MICA - Mechanism of action of targeted lung denervation in COPD: clinical, physiological, molecular and structural assessments

为什么需要这项研究：慢性阻塞性肺疾病(COPD)是一种通常由吸烟引起的肺部疾病。它影响了3亿多人，是全球第四大主要死亡原因。在慢性阻塞性肺疾病患者中，呼吸道变窄，治疗的目的是打开呼吸道以帮助呼吸。吸入器可能会引起副作用，包括严重的胸部感染(肺炎)，而且它们的影响是暂时的，这意味着必须至少每天服用。即使在服用它们的时候，许多患者也会出现呼吸困难、喘息、咳嗽和痰。这些症状可能会非常令人痛苦，并阻止人们进行洗涤、穿衣和出门等日常活动。可能会发生胸部感染和发炎，并可能导致需要入院的人。人们迫切需要治疗慢性阻塞性肺病的新疗法。我们计划做什么以及为什么：我们计划研究一种潜在的治疗慢性阻塞性肺疾病的新方法，称为“靶向肺去神经”或“TLD”。这是一种一次性的手术，目的是在不做任何手术的情况下打开呼吸道。它包括将一个小型摄像机(支气管镜)插入呼吸道，并将一个小型设备(导管)插入其中。一旦放置到位，导管就会将一种称为射频能量的电能输送到呼吸道。这会影响呼吸道的神经，应该会导致呼吸道开放和呼吸改善。它的工作方式很可能与目前常用的一种吸入器相似，但其优点是只需做一次。在少数患者中进行的初步研究非常有希望，并表明接受TLD治疗的患者症状有所改善，突发事件较少。我们需要更多地了解这种治疗方法，包括它对肺部的影响以及它是如何起作用的。它还将教我们更多关于呼吸道神经供应的知识。我们计划如何做到这一点：Airflow-3研究是一项在世界各地进行的试验，将包括300-400名COPD患者。我们计划在英国招募大约30名患者。患者将被仔细挑选，以确保手术对他们来说是安全的，并确保他们有合适的肺部疾病类型可以受益。然后，患者将被随机分配到接受TLD治疗或“假”程序，即将设备放置到呼吸道中，但不提供任何治疗。最初没有得到治疗的患者将可以选择在一年后接受TLD。患者和研究人员都不会知道患者是接受了真正的治疗，还是没有接受治疗的程序。作为Airflow-3研究的一部分，患者将接受为期5年的跟踪调查，大部分数据都是在前12个月收集的。我们将衡量的是：为了让我们彻底了解治疗是如何起作用的，我们对一些不同的结果感兴趣。我们将在治疗前和治疗后使用问卷对症状进行评估。我们将通过测试来评估对肺工作方式的影响，在测试中，通过向不同的管道吹气，以及在不同的物质中呼吸来测量肺的大小和功能。我们将使用扫描来检查呼吸道的结构。我们还将通过在实验室处理过程中采集组织和细胞样本来研究治疗对肺部细胞的影响。这也将帮助我们了解治疗如何影响呼吸道炎症以及细胞和神经。我们将研究特定的基因，看看它们是否会随着治疗而改变。将对结果进行分析和比较，看看接受过治疗的人与没有接受治疗的人是否有任何差异。我们还将寻找患者在治疗前后的差异。通过更多地了解这种潜在的新疗法及其工作原理，我们将能够决定它如何最大限度地造福于患者。

Why the research is needed: Chronic obstructive pulmonary disease (COPD) is a disease of the lungs usually caused by smoking. It affects more than 300 million people and is the fourth main cause of death worldwide. In COPD airways become narrow and treatments are aimed at opening up the airways to help breathing. Inhalers can cause side effects including serious chest infections (pneumonia) and their effects are temporary, meaning they must be taken at least daily. Even when taking them, many patients struggle with breathlessness, wheeze, cough and phlegm. These symptoms can be very distressing and stop people from doing everyday activities such as washing, dressing and leaving the house. Chest infections and flare ups can occur and may result in people needing admission to hospital. New treatments for COPD are desperately needed. What we plan to do and why: We plan to study a potential new treatment for COPD called "Targeted Lung Denervation" or "TLD". It is a one-off procedure which aims to open up the airways without any surgery. It involves inserting a small camera (bronchoscope) into the airways, and passing a small device (catheter) inside. Once in position, the catheter delivers a type of electrical energy called radiofrequency energy to the airways. This affects the nerves in the airways, and should result in the airways opening and an improvement in breathing. It is likely to work in a similar way to one of the current commonly used inhalers, but has the advantage of only needing to be done once. Initial studies in small numbers of patients have been very promising, and have shown patients treated with TLD have improved symptoms and fewer flare ups. We need to learn more about this treatment including the effects it has on the lungs and how it works. It will also teach us more about the nerve supply to the airways.How we plan to do it: The AIRFLOW-3 study is a trial taking place across the world which will include 300-400 patients with COPD. We plan to recruit around 30 patients in the UK. Patients will be carefully selected to ensure that the procedure is safe for them, and that they have the right type of lung disease to benefit. Patients will then be randomly allocated to receive either treatment with TLD, or a "sham" procedure where the device is placed into the airways, but no treatment is delivered. Patients who do not initially get treatment will have the option to have TLD after one year. Neither the patient nor the researcher will know whether the patient has had the real treatment or the procedure where no treatment was given. As part of the AIRFLOW-3 study patients will be followed up for 5 years, with the majority of data looking at the way the treatment works being collected in the first 12 months. What we will measure: In order for us to gain a thorough understanding of how the treatment works, we are interested in a number of different outcomes. We will assess symptoms using questionnaires before and after treatment. We will evaluate the effects on how the lungs are working with tests where the size and function of the lungs are measured by blowing into different tubes, and breathing in different substances. We will examine the structure of the airways using scans. We will also study how the treatment affects the cells in the lungs by taking samples of tissue and cells during the procedure which will be processed in the laboratory. This will also help us understand how the treatment affects inflammation of the airways, and the cells and nerves. We will study particular genes to see if they change with treatment. The results will be analysed and compared to see if there is any difference in people who have been treated compared to those who have not. We will also look for differences in patients before and after treatment. By understanding more about this potential new treatment and how it works, we will be able to decide how it may best be of benefit to patients.