Wenzel Sally E
National Jewish Medical and Research Center, and the University of Colorado Health Sciences Center, 1400 Jackson St, Denver, CO 80206, USA.
Prostaglandins Leukot Essent Fatty Acids. 2003 Aug-Sep;69(2-3):145-55. doi: 10.1016/s0952-3278(03)00075-9.
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.
白三烯（LT），包括半胱氨酰白三烯LTC₄、LTD₄和LTE₄以及LTB₄，均与哮喘的临床病程、生理变化及发病机制有关。半胱氨酰白三烯是强效支气管收缩剂，对血管、黏液纤毛清除及嗜酸性粒细胞炎症还有其他作用。此外，半胱氨酰白三烯由通常与哮喘相关的细胞生成，包括嗜酸性粒细胞和肥大细胞。LTB₄在哮喘中的作用尚不明确，它是中性粒细胞和嗜酸性粒细胞的强效趋化剂（及细胞激活剂）。在过去5年中，已研发出可阻断这些介质作用或生成的药物。临床和生理学研究表明，它们是适度短效的支气管扩张剂，在双盲、安慰剂对照临床试验中，FEV₁可持续改善长达6个月。这些药物已证明可有效预防由白三烯、过敏原、运动及其他因素引起的支气管收缩。此外，有多项已发表的研究表明，这些药物可改善成人和儿童的哮喘症状、减少β受体激动剂的使用，重要的是还可减少哮喘发作。与吸入性糖皮质激素（ICS）的比较研究表明，在中度持续性哮喘中，ICS优于白三烯调节剂。然而，目前多项已发表的研究表明，将白三烯调节剂添加到正在进行的ICS治疗中是有效的，既可以改善当前症状，也可以减少维持控制所需的ICS剂量。虽然提示有抗炎作用，但需要进行长期、早期干预研究，以确定这些化合物是否会对疾病的自然病程产生影响。
