Current treatment of asthma--focus on leukotrienes

Since their identification in 1979, the cysteinyl leukotrienes (cysLTs) have been shown to be prominent in many inflammatory conditions, including asthma, allergic rhinitis, rheumatoid arthritis, psoriasis, cystic fibrosis and inflammatory bowel disease. They are potent pro-inflammatory agents, as well as causing bronchoconstriction, and undoubtedly have a role in asthma. The cysLTs are products of arachidonic acid metabolism and have been shown to have effects via a cysteinyl leukotriene receptor (CysLTR1) on vascular permeability, mucus production, chemotaxis and bronchial smooth muscle. Their detection in certain body fluids in allergic, aspirin-sensitive and exercise-induced asthma is well documented and potential roles in pathogenesis, proposed. The development of agents affecting production or action offers an exciting new approach to the treatment of asthma. Two approaches to antileukotriene therapy have been developed: blocking their production by inhibiting the action of 5-lipoxygenase enzyme or blocking the CysLTR1. Both approaches have been tried in studies in asthma and overall the results are encouraging, with a decrease in both daytime and nocturnal symptoms, a decrease in additional beta 2 agonist usage and improvement in lung function. The changes, however, are small in some studies. This may be a reflection of disease severity in the study subjects, but of note is a heterogeneity of response to these treatments that may be genetically determined. Antileukotriene therapy has been shown to have an effect in specific types of asthma where the role of cysLTs seems well established--aspirin-sensitive/intolerant asthma and exercise-induced asthma. Longer term studies are needed in other areas such as severe asthma and chronic persistent asthma in both children and adults to provide evidence for the appropriate placement of antileukotriene treatment in current asthma guidelines, in comparison with other established treatments.