Diagnostic Utility of Urinary LTE4 in Asthma, Allergic Rhinitis, Chronic Rhinosinusitis, Nasal Polyps, and Aspirin Sensitivity

Abstract

BACKGROUND Urinary leukotriene E4 (LTE4) is a well-validated marker of the cysteinyl leukotriene pathway, and LTE4 elevation has been described in conditions such as asthma, aspirin sensitivity, and chronic rhinosinusitis (CRS). There have been a number of reports investigating the role of spot urine LTE4 to predict aspirin sensitivity; however, variability in urinary LTE4 may affect the accuracy of this approach. OBJECTIVE Here, we explored the utility of 24-hour urinary LTE4 in 5 clinical diagnoses of allergic rhinitis, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), CRS without nasal polyps, and aspirin sensitivity. METHODS This was a retrospective review of patients who had 24-hour quantification of urinary LTE4 by a clinically validated liquid chromatography tandem mass spectrometry method and their assigned diagnoses after assessment and clinical care. RESULTS Twenty-four-hour urinary LTE4 elevations were seen in those with asthma and those with CRSwNP but influenced by underlying aspirin sensitivity. Elevation in LTE4 was significant in those with CRSwNP after adjusting for aspirin sensitivity. Allergic rhinitis was not associated with elevated LTE4 excretion. Receiver operator characteristic analysis of 24-hour urinary LTE4 showed that a cutoff value of 166 pg/mg Cr suggested the presence of history of aspirin sensitivity with 89% specificity, whereas a cutoff value of 241 pg/mg Cr discriminated “challenge-confirmed” aspirin-sensitive subjects with 92% specificity. CONCLUSIONS Elevated 24-hour excretion of urinary LTE4 is a reliable and simple test to identify aspirin sensitivity in patients with respiratory diagnoses.

Prostaglandin E2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin

“…This biomarker has variable concentration in spot urine samples. Recently, benefits of 24‐h urine collection were presented . In our study, Cys‐LTs were released following the ingestion of aspirin and correlated with bronchial symptoms similarly to previously reported .…”

“…Lipid mediators are especially interesting in NERD because cyclooxygenases are the pharmacological targets for NSAIDs. Elevated systemic biosynthesis of LTE 4 is a common feature of NERD . The main aim of the study was to measure the concentration of anti‐inflammatory PGE 2 and its stable degradation product, tetranor‐PGE‐M, before and after a clinically relevant oral dose of aspirin.…”

“…NERD asthmatics overproduce Cys‐LTs, particularly LTE 4 . This biomarker has variable concentration in spot urine samples.…”

Aspirin-Exacerbated Respiratory Disease: Prevalence, Diagnosis, Treatment, and Considerations for the Future

“…44,45 Follow-up studies demonstrated that Ն166 pg LTE 4 /mg creatinine indicates the presence of AERD with 89% specificity, whereas a Ն241 pg LTE 4 /mg creatinine discriminated subjects with "challenge-confirmed" aspirin sensitivity with 92% specificity. 46 Exhaled nitric oxide (FeNO) levels is used as a biomarker for assessing acute bronchospasm and for supervising asthma control over time. 44,47,48 A recent study discovered that giving low-dose aspirin (40 mg) and measuring FeNO levels 1 hour later produced a significant decrease from baseline in mean FeNO by 19% in patients with AERD.…”

A Review of Classification Schemes for Chronic Rhinosinusitis with Nasal Polyposis Endotypes

“…The significance of CysLT in the pathophysiology of AERD and possibly other CRSwNP patients, highlights its use as a biomarker for a distict CRS endotype . Because CysLT is metabolized and excreted through the urine, the 24‐hour urinary measurement of LTC 4 has been suggested as a means to identify CRSwNP patients who have the AERD variant . The classification of CysLT‐mediated CRS may then provide a guide toward therapy utilizing leukotriene modifiers and aspirin desensitization .…”