Lung Volume Reduction: A personalised medicine approach
Lung volume reduction is an effective therapy for symptoms in patients with hyperinflation due to emphysema and COPD. Despite its clinical effectiveness its role has been limited in the UK. This has changed more recently with the development of new techniques (e.g. endobronchial valves). However, it is not clear which treatment is right option for individual patients.
Leicester has the largest historical cohort of LVR procedures in the UK, performing the most surgical procedures in the UK. This offers a rich source of data for research and development of fellowships.
- It is possible to identify patients more likely to clinically respond to different LVR techniques (LVRS, endobronchial valves and coils)
- Newer imaging techniques (e.g. V/PSPECT, quantitative CT) are better able to identify target areas for LVR than traditional techniques
- Using existing cohort data (and prospectively collect further data) to investigate the clinical response to LVR, for surgery, valves and coils.
- Assess the accuracy of V/PSPECT and quantitative CT compared with Q scan and non-quantitative CT in the identification of target areas for LVR
Develop a decision pathway for patients potentially undergoing lung volume reduction.
Qualitative and quantitative evaluation of acceptance of exercise intervention in lung cancer patients
Prescribed exercise has shown to improve survival in patients receiving curative chemotherapy for breast cancer (EBBA2 study). In advanced lung cancer, previous attempts to deliver prescribed exercise programmes have been challenging due to fitness and comorbidities with these patients. Part of the challenge with recruiting advanced NSCLC patients has been the timing of exercise intervention, generally these studies have been at diagnosis when patients are receiving other forms of anticancer treatment.
The main aim of this proposed project would be to assess when exercise intervention would be possible and acceptable to lung cancer patients. Two time points being 12 weeks at the end of a course of treatment and at 12 months if their disease state is either responding or stable. Quantitative and qualitative measures of health status would be taken; activation (PAM), Quality of life measures, psychological wellbeing, frailty measures, muscle strength and activity levels.
This will give an assessment of fitness and health status measures at these important time points for lung cancer patients receiving treatment, enabling the team to take this further to provide important feasibility data before a randomised controlled study of exercise intervention in lung cancer can be planned and executed.
Qualitative methodologies will be used to determine readiness to undertake a progressive exercise programme together with its acceptability in terms of timing, location and content.
Genetic determinants of Interstitial Lung Disease
Interstitial lung disease (ILD) is a heterogeneous grouping of >200 conditions whereby the gas-exchange interface of the lung is affected by inflammation or scarring. ~40% of ILD patients have idiopathic pulmonary fibrosis (IPF); this is diagnosed in >6,000 cases per year, has a median survival of 3 years and accounts for 1% of UK deaths. Professor Wain’s studies have identified around 14 regions of the genome affecting IPF risk (multiple GWAS hits). However, the genetic determinants of other ILDs remain poorly understood. The ILD Chronic Hypersensitivity Pneumonitis (cHP) classically arises from environmental antigen inhalation, but in ~50% of cases no antigen is identifiable. cHP shares many clinical similarities with other ILD, including IPF, leading to challenges in diagnosis and management. A clearer understanding of both shared and distinct genetic architectures of these diseases would improve our ability to discriminate cHP and personalise management. To address this, you will:
- Utilise new and existing genetic datasets to investigate the genetic architecture of ILD.
- Lead recruitment of a prospective cohort of individuals with cHP, collecting clinical data and blood for multi-omic assays.
- Support ongoing national and international collaborations to develop resources for genetic studies of cHP.
Physical activity and sedentary behaviour of patients with chronic respiratory disease: Pooled analysis from four low- and middle-income countries
Chronic respiratory diseases (CRDs) are accountable for some of most common causes of death worldwide. People living with CRD are frequently disabled by their breathlessness and, as such, often experience a reduced exercise capacity, poor quality of life and can become depressed, socially isolated and unable to work. Low- and middle-income countries (LMICs) experience the greatest disease burden but we know very little about these populations.
The NIHR funded Global RECHARGE project is collecting objectively measured physical activity data from people living with CRDs in LMICs (India, Kyrgyzstan, Sri Lanka, Uganda). Data collection will span a full calendar year for each country and the total sample size is expected to be >400 patients each with 7 days of monitoring.
The objectives of the research projects will be to:
- Derive a standardised methodology for the processing and analysis of objectively measured physical activity data from people living with CRD in LMICs
- Profile the physical activity of people living with CRD in LMICs; including, volume (e.g. step count and intensity) and patterns (e.g. bouts of activity, time of day and day of week) of physical activity
- Identify correlates of physical activity by examining a range of physical, psychological, social and environmental measures
The Impact of Pulmonary Tuberculosis on Muscle and Fat Wasting
Tuberculosis (TB) remains a global epidemic that is associated with considerable morbidity attributable to the systemic effects of infection. The classical symptoms of weight loss, fatigue and muscle wasting are clinically well recognised and the long term burden of systemic inflammation is thought to contribute to declining lung function. However, there is little published work profiling these clinical observations and the effects this may have on the host immune response to TB infection.
This project is a prospective clinical cohort study investigating whole body composition (using DEXA scans and multi-frequency bioelectrical impedence), lung function decline (corrected for cigarette and cannabis smoking), lung damage (quantified by cross-sectional analysis of radiological (CT) imaging) and the host immune response (T-cell function and genome (transcriptomic) analysis) in patients with active Pulmonary TB. Additionally, the longitudinal changes that occur during TB treatment and recovery will be examined.
The main objective of this project is to identify systemic biomarkers that link the inflammatory response and the muscle wasting seen in active TB and compare these with established and novel biomarkers in a cohort of COPD patients. A secondary aim is to describe the effects of cannabis smoking on the immune response, muscle wasting and lung function decline.
The ACF will be involved in the collection of whole body mass and appendicular measures of muscle and fat using techniques such as DEXA and bioelectrical impedance.
Determining the clinically relevant anatomy to teach UG medical students
Human anatomy has been a core component of undergraduate medical education for many years, and while it continues to be a key theme, the depth of anatomy taught has seen a steady decline. The need for a solid foundation of anatomical knowledge, while more readily appreciated as essential for those pursuing surgical careers, is important for any practicing clinician. Clearly, which areas of anatomy are most relevant will vary depending on the postgraduate speciality. With ever increasing pressures on space within the UG curriculum, there is obvious priority to ensuring what is taught best enables students to meet the demands of the breadth of future clinical practice.
While the GMC do not currently stipulate specific outcomes for the level of anatomy within the UG medical curriculum, the future introduction of the UK Medical Licensing Assessment will likely lead to efforts to better establish ILOs for the basic sciences, as a whole. In 2016, in response to the lack of consensus and guidance on the appropriate level of anatomy, the Anatomical Society defined a core regional anatomy syllabus of 156 ILOs, which were to help curriculum planners determine the clinically relevant anatomy to teach UG medical students. The proposed ILOs were determined by a Delphi panel of experts, which included surgeons, radiologists and anatomists.
The first step of the project will involve a series of focus groups and surveys with a variety of early clinical trainees from medicine, surgery and primary care. The purpose of this will be to identify whether there are elements of the 156 identified ILOs that represent a base of anatomical knowledge common across a breadth of specialities (surgical and non-surgical). The second step will be to explore how well they perceive (by self-report) to have retained knowledge of those areas of anatomy (identified in the first step of the project).
The findings from this project will help to better define areas of anatomy that are seen as most important, relevant and common to a breadth of clinical specialities. Further work/projects could explore how this anatomy could be prioritised or given greater attention within the UG medical curriculum, or early postgraduate period and whether there are any interventions that can be applied to improve retention of knowledge in those areas.