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

MICA - 慢性阻塞性肺病中靶向肺去神经术的作用机制：临床、生理、分子和结构评估

• 批准号: MR/V00171X/1
• 负责人: Francesca Conway
• 金额: $ 38.1万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV00171X%2F1
• 关键词: MICA; Mechanism; action; targeted; lung

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.

为什么需要研究：慢性阻塞性肺疾病（COPD）是一种通常由吸烟引起的肺部疾病。它影响着3亿多人，是全球第四大死亡原因。在COPD中，气道变得狭窄，治疗旨在打开气道以帮助呼吸。吸入剂可能会引起副作用，包括严重的胸部感染（肺炎），而且它们的影响是暂时的，这意味着它们必须至少每天服用。即使服用这些药物，许多患者也会呼吸困难，气喘，咳嗽和痰。这些症状可能非常令人痛苦，并阻止人们进行日常活动，如洗涤，穿衣和离开家。胸部感染和突发事件可能会发生，并可能导致人们需要入院治疗。迫切需要新的COPD治疗方法。我们计划做什么和为什么：我们计划研究一种潜在的COPD新治疗方法，称为“靶向肺去神经支配”或“靶向肺去神经支配”。这是一个一次性的程序，旨在开放气道，而无需任何手术。它包括将一个小摄像头（支气管镜）插入气道，并将一个小装置（导管）插入其中。一旦就位，导管将一种称为射频能量的电能输送到气道。这会影响气道中的神经，并应导致气道开放和呼吸改善。它可能以类似于目前常用的吸入器之一的方式工作，但优点是只需要做一次。在少数患者中进行的初步研究非常有希望，并且已经显示接受抗抑郁药治疗的患者症状得到改善，发作次数减少。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工作的。我们计划如何进行：AIRFLOW-3研究是一项在全球范围内进行的试验，将包括300-400名COPD患者。我们计划在英国招募约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，并且他们有合适的肺部疾病类型。然后，患者将被随机分配，接受使用呼吸机的治疗，或接受“假”手术，即将设备放置到气道中，但不进行治疗。最初没有接受治疗的患者将可以选择在一年后接受治疗。患者和研究人员都不知道患者是否接受了真实的治疗或没有接受治疗的手术。作为AIRFLOW-3研究的一部分，患者将接受5年的随访，大部分数据将在前12个月内收集治疗的方式。我们将测量：为了让我们彻底了解治疗是如何工作的，我们对许多不同的结果感兴趣。我们将在治疗前后使用问卷调查评估症状。我们将评估对肺如何工作的影响，通过向不同的管道吹气和吸入不同的物质来测量肺的大小和功能。我们将使用扫描检查气道的结构。我们还将通过在实验室处理的过程中采集组织和细胞样本来研究治疗如何影响肺部细胞。这也将帮助我们了解治疗如何影响气道，细胞和神经的炎症。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，以确定接受治疗的人与未接受治疗的人相比是否有任何差异。我们还将寻找治疗前后患者的差异。通过更多地了解这种潜在的新治疗方法及其工作原理，我们将能够决定它如何最好地造福于患者。

项目成果

Targeted Lung Denervation for Chronic Obstructive Pulmonary Disease: 12-Month Crossover Data from the AIRFLOW-2 Trial

慢性阻塞性肺疾病的靶向肺去神经术：来自 AIRFLOW-2 试验的 12 个月交叉数据

• DOI: 10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1021
• 发表时间: 2021
• 作者: Conway F

Two-Year Outcomes for the Double-Blind, Randomized, Sham-Controlled Study of Targeted Lung Denervation in Patients with Moderate to Severe COPD: AIRFLOW-2.

• DOI: 10.2147/copd.s267409
• 发表时间: 2020
• 期刊: International journal of chronic obstructive pulmonary disease
• 影响因子: 2.8
• 作者: Valipour A;Shah PL;Herth FJ;Pison C;Schumann C;Hübner RH;Bonta PI;Kessler R;Gesierich W;Darwiche K;Lamprecht B;Perez T;Skowasch D;Deslee G;Marceau A;Sciurba FC;Gosens R;Hartman JE;Conway F;Duller M;Mayse M;Norman HS;Slebos DJ;AIRFLOW-2 Trial Study Group
• 通讯作者: AIRFLOW-2 Trial Study Group