Leukotrienes (LT), both the cysteinyl LTs, LTC(4), LTD(4) and LTE(4), as well as LTB(4) have been implicated in the
clinical course, physiologic changes, and pathogenesis of
asthma. The cysteinyl LTs are potent
bronchoconstrictors, which have additional effects on blood vessels, mucociliary clearance and eosinophilic
inflammation. In addition, the cysteinyl LTs are formed from cells commonly associated with
asthma, including eosinophils and mast cells. LTB(4), whose role is less well defined in
asthma, is a potent
chemoattractant (and cell activator) for both neutrophils and eosinophils. In the last 5 years, drugs have been developed which block the actions or formation of these mediators. Clinical and physiologic studies have demonstrated that they are modest short-acting
bronchodilators, with sustained improvement in FEV(1) occurring in double-blind, placebo-controlled clinical trials for up to 6 months. These drugs have demonstrated efficacy in preventing bronchoconstriction caused by LTs,
allergen, exercise and other agents. Additionally, there are multiple published studies which have demonstrated improvement in
asthma symptoms, beta agonist use and, importantly, exacerbations of
asthma in both adults and children. Comparison studies with inhaled
corticosteroids (ICS) suggest that ICS are superior to
leukotriene modifying drugs in moderate persistent
asthma. However, several published studies now suggest that
leukotriene modifying drugs are effective when added to ongoing
therapy with ICS, either to improve current symptoms or to decrease the dose of ICS required to maintain control. While an anti-inflammatory effect is suggested, longer-term, earlier intervention, studies are needed to determine whether these compounds will have any effect on the natural history of the disease.