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

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 EA...

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Veröffentlicht in:Journal of allergy and clinical immunology 2005-10, Vol.116 (4), p.768-772
Hauptverfasser: Davis, Beth E., Todd, David C., Cockcroft, Donald W.
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Sprache:eng
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Zusammenfassung: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. We sought to evaluate the effect of desloratadine and montelukast, administered alone and in combination, on the EAR to inhaled allergen. 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 FEV 1 (PC 20). The geometric mean allergen PC 20 (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 PC 20 4.8-fold, and combination therapy increased the allergen PC 20 8.9-fold. The effect of the combination was greater than that with montelukast alone ( P < .02). Desloratadine treatment was no different than placebo. 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.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2005.06.014