Urinary Leukotriene E4 as a Biomarker in NSAID-Exacerbated Respiratory Disease (N-ERD): a Systematic Review and Meta-analysis

Purpose of Review Non-steroidal exacerbated respiratory disease (N-ERD) currently requires aspirin challenge testing for diagnosis. Urinary leukotriene E4 (uLTE 4 ) has been extensively investigated as potential biomarker in N-ERD. We aimed to assess the usefulness of uLTE 4 as a biomarker in the diagnosis of N-ERD. Recent Findings N-ERD, formerly known as aspirin-intolerant asthma (AIA), is characterised by increased leukotriene production. uLTE 4 indicates cysteinyl leukotriene production, and a potential biomarker in N-ERD. Although several studies and have examined the relationship between uLTE 4 and N-ERD, the usefulness of uLTE 4 as a biomarker in a clinical setting remains unclear. Findings Our literature search identified 38 unique eligible studies, 35 were included in the meta-analysis. Meta-analysis was performed (i.e. pooled standardised mean difference (SMD) with 95% confidence intervals (95% CI)) and risk of bias assessed (implementing Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (Cochrane DTA)). Data from 3376 subjects was analysed (1354 N-ERD, 1420 ATA, and 602 HC). uLTE 4 was higher in N-ERD vs ATA ( n = 35, SMD 0.80; 95% CI 0.72–0.89). uLTE4 increased following aspirin challenge in N-ERD ( n = 12, SMD 0.56; 95% CI 0.26–0.85) but not ATA ( n = 8, SMD 0.12; CI − 0.08–0.33). This systematic review and meta-analysis showed that uLTE 4 is higher in N-ERD than ATA or HC. Likewise, people with N-ERD have greater increases in uLTE 4 following aspirin challenge. However, due to the varied uLTE 4 measurement and result reporting practice, clinical utility of these findings is limited. Future studies should be standardised to increase clinical significance and interpretability of the results.