A considerable increase in the prevalence of childhood
asthma over the last few decades has been mirrored by a dramatic increase in usage of anti-
asthma drugs; however, there has been no reduction in the numbers of patients dying of
asthma. Concern has been expressed about the development of tolerance with continuous use of inhaled beta-agonist
bronchodilators and about the potential adverse systemic effects of high-dose inhaled
corticosteroids in children. Moreover, patient compliance with inhaled
therapy tends to be poor. The
leukotriene receptor antagonists, including
montelukast,
pranlukast and
zafirlukast, are orally administered agents with proven benefits in
asthma. In a large, placebo-controlled pediatric trial,
montelukast significantly (P < 0.02) reduced requirements for rescue beta-agonist
bronchodilators, improved quality of life, reduced the circulating level of blood eosinophils and produced improvements in lung function. In adult studies,
montelukast reduced sputum eosinophils and attenuated early and late phase
allergen-induced reactions.
Montelukast has also demonstrated protective effects against
exercise-induced bronchospasm in both adults and children, and this protection was maintained during the trough period at the end of the once-daily administration interval (namely, 20-24 h post-dose). Several studies have demonstrated that the formation of cysteinyl
leukotrienes in the airways of asthmatic patients is not suppressed by
corticosteroids; thus, it is not surprising that
montelukast demonstrates complementary effects when given with inhaled
corticosteroids. Currently, the most compelling evidence from published trials suggests that
leukotriene receptor antagonists can be used as add-on
therapy to inhaled
corticosteroids to allow tapering of
corticosteroid dose and reduction in beta-agonist use. Recent clinical trial results suggest there may also be a role for these agents as first-line
therapy in children with mild
asthma.