Acute additive effect of montelukast and beclomethasone on AMP induced bronchoconstriction

Abstract

Bronchial hyperresponsiveness to 5-adenosine mono-phosphate (AMP) is a marker of airway inflammation. Inhaled corticosteroids and antileukotrienes are used as anti-inflammatory drugs for the treatment of asthma. To find out if these two drugs exert their protection in an additive fashion, we compared the effects of acute treatment with inhaled beclomethasone (BDP) and montelukast (ML), alone or in combination, on methacholine and AMP induced bronchoconstriction. 15 asthmatic patients undertook methacholine and AMP challenges at baseline and after receiving ML or BDP, alone or in combination, in a randomized, double-blind, double-dummy placebo-controlled, crossover design. BDP pretreatment significantly increased the AMP PC(20) value (68.34+/-15.9mg/mL) as compared to placebo (22.87+/-5.7mg/mL). Combined treatment, BDP plus ML, afforded a further significant increase of AMP PC(20) (154.57+/-55.0mg/mL) as compared to each single treatment. The significant protection exerted by combined treatment as compared to each single active treatment was also demonstrated by the change of AMP PC(20) doubling dose as compared to placebo and each single active treatment. Our findings suggest that these two agents exert their acute additive protection against AMP induced bronchoconstriction acting on distinct inflammatory pathways and their combined use might provide greater protection against inflammatory response elicited by AMP than either drug alone.