Wagener M
Abteilung Chirurgie I, Kantonsspital Nidwalden.
Praxis (Bern 1994). 1998 Feb 18;87(8):271-5.
Today it is generally acknowledged that bronchial asthma is a chronic inflammatory airway disease which is marked by recurrent bronchial obstructions and hyperreactivity of the airways. The best anti-inflammatory characteristics are shown by corticosteroids. However these can have considerable side-effects in long-term, systemic use. The search for alternative forms of therapy has for some time concentrated on the development and testing of leukotriene antagonists. These can limit the effect of leukotrienes via receptor antagonism or synthesis inhibition. The leukotrienes B4, C4, and D4 count as important key mediators in bronchial asthma. They are released by numerous inflammatory cells, have a bronchoconstricting effect and chemotactic characteristics, promote vessel permeability and increase mucous secretion. In addition, they probably increase bronchial hyperreactivity. Among biosynthesis restrictors, the 5-lipoxygenase restrictors have shown an anti-inflammatory effect in both experimental asthma models and in clinical use. In mild to moderate asthma, lung function improved and the use of a concomitant beta-agonist medication was reduced. While the older leukotriene receptor antagonists were rather disappointing, the newer substances display a significantly improved effect, are generally well tolerated and can also be given orally. In experimental asthma models, receptor antagonists, after antigen provocation, led to a marked reduction in bronchoconstriction and a decrease in the number of inflammatory cells (lymphocytes and eosinophils) in bronchial alveolar fluid. In clinical studies, this new class of drugs showed a reduction in clinical symptoms and an improvement in lung function in mild to moderate asthma. In addition, a bronchodilatatory effect was shown. The option of oral administration and good tolerance should improve compliance. The potential and long-term efficacy in severe asthma remains unclear. Further studies are required to elucidate the scope of their role and define their place in the treatment of asthma.
如今,人们普遍认为支气管哮喘是一种慢性炎症性气道疾病,其特征为反复出现的支气管阻塞和气道高反应性。皮质类固醇具有最佳的抗炎特性。然而,这些药物长期全身使用时可能会产生相当多的副作用。一段时间以来,寻找替代治疗方法的研究主要集中在白三烯拮抗剂的开发和测试上。这些拮抗剂可通过受体拮抗或合成抑制来限制白三烯的作用。白三烯B4、C4和D4被视为支气管哮喘的重要关键介质。它们由众多炎症细胞释放,具有支气管收缩作用和趋化特性,可促进血管通透性并增加黏液分泌。此外,它们可能会增加支气管高反应性。在生物合成抑制剂中,5-脂氧合酶抑制剂在实验性哮喘模型和临床应用中均显示出抗炎作用。在轻度至中度哮喘中,肺功能得到改善,同时β-激动剂药物的使用减少。虽然较老的白三烯受体拮抗剂效果相当令人失望,但较新的药物显示出显著改善的效果,通常耐受性良好,也可口服给药。在实验性哮喘模型中,受体拮抗剂在抗原激发后可导致支气管收缩明显减轻,支气管肺泡液中炎症细胞(淋巴细胞和嗜酸性粒细胞)数量减少。在临床研究中,这类新药在轻度至中度哮喘中显示出临床症状减轻和肺功能改善。此外,还显示出支气管扩张作用。口服给药的选择和良好的耐受性应可提高依从性。其在重度哮喘中的潜力和长期疗效仍不明确。需要进一步研究以阐明其作用范围,并确定它们在哮喘治疗中的地位。