BRC funded PhD
Lung hyperinflation is associated with advanced COPD and severe breathlessness. It remains unclear how hyperinflation and associated disordered pulmonary mechanics impact on the extra-pulmonary manifestations of COPD including nutritional status, muscle function and cardiac function. Linking with Leicester’s established clinical service, this project will carefully phenotype patients with COPD and hyperinflation with particular focus on markers of sarcopenia (muscle mass and strength). For some patients with COPD and lung hyperinflation lung volume reduction (LVR) may reduce breathlessness and improve exercise tolerance. The extra-pulmonary effects of LVR clinical intervention are not well characterised. Here we aim to perform detailed extra-pulmonary phenotyping in individuals suitable for LVR to include: nutritional assessment; MRI (muscle quality and cardiac function); bioelectrical impedance / DEXA (body composition); cardiopulmonary exercise testing; isokinetic dynamometry (muscle strength and fatiguability); and tri-axial accelerometry (habitual physical activity monitoring). By observing changes in these measures following LVR we hope to identify characteristics that influence the whole-body response to LVR. Further we will assess the influence of skeletal muscle and cardiac function on the recovery (or failed recovery) of physical function in people who have undergone LVR.
Aim: To study the extra-pulmonary characteristics of people with lung hyperinflation and relate these to recovery of physical function after lung volume reduction (LVR) treatment. This project will produce detailed extra-pulmonary phenotyping in people with hyperinflation accessing the COPD clinical service.
Background: High lung volumes associated with severe emphysema place respiratory muscles at a mechanical disadvantage and increased intrathoracic pressure compromises cardiac output. Patients’ quality of life is compromised by extreme dyspnoea, severely curtailed exercise capacity, and fatigue. For suitable individuals, LVR via endobronchial or surgical intervention can reduce lung volumes, increase exercise capacity, improve quality of life and reduce mortality (NETT Trial, AJRCCM, 2011) with specialist centres now commissioned by NICE.
There is relatively little known about the impact of LVR beyond the lungs. Nutritional status is associated with LVR outcomes (non-obese patients who gain weight after LVR have better lung function outcomes, Kim, AJRCCM, 2012,). Body composition and skeletal muscle are likely important: muscle dysfunction in COPD curtails exercise capacity and better predicts hospital admission and death than traditional measures of lung function (Greening et al, AJRCCM, 2015; Swallow et al, Thorax, 2007). We do not fully understand the mechanisms driving an individuals’ recovery (or failure to recover) exercise capacity after LVR: nutritional status; muscle function; exercise performance; muscle mass; and importantly muscle quality have not been carefully characterised. There is also a paucity of data on the impact of LVR on cardiac function; both the direct influence via reduction in intrathoracic pressure and the indirect effects that may occur through changes in exercise behaviors are worthy of investigation.
Glenfield Hospital represents one of the largest regional centers for LVR in the UK. The proposed project would recruit patients accessing the complex COPD service and those referred through the LVR clinical pathway to address the following questions: 1) How does hyperinflation influence systemic features of COPD including skeletal muscle, nutritional status, and cardiac function? 2) What are the changes in skeletal muscle function, mass and quality following LVR and removal of ventilatory limitation? 3) Does the reduction of hyperinflation following LVR improve cardiac muscle remodeling and diastolic filling?
Research Plan: There will be three principal data-generating workstreams to this research training:
1) Systematic review of the existing literature relating to body composition (sarcopenia/nutritional status) changes associated with LVR.
2) In hyperinflated patients who attend the complex COPD clinic, collect and analyse phenotypic data. Integrating with BRC research infrastructure embedded in the COPD service provides an opportunity to collect longitudinal data for clinical measures, e.g. nutritional status, regional muscle mass by multi-frequency bioelectrical impedance.
3) In patients who progress through to the LVR service, perform detailed extra-pulmonary phenotyping to include: nutritional assessment; MRI (muscle quality and cardiac function); bioelectrical impedance / DEXA (body composition); cardiopulmonary exercise testing; isokinetic dynamometry (muscle strength and fatiguability); tri-axial accelerometry (habitual physical activity monitoring). For those individuals who receive LVR intervention perform repeat measures 6-months post-LVR.
Expected outcomes and impact: Peer-reviewed publications, dissemination at local, national and international scientific conferences, basis of grant applications.
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