Mechanisms of asthma and allergic inflammation
Urine leukotriene E4 levels are associated with decreased pulmonary function in children with persistent airway obstruction

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Background

Use of leukotriene receptor antagonists improves disease control in children and adults with asthma. However, the relationship between cysteinyl leukotriene levels and indices of daily asthma control has not been studied directly.

Objectives

We sought to assess the relationship between daily variability in urinary leukotriene E4 (LTE4) levels and daily lung function in children primarily taking inhaled corticosteroids (ICSs) and long-acting β-agonists (LABAs).

Methods

Fifty children primarily with moderate-to-severe asthma were followed with measurements of urinary LTE4, monitoring of FEV1, and albuterol use.

Results

Increasing urinary LTE4 levels were associated with significant (P = .006) decreases in percent predicted FEV1 (ppFEV1) averaging 4.7% per interquartile range increase in LTE4 and accompanied by increased albuterol use (P = .03). Children with lower FEV1/forced vital capacity ratios demonstrated larger LTE4-related FEV1 decreases (6.4%) compared to those with higher ratios (4.2%, P = .009). This association was blunted in children taking montelukast (1.4% ppFEV1 decrease) compared with that in children not taking this medication (5.4% ppFEV1 decrease, P = .05). Children with lower lung function ratios demonstrated greater blunting of the LTE4 effect with montelukast (0.9% ppFEV1 decrease) compared to those with higher ratios (3.6% ppFEV1, P = .0002).

Conclusions

Daily variability in LTE4 levels is associated with clinically significant decreases in pulmonary function. In children who demonstrate a response associated with an increase in urinary LTE4 levels, leukotriene receptor antagonists protect against daily FEV1 decreases. This protection might be greatest in those with persistent airway obstruction despite use of ICS and LABA therapy.

Clinical implications

Therapies designed to block cysteinyl leukotriene production or function might benefit children receiving ICS and LABA therapy who continue to experience persistent disease.

Section snippets

Patients

Fifty schoolchildren (age, 6-14 years) who attended the Kunsberg School at the National Jewish Medical and Research Center and had physician-diagnosed asthma were followed over a 5-month period (October 16, 2002, to March 14, 2003). The Kunsberg School is a public elementary school designed to address the educational needs of children with asthma that interferes with regular school attendance and progress. Ethical and scientific approval for this study was obtained from the National Jewish

Demographics and asthma severity

Table I summarizes demographic information and asthma severity based on a screening questionnaire administered to the parents before the study. Children were 6 to 14 years old (mean age, 10 years), and many (48%) were African American or urban-poor (64% received Medicaid assistance). A high percentage (46%) had been admitted into an intensive care unit for an asthma exacerbation at least once in their lifetime. Despite the fact that most (58%) of these children were prescribed therapy with

Discussion

ICSs with or without LABAs are effective medication regimens for most patients with asthma. However, among adult patients, 40% remain symptomatic, and symptoms remain difficult to control in 5% to 10% despite ICS and LABA therapy.9 In our group of children, many of whom continued to have persistent airway obstruction and undercontrolled asthma symptoms despite use of these medications, LTE4 changes were strongly associated with acute decreases in ppFEV1. These decreases were robust, averaging

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    • Cited by (0)

    Supported by the Environmental Protection Agency, Thrasher Research Fund.

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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    Copyright © 2006 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.