Dept of Respiratory & Sleep Medicine, Royal Hospital for Sick Children, Sciennes Road, Edinburgh, EH9 1LF
Telephone: 0131 536 0641
Summary of Research
Respiratory Disease in Children including Cystic Fibrosis (pulmonary gene therapy, new treatments and physiological assessments), Bronchiolitis and Rare Respiratory Disease in Children.
(1) Cystic Fibrosis Gene Therapy Consortium:
The UK CFGTC (www.cfgenetherapy.org.uk/) is a consortium of scientists and clinicians in Edinburgh, London (Imperial) and Oxford. Clinical sites for the consortium are the Royal Brompton Hospital in London, and NHS Lothian Western General and Royal Hospital for Sick Children. Funding has been provided by the UK MRC and NIHR for a multidose trial of pulmonary gene therapy. The Phase 2B double blind randomised controlled trial will commence in May 2012 and provided monthly doses for 12 months to approximately 130 patients 12 years of age and older. Children participating in the trial will utilise the RHSC Children’s Clinical Research Facility and Scottish Children’s Research Network nurses. It is anticipated that the trial will conclude in 2014.
(2) Cystic Fibrosis new therapies:
Working with Vertex Pharmaceuticals, the department has worked on a Phase II study of VX770 (Study 106: http://clinicaltrials.gov/ct2/show/NCT01262352 ), utilising multiple breath washout to gauge potential early benefit of VX770 (Kalydeco) in children with FEV1 in the normal range.
Our group continues to work with pharmaceutical companies assessing novel products in cystic fibrosis.
(3) Cystic Fibrosis physiological assessment:
Our group have utilised the photoacoustic SF6 analyser within an adapted Innocor Device to measure multiple breath washout and the lung clearance index (LCI). The technology has been used to assess health and disease in children with cystic fibrosis, asthma and cerebral palsy.
(4) Cystic Fibrosis: Relation of ventilation inhomogeneity for SF6 washout and He3 MRI.
Funded by the UK Cystic Fibrosis Trust, collaborative research with the University of Sheffield (Professors Jim Wild and Chris Taylor) and University of Manchester (Alex Horsley) is assessing the relationship of ventilation inhomogeneity SF6 multiple breath washout and He3MRI (http://www.cftrust.org.uk/research/areasresearch/researchcurrentlyfunded/#PLD ).
Dr Steve Cunningham is Chief Investigator the HTA funded trial ‘ Bronchiolitis of Infancy Discharge Study’ (http://www.hta.ac.uk/project/2390.asp ). This is a multicentre trial to assess the effect of supplemental oxygen on recovery from bronchiolitis once oxygen saturation has reached 90% in air (compared to usual 94% in air). The study is co-ordinated by the Edinburgh Clinical Trials Unit (http://www.clinicaltrials.ed.ac.uk/CurrentTrials.aspx ) and utilises the RHSC Children’s Clinical Research Facility and Scottish Children’s Research Network nurses (http://www.scotcrn.org/bids/ ). The study will recruit over two winter seasons and has just completed Season 1 (Oct 2011 – March 2012). Season 2 will recruit Oct 2012 – March 2013 with results anticipated in late 2013.
(6) Rare Respiratory Disease in Children:
Dr Steve Cunningham is Chair of the British Paediatric Orphan Lung Disease (BPOLD) Registry which is funded by Edinburgh University Research and Development Department (2009-2014). The Registry enables Respiratory Paediatricians within the UK to register cases of nine rare (orphan) respiratory diseases in children for future study (www.bpold.co.uk).
The Respiratory Department actively seeks to support well planned research activities; Current studies include
- TORPEDO. A study of treatment for first isolation of pseudomonas aeruginosa (HTA funded. http://www.controlled-trials.com/ISRCTN02734162/)
- UK Empyema Surveillance (David Spencer, Newcastle UK)
- PAGES. Asthma and Genetics Database (Dr Steve Turner, Aberdeen UK).
- UK Neonatal High Frequency Oscillation study Follow up (http://www.hta.ac.uk/project/2245.asp)
Publications from 2000
- Cunningham S, McColm J, Ho LP, Greening A, Marshall TG. Measurement of inflammatory markers in the breath condensate of children with cystic fibrosis. European Respiratory Journal 2000:15;955-977.
- McColm J, Cunningham S. A computer controlled system to simulate small, rapid oxygen fluctuations experienced by preterm infants developing retinopathy of prematurity. Journal of Medical Engineering and Technology 2000;24:45-52.
- McIntosh N, Becher JC, Cunningham S, Stenson B, Laing I, Lyon A, Badger P. The Clinical Diagnosis of Pneumothorax is Late: Use of Trend Data and Decision Support Might Allow Preclinical Detection. Pediatric Research 2000;48:408-415.
- Bath LE, Cunningham S, McIntosh N. Medical students’ perception of caring for a young infant – influence of mothering a doll on these beliefs. Archives of Disease in Childhood 2000:83:521-523.
- Cunningham S, McColm JR, Wade J, Sedowofia K, McIntosh N, Fleck B. A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat. Investigative Ophthalmology and Visual Science 2000:41;4275-80.
- Cunningham S, Prasad A, Collyer L, Carr S, Balfour-Lynn I, Wallis C. Bronchoconstriction in response to nebulised colistin in cystic fibrosis. Archives of Disease in Childhood 2001:84:432-433.
- Cunningham S, Meng QH, Klein N, McAnulty RJ, Hart SL. An evaluation of a porcine model for pulmonary gene transfer using a novel synthetic vector. Journal of Gene Medicine 2002:4;438-446.
- Hodson ME, Gallagher CG, Govan JRW et al (Co-author). A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis. European Respiratory Journal 2002:20;658-664.
- Cunningham S, McColm JR, Mallinson A, Boyd I, Marshall TG. Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis. Pediatric Pulmonology 2003:36;43-48.
- McColm JR, Cunningham S, Wade J, Sedowofia K, Gellen B, Sharma T, McIntosh N, Fleck BW. Hypoxic oxygen fluctuations produce less severe retinopathy than hyperoxic fluctuations in a rat model of retinopathy of prematurity. Pediatr Res. 2004;55:107-13.
- MacGregor G, Ellis S, Andrews J, Imrie M, Innes A, Greening AP, Cunningham S
- Breath Condensate Ammonium is lower in Children with Chronic Asthma. Eur Resp J 2005;26:271–276.
- White A, McColm JR, Wade J, Yaqoob Z, Sedowofia K, Fleck B, McIntosh N, Hislop A, Cunningham S. Low Oxygen Exposure Does Not Cause Pulmonary Injury In The Newborn Rat. Early Human Development 2006:82;335-340
- Cunningham S, McMurray A. The availability and use of oxygen saturation monitoring in primary care in order to assess asthma severity. Primary Care Resp J 2006;15:98-101.
- Brodlie M, McMurray A, Cunningham S. Compliance with inhaled corticosteroids should be considered when determining which children with asthma should be tested for adrenal suppression. European Journal of Paediatrics 2007;166:493-4.
- Reynolds B, Beattie T, Cunningham S. The impact of national guidelines on the assessment and management of acute paediatric asthma presenting at a tertiary children’s emergency department. European Journal of Emergency Medicine 2007;14:142-6.
- McMaster MJ, Glasby MA, Singh H, Cunningham S. Lung function in congenital kyphosis and kyphoscoliosis. Journal of Spinal Disorders & Techniques 2007;20:203-208.
- Cunningham S, Logan C, Lockerbie L, Dunn MJG, McMurray A, Prescott R. Effect of an integrated care pathway on length of stay in hospital for children with acute asthma: cluster randomised trial. Journal of Pediatrics 2008;152:315-320.
- Alex R Horsley, Per M Gustafsson, Kenneth Macleod, Clare Saunders, Andrew P Greening, David Porteous, Jane Davies, Steve Cunningham, Eric Alton, J Alastair Innes. Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. Thorax 2008:63;135-140.
- Sedowofia, Kofi; Giles, David; Wade, Jean; McColm, Janet; Cunningham, Steve; Minns, Robert; McIntosh, Neil. Myelin Expression is Altered in the Brains of Neonatal Rats Reared in a Fluctuating Oxygen Atmosphere. Neonatology 2008;94:113-122
- Stefan Unger, Steve Cunningham. Effect of oxygen supplementation on length of stay in infants hospitalized with acute viral bronchiolitis. Pediatrics 2008;121: 470-475
- A. Laverty, A. Jaffé, S. Cunningham. Establishment of a web-based registry for rare (Orphan) paediatric lung diseases in the United Kingdom – The BPOLD Registry. Pediatric Pulmonol 2008;43:451-456.
- Alex Horsley, Andrew Robson, Jill Lenney, Kenneth Macleod, Steve Cunningham, Andrew Greening, Per Gustafsson, J Alastair Innes. Effects of cystic fibrosis lung disease on gas mixing indices derived from alveolar slope analysis. Respiratory Physiology & Neurobiology 2008:162;197-203.
- De Pontual L, Trochet D, Caillat-Zucman S, Abou Shenab OA, Bougneres P, Crow Y, Cunningham S et al. Delineation of late onset hypoventilation associated with hypothalamic dysfunction syndrome. Pediatr Res 2008:64;689-94.
- Jane C Davies, Steve Cunningham, Eric WFW Alton, Alastair Innes. Lung clearance index in CF: a sensitive marker of lung disease severity. Thorax 2008:63;96-97. (Editorial)
- Macleod KA, Horsley AR, Bell NJ, Greening AP, Innes JA, Cunningham S. Ventilation heterogeneity in well controlled asthmatic children, with normal spirometry, indicates residual airways disease. Thorax 2009:64;33-37.
- Schmoll C, Macrae M, Mulvihill A, Murray R, Cunningham S, McKenzie K. Tuberculous Dacryoadenitis in a Scottish Teenager. Br J Ophthalmol 2009;93:137-8
- Wefers B, Cunningham S, Stephen R, McIntosh N. Neonatal blood pressure waves are associated with surges in noradrenaline. Arch Dis Child 2009;94:F149-F151
- Cunningham S. ‘A Hospital is no Place to be Sick’ (commentary on bronchiolitis home oxygen)
- Arch Dis Child 2009;94:565 (Editorial)
- Turner SW, Ayres JG, Macfarlane TV, Mehta A, Mehta G, Palmer CN, Cunningham S et al. A methodology to establish a database to study gene environment interactions for childhood asthma. BMC Med Res Methodol. 2010;10:107
- Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society Guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58.
- Horsley A, Cunningham S, Innes A. 2010. Cystic Fibrosis. Oxford University Press. Editors.
- Steve Cunningham. Nebulized Hypertonic Saline Solution for Acute Bronchiolitis in Infants: What,
- Where, When and How?. Evid.-Based Child Health 2010:5;1276–1278 (Commentary)
- Steve Cunningham, Ann McMurray. Effect of Oxygen Saturation Limits on Time Fit for Hospital Discharge in Recovering Acute Bronchiolitis. Arch Dis Child 2012;97:361-363
- Alton EW, Boyd AC, Cheng SH, Cunningham S, Davies JC, Gill DR, Griesenbach U, Higgins T, Hyde SC, Innes JA, Murray GD, Porteus DJ. A randomised, double blind, placebo-controlled phase IIB clinical trial of repeated application of gene therapy in patients with cystic fibrosis. Thorax 2013; (In press)
- Bush A, Anthony G, Barbato A, Cunningham S, Clement A, Epaud R, Gilbert C, Goldbeck L, Kronkeld K, Nicholson AG, Schwerk N, Griese M. Thorax 2013; (In press)
- Horsley AR, Davies JC, Gray RD, Macleod KA, Donovan J, Aziz ZA, Bell NJ, Rainer M, Mt-Isa S, Voase N, Dewar MH, Saunders C, Gibson JS, Parra-Leiton J, Larsen MD, Jeswiet S, Soussi S, Bakar Y, Meister MG, Tyler P, Doherty A, Hansell DM, Ashby D, Hyde SC, Gill DR, Greening AP, Porteous DJ, Innes JA, Boyd AC, Griesenbach U, Cunningham S, Alton EW. Changes in physiological, function and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation. Thorax 2013; (In press)
Current sources of funding
Funding Body: HTA NIHR
Title: Bronchiolitis of Infancy Discharge Study
Principal Grant Holder: Dr Steve Cunningham
Co-applicants: Steff Lewis, Kay Riding, Emma McIntosh.
Start Date: July 2011.
Funding Body Reference number: http://www.hta.ac.uk/2390
Funding Body: Cystic Fibrosis Trust
Title: Combination of lung MR imaging with physiological assessment to identify and monitor ventilation heterogeneity in early CF lung disease.
Principal Grant Holder: Professor Chris Taylor
Co-applicants: Professor Jim Wild, Dr Alex Horsley, Dr Steve Cunningham
Start Date: 01.08.2012.
Funding Body Reference number: http://www.cftrust.org.uk/research/areasresearch/researchcurrentlyfunded/
Funding Body: European Union FP7
Title: Child-EU Rare Disease Trial in Europe
Griese M, Cunningham S, et al
Value: 3,000,000 Euros (Funding direct to UoE = 404,000 Euros)
Funding Body: Asthma UK Centre for Applied Research
Principal Grant Holder: Aziz Sheikh
Qualifications / Degrees:
MBChB 1987 (Dundee University)
MRCP (UK) 1991
PhD (Medicine:Edinburgh) 1994
Selected Invited Lectures
- CF year in review. European Respiratory Society Plenary. Munich, Germany. September 2006.
- CF and genetics. European Society for Paediatric Research/European PICU society. Barcelona, Spain. October 2006.
- Use of non-invasive ventilation in neuromuscular disease. British Paediatric Neurology Association. January 2007. Edinburgh.
- The use of Palivizumab in infants born prematurely – should it be used more in the UK. Royal College of Paediatrics and Child Health Conference, York March 2007.
- The British Paediatric Orphan Lung Disease Registry. British Paediatric Respiratory Society Annual Summer Meeting 2008.
- Novel Therapies that might work in Cystic Fibrosis. Great Ormond Street Respiratory Update Course. October 2009
- Bronchiolitis – what is the evidence? European Paediatric Association/Excellence in Paediatrics. London December 2010.
- Lung Clearance Index – in health and disease. ARTP. Dublin. October 2011.
- Cystic Fibrosis – what’s new in treatment. Excellence in Paediatrics. Istanbul December 2011.
- Infectious Diseases Grand Round. Antimicrobial Treatment of non-CF bronchiectasis. European Respiratory Society Vienna 2012.
- The British Paediatric Orphan Lung Disease Registry. British Thoracic Society Winter Meeting London 2012.
- Research poor and rich management of Cystic Fibrosis. Excellence in Paediatrics. Madrid December 2012.
- Higher Degree Examiner
- March 2009: External Examiner PhD. Lung physiology in infants with recurrent wheeze. S Sonnappa. Institute of Child Health, London.
- May 2009: External Examiner MD. Stem Cells in Paediatric Lung Disease. H Spencer. Institute of Child Health, London.
- August 2009: Internal Examiner MD. Studies and Observations on Different kinds of Oxygen Monitoring, Oxygen Therapy and Associated Morbidities in Preterm Infants. David Quine. University of Edinburgh.
- September 2009: External Examiner MPhil. Factors that Acutely Influence Exhaled Nitric Oxide in Asthmatic and Health Children. I A Abuzayn. University of Aberdeen.
- September 2011: External Examiner PhD. Pharmaco-epidemiology, effectiveness and adherence to therapy in childhood asthma: Utility of routinely acquired primary care data. Hajer Elkout. University of Aberdeen.
- Cystic Fibrosis – what’s new in treatment. Excellence in Paediatrics. Istanbul December 2011.
- Lung Clearance Index as an outcome in clinical trials. European Cystic Fibrosis Society meeting. Dublin Ireland June 2012.
- The British Paediatric Orphan Lung Disease Registry. British Thoracic Society Winter Meeting London Dec 2012.
- Cystic Fibrosis Management in two healthcare settings. Excellence in Paediatrics. Madrid Dec 2012.
- Orphan Lung Diseases. Association of Respiratory Physiologists and Technologists. Leicester. January 2013.
- MHRA Expert Advisory Panel – Paediatrics (PM EAG)
- MHRA Expert Advisory Panel – Respiratory (CDRRA EAG)
- Specialist Advisor (Respiratory) – European Medicines Agency
- Panel Member NIHR HTA Psychological and Community Therapies Panel (2008-2012)
- Member of the General Medical Council Professional and Linguistics Board (2011- current)
- Chair of British Paediatric Orphan Lung Disease Project
- Chair of Asthma UK Scottish Advisory Group
- Chair of SIGN Bronchiolitis guideline group (2003-6)
- Chair Lothian QIS Children’s Asthma Group and lead for QIS visit 2007
- SIGN/BTS asthma guideline member: Therapeutics
- British Thoracic Society Bronchiectasis guideline group
- British Thoracic Society Orphan Lung Disease group
- Specialist Advisor to Scottish Medicines Consortium
- Specialist Advisor to the Health Technology Agency
- Editorial Board: American Journal of Respiratory and Critical Care Medicine (2008-2011).
- German BMBF June 2008
- E-Rare European Rare Disease Board. Member of the International Scientific Committee. 2009, 2011, 2012.
- Editorial Advisory Panel Invite for Treatment Strategies – Respiratory (including AARC 2010 Review Supplement)
- Editorial Advisory Panel Invite for Treatment Strategies – Paediatrics
- Editorial Board. Journal of Co-Morbidity (2011 – current)
- Academic Foundation Programme Director SE Scotland (July 2011 – current)
- UK Cystic Fibrosis Trust Registry Steering Committee (July 2011 – current)
- UKOS Steering Committee 2010 – 2014.
- RCPCH START Assessor 2012 – current
Current Research Activities
(in addition to gene therapy, BIDS and FP7 rare lung disease grants).
VX10-770-106 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of VX-770 on Lung Clearance Index in Subjects with Cystic Fibrosis, the G551D Mutation, and FEV1 >90% Predicted
VX12-770-110 A Phase 3b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With CF who have the R117H-CFTR Mutation
VX12-770-112 A Phase 3, Two-Arm, Rollover Study to Evaluate the Safety of Long-Term Ivacaftor Treatment in Subjects 6 Years of Age and Older with Cystic Fibrosis and a Non-G551D CFTR Mutation
VX11-770-108 A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who are 2 Through 5 Years of Age and Have a CFTR Gating Mutation
Trial Steering Committee
United Kingdom High Frequency Oscillation Study: Follow Up. HTA funded study.
Professor Anne Greenough, London. 2011-2014.
Data Monitoring Committee
Cystic Fibrosis Foundation Therapeutics’ Data and Safety Monitoring Board.
Vertex Pharmaceuticals Studies.
VX12-809-103 and VX12-809-104