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

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 onALOX15,CLC,CYSLTR2,HRH4, andSMPD3to investigate their role in T2-asthma patients. The study included 100 healthy controls (HCs) and 103T2-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 thatALOX15was exclusively present in the non-comorbidity group,SMPD3andCLCin the comorbidity groups, andHRH4in all patient groups.ALOX15, CYSLTR2, andSMPD3expression 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, especiallySMPD3, may improve the diagnosis.CLCandCYSLTR2expressions 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.