Beyond type 2 asthma biomarkers: risk stratification for NSAID-exacerbated respiratory disease

Abstract

IntroductionType 2 (T2) asthma is often associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Additionally, nonsteroidal anti-inflammatory drug (NSAID) intolerance leads to NSAID-exacerbated respiratory disease (N-ERD). Previous transcriptomic data in non-CRSwNP T2 asthma patients showed differentially expressed genes. We focused onALOX15,CLC,CYSLTR2,HRH4andSMPD3to investigate their role in T2 asthma.MethodsThe study included 100 healthy controls and 103 T2 asthma patients, divided into patients with asthma (n=54), patients with asthma and CRSwNP (n=29) and patients with N-ERD (n=20). Quantitative PCR analysis was performed on blood-derived RNA samples first to validate the five differentially expressed genes. The data were further analysed to find potential associations and biomarkers.ResultsPatients, regardless of stratification, exhibited significantly higher gene expression than healthy controls. The patterns of association revealed thatALOX15was exclusively present in the non-comorbidity group,SMPD3andCLCin the comorbidity groups, andHRH4in all patient groups.ALOX15,CYSLTR2andSMPD3expression showed potential as biomarkers to confirm the diagnosis of T2 asthma using peripheral blood eosinophils as the initial criterion. Peripheral blood eosinophils combined with gene expression, especiallySMPD3, may improve the diagnosis.CLCandCYSLTR2expression play a specific role in discriminating N-ERD.DiscussionWe validated the transcriptomic data of five differentially expressed genes in T2 asthma. Different patterns of association were identified in patient stratification, suggesting that different molecular mechanisms underlie 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.