Cysteinyl leukotrienes antagonists as a treatment for children with asthma
Robert KLEINMAN, Marco MURA, Ming-Yao LIU
Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Departments of Surgery, Medicine and Physiology, Faculty of Medicine, University of Toronto, Toronto M5G 2C4, Canada
Abstract Children have the highest prevalence of asthma, an obstructive lung disease characterized by bronchoconstriction, persistent airway inflammation and airway remodeling. Inhaled corticosteroids and β2-agonists add-on therapies are used to treat these children but these medications are not always effective, and inappropriately high doses of corticosteroid may lead to serious side effects such as osteoporosis, growth retardation, and glaucoma. Oral anti-leukotrienes are new treatments for children suffering from asthma that work by antagonizing leukotrienes and inhibiting their synthesis. Leukotrienes are lipids synthesized from arachidonic acids in the 5-lipoxygenase pathway by mast cells, eosinophils, and alveolar macrophages in the lungs. Leukotrienes are involved in the asthmatic response by binding to the CysLT1 receptor on the airway smooth muscles, causing bronchoconstriction. Recent studies have shown that the cysteinyl-leukotrienes may mediate subepithelial collagen deposition and smooth muscle hypertrophy and hyperplasia, causing irreversible airway remodeling and airway obstruction. Experimental studies and preliminary clinical reports on pediatric patients have shown that the leukotriene antagonist montelukast may prevent airway remodeling and reduce asthmatic symptoms when used as an add-on treatment to reduce the intake of corticosteroids and β2-agonists. However, the efficacy of anti-leukotrienes drugs still needs to be confirmed by randomized, double-blind and multicenter clinical trials.
