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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11882-022-01049-8.