MICA: The Role of GABAB Receptor Mechanisms in Chronic Cough

MICA：GABAB 受体机制在慢性咳嗽中的作用

• 批准号: MR/K015141/1
• 负责人: Jacky Smith
• 金额: $ 45.49万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK015141%2F1
• 关键词: MICA; Role; GABAB; Receptor; Mechanisms

Coughing is the most common reason for which people visit their GP, but currently we know very little about why people cough and the current medications for treating cough are not helpful. Some people suffer from severe coughing which can last from eight weeks to many years, and yet they seem to have no obvious cause for their cough. This is known as a Chronic Cough. One theory is that chronic cough might be a response to a condition known as gastro-oesophageal reflux, where food and acid in the stomach flow back into the oesophagus (food pipe). Gastro-oesophageal reflux usually causes heartburn and indigestion which can get better with acid blocking medicines, but in people who develop cough, rather than heartburn, acid does not seem to be the problem and these treatments do not work. Previous research has suggested that in up to 50% of patients with chronic cough, the coughing may be triggered by gastro-oesophageal reflux.This project will study a new medicine, known as a GABA-B receptor agonist, developed to reduce the amount of gastro-oesophageal reflux. Although this medicine was not found to be helpful in patients with heartburn who were already taking acid blocking treatments, but we will test whether it improves chronic cough which has been triggered by reflux. This new medicine may also reduce the sensitivity of the nerves that make people cough and could also be helpful in chronic cough patients where reflux is not a problem for them. We plan two studies using this medicine. Firstly we will test this treatment in healthy people to see whether it reduces the sensitivity of the nerves responsible for coughing. Secondly we will test the treatment in patients with chronic cough and measure any reduction in the number of times people cough compared to a placebo (dummy) treatment. In this study we will also measure gastro-oesophageal reflux and the sensitivity of the cough reflex to work out which patients might find this medication helpful in the future.If these studies show this GABA-B receptor agonist improves chronic cough, then this could lead to the development of more effective treatments for coughing, which in turn may help more patients that just those with chronic cough.

咳嗽是人们去看医生的最常见原因，但目前我们对人们咳嗽的原因知之甚少，目前治疗咳嗽的药物也没有帮助。有些人患有严重的咳嗽，可以持续八周到多年，但他们似乎没有明显的咳嗽原因。这被称为慢性咳嗽。有一种理论认为，慢性咳嗽可能是对胃食管反流的一种反应，胃中的食物和酸流回食管（食物管道）。胃食管反流通常会导致胃灼热和消化不良，这可以通过阻酸药物得到改善，但在发展咳嗽而不是胃灼热的人中，酸似乎不是问题，这些治疗方法不起作用。以往的研究表明，高达50%的慢性咳嗽患者的咳嗽可能是由胃食管反流引起的。本项目将研究一种名为GABA-B受体激动剂的新药，以减少胃食管反流量。虽然这种药物没有被发现对已经服用酸阻断治疗的胃灼热患者有帮助，但我们将测试它是否可以改善由反流引发的慢性咳嗽。这种新药还可以降低使人们咳嗽的神经的敏感性，并且对慢性咳嗽患者也有帮助，因为他们的反流对他们来说不是问题。我们计划使用这种药物进行两项研究。首先，我们将在健康人身上测试这种治疗方法，看看它是否能降低引起咳嗽的神经的敏感性。其次，我们将测试慢性咳嗽患者的治疗，并测量与安慰剂（模拟）治疗相比，人们咳嗽次数的减少。在这项研究中，我们还将测量胃食管反流和咳嗽反射的敏感性，以确定哪些患者可能会发现这种药物在未来有帮助。如果这些研究表明这种GABA-B受体激动剂改善慢性咳嗽，那么这可能会导致更有效的咳嗽治疗方法的发展，这反过来可能会帮助更多的患者，而不仅仅是那些慢性咳嗽。

项目成果

Heartburn as a Marker of the Success of Acid Suppression Therapy in Chronic Cough.

• DOI: 10.1007/s00408-021-00496-w
• 发表时间: 2021-12
• 期刊: Lung
• 影响因子: 5
• 作者: Badri H;Satia I;Bansal V;Mangi MA;Tangaroonsanti A;DeVault KR;Lee AS;Houghton LA;Smith JA
• 通讯作者: Smith JA

A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough

• DOI: 10.1183/23120541.00546-2021
• 发表时间: 2022-01-01
• 期刊: ERJ OPEN RESEARCH
• 影响因子: 4.6
• 作者: Badri, Huda;Gibbard, Carmen;Smith, Jacky A.
• 通讯作者: Smith, Jacky A.

Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate.

• DOI: 10.1016/j.jaci.2015.10.044
• 发表时间: 2016-07
• 期刊: The Journal of allergy and clinical immunology
• 作者: Bonvini SJ;Birrell MA;Grace MS;Maher SA;Adcock JJ;Wortley MA;Dubuis E;Ching YM;Ford AP;Shala F;Miralpeix M;Tarrason G;Smith JA;Belvisi MG
• 通讯作者: Belvisi MG

Anatomy and neurophysiology of cough: CHEST Guideline and Expert Panel report.

• DOI: 10.1378/chest.14-1481
• 发表时间: 2014-12
• 期刊: Chest
• 影响因子: 9.6
• 作者: Canning BJ;Chang AB;Bolser DC;Smith JA;Mazzone SB;McGarvey L;CHEST Expert Cough Panel
• 通讯作者: CHEST Expert Cough Panel

Gastro-oesophageal reflux and cough.

胃食管反流和咳嗽。

• 发表时间: 2013
• 期刊: The Journal of the Association of Physicians of India
• 作者: Abdulqawi R