Habitual Gait Speed: A Novel Marker of Exercise Intolerance and Prognosis in COPD

Lead Research Organisation: Royal Brompton & Harefield NHS Fdn Trust
Department Name: Respiratory Medicine

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a very common lung disease that is usually smoking-related. People with COPD are often breathless, particularly when exerting themselves. COPD is responsible for over 25,000 deaths in the UK annually and is predicted by 2020 to be the third leading cause of death and the fifth leading cause of disability worldwide. Currently it is very difficult to objectively assess disease severity as there are many aspects to the condition that influence patients? symptoms, some of which are not focused on the lungs. Traditionally, the amount of air you can blow out in one second (FEV1) has been used to assess severity in COPD. Regulatory authorities use an improvement in FEV1 to make decisions about the approval of new drugs for COPD. However FEV1 is relevant to only some of the processes involved and hence over-reliance on this measurement would bias against treatments where the main action is outside the lungs.
In healthy older people, usual walking speed predicts loss of independence, falls, nursing home admissions, dementia and death, and is very easily measured. Walking speed may slow due to lung function decline, muscle weakness, breathlessness, the presence of multiple medical problems, poor balance, low mood and cognitive decline ? all factors seen in COPD, and it may be a simple but global marker of disease progress. The proposed research study aims to assess whether usual walking speed is a useful marker of disease severity in COPD, whether it relates to measures of exercise capacity and whether it has value in predicting hospital admission and death in patients with COPD. The research should be of interest to all health care workers involved in the care of COPD patients as it will validate a simple test that could easily be introduced into clinical practice. This research should also be of interest to the pharmaceutical industry as it could help guide the development and assessment of new and more effective medicines for COPD.

Technical Summary

Chronic Obstructive Pulmonary Disease (COPD) is responsible for over 25,000 deaths in the UK annually and is predicted by 2020 to be the third leading cause of death and the fifth leading cause of disability worldwide. The Forced Expiratory Volume in 1 second (FEV1) is the only physiological marker acceptable to new drug regulatory authorities. However FEV1 has several limitations. COPD is a heterogeneous disease, and FEV1 is relevant to only some of the patho-physiological processes and does not address systemic manifestations such as skeletal muscle dysfunction or the influence of co-morbidities. The minimal clinically important difference for FEV1 has not been universally established, and although FEV1 correlates with mortality, this correlation is weak. In advanced disease, FEV1 has little predictive value.
In healthy older people, habitual gait speed (over 4 metres) predicts loss of independence, falls, nursing home admissions, dementia and death. Reasons for a slowing of habitual gait speed include lung function decline, skeletal muscle dysfunction secondary to sarcopaenia and de-conditioning, worsening dyspnoea, the presence of co-morbidities, poor balance, mood disorder and cognitive decline ? all factors observed in COPD. The proposed research study aims to evaluate the validity of gait speed as a marker of exercise intolerance and prognosis in COPD. Stable COPD patients will perform the 4-metre gait speed on two separate occasions a week apart to calculate inter-observer and inter-occasion reproducibility. Gait speed in COPD patients will be compared with healthy, age-matched, never smoking controls. The association between gait speed and existing measures of exercise capacity (both walking fields test and treadmill / cycle ergometry tests) will be assessed. The ability of gait speed to predict early hospital readmission in hospitalized patients at discharge following acute exacerbation of COPD will be prospectively evaluated. Furthermore, the ability of gait speed to predict mortality will be prospectively assessed in a cohort of 300 stable COPD patients followed up for a minimum of two years.
Additional validated markers are required in COPD to provide a more comprehensive and clinically meaningful assessment of patients, particularly of the extra-pulmonary manifestations of the disease. The proposed research should be of interest to clinicians involved in the care of COPD patients, and also to the pharmaceutical industry as a validated marker of functional capacity and prognosis could guide the development and assessment of new therapies for COPD, particularly those where the primary focus is not on the lung.

Publications

10 25 50
 
Description Developmental Clinical Studies
Amount £507,350 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2012 
End 09/2015
 
Description Doctoral Fellowship (Primary Supervisor for Claire Nolan)
Amount £239,042 (GBP)
Funding ID DRF-2014-07-089 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2015 
End 12/2017
 
Description NIHR Pump Priming Award
Amount £14,939 (GBP)
Organisation Royal Brompton & Harefield NHS Foundation Trust 
Department NIHR Biomedical Research Unit
Sector Public
Country United Kingdom
Start 12/2014 
End 11/2015
 
Description Research for Patient Benefit
Amount £247,271 (GBP)
Funding ID PB-PG-0213-30003 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2014 
End 07/2016
 
Description COPD MAP 
Organisation Medical Research Council ABPI COPD collaborative
Department WP4
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual; development of SOPs for measurement of performance measures
Collaborator Contribution Data
Impact Adoption of the SPPB and 4 metre gait speed as outcome measures in a longitudinal cohort study
Start Year 2011
 
Description Hillingdon Pulmonary Rehabilitation Collaborative 
Organisation National Institute for Health Research
Department NIHR CLAHRC for Northwest London
Country United Kingdom 
Sector Public 
PI Contribution Academic Clinical Lead
Collaborator Contribution Financial, access to PPI
Impact Several research abstracts accepted to national / international conferences 1 published paper in Thorax
Start Year 2011