Antileukotriene therapy in asthma

Asthma is a heterogeneous disease characterized by chronic inflammation in which many cells and cellular elements play a role, in particular mast cells, neutrophils, T lymphocytes, eosinophils, and epithelial cells. Inflammation contributes to the variable airway obstruction and bronchial hyperresponsiveness characteristic of asthma. Many mediators contribute to this process, including, for example, leukotrienes. Cell membranes are composed of arachidonic acid, which can be metabolized into biological fatty acids such as leukotrienes. A role for leukotrienes in asthma has been suggested based upon the similarity of their biological activities and the clinical manifestations of asthma. The FDA in the United States has recently approved the use of three drugs aimed specifically at antagonizing leukotriene effects either through inhibiting production of leukotrienes (5- lipoxygenase inhibitors, zileuton [Zyflo®]) or blocking leukotriene binding to its cellular receptors (leukotriene D₄ receptor antagonists, zafirlukast [Accolate®] and montelukast [Singalair®]). This article will consider the biochemistry of leukotrienes, their role in asthma, the therapeutic potential of leukotriene antagonistic drugs, and their positioning in the treatment paradigms of asthma.