P200 Urinary leukotriene E4 as a biomarker in NSAID exacerbated respiratory disease (N-ERD): a systematic review and meta-analysis

IntroductionNSAID exacerbated respiratory disease (N-ERD) - formerly aspirin-induced asthma (AIA), is an asthma phenotype characterised by increased leukotriene production. Urinary Leukotriene E4 (uLTE4) indicates cysteinyl leukotriene production and activity.ObjectivesTo evaluate whether baseline uLTE4 in N-ERD are different from post-aspirin challenge uLTE4 in N-ERD and whether baseline uLTE4 in N-ERD are different from aspirin-tolerant-asthma (ATA) patients and healthy controls (HC).MethodsA systematic literature search (Medline, EMBASE, EMCARE, CINAHL, PsychINFO) was performed from database inception to January 2021, to identify 1) studies reporting baseline uLTE4 in both AIA/N-ERD and ATA asthmatics, and 2) uLTE4pre- and post-aspirin challenge tests. 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).ResultsOf 522 study records reviewed, qualitative synthesis and meta-analysis were performed on n=36 and n=33 studies respectively (Meta-analysis; n= 1273 AIA, 1305 ATA, and 582 HV across 8 countries). Criteria for aspirin intolerance were (i) positive aspirin challenge alone (n=26), (ii) convincing clinical history (n=2), and (iii) either challenge or history (n=8). Methodologies used for uLTE4 analysis were (i) Amersham-enzyme immunoassay (A-EIA) (n=8), (ii) Cayman-enzyme immunoassay (C-EIA) (n=18), (iii) mass spectrometry (MS) (n=5), and (iv) radioimmunoassay (RIA) (n=6).uLTE4 was higher in AIA vs ATA (SMD: 0.80; 95% CI: 0.71–0.89) and distinguished ATA from HC (SMD: 0.52; 95% CI: 0.23–0.81). For studies reporting uLTE4 at baseline and post-challenge, uLTE4 increased following aspirin challenge in AIA (n=12, SMD: 0.56; 95% CI: 0.26–0.85) but not ATA (n=8, SMD: 0.12; CI: -0.08–0.33). Risk of bias was acceptable across all studies, however 30.6% of quality assessment items were unfulfilled.ConclusionsThis comprehensive systematic review and meta-analysis showed that uLTE4 is significantly higher in N-ERD than ATA or HC. Likewise, people with N-ERD have greater increases in uLTE4 following aspirin challenge. Because of heterogeneity, and lack of original data point reporting, diagnostic accuracy evaluation for uLTE4 was not possible. In patients not fit to undergo confirmatory challenge tests for N-ERD, uLTE4 can serve as a useful adjunct to diagnostic process.Please refer to page A1