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[白三烯在哮喘病理生理学中的地位。抗白三烯治疗的必要性]

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

作者信息

Fal Andrzej M, Kopeć Agnieszka

出版信息

Pneumonol Alergol Pol. 2010;78(1):68-73.

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.

摘要

哮喘是一种有多种炎症细胞和介质参与的慢性炎症性气道疾病。吸入性糖皮质激素(ICs)被推荐为目前可用于治疗哮喘的最有效的抗炎药物。然而,即使这些药物以高剂量单药治疗或与长效β2受体激动剂联合使用,一些患者仍无法实现哮喘控制。在哮喘炎症过程中,各种细胞途径被激活。其中白三烯合成途径非常重要。白三烯,如白三烯C4、D4、E4(称为“半胱氨酰白三烯”)既是强效支气管收缩剂又是炎症刺激剂。它们增加血管通透性、支气管黏液分泌,并可能导致气道重塑。它们对各种炎症细胞(嗜酸性粒细胞、肥大细胞、中性粒细胞)的趋化作用有助于维持气道的慢性炎症。这些生物学活性表明白三烯在哮喘发病机制中起重要作用。尽管ICs可抑制哮喘炎症的许多成分,但它们不影响白三烯合成。因此,对白三烯拮抗剂的额外治疗可能对这组哮喘患者有益。充分的文献证明抗白三烯药物具有抗炎和支气管保护作用。它们在阿司匹林敏感性哮喘患者和伴有过敏性鼻炎的患者中特别有效。抗白三烯药物也用于预防运动和冷空气诱发的支气管收缩。作为ICs的附加治疗,抗白三烯药物单药治疗效果较差,但可改善哮喘控制,减少哮喘发作频率、短效β2受体激动剂的使用,并改善肺功能。这篇综述总结了关于白三烯在哮喘发病机制中的作用以及抗白三烯药物治疗的临床方面的当前知识。

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