Leukotriene modifiers in pediatric asthma management

Cysteinyl leukotrienes (Cys-LTs) are mediators released in asthma and virus -induced wheezing. Corticosteroids appear to have little or no effect on th is release in vivo. Cys-LTs are both direct bronchoconstrictors and proinfl ammatory substances that mediate several steps in the pathophysiology of ch ronic asthma, including inflammatory cell recruitment, vascular leakage, an d possibly airway remodeling. Blocking studies show that Cys-LTs are pivota l mediators in the pathophysiology of asthma. Cys-LTs are key components in the early and late allergic airway response and also contribute to bronchi al obstruction after exercise and hyperventilation of cold, dry air in asth matics. LT modifiers reduce airway eosinophil numbers and exhaled nitric ox ide levels. Together these findings support an important role for the Cys-L Ts in the asthma airway inflammation. Cys-LT receptor antagonists (Cys-LTRA ) are generally well-tolerated. Phase III randomized, controlled clinical t rials (RCT) show that LT modifiers are moderately effective, apparently wit h a particular between-patient variability in their clinical response. The clinical effects of LT modifiers are additive to those of beta -agonists an d corticosteroids. The onset of action of LT modifiers is within 1 to sever al days, and not rapid enough to make them useful as rescue treatment. Alth ough LT modifiers possess some antiinflammatory activity, they cannot subst itute for corticosteroids for inflammation control. LT modifiers are altern atives to long-acting beta -agonists as complementary treatment to inhaled corticosteroids in pediatric asthma management because they provide broncho dilation and bronchoprotection without development of tolerance, and comple ment the antiinflammatory activity unchecked by steroids. In addition, the Cys-LTRA montelukast has been shown to ameliorate asthmatic symptoms and pr ovide bronchoprotection in asthmatic preschool children from 2 years of age , which is of particular importance in this difficult-to-manage group of as thmatics. Given their efficacy, antiinflammatory activity, oral administrat ion, and safety, LT modifiers will play an important role in the treatment of asthmatic children.