Title: Attenuating the effects of hospital-associated disability in exacerbations of Chronic Obstructive Pulmonary Disease using an anabolic intervention: a randomised controlled feasibility study
Funder: Department of Health and Social Care

Abstract: Background The age of the UK population is increasing, with a greater prevalence of chronic disease. People with chronic disease are more likely to be hospitalised with acute crises of their condition and account for 70% of all emergency hospital bed days in the NHS. These patients are often frail with reduced physical function and muscle wasting. Admission and time spent in hospital can have detrimental consequences, known as hospital associated disability (HAD), often driven through muscle atrophy, leading to increased disability and poorer health. This may then lead to further readmission to hospital and a cycle of deterioration. Chronic obstructive pulmonary disease (COPD) is one of the major long term conditions that lead to hospitalisation, through flare-ups or exacerbations of the disease. It is the second largest cause for unscheduled admission to hospital in the UK with nearly 50% of patients readmitted within three months. Systemic consequences of COPD are well recognised, in particular skeletal muscle dysfunction. This means patients with COPD are likely to be at high risk of HAD . Despite the detrimental effects of hospitalisations being recognised it is a poorly understood process, with little knowledge of the natural history including the recovery process. It is also unknown who is at high risk of hospital associated disability. Treatment for this has been limited. Completion of an exercise based programme (pulmonary rehabilitation) within a month of hospitalisation has been shown to be of benefit, but only 9% of potential patients complete the intervention. Other exercise interventions, delivered early in the hospitalisation to prevent the initial effects of hospital associated disability and to enhance recovery have been negative. Other strategies, such as anabolic pharmacological interventions, are of potential benefit and may have a role in the acute setting.Aims (1) To establish the assessment and understanding of the process of HAD in patients hospitalised for an exacerbation of COPD. (2) Whether it is feasible to test an anabolic drug intervention compared to usual care in the acute care setting in patients admitted with an exacerbation of COPD, aimed to ameliorate the effects of hospital associated disability.Study Design This fellowship will comprise of two stages. The first will be a observational study, including a prospective cohort study. This will recruit patients at time of admission to hospital with an exacerbation and follow them through the period of acute illness and recovery. It will measure markers of walking, frailty, activities of daily living and muscle size. This will allow understanding of the natural history of HAD. It will also identify patients at high risk of developing HAD. The second stage of the fellowship will be a randomised controlled feasibility trial of an anabolic agent starting at the time of hospitalisation for an exacerbation of COPD. The primary outcome to estabilsh the feasibility of delivering an anabolic drug agent in the acute care setting and to power a clinical effectiveness trial. Secondary outcomes will include measures of frailty and walking (short performance battery test), activities of daily living and health related quality of life. A nested qualitative study will also be performed in stage one, to understand patients perceptions and understanding of drug interventions to prevent HAD.Potential Benefits This fellowship may provide large potential benefits for patients admitted to hospital, for which there is a large unmet need, particularly patients with long term conditions. This fellowship will improve the understanding of the effects of hospitalisation in COPD, and provide feasibility for a novel anabolic drug treatment. If successful this would lead to a definitive clinical effectiveness trial, and may have implications beyond COPD into patients with other chronic conditions.

Lay abstract: Background 1 in 4 people in the UK have at least one long term, or chronic, condition. These people are commonly at risk of developing both acute crises of their long term illness and additional illness and ending up in hospital. While the aim of being in hospital is to improve the acute illness, it can have detrimental effects, reducing the ability to walk, do everyday tasks and cause muscle wasting. This is known as hospital-associated disability. One group at particular risk are patients with smoking related lung damage- Chronic Obstructive Pulmonary Disease (COPD). COPD is currently the 4th largest cause of disability and the 2nd most likely cause of unscheduled or emergency admission to hospital in the UK. This is due to flare-ups of their disease, also known as exacerbations. Whilst patients with COPD mainly have problems with their lungs they can also develop systemic consequences, of which muscle weakness and wasting are well recognised. This combination of pre-existing muscle disease and high risk of admission to hospital make them prone to hospital-associated disability (HAD) Despite the recognition of the importance of HAD and hospitalisation for an exacerbation of COPD very little is understood about the process and about potential treatments to minimise the effects. This fellowship aims to address these issues.Aims (1) Establish the assessment and understanding of hospital-associated disability in people admitted to hospital with exacerbations of COPD (2) Test whether it is possible to conduct a clinical trial where a drug that builds up muscle- also known as an anabolic drug- can prevent the effect of hospital associated disability.Study Design The research will be done in two stages. The first stage will observe patients through their admission to hospital for an exacerbation of COPD until they are recovered. Stage two will test whether it is possible to give an anabolic drug when people are admitted to hospital. Stage One We plan to follow patients admitted to hospital with an exacerbation of COPD and see how they are affected by HAD and the process of recovery. We also want to be able to identify patients at high risk of developing HAD. People will be ask to join the study when they come in hospital and will be seen for eight weeks. We will do some measures to look at walking, standing, their symptoms, their quality of life, and muscle size and strength. We will also ask them how best we can recruit people to a trial in this setting. We will also see people again eight weeks later, when they have recovered from their hospital admission. Stage Two Once we better understand the process of HAD we want to test an intervention to see if can help prevent it. This will be done using a drug that builds up muscle called an anabolic agent. There are several anabolic agents that exist and in development. We want to use one and give it to people when they are first admitted to hospital to prevent hospital associated disability. We will measure whether it is possible to recruit people to the study and also see if people are see if people can walk more easily. If we find that the treatment works in this fellowship and in the longer term we would then hope to test if it prevents people coming back into hospital. Potentially this treatment could help many people and may not just be limited to people with COPD. At the end ot the studies we will publish our results in medical journals and present them at medical conferences. We will also have a local day for the public and patients, involving the local charities to tell them about our results.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY