Leukotrienes as a target in asthma therapy

Abstract

Asthma is a chronic inflammatory condition characterised by bronchial hyper-responsiveness and reversible airways obstruction. Research has demonstrated that these effects are mediated by a wide range of compounds. In the last decade leukotrienes have been identified as products of arachidonic acid metabolism. Their effects mimic the pathological changes seen in asthma both in vitro and in vivo. Further research has demonstrated increased production of leukotrienes both during episodes of asthma and in patients with stable asthma. The demonstration that leukotrienes have proinflammatory biological properties relevant to the pathogenesis of asthma has stimulated the development of many potential therapeutic compounds to block these actions. Early studies in laboratory-induced asthma in human volunteers have shown the efficacy of some of these compounds. They have been shown to attenuate the bronchoconstriction caused by allergen challenge, exercise, aspirin and exposure to cold air. Most encouraging of all have been recent placebo-controlled studies in clinical asthma where significant improvements in terms of spirometry, symptoms and beta 2-agonist use have been demonstrated. Leukotriene receptor antagonists and synthesis inhibitors are the first mediator antagonists to have been shown to be effective in treating clinical asthma and as such represent one of the most interesting new classes of antiasthma drugs in development at present.