Title: Understanding the role of portable handheld non-invasive ventilation to reduce 30-day hospital readmissions following severe exacerbations of Chronic Obstructive Pulmonary Disease: a mixed methods feasibility study
Funder: Department of Health and Social Care

Abstract: Background Chronic Obstructive Pulmonary Disease (COPD) is a common, progressive lung disease. The disease course is punctuated by acute exacerbations (AECOPD) which require hospital admission if severe. Treatment failure is common, with 24% of patients readmitted within 30 days of hospital discharge. This problem imposes substantial burdens onto patients and the National Health Service (NHS) and is cited as an unmet need by patients, clinicians and the scientific community. Current interventions to prevent 30-day readmission following severe AECOPD have demonstrable limitations. Non-invasive ventilation (NIV), which ventilates the patient through a mask and assists with respiratory muscle unloading, improves exercise endurance and breathlessness during exercise and can reduce hospital readmissions amongst COPD patients. Although NIV has been shown to improve patient outcomes when used during sleep, the technical, uncomfortable and bulky equipment limits its use during daily activities. This research will investigate a novel portable handheld NIV device which may overcome these limitations and so alleviate the problem of 30-day readmission following severe AECOPD.Aim To undertake quantitative and qualitative feasibility studies evaluating the use of a portable handheld NIV device which will inform the design of a Phase III multicentre randomised controlled trial (RCT).Methods This will be a single-centre feasibility RCT at St Thomas' Hospital, London, aiming to recruit 80 patients over 20 months. Patients aged 45-85 with a primary diagnosis of AECOPD will be recruited within 24 hours of hospital admission. Participants will be randomised to receive either handheld NIV or no intervention prior to discharge. All participants will receive usual clinical care from the responsible clinical team (inhaled bronchodilators, steroids and antibiotics if indicated) and 30-day study follow-up.Feasibility outcomes will include participant recruitment rate, willingness to be randomised, adherence with completing outcome measures, handheld NIV usage pattern and estimated standard deviations of selected clinical outcome measures to inform a sample size calculation. Qualitative evaluation using face-to-face interviews of 15 participants in the intervention arm will be used to explore patients' acceptance of handheld NIV. Clinical outcomes of change in neural respiratory drive, 30-day hospital readmission, non-readmission exacerbations, change in breathlessness, physical activity and health-related quality of life will be measured using clinical assessments, weekly telephone calls, daily symptom diaries and wrist-worn monitors.A statistical analysis plan has been devised with a senior statistician. Outcome measures will be reported using descriptive statistics. Mean differences between the two groups with 95% confidence intervals for each outcome measure will identify a suitable primary outcome and inform a sample size calculation.A randomised crossover Proof-of-Concept study of 20 participants will be performed to investigate the physiological effects of handheld NIV on the respiratory system during recovery from acute breathlessness.Anticipated impact Handheld NIV has the potential to alleviate the immense burdens of 30-day readmission following severe AECOPD on patients and the NHS. This study will evaluate feasibility outcomes, acceptability of handheld NIV and its effects on the respiratory system and will estimate standard deviations of five patient-centred outcomes to inform the design of a Phase III multicentre randomised controlled trial.

Lay abstract: Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease that affects 1.2 million people in the United Kingdom. COPD patients suffer with episodes of worsening breathing symptoms, particularly breathlessness, called exacerbations. Exacerbations occur more often as the disease progresses and are a leading cause of emergency hospitalisation. Patients recovering from exacerbations are at high risk of deteriorating, with one quarter readmitted to hospital within thirty days.COPD imposes immense burdens on the National Health Service (NHS), costing 1.9 billion every year. Exacerbations account for the majority of these costs. Furthermore, hospitals are penalised if patients are readmitted within thirty days of discharge. During their recovery, patients experience disabling breathlessness which limits their day-to-day activities, reducing their quality of life and increasing their risk of hospitalisation and death.Treatments to prevent hospital readmissions are currently limited. Studies have shown that a technique called Non-Invasive Ventilation (NIV) improves COPD patients' breathlessness and exercise ability and can prevent hospital readmissions. NIV currently involves breathing through a tight-fitting mask connected to a machine which is uncomfortable and requires specialist expertise to use. These obstacles prevent patients using NIV during day-to-day activities. Simple, portable, handheld NIV devices have recently been developed which may overcome these obstacles and provide quick and easy breathlessness relief.My research will investigate patients' experiences of using handheld NIV, examine the effects it has on the breathing system and estimate if it reduces hospital readmissions and re-exacerbations and improves breathlessness, physical activity and quality of life for 30 days after hospital discharge following severe COPD exacerbations. This research will help design a larger study which could have a profound impact on patients' lives and the NHS if handheld NIV is shown to be effective.I will recruit 80 patients admitted to St Thomas' Hospital, London with COPD exacerbations and give 40 patients handheld NIV devices and training before they are discharged. A computer-generated random order will choose who receives a device. All patients will receive their usual medical care from the hospital team caring for them. This includes inhalers, steroids and antibiotics if the exacerbation is caused by infection. I will follow-up patients for 30 days after hospital discharge using weekly telephone calls, daily symptom diaries and wrist-worn watch-like devices that detect physical activity. These will allow me to monitor patients' symptoms and quality of life and whether they are readmitted to hospital. After the 30-day follow-up, I will interview 15 patients who received handheld NIV to explore their experiences of using it. To investigate the effects of handheld NIV on the breathing system, I will perform detailed breathing tests on 20 patients after the 30-day follow-up. This involves patients doing two exercises on an exercise cycle until they are too breathless to continue, with a 1-hour rest in between. After each exercise, patients will be given either handheld NIV or no intervention. I will time how long it takes to recover from their breathlessness and measure their breathing muscles' electrical activity. The random order that patients receive the interventions will be generated by a computer.This study and lay summary has been designed with the help of the Respiratory Critical Care Patient and Public Involvement (PPI) Group and Biomedical Research Centre PPI Advisory Group at Guy's and St Thomas' NHS Foundation Trust and the Research and Design Service's Fast-Track Review Service. I will meet the Respiratory Critical Care PPI Group twice yearly throughout my research. I will share results summaries with study participants, patients and the Respiratory Critical Care PPI group and highlight the results of my study to other healthcare professionals nationally and internationally to improve clinical care.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: RESPIRATORY