometry measurements at study visits (triangles). ACQ-5 and symptoms scores values are represented for both home measurements (solid lines and squares) and at study visits (triangles). Error bars represent the standard error of the mean.
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