Sakai Tamami, Hara Johsuke, Yamamura Kenta, Okazaki Akihito, Ohkura Noriyuki, Sone Takashi, Kimura Hideharu, Abo Miki, Yoshimura Kenichi, Fujimura Masaki, Kasahara Kazuo, Nakao Shinji
a Respiratory Medicine , Kanazawa University Hospital , Ishikawa , Japan.
b Innovative Clinical Research Center , Kanazawa University Hospital , Ishikawa , Japan.
Exp Lung Res. 2018 Dec;44(10):455-463. doi: 10.1080/01902148.2019.1590883. Epub 2019 Apr 1.
Purpose/Aim of the study: Methacholine chloride (MCh) inhalation causes bronchoconstriction and cough. Following MCh-induced bronchoconstriction, metabolic products of prostaglandin I (PGI) increase in bronchoalveolar lavage fluid (BALF), suggesting that PGI plays a role in the cough response. Accordingly, we used an experimental guinea pig model to evaluate the role of PGI in the bronchoconstriction-triggered cough response.
Experiment 1: The concentration of PGF, a stable metabolite of PGI, in BALF was assessed in animals exposed to nebulized MCh and animals exposed to nebulized saline. Experiment 2: Bronchoconstriction and cough were assessed in 3 groups of animals after MCh inhalation (a saline group, low-dose PGI group, and high-dose PGI group). Enhanced pause (Penh) was used as a measure of bronchoconstriction. Experiment 3: Bronchoconstriction and cough were assessed in 3 groups of animals (groups administered saline, a low dose of a specific antagonist of the PGI receptor (IP antagonist), and a high dose of a specific IP antagonist).
The PGF concentration in BALF was significantly higher in the bronchoconstriction group than in the control group. In animals administered high-dose PGI, the MCh-induced increase in Penh was significantly suppressed, and the number of coughs induced by bronchoconstriction was significantly decreased. In animals treated with a high dose of an IP antagonist, the MCh-induced increase in Penh was not affected, and the number of coughs increased.
Our results suggest that PGI ameliorates a bronchoconstriction-triggered cough. The measurement and administration of PGI may assist in the diagnosis and treatment, respectively, of the cough response triggered by bronchoconstriction.
研究目的：吸入氯化乙酰甲胆碱（MCh）会导致支气管收缩和咳嗽。在MCh诱导的支气管收缩后，支气管肺泡灌洗液（BALF）中前列腺素I（PGI）的代谢产物增加，这表明PGI在咳嗽反应中起作用。因此，我们使用实验性豚鼠模型来评估PGI在支气管收缩引发的咳嗽反应中的作用。
实验1：评估雾化吸入MCh的动物和雾化吸入生理盐水的动物BALF中PGI的稳定代谢产物PGF的浓度。实验2：对3组吸入MCh后的动物（生理盐水组、低剂量PGI组和高剂量PGI组）进行支气管收缩和咳嗽评估。增强暂停（Penh）用作支气管收缩的指标。实验3：对3组动物（给予生理盐水、低剂量PGI受体特异性拮抗剂（IP拮抗剂）和高剂量特异性IP拮抗剂的组）进行支气管收缩和咳嗽评估。
支气管收缩组BALF中PGF浓度显著高于对照组。给予高剂量PGI的动物中，MCh诱导的Penh增加显著受到抑制，支气管收缩诱导的咳嗽次数显著减少。给予高剂量IP拮抗剂治疗的动物中，MCh诱导的Penh增加未受影响，咳嗽次数增加。
我们的结果表明PGI可减轻支气管收缩引发的咳嗽。PGI的测量和给药可能分别有助于支气管收缩引发的咳嗽反应的诊断和治疗。
