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 this release in vivo. Cys-LTs are both direct bronchoconstrictors and proinflammatory substances that mediate several steps in the pathophysiology of chronic asthma, including inflammatory cell recruitment, vascular leakage, and possibly airway remodeling. Blocking studies show that Cys-LTs are pivotal mediators in the pathophysiology of asthma. Cys-LTs are key components in the early and late allergic airway response and also contribute to bronchial obstruction after exercise and hyperventilation of cold, dry air in asthmatics. LT modifiers reduce airway eosinophil numbers and exhaled nitric oxide levels. Together these findings support an important role for the Cys-LTs in the asthma airway inflammation. Cys-LT receptor antagonists (Cys-LTRA) are generally well-tolerated. Phase III randomized, controlled clinical trials (RCT) show that LT modifiers are moderately effective, apparently with a particular between-patient variability in their clinical response. The clinical effects of LT modifiers are additive to those of beta-agonists and corticosteroids. The onset of action of LT modifiers is within 1 to several days, and not rapid enough to make them useful as rescue treatment. Although LT modifiers possess some antiinflammatory activity, they cannot substitute for corticosteroids for inflammation control. LT modifiers are alternatives to long-acting beta-agonists as complementary treatment to inhaled corticosteroids in pediatric asthma management because they provide bronchodilation and bronchoprotection without development of tolerance, and complement the antiinflammatory activity unchecked by steroids. In addition, the Cys-LTRA montelukast has been shown to ameliorate asthmatic symptoms and provide bronchoprotection in asthmatic preschool children from 2 years of age, which is of particular importance in this difficult-to-manage group of asthmatics. Given their efficacy, antiinflammatory activity, oral administration, and safety, LT modifiers will play an important role in the treatment of asthmatic children.
Bisgaard
H
H
Department of Paediatrics, Copenhagen University Hospital, Copenhagen, Denmark. bisgaard@copsac.dk
D000085:Acetates / Q000627:therapeutic use; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D003521:Cyclopropanes; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007211:Indoles; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D015289:Leukotrienes / Q000096:biosynthesis / Q000502:physiology*; D008565:Membrane Proteins; D048448:Phenylcarbamates; D011804:Quinolines / Q000627:therapeutic use; D018077:Receptors, Leukotriene; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000627:therapeutic use
D000085:Acetates; D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D007211:Indoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D008565:Membrane Proteins; D048448:Phenylcarbamates; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; C093875:montelukast; C063449:zileuton; D006918:Hydroxyurea; C062735:zafirlukast