Recent advances in antileukotriene therapy.
OBJECTIVE
Despite profound effects of leukotrienes in experimental models, clinical responses to antileukotriene drugs are highly heterogeneous. This review discusses recent advances concerning the molecular mechanisms of antileukotrienes as well as their efficacy in various clinical scenarios and patient groups.


RESULTS
Appreciation of the role of leukotriene E4 and the existence of its distinct receptors may explain the limited efficacy of current leukotriene receptor antagonists. Pharmacogenetic studies highlight the influence of several leukotriene pathway genes on clinical responsiveness. Benefits of addition of antileukotrienes to inhaled corticosteroids in chronic adult asthmatics have been shown, but their role in acute asthma is unclear. Evidence suggests they are not a first-line treatment for allergic rhinitis or urticaria, but may provide useful additional therapy. In children antileukotrienes provide symptomatic benefit in preschool wheezers, but have no clear role in bronchiolitis or acute asthma. Adherence to montelukast appears superior to inhaled corticosteroids. Use in sleep-disordered breathing and eosinophilic gastroenteropathies warrants further investigation. Despite recent concerns thorough analysis of existing data suggests antileukotrienes are well tolerated drugs. The possible link with Churg-Strauss syndrome requires further investigation.


CONCLUSIONS
The leukotriene pathway remains an attractive target in asthma and allergic disease, particularly in light of renewed appreciation of the role of leukotriene E4. Clarification of the clinical role of antileukotrienes is needed.
Scadding
Guy W
GW
Department of Allergy and Clinical Immunology, Imperial College, London, UK. g.scadding@imperial.ac.uk
Scadding
Glenis K
GK
D000293:Adolescent; D000328:Adult; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D006168:Guinea Pigs; D006801:Humans; D020024:Leukotriene Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D017999:Leukotriene E4 / Q000378:metabolism; D051379:Mice; D012220:Rhinitis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
D018927:Anti-Asthmatic Agents; D020024:Leukotriene Antagonists; D017999:Leukotriene E4