Urinary Leukotriene E4

doi:10.1016/j.iac.2007.09.004

Immunology and Allergy Clinics of North America

Volume 27, Issue 4, November 2007, Pages 651-664

https://doi.org/10.1016/j.iac.2007.09.004 Get rights and content

Measurement of urinary leukotriene E4 (LTE₄) is a sensitive and noninvasive method of assaying total body cysteinyl leukotriene production and changes in cysteinyl leukotriene levels in specific microenvironments, such as the airway. Urinary LTE₄ measurements can be used as sensitive biomarkers of exposure to asthma triggers, such as air pollution and viral infections. Recent studies suggest the potential of using urinary LTE₄ concentrations as predictors of asthma control and markers of susceptibility to treatment with leukotriene receptor antagonists.

Section snippets

Measurement

Measurement of urinary LTE₄ can be a useful noninvasive method to assess changes in the rate of total body CysLT levels. Levels of LTE₄ are too low to measure in serum [2], [3] but can be measured after excretion into the urine. Studies have shown that inhalation of LTC₄ or LTD₄ leads to a dose-dependant increase in urinary LTE₄ [4]. Approximately 5% of airway CysLTs are eventually eliminated in the urine [5], almost all in the form of LTE₄, with little if any measurable urinary LTC₄ or LTD₄ [6]

Age and genetics

Because no standardized methodology currently exists, reported values for basal LTE₄ levels in normal individuals vary depending on the measurement technique and whether purification techniques are used in immunoassays. Based on some studies, basal levels of LTE₄ seem to be partly age-related. In one study, for example, healthy children aged 3 to12 years showed mean LTE₄ levels that were higher than those for healthy adults, measuring 103 pg/mg compared with 80 pg/mg, respectively [9]. In

Leukotriene E₄ as an indicator of cysteinyl leukotriene disease pathogenesis

Because the CysLTs and other inflammatory mediators closely interact, increases in many inflammatory mediators, including multiple cytokines, will induce CysLT production and vice versa. Therefore, whether increased levels of LTE₄ in a given disease state indicate that CysLTs are mediators of disease or are just biomarkers of increased inflammation during disease exacerbation is difficult to determine. Elevated levels of urinary LTE₄ have been reported after episodes of unstable angina and

Leukotriene E₄ as a marker of asthma incidence and severity

A few studies have reported increased LTE₄ levels in individuals who have asthma compared with those who do not, although other studies have not observed these relationships. Asano and colleagues [56] measured 16 consecutive 4-hour urine samples in five normal subjects and eight who had asthma. The mean urinary LTE₄ excretion rate was 84 pg/mg in normal subjects; in patients who had asthma, the urinary LTE₄ excretion rate (110 pg/mg creatinine) was significantly (P<.05) higher. Similar

As a marker of medication susceptibility

The heterogeneity of the clinical response to pharmacotherapy is of great practical interest. The few studies assessing urine LTE₄ levels as predictors of response to LTRA treatment are presented below. Szefler and colleagues [74], and Zeiger and colleagues [75] reported significant variability in the response to montelukast in a population of children aged 6 to 17 years. Markers related to lung function response included low levels of exhaled nitric oxide and increased levels of urinary LTE₄.

Summary

Measurement of urinary LTE₄ is a sensitive and noninvasive method of assaying total body CysLT production and changes in CysLT production in specific microenvironments, such as the airway. Although more confirmatory work must be performed, studies suggest the potential for using urinary LTE₄ measurements as biomarkers of environmental exposures, predictors of asthma control, and markers of susceptibility to leukotriene receptor antagonists.

Acknowledgments

The author would like to thank Debra Chris from Merck Inc. for assistance in selecting some of the manuscript's illustrations and Gretchen Hugen for assistance in preparing the manuscript.

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