Urine leukotriene E₄ levels are associated with decreased pulmonary function in children with persistent airway obstruction

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.

Key words: Asthma, children, cysteinyl leukotrienes, pulmonary function, airway obstruction, montelukast

Abbreviations used: CysLT, Cysteinyl leukotriene, FVC, Forced vital capacity, ICS, Inhaled corticosteroid, IQR, Interquartile range, LABA, Long-acting β-agonist, LTE₄, Leukotriene E₄, LTRA, Leukotriene receptor antagonist, ppFEV₁, Percent predicted FEV₁