Oribe Y, Fujimura M, Kita T, Katayama N, Nishitsuji M, Hara J, Myou S, Nakao S
Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa 920, Japan.
Clin Exp Allergy. 2005 Mar;35(3):262-7. doi: 10.1111/j.1365-2222.2005.02158.x.
Gastrooesophageal reflux (GER) is a frequent cause of chronic cough. Several investigators have indicated that inhibitors of H(+)K(+)ATPase (proton pump inhibitors; PPIs) could relieve coughing via inhibition of acid reflux. However, we considered that PPIs might directly inhibit increased cough reflex sensitivity.
The present study was designed to examine whether PPIs directly inhibit antigen-induced increase in cough reflex sensitivity and to elucidate the mechanism.
Actively sensitized guinea-pigs were challenged with aerosol antigen (ovalbumin, OVA) and cough reflex sensitivity to inhaled capsaicin was measured 24 h later. The PPIs (omeprazole and rabeprazole) or the histamine H(2) blocker cimetidine were administered intraperitoneally 1 h before OVA challenge and before measuring cough reflex sensitivity, then bronchoalveolar lavage fluid (BALF) was immediately collected. The pH of the fluid obtained by bronchial washing was determined after examining the effect of rabeprazole on the cough response to capsaicin.
The number of coughs elicited by capsaicin was significantly increased 24 h after challenge with OVA compared with saline, indicating antigen-induced increase in cough reflex sensitivity. Both PPIs dose dependently and significantly inhibited antigen-induced cough hypersensitivity. Omeprazole did not influence the antigen-induced increase in the total number of cells or ratio (%) of eosinophils in BALF. Cimetidine did not affect the antigen-induced cough hypersensitivity or cellular components of BALF. The pH of the bronchial washing fluid was significantly decreased in antigen-challenged animals. Rabeprazole did not affect the antigen-induced decrease in the pH of bronchial washing fluid.
These findings show that PPIs, but not histamine H(2) blockers, can directly decrease antigen-induced cough reflex hypersensitivity, while the mechanism remains unclear.
胃食管反流（GER）是慢性咳嗽的常见原因。一些研究人员指出，H(+)K(+)ATP酶抑制剂（质子泵抑制剂；PPIs）可通过抑制酸反流来缓解咳嗽。然而，我们认为PPIs可能直接抑制咳嗽反射敏感性的增加。
本研究旨在检测PPIs是否直接抑制抗原诱导的咳嗽反射敏感性增加并阐明其机制。
用气溶胶抗原（卵清蛋白，OVA）对主动致敏的豚鼠进行激发，24小时后测量对吸入辣椒素的咳嗽反射敏感性。在OVA激发前1小时及测量咳嗽反射敏感性前，腹腔注射PPIs（奥美拉唑和雷贝拉唑）或组胺H(2)受体阻滞剂西咪替丁，然后立即收集支气管肺泡灌洗液（BALF）。在检测雷贝拉唑对辣椒素咳嗽反应的影响后，测定支气管冲洗液的pH值。
与生理盐水相比，OVA激发24小时后辣椒素引发的咳嗽次数显著增加，表明抗原诱导咳嗽反射敏感性增加。两种PPIs均剂量依赖性且显著抑制抗原诱导的咳嗽超敏反应。奥美拉唑不影响抗原诱导的BALF中细胞总数或嗜酸性粒细胞比例（%）的增加。西咪替丁不影响抗原诱导的咳嗽超敏反应或BALF的细胞成分。抗原激发动物的支气管冲洗液pH值显著降低。雷贝拉唑不影响抗原诱导的支气管冲洗液pH值降低。
这些发现表明，PPIs而非组胺H(2)受体阻滞剂可直接降低抗原诱导的咳嗽反射超敏反应，但其机制尚不清楚。
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