Urinary leukotriene E4 as a biomarker in NSAID-exacerbated respiratory disease (N-ERD): A systematic review and meta-analysis

Malcolm Marquette, Bhavesh V. Tailor, Philip C. Calder, Peter J. Curtis, Yoon Loke, Andrew M. Wilson

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)
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Purpose of Review: Non-steroidal exacerbated respiratory disease (N-ERD) currently requires aspirin challenge testing for diagnosis. Urinary leukotriene E4 (uLTE4) has been extensively investigated as potential biomarker in N-ERD. We aimed to assess the usefulness of uLTE4 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. uLTE4 indicates cysteinyl leukotriene production, and a potential biomarker in N-ERD. Although several studies and have examined the relationship between uLTE4 and N-ERD, the usefulness of uLTE4 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). uLTE4 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 uLTE4 is higher in N-ERD than ATA or HC. Likewise, people with N-ERD have greater increases in uLTE4 following aspirin challenge. However, due to the varied uLTE4 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
Original languageEnglish
Pages (from-to)209–229
Number of pages21
JournalCurrent Allergy and Asthma Reports
Issue number12
Early online date14 Nov 2022
Publication statusPublished - Dec 2022


  • Aspirin-intolerance
  • Asthma
  • N-ERD
  • Non-steroidal anti-inflammatory respiratory disease
  • Samter’s
  • Urinary leukotrienes E4

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