Lipid mediator pathways in the lung: leukotrienes as a new target for the treatment of asthma.

Abstract

This article summarizes recent evidence supporting that antileukotriene drugs represent a new treatment of asthma which may be particularly effective when combined with drugs that have complementary effects on airway obstruction and inflammation. Firstly, it has been documented that glucocorticosteroids do not inhibit in vivo production of leukotrienes in asthmatics. In line with such findings, addition of antileukotriene drugs to a group of aspirin-intolerant asthmatics maintained on conventional therapy was found to result in an improvement of the asthma over and above the effect of the baseline treatment with inhaled and/or oral glucocorticosteroids. Likewise, in a 6-week trial in a group of severe asthmatics, the asthma deterioration caused by a reduction of the dose of inhaled steroids by half, was prevented by addition of a leukotriene antagonist to the lowered dose of glucocorticosteroids. Current evidence therefore supports that antileukotriene drugs treat components of the pathophysiology which are left unaffected by treatment with glucocorticosteroid. Secondly, in experimental studies as well as in a recent allergen bronchoprovocation study in asthmatics, it has been found that the combination of antihistaminics with antileukotriene drugs will result in a profound inhibition of both the early and the late phase of allergen-induced airway obstruction. It is hypothesized that such a combination may be useful against bronchoconstriction induced by other asthma trigger factors as well as in the treatment of asthma and rhinitits.