Beyond T2-asthma biomarkers: risk stratification for NSAID-Exacerbated Respiratory Disease

Abstract

[EN]Type 2 (T2)-asthma is often associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Additionally, non-steroidal anti-inflammatory drug intolerance leads to NSAID-exacerbated respiratory disease (N-ERD). Previous transcriptomic data in non-CRSwNP T2-asthma patients showed differentially expressed genes (DEGs). Of them, we focused on ALOX15, CLC, CYSLTR2, HRH4, and SMPD3 to investigate their role in T2-asthma patients. The study included 100 healthy controls (HCs) and 103 T2-asthma patients, divided into asthmatics (54), asthmatics with CRSwNP (30), and N-ERD (19). Quantitative PCR analysis was performed on blood-derived RNA samples first to validate the five DEGs. The data were further analyzed to find potential associations and biomarkers. Patients, regardless of stratification, exhibited significantly higher gene expressions than HCs. The patterns of association revealed that ALOX15 was exclusively present in the non-comorbidity group, SMPD3 and CLC in the comorbidity groups, and HRH4 in all patient groups. ALOX15, CYSLTR2, and SMPD3 expression showed potential as biomarkers to confirm the diagnosis of T2-asthma using peripheral blood eosinophils (PBE) as the initial criterion. PBE combined with gene expressions, especially SMPD3, may improve the diagnosis. CLC and CYSLTR2 expressions play a specific role in discriminating N-ERD. We validated the transcriptomic data of five DEGs in T2-asthma. Different patterns of association were identified in patient stratification, suggesting different molecular mechanisms underlying the spectrum of T2-asthma. Potential biomarkers were also found and used to design an algorithm with practical diagnostic utility for T2-asthma, including risk stratification for N-ERD.