'FROM DISCOVERY TO RECOVERY'
My principal research interests are as follows:
1. Clinical assessment and mechanisms of difficult asthma including identification and management of poor adherence.
Difficult asthma represents 5 - 10% of adult asthmatics but this group utilises ca 60% of NHS asthma spend, with repeated unscheduled healthcare contact. Our initial programme of research developed and validated a multi-disciplinary systematic assessment / management model for difficult asthmatics, and defined best practice in this area.
I founded and now co-ordinate the BTS UK Severe Asthma Network and National Registry on Difficult Asthma (see above). The Registry, as well as standardising UK specialist clinical services, facilitates research into the assessment and clinical management of difficult asthma.
My non-adherence research programme has defined, for the first time, the significant scale of this problem in difficult asthma (30 - 50% of subjects) and my Research Nurse, Dr Gamble PhD was awarded Royal College of Nursing Research Nurse of the Year 2010, received a Special Research Award from Asthma UK and was awarded the JD Williamson prize 2010 for best doctoral research in QUB.
My group's current research is developing methods to better identify and manage this problem in the clinic and we have recently developed a novel clinical test using exhaled nitric oxide suppression, and for this work, my Clinical Fellow, Dr McNicholl, won an American Thoracic Society 2010 Travel Award, the UK Respiration Forum Young Investigator Award 2009, and the 2010 Research Medal, NICHS 6th Research Conference.
In collaboration with Genentech, we are developing clinical biomarkers for steroid resistance and exposure and validating the latter as a clinical test for non-adherence. We are developing important collaborations with Professors Rob Horne (University of London) & Professor Paul Cullinan (Imperial) in this area.
We are also examining the role of managing co-morbidity e.g. depressive illness, hyperventilation in this difficult asthma patient group.
2. Epithelial / environmental interactions and onset of wheezing in childhood.
I have pioneered non-bronchoscopic sampling of paediatric airways and have established important in vitro cell models, including a differentiated paediatric epithelial cell model. My group has identified important fundamental differences in the paediatric asthmatic epithelium and our current focus is to examine the mechanism of these abnormalities at transcriptional and translational level. This work has won a number of Research prizes, including the Young Investigator Prize at the British Thoracic Society Winter Meeting 2009.
We have also developed a differentiated nasal epithelial model and have demonstrated using this differentiated system that the nasal response is different and not representative of the bronchial system (manuscript in preparation). With colleagues, I am currently examining opportunities to expand this model to a co-culture system with bronchial smooth cells and differentiated neuronal cells.
In addition, using our paediatric epithelial cell culture model, we have developed a programme with a long-term goal of developing a Respiratory Syncytial Virus vaccine (with Dr U Power, QUB), and we are currently in a programme defining a genetic signature of severe RSV disease.
3. Mechanistic studies in refractory asthma.
The hallmark of refractory asthma is relative steroid resistance and the precise mechanism of this remains unclear; we have recently demonstrated that 2 favoured mechanisms, specifically downregulation of HDAC2 / upregulation of GR-b (dominant negative isoform of glucocorticoid receptor) expression are not as relevant in refractory asthma as previously thought (manuscript under review). My current research strategy, in separate collaborations with Industrial partners [Genentech Inc and Medimmune] is to utilise whole genome expression profiling in bronchial biopsies and epithelial cell brushings to examine other steroid resistance pathways in this refractory group.
Any Translational Medical strategy must utilise early ‘proof of concept' studies and subsequent larger multi-Centre clinical trials. I have substantial experience of interaction with the Pharmaceutical Industry in Phase II / III clinical trials in including study concept and design, establishment of methodology, final protocol review and data analysis.
Vice Chairman Northern Ireland Medical Academic Specialist Committee - 2002 - 2007
NI Medical Academic Specialist Committee Representative to Northern Ireland Council 2002 - 2007
NI Medical Academic Specialist Committee negotiator to NI Consultants and Specialists Committee - 2002 - 2007
Royal College of Physicians Tutor for Medical Senior House Officers, Belfast City Hospital Trust, 2002 - 2005
Member of Royal College of Physicians
Member of British Medical Association, British Thoracic Society, Royal College of Physicians of London, Ulster Thoracic Society, Irish Thoracic Society, European Respiratory Society,
Member of Clinical Management Group, Northern Ireland Clinical Trials Network, 2007 - current.
Consultant for MDS Pharma [Multi-national Contract Research Organisation], Phase IIa Respiratory Clinical Trial Programme, 2003 - 2005 - the major focus was the development of a Phase IIa Respiratory Clinical Trial programme in collaboration with Pharmaceutical companies. In this capacity, I have been involved in study concept and design, establishment of methodology, final protocol review and data analysis.
Chairman of the British Thoracic Society National Registry of Difficult Asthma which has a number of ongoing service development initiatives and research projects - examples include:
- AUGOSA study (in collaboration with Professor Ian Hall, University of Nottingham) - genome wide UK severe asthma study - funded by Asthma UK and using the Registry as the phenotyping dataset;
- Defining the heterogeneity of severe asthma: a BTS severe asthma network pilot study (in collaboration with Professor John Thompson, University of Leicester) - funded by Asthma UK this will use the Registry and biostatistical techniques to examine heterogeneity in refractory asthma;
- Health Economics analysis of refractory asthma - supported by GSK (in collaboration with Professor Ciaran O'Neill University of Galway, ROI).
- Work Package Lead to AirPROM (WP1) - an FP7 application using a systems biology approach to analyse airway morphology and geometry in refractory asthma and its relationship to physiological and inflammatory indices.
UK Chief Investigator for 2 multi-centre pivotal clinical trials - Lebrikizumab oral steroid sparing study in refractory asthma (2012) and BOBCAT study [Bronchoscopic Exploratory Research Study Biomarkers in Corticosteroid-Refractory Asthma], Genentech Inc, US (2010 - bronchoscopic / sputum study in refractory asthma).
Consultant for Phase II / III new Clinical Trials - Medimmune, GSK, Genentech - current.
Conference Organisation
Difficult Asthma: past, present and future, Belfast 26th / 27th March 2009 - International meeting of academic and clinical leaders in difficult asthma
Co-Chair American Thoracic Society / European Respiratory Society Task Force meeting, European Society Congress, Barcelona September 2010
British Thoracic Society Winter Meeting 2010 - Session Chair - Clinical and experimental studies in asthma
British Thoracic Society Winter Meeting 2011 - Session Chair - Severe asthma in adults and children
British Thoracic Society Summer Meeting 2012 - Session Chair - Asthma - beyond the airways
INVITED LECTURES / MEEETINGS
1. Invited International Expert to Translational Immunology Summit, Genentech Inc., December 14 - 16, 2011, San Diego, California.
2. European Respiratory Annual Congress 2011 - Glaxo Smith Kline - Pro-Con debate with Professor Ian Pavord, University of Leicester - The majority of asthmatics can be well controlled with optimal use of existing medications."
3. Genentech Key Opinion Lecture, San Francisco "Difficult Asthma: a clinical perspective", July 2011.
4. Respiratory Connections Education Programme - Cheshire, Milton Keynes, Leeds, September - November 2011 - ‘How to personalise treatment in airways disease- rather than one size fits all' - joint symposium with Professor Wisia Wedzicha, University College London.
5. National Respiratory Meeting, Novartis UK, Birmingham June 2011"Non-adherence in difficult asthma"
6. Co-Chair American Thoracic Society / European Respiratory Society Task Force meeting, European Society Congress, Barcelona September 2010.
7. Genentech Advisory Board, San Francisco, US - November 4th - 5th November 2010.
8. Advances in Respiratory Therapeutics Forum, Rome June 2010 - Assessing adherence in difficult to control asthma.
9. Invited Major Symposium Speaker BTS Winter meeting December 2010 - Symposium - ‘Assessing and modifying adherence in difficult asthma.
10. Scottish Thoracic Society April 2010, Perthshire - Assessment and management of Difficult Asthma - plenary lecture.
11. Difficult Asthma - major symposium, British Thoracic Society Summer meeting, Bournemouth 2009.
12. Difficult Asthma; psychology or pathology - major symposium, British Thoracic Society Winter meeting London 2008.
13. Severe Asthma; a Clinical Update (International Expert Consensus meeting) Leuven, Belgium, March 2007.
14. The role of anti-TNF in severe asthma - major symposium, British Thoracic Society Winter meeting 2007.
15. Assessment of Difficult Asthma - University of Aberdeen - June 2007
16. European Academy of Allergy and Immunology, Vienna June 2006. Neurogenic inflammation in asthma.
17. ARENA Post-graduate Teaching Symposium, Glasgow, Difficult Asthma. April 2006.
18. University of Leicester, Update in assessment and management of Difficult Asthma, October 2006.
19. Royal Society of Medicine, Difficult Asthma Symposium - Assessment and adherence, Wythenshawe Hospital, Manchester, 28th February 2006
20. British Thoracic Society Working Group on Difficult Asthma - Assessment of difficult asthma, Leicester 15th November 2005
21. Northern Ireland Centre for Postgraduate Pharmaceutical Education and Training - Keynote Lecture - Asthma (2002 and 2005)
22. Respiratory Education Training Centre Meeting 2004. Difficult asthma or Difficult patients
23. British Thoracic Society Annual Summer Meeting Manchester June 2004. Protocolised assessment of difficult asthma.
24. Ninewells Hospital Dundee January 2004. Assessment of Difficult Asthma
25. University of Aberdeen / Aberdeen Royal Infirmary January 2004. Predictors of therapy resistant asthma.
26. Irish Respiratory Specialist Registrar Training Day, Beaumont Hospital, Dublin Feb 2004. Assessment of Difficult Asthma.
27. All-Ireland Institute of Psychiatrists (Joint Meeting of the Royal College of Psychiatrists / Irish College of Psychiatrists) November 2004. Psychiatric and psychological disorders in asthma.
28. The Breathing Club, Lyons, France September 2003. Acute COPD - what to do and why?
29. Institute of Molecular Pharmacology, Berlin, Germany May 1993. Neuropeptides, mast cells and asthma.
30. Royal College of Physicians of Edinburgh Annual Symposium November 2000. Difficult Asthma.
31. Respiratory Specialist Registrar Symposium, Irish Thoracic Society November 1999. Assessment of difficult asthma.
32. Clinical Allergy Symposium. National Heart and Lung Institute, London April 1998. Non-bronchoscopic lavage - a gateway to understanding paediatric asthma.
I regularly lecture at Postgraduate meetings for GP's and specialist nurses and medical colleagues
Academic Collaborations
University of Nottingham, (Professor Ian Hall) AUGOSA study - genome wide UK severe asthma study - funded by Asthma UK and using the BTS Registry as the phenotyping dataset;
University of Leicester (Professor John Thompson) - Defining the heterogeneity of severe asthma: a BTS severe asthma network pilot study - funded by Asthma UK.
AirPROM (FP7 - WP1) - an Work Package Lead to using a systems biology approach to analyse airway morphology and geometry in refractory asthma and its relationship to physiological and inflammatory indices.
University of Galway (Professor Ciaran O'Neill) - Health Economics analysis of refractory asthma - supported by GSK.
Imperial College (Professor Paul Cullinan) - Asthma exacerbations and prescribed treatment: an exploration of the THIN database (CSD EPIC).
University of London (Professor Rob Horne) - Non-adherence in Difficult Asthma.
Genentech Inc (USA) - genome wide expression analysis in severe asthma (DEL/CAST funded PhD studentship and Project Grant). UK Chief Investigator for BOBCAT study [Bronchoscopic Exploratory Research Study Biomarkers in Corticosteroid-Refractory Asthma], Genentech Inc, US - bronchoscopic / sputum study in refractory asthma. Project grant - Biomarkers for steroid resistance in refractory asthma.
Presentations
I have over 200 presentations and published abstracts presented at Local, National and International meetings including:
European Respiratory Society
American Thoracic Society
British Thoracic Society
American Academy of Asthma, Allergy and Immunology
European Histamine Research Society
European Academy of Allergy and Clinical Immunology
British Society of Allergy and Clinical Immunology
Irish Thoracic Society
Appointment to National / International Expert Advisory Bodies
Invited member of National Expert Asthma UK Advisory Panel to define their research strategy for the next 10 years 2011.
Chairman of the British Thoracic Society (BTS) Asthma Specialist Advisory Group (SAG) 2011 - (member of Asthma Specialist Advisory Group 2008 - 2010).
Invited member of British Lung Foundation National Advisory and Implementation Group 2011.
National Institute of Clinical Excellence UK Bronchial Thermoplasty Registry - appointed Co‑ordinator 2011
Peer nominated member of Association of Physicians of Great Britain and Ireland 2010.
Asthma UK Research Committee 2007 - 2010 (3 year tenure).
International Reviewer of World Health Organisation Statement on Severe Asthma 2009.
National Expert (Royal College of Physicians) to nominate key topics for National Audit of Asthma Care 2009
Co-ordinator / Founder of the British Thoracic Society National Registry in Difficult Asthma 2007 - current
Respiratory Framework for Northern Ireland - Lead author - Adult Asthma Section 2007.
Member of UK Steering Committee for British Thoracic Society & Scottish Intercollegiate Guideline Network Guidelines on Asthma Management - 2006 - current
Chairman of Evidence Review Group for Difficult Asthma on behalf of British Thoracic Society & Scottish Intercollegiate Guideline Network Guidelines on Asthma Management - 2006 - current
Member of British Thoracic Society Research Committee - 2006 - 2009.
Chairman of British Thoracic Society Research sub-committee on Difficult Asthma 2005 - 2007
Participant of British Thoracic Society UK Experts "Attitudes and assessment of Difficult Asthma" London December 2004
Honorary Appointments
Adjunctive Professor, School of Business and Economics (Health Economics), University of Galway 2011.
Academic Prizes
My clinical Fellows have won a number of important prizes in recognition of the high quality of their work:
Dr Gamble - JD Williamson prize 2010, Royal College of Nursing Research Nurse of the Year 2010, Special Research Award from Asthma UK 2010.
Dr McNicholl - American Thoracic Society 2010 Travel Award, UK Respiration Forum Young Investigator Award 2009, Research Medal, NICHS 6th Research Conference 2010 .
Dr Thavagnanam - Young Investigator Prize, British Thoracic Society Winter Meeting 2009.
Editorial Boards
International Editorial Board Primary Care Respiratory Journal.
Journal Review
In the past 10 years I have reviewed over 100 manuscripts in the field of respiratory medicine for major journals including the American Journal of Respiratory and Critical Care Medicine, American Journal of Respiratory Cell and Molecular Biology, British Medical Journal, Journal of Allergy and Clinical Immunology, Thorax, Chest, Journal of Leucocyte Biology, Primary Care Respiratory Journal, Neuropharmacology, Journal of Allergy and Clinical Immunology, Treatments in Respiratory Medicine, Trends in Molecular Medicine
Grant Review
I regularly review for the Medical Research Council (Project Grants and Training Fellowships), Chief Scientist's Office (Scotland) and for a number of National Bodies and Charities e.g. Asthma UK, Action Medical Research, Central Commissioning Facility [RfPB Competition] etc.
