Leukotriene pathway inhibitors in asthma and chronic obstructive pulmonary disease

Leukotrienes can be generated from a wide variety of cells including mast cells and eosinophils. The biological properties of these products include bronchial smooth muscle contraction, stimulation of mucous production, enhancement of vascular permeability, and recruitment of eosinophils. These properties can contribute significantly to the pathobiology of asthma. Recently, zafirlukast and montelukast, and zileuton, leukotriene D₄ receptor antagonists and 5-lipoxygenase inhibitors, respectively, have been developed and are available for treating asthma. Studies have found these compounds modify bronchospasm with exercise, the pulmonary reaction to aspirin in sensitive subjects, and the airway response to inhaled antigen. Furthermore, in patients with chronic asthma, leukotriene modifiers improve airflow obstruction, decrease the need for rescue medication, and diminish symptoms. Moreover, these drugs can prevent asthma exacerbations. However, there is little evidence that these medications have potent anti-inflammatory activity. Nonetheless, leukotriene modifiers represent new, and effective, therapeutics in the treatment of asthma; at present, the positioning of these products in relationship to inhaled corticosteroids, for example, in the treatment of asthma has not been fully defined but will emerge with further study and use in the clinic setting.