Holgate S T, Finnerty J P
Immunopharmacology Group, Southampton General Hospital, England.
J Allergy Clin Immunol. 1989 Feb;83(2 Pt 2):537-47. doi: 10.1016/0091-6749(89)90035-3.
Substantial evidence indicates that airway hyperresponsiveness in asthma is associated with the inflammatory response directed toward the airway epithelium and submucosa. Endogenously released spasmogenic mediators interacting with smooth muscle have a greater effect on hyperresponsive than on normal airways. Histamine, a bronchoactive and vasoactive mediator, is released in patients with naturally occurring or allergen-induced asthma. It is clear that mast cells are activated as part of the asthmatic response, and they have now been implicated as effector cells of mediator secretion based on the results of provocative tests. The advent of more potent histamine antagonists selective for H1 receptors has led to a reappraisal of antihistamine therapy in asthma. Drugs such as terfenadine and azelastine inhibit early bronchoconstriction and to some extent the late-phase asthmatic response as well. The efficacy of other new antihistamines (e.g., ketotifen and cetirizine) may extend beyond H1-receptor blockade to inhibit some of the chronic (and perhaps more important) cellular events in asthma.
大量证据表明，哮喘中的气道高反应性与针对气道上皮和黏膜下层的炎症反应相关。内源性释放的与平滑肌相互作用的致痉介质对高反应性气道的影响比对正常气道的影响更大。组胺是一种支气管活性和血管活性介质，在自然发生或变应原诱导的哮喘患者中会释放。很明显，肥大细胞作为哮喘反应的一部分被激活，根据激发试验的结果，它们现在被认为是介质分泌的效应细胞。对H1受体具有更高选择性的组胺拮抗剂的出现，促使人们重新评估抗组胺药在哮喘治疗中的作用。特非那定和氮卓斯汀等药物可抑制早期支气管收缩，并在一定程度上抑制迟发性哮喘反应。其他新型抗组胺药（如酮替芬和西替利嗪）的疗效可能不仅限于H1受体阻断，还可抑制哮喘中的一些慢性（可能更重要）细胞事件。
