AU - Smith、Jaclyn A. AU - Kitt、Michael M. AU - Butera、Peter AU - Smith、Steven A. AU - Li、yuuping AU - Xu、zhijin AU - Holt、Kimberley AU - Sen、Shilpi AU - Sher、Mandel R. AU - Ford、背景Gefapixant在高日剂量治疗难治性慢性咳嗽中已被证实有效。目的探讨P2X3受体拮抗剂gefapixant采用剂量递增法治疗慢性咳嗽的疗效和耐受性。材料和方法两项随机、双盲、安慰剂对照、交叉、剂量递增研究招募了难治性慢性咳嗽的参与者。患者被分配接受上升剂量的gefapixant(研究1:50-200 mg，研究2:7.5-50 mg)或安慰剂16天，然后在洗脱后进行交叉治疗。主要终点是在基线和每剂量第4天使用24小时动态咳嗽监测器评估清醒咳嗽频率。患者报告的结果包括咳嗽严重程度视觉模拟量表(VAS)和咳嗽严重程度日记(CSD)。结果在临床研究中，与安慰剂相比，gefaixant剂量≥30 mg对咳嗽频率的改善最大(p<0.05);报告的咳嗽严重程度指标在相同剂量下有所改善。味觉障碍表现出不同的剂量关系，明显最大的剂量≥150 mg。结论与gefapixant相比，P2X3在较低剂量下表现出抗咳的疗效和改善的耐受性。需要进行更长时间的研究。FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr Smith reports grants and personal fees from Merck Inc, during the conduct of the study; grants and personal fees from Glaxosmithkline, grants and personal fees from NeRRe Pharmaceuticals, grants and personal fees from Menlo, grants and personal fees from Bayer, personal fees from Boehringer Ingleheim, personal fees from Genentech, personal fees from Neomed, non-financial support from Vitalograph, personal fees from Cheisi, grants and personal fees from Afferent, personal fees from Bellus, grants and personal fees from Axalbion, personal fees from AstraZeneca, outside the submitted work; In addition, Dr Smith has a patent A method for generating output data licensed.Conflict of interest: Dr Kitt reports other from Merck/Afferent, during the conduct of the study; other from Merck/Afferent, outside the submitted work.Conflict of interest: Dr Butera reports other from Afferent Pharmaceuticals, Inc., during the conduct of the study; other from Afferent Pharmaceuticals, Inc., outside the submitted work; and I was an employee of Afferent Pharmaceuticals, Inc..Conflict of interest: Mr. Smith reports personal fees from Afferent Pharmaceuticals, during the conduct of the studyConflict of interest: Dr Li reports personal fees from Afferent/Merck &amp; Co., Inc, during the conduct of the study.Conflict of interest: Dr Xu has nothing to disclose.Conflict of interest: Ms. Holt has nothing to disclose.Conflict of interest: Dr Sen has nothing to disclose.Conflict of interest: Dr sher reports personal fees from Afferent, personal fees from Merck, during the conduct of the study; and Consultant to Bellus, Bayer, NeRRe with clinical studies with Menlo and NeRRe.Conflict of interest: Dr Ford has nothing to disclose. ER -