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

https://doi.org/10.1016/j.jaip.2016.03.004Get rights and content

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.

Section snippets

Study design

This was a retrospective study of all subjects who underwent measurement of 24-hour urinary LTE4 at our institution between March 2014 and April 2015. The study was approved by the institutional review board of the Mayo Clinic.

Subjects and diagnosis

All patients who underwent LTE4 testing were selected for analysis from a laboratory list. Patients' charts were reviewed for the diagnoses after completion of care and visit to ensure only final diagnoses were considered for analyses. Patients who were found to have mast

Characteristics of subjects in the study

The characteristics of the patients included in the study are presented in Table I. The criteria for inclusion of controls are presented in Table E1 and objective data related to the respiratory diagnoses of asthma, allergic rhinitis, and CRS are presented in Table E2 in this article's Online Repository at www.jaci-inpractice.org. Of the 194 patients in the study, females comprised 60% of the study population. Sixty-two patients (31.9%) in the study carried a respiratory-related diagnosis that

Discussion

LTE4 is a stable end product of the cystinyl leukotriene pathway and its measurement in urine as a biomarker of activity of this metabolic pathway is well validated. Increased LTE4 excretion has been demonstrated in allergen-induced asthma, asthma exacerbations, aspirin challenge, and increased basal excretion in AERD.11, 12, 13, 17, 18, 19 In this study, we wished to determine the diagnostic utility of 24-hour urinary LTE4 based on established and derived values. Because aspirin sensitivity

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  • Cited by (0)

    Mayo Clinic Foundation supported this study.

    Conflicts of interest: R. Divekar is employed by Mayo Clinic and has an unrelated web blog through Google.com. J. Hagan has received research support from the National Institutes of Health, GlaxoSmithKline, AstraZeneca, MedImmune, and Teva. M. Park has received consultancy fees from Baxter as an advisory board member. J. Butterfield declares that he has received licensing payments by pharmaceutical companies using HMC-1.1 and HMC-1.2 cell lines obtained from our laboratory. The rest of the authors declare that they have no relevant conflicts of interest.

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