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在研的哮喘药物

Author
Richard J Martin, MD
Section Editors
Bruce S Bochner, MD
Robert A Wood, MD
Deputy Editor
Helen Hollingsworth, MD
Translators
高亚东, 副主任医师，副教授

引言

哮喘患者的标准治疗基于避免接触触发因素、支气管扩张和抗炎治疗。β受体激动剂、吸入性和全身性糖皮质激素(glucocorticoid, GC)、白三烯调节剂、奥马珠单抗以及(作用程度相对较小的)甲基黄嘌呤类和抗胆碱能药物均在哮喘的常规治疗中起到了一定作用。然而，一些患者使用常规治疗并未取得充分的哮喘控制，或者使用常规药物出现了不良反应。正在进行中的研究试图找到效果更好且毒性更小的药物来控制哮喘。

本文将总结哮喘治疗的在研方案，包括有前景的方案和未能成功的方案。哮喘的标准治疗方案，以及补充性、替代性和综合性处理方案将单独讨论。 (参见“哮喘管理概述”和“哮喘的补充、替代和整合疗法”)

前列腺素D2受体拮抗剂

前列腺素是花生四烯酸代谢产物的主要类型之一，花生四烯酸代谢产物还包括血栓素和白三烯(图 1)。前列腺素D2(prostaglandin D2, PGD2)是由肥大细胞产生的一种主要的前列腺素，还可由Th2淋巴细胞和树突状细胞产生。PGD2具有支气管收缩和化学动力作用，这些作用可能参与了哮喘的发病机制，例如PGD2作为嗜酸性粒细胞的强效趋化因子。PGD2作用于肥大细胞、嗜酸性粒细胞和嗜碱性粒细胞上的PGD2受体2(DP2受体)。DP2受体具有介导Th2淋巴细胞移行，延迟Th2细胞凋亡，以及刺激Th2细胞产生IL-4、IL-5和IL-13等作用。 (参见“哮喘的发病机制”，关于‘早发相和迟发相反应’一节)

fevipiprant是一种在研的DP2受体拮抗剂，一项临床试验对其进行了评估，该试验纳入了61例痰液嗜酸性粒细胞计数升高(≥2%)的中至重度持续性哮喘患者[1]。受试者被随机分配至口服225mg的fevipiprant或安慰剂，一日2次，持续12周。fevipiprant组痰液嗜酸性粒细胞百分比显著下降，其几何均数从初始5.4(95%CI 3.1-9.6)降至1.1(95%CI 0.7-1.9)，而安慰剂组从4.6(95%CI 2.5-8.7)降至3.9(95%CI 2.3-6.7)。采用哮喘控制问卷7(Asthma Control Questionnaire 7, ACQ-7)对患者症状进行评估，发现两组无差异。哮喘生存质量问卷(Asthma Quality of Life Questionnaire, AQLQ)评分显示fevipiprant组有改善。支气管扩张剂后的肺量计检查结果显示有边缘获益，但支气管扩张剂前的并非如此。未报道有死亡和严重不良事件。还需要进一步的研究来探讨fevipiprant对肺功能和哮喘发作的作用。

生物制剂

已开发了若干靶向作用于哮喘炎症相关细胞因子级联反应中的环节的生物制剂，希望能改善作为慢性哮喘基础的炎症。新型GC受体激动剂通过激活GC受体以不同方式影响免疫调节，但可能没有传统GC的常见不良反应。 (参见“哮喘的发病机制”，关于‘气道炎症’一节)

                       

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Literature review current through: 2017-06 . | This topic last updated: 2017-06-05.
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