Title: Comparative effectiveness of lung volume reduction surgery and bronchoscopic lung volume reduction with valve placement in patients with emphysema
Funder: Department of Health and Social Care

Abstract: Background: Emphysema is one of the lung pathologies in chronic obstructive pulmonary disease (COPD). Emphysematous areas expand and trap air at the expense of relatively healthier parts of the lung causing breathlessness. Lung volume reduction surgery (LVRS) is an established, evidence-based therapy known to improve quality of life, exercise capacity and survival in selected patients with emphysema. An alternative approach to volume reduction in emphysema patients is to place endobronchial valves (BLVR) to occlude the worst affected part of the lung causing the target area to collapse. This has been shown to improve lung function but comparative data are not available to enable patients and commissioners to choose the most effective approach. Surgery carries the greatest upfront morbidity but as a definitive procedure may produce a more sustained benefit whereas BLVR may serve simply to delay subsequent LVRS. BLVR itself also carries a risk of serious complications. Plan of investigation: We will conduct an assessor blinded, randomised controlled trial comparing a surgical lung volume reduction strategy to one where endobronchial valves are available. The study will enrol adult patients with COPD and a heterogeneous pattern of emphysema with target areas for lung volume reduction. It will be carried out at two teaching hospitals (London and Leicester) which have established multidisciplinary teams to assess patients with emphysema for lung volume reduction. Prior to the start of the study we will conduct focus groups of patients who have undergone these procedures to ensure key qualitative outcomes that they consider are included as well as standard health status measures. Patients will be included if they have upper lobe predominant emphysema, an FEV1100% RV>150%) and an MRC dyspnoea score of 3 or above. Exclusion: patients will be excluded if they have FEV1, TLco and Kco all below 20% predicted, if PaO2 The primary efficacy endpoint will be a comparison of change in the i-BODE score from baseline between groups 12 months post initial procedure. This score includes BMI, airflow obstruction (forced expiratory volume in one second (FEV1)), breathlessness (mMRC dyspnoea score) and exercise capacity (incremental shuttle walk test distance). Secondary endpoints will be change in residual volume (RV) and health status (CAT score and EQ-5D). Data on NHS costs including hospital admissions and medication together with repeat procedures will be collected together with EQ-5D to allow cost effectiveness to be analysed. Based on a change in i-BODE in the LVRS arm of 3.1(1.9) [Imfield 2006] and of 1.6(1.9) in the BLVR arm requires, at a 5% significance level and 90% statistical power, 34 patients in each treatment arm. Allowing for 10% drop-outs we will enrol 76 individuals. Participants will be asked to consent to collection of linked data on hospital admissions and survival to allow for longer term follow up. Benefits to the NHS At present there are no data to compare these two approaches directly. Both LVRS and BLVR are being performed more frequently and patients, health professionals and commissioners need to be able to evaluate them to make a rational decision about which treatment approach to adopt.

Lay abstract: People with emphysema have lungs that become baggy and full of holes meaning that they are unable to breathe out fully. This is called &ldquo;gas trapping&rdquo;. As emphysema progresses this causes breathlessness, limits how far they can walk and can be fatal. Lung volume reduction surgery (LVRS) is an operation to remove the worst affected part of the lung making more space for the remaining healthier lung to function. There is good evidence that in properly selected individuals this can improve breathlessness and increase life expectancy. It is a significant operation and does carry a risk of complications. A more recent approach is to use a fibreoptic camera (bronchoscope) to place valves into the airways of the lung. These stop air entering the worst-affected section of the lung causing it to collapse with similar benefits to surgery. No studies have compared the two approaches so we do not know which is more effective and how to balance the risks and benefits. We will recruit 76 people with severe emphysema. Half will have LVRS and half bronchoscopic lung volume reduction with valves (BLVR). At one year we will compare lung function, walking distance and breathlessness to see which group have done better. We will look at complications such as hospital admissions, chest infections or the need for further procedures to compare the cost of the two approaches. This will allow us to decide which approach is better value for patients and the healthcare system. Our British Lung Foundation Breathe Easy Group have identified this as a key area for research and will assist with developing materials for the project such as patient information sheets. The results will be published in medical journals and in the media more widely. They will be used to help develop guidelines for the management of emphysema.

Research activity codes: 6.4 SURGERY
Health categories: RESPIRATORY