Work

Two Distinct Transcriptional Subtypes of Severe Type 2 Asthma in NSAID ‐Exacerbated Respiratory Disease

Year: 2026

Type: article

Abstract: ABSTRACT Background Previous studies demonstrated the heterogeneity of the nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease (N‐ERD) phenotype. Patients with severe asthma and aspirin hypersensitivity may exhibit differences in sputum mRNA gene expression. The aim of the study was to identify distinct transcriptional subtypes of severe asthma with aspirin hypersensitivity using unsupervised cluster analysis. Methods Sputum induction was performed in 27 patients with severe asthma and aspirin hypersensitivity who met 2022 Global Initiative for Asthma criteria for type 2 (T2) severe asthma. Using the transcriptional signatures of 87 genes, along with clinical characteristics and biomarker measurements, 2 distinct subtypes were identified and compared between study participants. Results Two clusters were identified: cluster 1 ( n = 10) and cluster 2 ( n = 17). In cluster 1, low GATA3 expression was observed, along with several activated inflammatory genes, while cluster 2 was characterised by high GATA3 expression. Cluster 1 was characterised by increased sputum eosinophil count ( p = 0.04) and percentage ( p = 0.035), and decreased sputum macrophage count ( p = 0.003) and percentage ( p = 0.003). Patients in cluster 1 had increased sputum supernatant prostaglandin D 2 levels ( p = 0.031). Patients in cluster 1 tended to have a higher Lund‐Mackay score ( p = 0.074) and elevated peripheral blood eosinophilia ( p = 0.059). Conclusion Patients in cluster 1 exhibited T2 inflammation with low GATA3 expression, while those in cluster 2 showed T2 inflammation with high GATA3 expression. Sputum GATA3 expression may serve as a useful biomarker for differentiating distinct severe asthma subtypes in patients with N‐ERD.

Source: Clinical & Experimental Allergy

DOI: 10.1111/cea.70253

Authors: Radosław Kacorzyk, Piotr Szatkowski, Bogdan Jakieła, Adam Ćmiel, Marek Sanak, Lucyna Mastalerz

Institutions: Jagiellonian University, AGH University of Krakow

Language: English

Topic: Asthma and respiratory diseases

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Narodowe Centrum Nauki, Narodowym Centrum Nauki