THE LONDON COPD EXACERBATION COHORT (The EXCEL Cohort)

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

Patients with chronic obstructive pulmonary disease (COPD) may often experience episodes of acute worsening of symptoms called exacerbations or ?attacks?. These exacerbations are an important cause of physical and mental ill-health, poor quality of life and death. Exacerbations also impose a considerable cost on the NHS, the patient and their families through time off work, hospital admissions and additional treatments. Finding the cause of these episodes is difficult because they can be due to different types of bacteria and viruses, and their timing is unpredictable so that the patient must be seen as soon as possible after the start of the infection. There is still an urgent need for more studies of COPD exacerbations but researchers need access to patients in whom exacerbations are likely to occur.

The London COPD Exacerbation Cohort (EXCEL Cohort) is a small established cohort of COPD patients recruited and specifically trained and monitored to report their attacks (exacerbations) to the research team to enable the exacerbation to be studied (and also the patient to receive treatment as quickly as possible). Our skills in running this cohort and research that we have published has gained us an international reputation and we have received both charity and industry research grants over the last 10 years. We are now seeking funding to increase the size of our cohort from 150 to 300 patients, and to study our patients in even greater detail with investigations including x-ray scanning measures of thickness of the lung airways and emphysema, state-of-the-art detection of bacteria and viruses using modern molecular methods, airway and systemic inflammation and ultrasound imaging of the heart. This will provide important information that will allow new treatments and ideas to be tested more efficiently. Our cohort has previously been involved in many studies, both on our own and in collaboration with other researchers world-wide. This proposed enlargement of our cohort has received support from multi-national pharmaceutical companies and the NHS as it provides a cost-effective resource to carry out smaller studies on specific groups of COPD patients.

Technical Summary

Chronic obstructive pulmonary disease (COPD) exacerbations are acute episodes of worsening symptoms and an important cause of morbidity and mortality associated with the condition. They are also a major outcome measure for therapeutic intervention studies. The triggers and mechanisms of COPD exacerbations are still not clearly understood and more study of exacerbations is required if the economic and health burden of these disease is to be reduced. Exacerbations are heterogeneous in severity, occur unpredictably and must be sampled early before they are treated and resolve. Thus studies of COPD exacerbations must have access to patients who develop exacerbations and who are trained in detection and reporting of these exacerbations to the study team.

The London COPD Exacerbation Cohort (EXCEL Cohort) is an established cohort designed to study mechanisms of COPD exacerbations and their impact on health status and disease progression. Our work has contributed greatly to the understanding of COPD exacerbations. The cohort has already participated in observational studies, proof of concept studies, both grant funded and industry funded, to reduce the frequency and severity of these important events. We will utilize our existing strengths for accurately determining exacerbation frequency and severity with robust methodology previously developed by our group. Patients will be trained to monitor their symptoms electronically and detect and report exacerbations promptly, so that their exacerbations can be sampled early after symptom onset. With the specific funding, the cohort will be increased to recruit a total of 300 COPD patients, who will be phenotyped on the basis of exacerbation frequency, usual long term therapy, lung function, health status and psychological function, airway bacterial and viral infection by quantitative molecular methods. The funding requested will allow further phenotyping by CT scanning on the basis of airway wall thickness and emphysema, novel airway and systemic inflammatory markers and cardiovascular function. The exacerbation cohort will be suitable for epidemiological studies of the natural history and mechanisms of exacerbations, interventions to reduce exacerbation severity and frequency and also studies of interventions to treat individual exacerbations. Enlargement of our cohort has received support from two multi-national drug companies as it provides them with a cost-effective resource to carry out targeted proof of concept trials on specific groups of COPD patients.

Publications

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Alahmari AD (2016) Physical activity and exercise capacity in patients with moderate COPD exacerbations. in The European respiratory journal

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Beeh KM (2017) How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease? in American journal of respiratory and critical care medicine

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Bewley MA (2018) Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists. in American journal of respiratory and critical care medicine

 
Description COPD strategy
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact I am a member of the programme Committee for the COPD srategy and clinical lead for the Home Oxygen Service. our cohort work has influenced both acute and chronic care within the strategy.
 
Description Citations in reviews
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
Impact The paper by Hurst et al from the cohort shows the improtance of exacerbation clustering and why follow up is important after hospital admission and exacerbation.
 
Description European Respiratory Society COPD exacerbation Guideline Committee/Chair
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
Impact Chair of group developing guidelines on COPD exacerbations
 
Description Expert Clinical Advisor to NICE
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Member of DoH Respiratory Programme Board
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact Our experience with the cohort enabled influence on matters relating to COPD exacerbations
 
Description Member of NICE Quality Standard Group
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Development of NICE Quality standards relating to COPD exacerbations
 
Description NICE COPD guidelines
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact We have shown the importance of exacerbations in COPD and why they are an important outcome in studies for clinical and economic reasons.
 
Description BLF Project grants
Amount £120,000 (GBP)
Organisation British Lung Foundation (BLF) 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2011 
End 04/2013
 
Description British Lung Foundation Early COPD Consortium
Amount £3,500,000 (GBP)
Organisation Industry Partners 
Sector Private
Country United States
Start 07/2018 
End 06/2021
 
Description MRC Clinical Research Fellowship
Amount £212,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2010 
End 04/2013
 
Description MRC Population Scientist Award
Amount £621,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2010 
End 04/2014
 
Description NIHR Applied Programme Grant
Amount £2,000,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2011 
End 10/2016
 
Title COPD cohort diary 
Description We have developed a daily diary card for patient use to detect exacerbations and reprot them promptly to healthcare professionals 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact This diary has been used to diagnose, define and detect exacerbations by other research groups. 
 
Title COPD database 
Description We developed a COPD database for the cohort data and including the daily diary card data. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2008 
Provided To Others? Yes  
Impact This database has allowed us to collect and analyse the data form the cohort more effiiciently and accurately. 
 
Title e-technology health diary using Blackberry 
Description We validated the use of e-monitoring for the detection of exacerbation symptoms and thus presentation 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2010 
Provided To Others? Yes  
Impact This is now being used in a randomised contrilled trial in COPD patients 
 
Description Airway epithelial cell studies in COPD 
Organisation University of Southampton
Department School of Medicine Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution COPD patients under go bronchoscopies and material available for collabortaive work.
Collaborator Contribution Development of other grant applications
Impact Success in MRC/ABPI call
Start Year 2009
 
Description CADSET 
Organisation University of Barcelona
Country Spain 
Sector Academic/University 
PI Contribution Contribution of cohort data
Collaborator Contribution Co chairs of the partnership and data sharing
Impact Editorial in European Respiratory Journal
Start Year 2018
 
Description EU IMI RESCEU 
Organisation University of Groningen
Country Netherlands 
Sector Academic/University 
PI Contribution Project on RSV infection in COPD and and at exacerbations
Collaborator Contribution Similar cohort follow up of patients by other partners
Impact Presentations to American Thoracic Society meetings in May 2019
Start Year 2018
 
Description Inflamamtory Therapeutic Capability Clusters (TRPs) 
Organisation Imperial College Healthcare NHS Trust
Department Respiratory Medicine
Country United Kingdom 
Sector Hospitals 
PI Contribution Developed the first protocol for drug development
Collaborator Contribution The Capability Cluster has been awarded to centres in the UK and we are one of the Centres - this includes Imperial, Nottingham, Manchester, KGT, Leicester, Southampton
Impact Collaboration recently commenced
Start Year 2010
 
Description MRC ABPI COPD Collaboration 
Organisation Imperial College Healthcare NHS Trust
Department Respiratory Medicine
Country United Kingdom 
Sector Hospitals 
PI Contribution Major part of this collaboration and the London COPD cohort is the main source of patient study and clinical samples
Collaborator Contribution Enabled the MRC ABPI consortium
Impact Contracts now signed and work packages under way
Start Year 2011
 
Description RSV infection and co-morbidity 
Organisation Imperial College Healthcare NHS Trust
Department Respiratory Medicine
Country United Kingdom 
Sector Hospitals 
PI Contribution Provide COPD patients from cohort that are wekll phenotyped. Studies of viral and bacterial infection and airway and systemic inflammatory markers
Collaborator Contribution Collaborators have provided experience on immunology of RSV
Impact In progress Abstracts to be presented at meetings. papers in preparation
Start Year 2010
 
Description Statistical modelling of COPD exacerbations 
Organisation McGill University
Department Department of Epidemiology, Biostatistics and Occupational Health
Country Canada 
Sector Academic/University 
PI Contribution Our COPD data used directly for this collaboration
Collaborator Contribution new developments - paper in preparationnew developments - paper in preparation
Impact Abstract submitted to meeting of American Thoracic Society emeting in Denver, USA 2011
Start Year 2010
 
Description Statistical modelling of COPD exacerbations 
Organisation University of Ottawa
Country Canada 
Sector Academic/University 
PI Contribution Our COPD data used directly for this collaboration
Collaborator Contribution new developments - paper in preparationnew developments - paper in preparation
Impact Abstract submitted to meeting of American Thoracic Society emeting in Denver, USA 2011
Start Year 2010
 
Description Studies of macrophage phagocytosis in COPD 
Organisation Imperial College Healthcare NHS Trust
Department Respiratory Medicine
Country United Kingdom 
Sector Hospitals 
PI Contribution Provision of samples form well phenotyped patients
Collaborator Contribution Expertise in phagocytosis experiments
Impact Original Paper published
Start Year 2009
 
Title Evaluation of domiciliary pulse oximetry 
Description Funding awarded to Dr John Hurst (applicant on MRC grant) for development of oximetry 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2010
Development Status Actively seeking support
Impact Published in peer review journal and presented at internatioal conference 
 
Description Patient cohort meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Regular meetings of our research cohort, where we discuss studies and also future ones. Review protocols etc.,
Year(s) Of Engagement Activity 2016
 
Description Patient groups 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Open day in Camden PCT for patients with COPD. My group presented on COPD and our research activities

Increased patient recruitment
Year(s) Of Engagement Activity 2010