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

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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.