[Status of leukotrienes in the pathophysiology of asthma. Necessity for antileukotrienes treatment]

Abstract

Asthma is a chronic inflammatory airway disease in which many inflammatory cells and mediators participate. Inhaled corticosteroids (ICs) are recommended as the most effective anti-inflammatory medications currently available for the treatment of asthma. However, some patients don't achieve asthma control even when these agents are used in high doses in monotherapy or in combination with long-acting beta2-mimetics. During asthmatic inflammation various cellular pathways are activated. Among them, leukotriene synthesis pathway is of great importance. Leukotrienes, such as leukotriene C4, D4, E4 (named "cysteinyl-leukotrienes") are known as both strong bronchoconstrictors and inflammation stimulators. They increase vascular permeability, mucus production in bronchi and may contribute to airway remodeling. Their chemotactic effect on various inflammatory cells (eosinophils, mast cells, neutrophils) contributes to the maintenance of chronic inflammation in the airways. These biological activities suggest a prominent role of leukotrienes in the pathogenesis of asthma. Although ICs suppress many of the components of asthmatic inflammation, they don't affect the leukotriene synthesis. Thus, additional therapy with leukotriene antagonists, may be beneficial for this group of asthmatics. It is well documented that antileukotrienes have anti-inflammatory and bronchoprotective effects. They are particularly effective in patients with aspirin-sensitive asthma and those with concomitant allergic rhinitis. Antileukotrienes are also used in the prevention of exercise- and cold-air-induced bronchoconstriction. Less effective in monotherapy, as add-on therapy to ICs, antileukotrienes improve asthma control resulting in the reduction of the frequency of asthma exacerbations and the use of short-acting beta2-mimetics as well as the improvement in lung function. This review summarizes current knowledge on the role of leukotrienes in the pathogenesis of asthma and clinical aspects of therapy with antileukotrienes.