TY - JOUR T1: P2X3拮抗剂gefapixant对咳嗽反射敏感性的影响:一项随机安慰剂对照研究摩根富林明-欧洲呼吸杂志》乔和J - 10.1183/13993003.00439 -2019欧元六世- 54 - 1 SP - 1900439 AU Morice Alyn h . AU -基特,迈克尔·m . AU -福特,安东尼·p . AU - Tershakovec安德鲁·m·吴盟——Wen-Chi AU -斑纹,Kayleigh AU -汤普森,瑞秋盟——Thackray-Nocera苏珊娜AU -赖特我们评估了gefapixant对诱发性咳嗽刺激的咳嗽反射敏感性的影响。在这项2期、双盲、两期研究中，慢性咳嗽(CC)患者和健康志愿者(HV)以交叉方式随机接受单剂量吉法吡ixant 100 mg或安慰剂。在给药后1、3和5小时，依次吸入ATP、柠檬酸、辣椒素和蒸馏水。与基线相比，剂量后引起≥2次咳嗽(C2)和≥5次咳嗽(C5)的平均浓度是共同的主要终点。对CC患者24小时内的客观咳嗽频率(咳嗽·h - 1)和咳嗽严重程度视觉模拟评分(VAS)进行评估。监测不良事件CC患者和12名HV患者随机分组(平均年龄分别为61岁和38岁)。在CC患者中，与安慰剂相比，吉法ixant对ATP的咳嗽攻毒阈值增加了4.7倍(C2, p≤0.001)和3.7倍(C5, p=0.007); in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (p<0.001) by a factor of 1.4 and 1.3, respectively, in CC patients. Gefapixant had no effect on capsaicin or citric acid challenge. Median cough frequency was reduced by 42% and the least squares mean cough severity VAS was 18.0 mm lower for gefapixant versus placebo in CC patients. Dysgeusia was the most frequent adverse event (75% of HV and 67% of CC patients).ATP-evoked cough was significantly inhibited by gefapixant 100 mg, demonstrating peripheral target engagement. Cough count and severity were reduced in CC patients. Distilled water may also evoke cough through a purinergic pathway.Gefapixant reduces coughing in patients and blocks ATP- and distilled-water-induced cough, but not cough evoked by citric acid or capsaicin, suggesting a unique TRPV4/ATP pathway may underlie cough hypersensitivity seen in chronic refractory cough http://bit.ly/2Gcr9Lr ER -