PI3K Signaling and Aberrant Neutrophil Function in COPD; Implications for Disease Susceptibility, Prognosis and Therapeutic Targeting

Lead Research Organisation: University of Birmingham
Department Name: Clinical and Experimental Medicine

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a term that describes conditions such as emphysema and chronic bronchitis which are characterised by narrowing of the breathing tubes (airways), and are associated with lung tissue destruction. It is debilitating, affects 3 million people in the UK, and is the 5th leading cause of death (25,000 deaths in the UK/year). It is the only chronic disease with a rising death rate. UK COPD costs are estimated at £3.2 billion per annum. Annual NHS costs are £900M, 50% of which are due to unscheduled hospital admissions due to deteriorating symptoms. Better disease management would reduce this disease burden, but currently no treatments prevent disease onset or halt progression.

COPD is a chronic inflammatory condition, where the continued presence of excessive inflammatory proteins and cells in the lung cause damage. Smoking cigarettes is the most important risk factor, but only 15% of smokers develop COPD, and the disease runs in families, suggesting there are genetic factors that predispose towards COPD. Inflammation and lung destruction continue even after smoking cessation. This is poorly understood, but we believe that COPD patients have abnormal immune responses that drive disease even after noxious stimuli (cigarette smoke) have gone. Presently we cannot predict who will develop COPD or if all disease features are caused by the same underlying immune problem. It is vital to understand this, as it will help direct new treatments.

Neutrophils are white blood cells crucial for fighting infection. They leave the blood, moving (migrating) accurately to areas of infection, where they ingest bacteria, killing them with an arsenal of proteins contained within the cell. These proteins cause damage and inflammation if they are released in the body's tissues. Neutrophils contain genes that control the cell by dictating what proteins are expressed. These proteins could be enzymes, controlling chemical reactions within the utrophil, or structural proteins, controlling how they move.

Neutrophils are central to COPD. COPD patients have many neutrophils in their lungs and the chemicals neutrophils release can cause the characteristic lung damage. Our data show that neutrophils from COPD patients are defective, migrating less accurately than cells from healthy subjects or people with other lung diseases and ingest less bacteria in models of infection. This is important, as inaccurate migration and reduced bacterial clearance could lead to more lung damage and poorer outcomes during infections; both of these are thought central in COPD. We have shown this harmful cell behaviour is due to increased activity of a protein enzyme called phophosinositide-3 kinase (PI3K). Abnormal PI3K signalling may be the cause of altered COPD neutrophil behaviour and correcting this may offer a new treatment in COPD.

We wish to investigate the molecular signals and identify the relevance of injurious neutrophil behaviour in COPD, using neutrophils isolated from blood and lung secretions of COPD patients, those at risk of developing COPD (family members of COPD patients) and healthy volunteers. This will determine how prevalent the defective neutrophil behaviour is across all the differing features of COPD, and whether you can predict who might develop the disease by assessing their neutrophils. We will then identify the cause of the defective neutrophil behaviour, by studying the activity of structural proteins and enzymes (and the genes that control them) within COPD neutrophils, using our extensive preliminary data and knowledge of cell signaling to focus our experiments.

Identifying the specific cause of defective neutrophil behaviour will allow us to form new targeted treatments for COPD, improving the health of patients with the disease. It may also allow us to predict who is most at risk of the COPD, developing a screening tool, helping to inform people about their lifestyle choices.

Technical Summary

COPD is a major cause of mortality and morbidity. Data supports a genetic basis but screening (limited to Alpha-1-antitrypsin deficiency) can detect <2% of cases. We cannot predict who else is at risk. COPD encompasses different clinical phenotypes, however it is unclear if the same disease mechanism underpins all disease pathologies. Neutrophils (PMNs) are central to the inflammation seen in all clinical phenotypes and we have demonstrated that circulating COPD PMNs have defective chemotactic and phagocytic responses. This is seen in all disease severities, including early disease, is not present in other pulmonary conditions and is associated with abnormal Phosphoinositide3 kinase (PI3K) signaling. We hypothesise that aberrant PI3K signaling causes chemotactic and phagocytic defects which contribute to COPD pathogenesis.

We will address the following questions: Does the aberrant PMN phenotype predict the onset or progression of COPD? Is the chemotactic defect due to aberrant PI3K signaling? What is the molecular basis of the defect?

We will study PMNs from patients with COPD, across disease phenotypes, compared to healthy smoking controls to determine if the cell phenotype bridges all clinical phenotypes or is limited to specific pathologies. We will study circulating and bronchoalveolar lavage PMNs to assess if migration to the tissues modulates the chemotactic phenotype. Crucially, we will study family members of index cases to assess if the PMN phenotype is preserved across families, providing evidence of a genetic association for both COPD and cell behavior. We will study PI3K signaling using immunohistology, phase, DIC and confocal microscopy, cell sorting, mass spectrometry, selective inhibitors and PCR to identify the protein signals involved, their role in cell functions, the sites of their activities and their individual molecular signatures. Identified targets will be tested across COPD families to determine if they are a signal of risk.

Planned Impact

Who will benefit from this research?
We believe that this research will lead to new therapeutic strategies in COPD and in time, new treatments that are likely to reduce prevalence, improve COPD outcomes, reduce hospital admissions and slow disease progression. Identification of molecular causes could also lead to the development of screening tools to identify people most at risk of disease. The non-academic beneficiaries of this research will be patients, their family, carers and Pharma, but may also include employers and potentially the UK economy

How will they benefit?
COPD is progressive, debilitating and associated with considerable mortality. Recent research suggests there are 3.7million people with COPD in the UK and the Health and Safety Executive report that 40% of COPD patients are below retirement age and one quarter of these people cannot work due to their symptoms. Direct COPD-associated health costs in the UK have been estimated at £900M per annum, with 50% of this being hospital admissions during exacerbations. In my hospital, we estimate that reducing COPD re-admissions by 10% or COPD-exacerbation length of stay by one day on average would save >£500,000 per year. However, despite the high mortality, morbidity, prevalence and cost of the disease, a survey by the British Lung Foundation suggested that most people within the UK have not heard of COPD. Treatments are limited, none prevent disease or halt decline. COPD needs to be better understood, have more treatments for early disease and its profile needs to be raised.

The proposed research will enhance understanding of the mechanisms of disease and identify novel therapeutic targets. Poor neutrophil migratory accuracy and bacterial phagocytosis are compatible with increased extracellular proteinase release, inflammation and tissue damage and reduced bacterial clearance and increased susceptibility to invasive infection. We have identified a potential mechanism for the aberrant behaviour that is rrectable in vitro. This is an exciting development in COPD pharmacologics and could be of significant benefit to patients and their families. Improved health, reduced hospitisations and lower COPD-related unemployment would have substantive public-health and economic benefits, and will be of interest to the media (raising COPD awareness), private commercial sector and policy makers.

Identifying the molecular mechanisms of COPD neutrophil behaviour will support the development of a COPD animal model based on a mechanism proven to be present in COPD patients. This would facilitate the development and assessment of emerging treatments in COPD and would be a considerable resource for the academic community and Pharma.

This project includes development opportunities for the applicants through collaborative exposure to well characterised patients and new assays. These skills will be shared among colleagues to support academic development in Birmingham and Cambridge. The project will also benefit researchers of other neutrophil-based inflammatory diseases. Methodologies and resources will be shared, to support UK academic excellence, raising the profile of UK-based research internationally.

Within 3 years, we will identify the mechanism of aberrant neutrophil function, the patients groups that demonstrate this abnormality (supporting either a focused phenotype or generic disease treatment strategy which will help with trial development) and will have identified candidate screening signals for people at risk of disease. Based upon this work, and on-going links with Pharma, we will test emerging tool compounds and will develop a murine model of COPD within 4 years, to be used in putative studies of new therapies. With emerging tool compounds being developed by Pharma, it is likely that human trials of medicants would require a further 5 years for development, including stage III clinical trials.

Publications

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Edgar RG (2017) Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review. in International journal of chronic obstructive pulmonary disease

 
Title Neutrophil animated film for educational purposes 
Description A animated film of neutrophils, from the blood stream, migrating through tissues, phagocytosis and NETS to help explain what these cells do to policy makers, funders and the publics 
Type Of Art Film/Video/Animation 
Year Produced 2015 
Impact Has been an incredibly useful tool when sharing my work and my plans. 
 
Title Women in Academic Research Arts project 
Description This is a celebration of women in science as part of Women's Day 2017 - where members of academic staff were painted as part of a large mural 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2017 
Impact Brought together a diverse group of academic researchers who were women to celebrate our contribution to science 
 
Description Botswana ageing policy group
Geographic Reach Africa 
Policy Influence Type Participation in a advisory committee
Impact A working group to discuss and inform policy changes in Botswana to protect rights of older people (not a protected characteristic in Botswana) Policy paper published and working group established
 
Description British Lung Foundation Advisory Committee
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description British Thoracic Society
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Design of International conference
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
Impact Bringing greater diversity to science meetings
 
Description Meeting with government ministers at BEIS
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description NICE AATD guidelines
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Patient working group on use of health data in reseach
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact Education saw an increase in the percentage of adults and children who would be willing to heave their health data used for research purposes through workshops which explained the potential good that can come from this
 
Description West Midlands Deanery LtFT Committee Member
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Designed clear template for LtFT training requirements to help trainnees and supervisors plan placements
 
Description AMS Lecturer Start Up Grant
Amount £24,000 (GBP)
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2011 
End 06/2014
 
Description British Lung Foundation Programme Grant
Amount £2,000,000 (GBP)
Organisation British Lung Foundation (BLF) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2017 
End 07/2019
 
Description ETHOS study: Enhancing the Health of NHS Staff - a pilot and feasibility study
Amount £750,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 05/2019 
End 12/2022
 
Description FP-7
Amount £400,000 (GBP)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 04/2013 
End 03/2017
 
Description MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research
Amount £204,500 (GBP)
Organisation Versus Arthritis 
Department Arthritis Research UK Centre for Musculoskeletal Ageing Research
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 10/2017
 
Description NIHR PhD Studentship
Amount £214,999 (GBP)
Organisation National Institute for Health Research 
Department NIHR Biomedical Research Centre
Sector Public
Country United Kingdom
Start 05/2015 
End 05/2019
 
Description Neutrophils in Pneumonia and sepsis
Amount £750,000 (GBP)
Funding ID MR/S002782/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 06/2019 
End 07/2022
 
Description Non clinical PhD studentship
Amount £160,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Research Training Fellowship
Sector Charity/Non Profit
Country United Kingdom
Start 10/2017 
End 10/2021
 
Description PIONEER- HDRUK Health and data research hub in Acute Care
Amount £1,200,000 (GBP)
Organisation Health Data Research UK 
Sector Private
Country United Kingdom
Start 09/2019 
End 05/2022
 
Title Neutrophil migration assay using whole blood 
Description This is a novel means to study facets of neutrophil function from whole blood (thereby avoiding issues of activating cells) that allows multiple experimental assays to take place simultaneously, thereby reducing the amount of blood needed to be drawn from patients to study these cells 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact We are still validating this, but the plan would be to share this for use in vulnerable groups where repeated larger volume blood loss would not be acceptable to patients 
 
Title Proteinase footprint assay to study proteinase activity 
Description 2 x Antibody ELISA assay that is specific and sensitive for neutrophil proteinase activity which can be measured in whole blood or tissue culture assays 
Type Of Material Antibody 
Provided To Others? No  
Impact We are continuing to validate this, but hope to publish data about it in 2017, ready for use by other groups in 2018 
 
Title Research collaboration with Cambridge 
Description Samples shared with Cambridge to allow completion of a project - they would not have access to these usually 
Type Of Material Biological samples 
Year Produced 2020 
Provided To Others? No  
Impact Abstract being presented at Neutrophil 2020 and paper under review 
 
Title AATD Database 
Description A database of over 700 patients with AATD with serial data on symptoms, medications and co-morbidities that has been in place for 5 years, allowing the study of decline and response to treatments 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact This has been shared with the NIHR funded Rare Disease AATD Collaborative to allow similar data collection across the UK 
 
Title COPD CDRC Cohort 
Description An database of patients with COPD, including in depth phenotyping of clinical characteristics 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact It is becoming an important tool in following changes in patients over time, and have led to the develop of a research grant to study the impact of small airways disease on the progression of emphysema 
 
Title Early COPD Cohort Database 
Description The BLF and Industry partners have funded an early COPD cohort to complement the more severe cohorts that are available internationally. This will be a unique resource for research and understanding the easiest signals in COPD. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact It has only just started and will be shared as an international resource once complete (pending ethical review of each data request) 
 
Title HDR-UK Database in acute care 
Description A curated database of > 2M health records from acute care episodes across the West Midlands 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Only just opened (Dec 2019) but already multiple requests for data access 
 
Description Biomarkers of exacerbations in AATD 
Organisation Alpha-1 Foundation
Country United States 
Sector Charity/Non Profit 
PI Contribution We are validating biomarkers of neutrophil proteinases (elastase and PR3) during exacerbations, using a diary card to monitor for exacerbation frequency. We are recruiting 40 patients to follow up over 2 years and perform serial measures of these in house developed biomarkers in the stable state and during exacerbation
Collaborator Contribution Alpha 1 Foundation funded the project
Impact This has just started, so there are no results outputs as yet, but the diary card has been validated for use
Start Year 2017
 
Description Birmingham Acute Care Research Group 
Organisation University Hospitals Birmingham NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution A research collaboration between health staff, management and research staff to increase the delivery of research in acute care. We have provided academic oversight and help with grant writing, publishing and data analysis
Collaborator Contribution Access to clinical data, more input from clinical staff, so research activity can be increased across both partner sites
Impact A number of publications from acute care including: What is the significance of monoclonal gammopathy of undetermined significance? Atkin C, Richter A, Sapey E. Clin Med (Lond). 2018 Oct;18(5):391-396. doi: 10.7861/clinmedicine.18-5-391. PMID: 30287433 Free PMC Article Assessing Fluid Resuscitation in Adults with Sepsis Who Are Not Mechanically Ventilated: a Systematic Review of Diagnostic Test Accuracy Studies. Seccombe A, McCluskey L, Moorey H, Lasserson D, Sapey E. J Gen Intern Med. 2019 Sep;34(9):1874-1883. doi: 10.1007/s11606-019-05073-9. Epub 2019 May 31. PMID: 31152360 Described Practices for Assessing Fluid Resuscitation in Acute Hospital Care: A Qualitative Study. Lloyd E, Ignatowicz A, Sapey E, Lasserson D, Seccombe A. Acute Med. 2019;18(4):223-231. PMID: 31912053 The prevalence and significance of monoclonal gammopathy of undetermined significance in acute medical admissions. Atkin C, Reddy-Kolanu V, Drayson MT, Sapey E, Richter AG. Br J Haematol. 2020 Jan 30. doi: 10.1111/bjh.16487. [Epub ahead of print] PMID: 31999849
Start Year 2019
 
Description British Lung Foundation Early COPD Cohort 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We will recruit patients to this cohort and conduct clinical characterisation and studies of innate immunity. This will include 50 participants aged 35 - 45 who smoke without symptoms, 50 who smoke with symptoms but normal lung function tests and 50 who smoke with COPD. It is helped that this collaborative partnership will help identify the earliest signals in COPD.
Collaborator Contribution The collaborative partners will help develop the database and provide a management structure for collection of data. Collaborative partners include Prof Wedzicha (NHLI), Prof Brightling (Leicester), Prof Whyte (Edinburgh), Prof Singh (Manchester), Prof Wilkinson (Southampton) as well as collaborative sites in Belfast, Nottingham. Each site will recruit the same number of patients as outlined above, and will participate in predefined tests of science.
Impact This has just started, and so there are no outputs. The collaboration includes clinical sites, research sites (we are both) and Pharma input and patient recruitment is planned for 2017
Start Year 2016
 
Description GSK COPD Neutrophils 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Studying the effects of new compounds on neutrophil functions and looking at pathways within these cells
Collaborator Contribution Providing compounds and helping with RNA pathway analysis
Impact American Thoracic Society Annual congress oral presentation European Respiratory Society oral presentations. British Thoracic Society Plenary talk
Start Year 2013
 
Description MRC ABPI COPD MAP Consortium 
Organisation Medical Research Council (MRC)
Country United Kingdom 
Sector Public 
PI Contribution Studying neutrophil functions in Chronic Obstructive Pulmonary Disease as part of a partnership between Imperial, Sheffield, Manchester, Nottingham
Collaborator Contribution Other partners are studying other cells, such as monocytes and macrophages
Impact Abstracts at American Thoracic Society, British Thoracic Society and European Respiratory Society meetings , publications and further grants
Start Year 2012
 
Description Multi morbidity with age and COPD 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Edinburgh University - Sonja Vermeren a
Collaborator Contribution We are working together with funding from Wellcome and GSK to have two shared pHD studentships across 2 sites, Birmingham and Edinburgh
Impact This has just started (October 2017) and so no outputs as yet
Start Year 2017
 
Description Neutrophil and macrophage functions in COPD 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We wished to see if patients with COPD who had aberrant neutrophil functions also had aberrant macrophage and monocyte functions. We recruit patients and perform neutrophil studies and UCL staff perform monocyte studies and then grow these into MDM for further studies
Collaborator Contribution A very collaborative project where we both carry out bench work after patient recruitment at UHB/UoB
Impact No outputs as yet, but abstract planned at British Thoracic Society and a grant application to follow this preliminary data generation
Start Year 2015
 
Description PIONEER HDR-UK 
Organisation Health Data Research UK
Country United Kingdom 
Sector Private 
PI Contribution PIONEER Health Data Hub in acute care has led to the curation of new linked data in acute care
Collaborator Contribution We direct and run the HDR-UK Hub, including the formation of procedures for data curation, linkage and release
Impact Outputs are still under generation but there is a YouTube video describing our plans
Start Year 2019
 
Description Small airways disease in COPD and AATD 
Organisation Alpha-1 Foundation
Country United States 
Sector Charity/Non Profit 
PI Contribution We recruited 90 patients with AATD and normal lung function for two year follow up study assessing clinical parameters, markers of inflammation and lung function decline including novel measures of small airways function
Collaborator Contribution The Alpha 1 Foundation paid for the research and will help coordinate dissemination, including a conference in Miami at their national meeting in October
Impact We have a publication in the European Respiratory Journal, we presented these data at the biennial AATD conference and wrote an editorial as to the utility of small airways tests in non AATD COPD
Start Year 2015
 
Title ETHOS staff health clinic = a trial to see if health screening can improve the health and well being of NHS staff 
Description We are currently conducting a feasibility study which is in set up 
Type Preventative Intervention - Behavioural risk modification
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2020
Development Status Under active development/distribution
Impact Initial feedback from staff has been very positive but the trial will enable formal evaluation 
 
Title PI3K delta inhibitor 
Description I have been working with GSK on the trial design for this product, with many others, and am national CI for the trial which has just started 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2018
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Inhaled PI3K delta inhibitor 
URL https://clinicaltrials.gov/show/NCT02593539
 
Title Simvastatin as an adjuvant during community acquired pneumonia 
Description The BLF funding which supported the pilot study has ended, we have positive results being written up for publication and are applying for MRC EME funding for a national multi-centre trial 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2016
Development Status Actively seeking support
Clinical Trial? Yes
UKCRN/ISCTN Identifier 110966/415929/20/441
Impact First intervention in sepsis which improves both survival, cellular functions and inflammation in sepsis 
URL https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002082-38
 
Title Ap to electronically capture exacerbations in COPD 
Description This is an Ap compatible with Android and Apple products which can be used as part of a validated diary card to track symptoms in COPD 
Type Of Technology Webtool/Application 
Year Produced 2017 
Impact We are starting to use this in a clinical trial 
 
Title HDR-UK new data platform for PIONEER 
Description A new digital platform for integrating clinical care data across primary and secondary providers 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2020 
Impact Allowing integrated data which is interoperable 
 
Description ABPI national events 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact An engagement event to showcase work to industry operatives and discuss future collaborations
Year(s) Of Engagement Activity 2019,2020
 
Description American Thoracic Society Annual Congress 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of new data regarding phagocytosis in COPD with helpful debate about methodology and bacterial strain chosen
Year(s) Of Engagement Activity 2015
 
Description BTS Science Plenary Lecture 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented at the BTS Science Plenary Lecture at the winter conference. The conference was attended by 3000 people and the audience was made up of medical staff, researchers, industry representatives and some patient groups
Year(s) Of Engagement Activity 2016
 
Description British Thoracic Society Plenary Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact BTS plenary science lecture about my neutrophil data in COPD and ageing. Lots of questions about my work which has led to a new collaboration and I have been asked to take part in a scientific committee for the BTS
Year(s) Of Engagement Activity 2008,2015
 
Description COPD MAP annual conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact An annual meeting where I have presented research to national experts and industry partners to discuss results, potential collaborative plans and dissemination plans
Year(s) Of Engagement Activity 2014,2015,2016
 
Description COPD9 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of research and next steps with an audience of scientific and clinical experts in the field of COPD. Lots of debate and a request to present data at Omaha, USA (2015) and Edinburgh (2016) to make more collaborative links
Year(s) Of Engagement Activity 2014
 
Description Chair of BTS Science Committee 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Designing the foremost meeting for Respiratory Clinicians and Scientists in the UK but with significant international presence
Year(s) Of Engagement Activity 2018,2019
 
Description Data presentation at Edinburgh University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation of data and a meet the researcher lunch at Edinburgh university
Year(s) Of Engagement Activity 2017
 
Description Data presentation to engage with collaborators - Southampton 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Data presentation to build towards an MRC application in 2017
Year(s) Of Engagement Activity 2016
 
Description EU Workshop on Ageing 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact An opportunity to discuss the effects of ageing on immune cell function and the need to plan for increased admissions for the elderly in new European countries that have a younger population
Year(s) Of Engagement Activity 2014
 
Description Interview for national news 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact A radio 4 interview about my research
Year(s) Of Engagement Activity 2017
 
Description MD Catapult national meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A meeting to discuss how to increase the pace and scale of adoption of new innovation within the. NHS
Year(s) Of Engagement Activity 2019,2020
 
Description Meeting a BEIS to discuss future health research funding 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact A meeting with government ministers, industry leaders at BEIS (Victoria st, London) to discuss new policies for research funding
Year(s) Of Engagement Activity 2020
 
Description NHS Expo and NIHR National Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact A presentation aimed at NHS England and DoH about the benefit of research in the NHS and how regional working can improve recruitment to clinical trials
Year(s) Of Engagement Activity 2016
 
Description Presentation at British Lung Foundation evening meeting to donors and patients 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact Presentation of research to help promote lung research to a mixed audience of lay people, experts and funders
Year(s) Of Engagement Activity 2016
 
Description Presentation at international conference in Italy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary lecture at International meeting
Year(s) Of Engagement Activity 2017
 
Description Presentation for British Lung Foundation for a stake holder national meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact An opportunity to feedback about my research to potential donors and stake holders at this main charity plus a laboratory workshop that I organised. Lots of interest from a group who initially wondered if investing in "benchwork" was a waste of money and afterwards who all stated they were happy to fund translational research
Year(s) Of Engagement Activity 2012,2015
 
Description Questionnaire on health data use 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Work shops and questionnaires about health data use in the UK - over 400 participants included in a series of events across the UK
Year(s) Of Engagement Activity 2019
 
Description Research presentation in Trinity College Dublin 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Presentation to Dublin Trinity College Medical School and researchers
Year(s) Of Engagement Activity 2017
 
Description Visit to University of Illinois to build collaborative links 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact To build collaborative links for a transfer of technology ready for grant application in 2017
Year(s) Of Engagement Activity 2017
 
Description Webinar on COPD research and management 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Pro/ Con debate by webinar to discuss new research in COPD (including my own) and new treatment pathways. Reportedly watched by over 300 people to date
Year(s) Of Engagement Activity 2015