Effect of combined montelukast and desloratadine on the early asthmatic response to inhaled allergen

Background

The early asthmatic response (EAR) to inhaled allergen results from IgE-mediated release of multiple mast-cell mediators, including leukotrienes and histamine, both of which cause bronchoconstriction. Combination therapy directed at blocking the effects of both mediators might protect against the EAR better than either therapy alone.

Objective

We sought to evaluate the effect of desloratadine and montelukast, administered alone and in combination, on the EAR to inhaled allergen.

Methods

Ten adults with mild-to-moderate atopic asthma participated in a randomized, 4-way crossover study design comparing placebo, 5 mg of desloratadine, 10 mg of montelukast, and the combination administered at 26 hours and 2 hours before each allergen challenge conducted at least 7 days apart. The primary end point was the concentration of allergen that resulted in a 20% decrease in FEV₁ (PC₂₀).

Results

The geometric mean allergen PC₂₀ (mean log ± SEM) for combination therapy, montelukast, desloratadine, and placebo was 697 U/mL (2.8433 ± 0.3253), 338 U/mL (2.5295 ± 0.2979), 123 U/mL (2.0883 ± 0.2102), and 104 U/mL (2.0166 ± 0.2553), respectively (n = 9; P < .00001, ANOVA). Montelukast increased the allergen PC₂₀ 4.8-fold, and combination therapy increased the allergen PC₂₀ 8.9-fold. The effect of the combination was greater than that with montelukast alone (P < .02). Desloratadine treatment was no different than placebo.

Conclusions

The early response to inhaled allergen was unchanged after desloratadine therapy and partially inhibited with montelukast therapy. The combination of desloratadine and montelukast provided superior efficacy to either blocker administered alone. Investigations into the possible mechanisms of the enhanced inhibition are necessary.

Key words: Antihistamine, leukotriene antagonist, allergen inhalation

Abbreviations used: AUC, Area under the curve, EAR, Early asthmatic response, H₁, Histamine receptor subtype 1, LAR, Late asthmatic response, LTRA, Leukotriene receptor antagonist, PC₂₀, Concentration of allergen that causes a 20% decrease in FEV₁