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Professor Chris O'Callaghan
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Respiratory, Critical Care and Anaesthesia
The multi-disciplinary research teams within the Respiratory, Critical Care and Anaesthesia (RCCA) Section at the UCL, Institute of Child Health investigate the causes, consequences and treatments of cardio-respiratory diseases in childhood. This work is of immense clinical importance because cardiorespiratory disease - the major cause of death in Western society - has its origins in childhood, and respiratory illness is the most common cause of paediatric admission to hospital in the UK.
The RCCA section includes several groups with complementary
research interests in clinical and basic science.
We focus on the following 7 main
Lead Contact: Dr Mike Grocott
Introduction The Applied Human Physiology research group encompasses the Centre for Altitude, Space and Extreme Environment Medicine (CASE Medicine).
This is a group of clinicians and scientists with specialist interests and training in the medicine and physiology of extreme environments.
As part of this activity CASE Medicine run three applied human physiology laboratories (two clinical and one research) where we conduct a variety of physiological measurements.
The clinical laboratories focus particularly on the use of cardiopulmonary exercise testing (CPET/CPX) use for the evaluation of patient risk prior to major surgery.
In addition, the group conduct research, teach courses and offer advice in the areas of space, aviation, high altitude, remote, dive and hyperbaric medicine.
Central to our work is the concept that the study of human systems stretched to breaking point in extreme environments can increase our understanding of critically ill patients.
- To learn more about physiological adaptation in critical illness by using the model of extreme environment physiological changes, and thereby improve patient care
- To engage the public in our research findings through public speaking engagements, internet initiatives, conference organisation and education, in order to improve public understanding of critical illness and extreme environment physiology
- Altitude: Current projects include ongoing analysis of the data gained on the 2007 Caudwell Xtreme Everest expedition, the use of an acute hypoxia tent to explore short-term hypoxic adaptation, and investigating the association between hypoxic adaptation and a variety of genetic polymorphisms. Further research treks will take place this year (2009) to build on knowledge gained from 2007. Further major projects are planned for 2010-2012.
- Space: CASE has collaborative projects with NASA exploring gene-environment (microgravity) interactions and the development of new medical technologies.
- Dive and Hyperbaric: Investigating the association between mitochondrial dysfunction and sepsis using hyperbaric hyperoxia. Currently completing a Cochrane Systematic Review of the role of hyperbaric oxygen therapy in necrotising fasciitis. Mixed gas diving and recompression table modelling.
Lead contact: Professor Janet Stocks
The Portex Respiratory Unit has an international reputation for the development and validation of lung function tests for use in infants and pre-school children, and the application of these measurements in epidemiological and clinical research studies.
This has helped elucidate the early determinants of airway function and establish objective phenotypic outcome measures of the nature and severity of lung disease and response to therapy in a range of paediatric respiratory illnesses, including cystic fibrosis (CF), asthma, and sickle cell disease.
- To develop and validate respiratory function tests for use in infants and young children
- To apply these tests in clinical and epidemiological studies to strengthen the scientific basis for the prevention and treatment of respiratory disease in early life
- To investigate the early determinants of lung growth and development in health and disease
Current and Recent Projects
- Overcoming ethnic differences: a 3D approach to body physique for predicting lung function in children (the SLIC study, funded by Asthma UK (pilot) and the Wellcome Trust (full study);
- Respiratory Follow up during infancy and at 11 years of age of children born extremely preterm (<26 weeks gestation) (the EPICure project, funded by the MRC);
- Establishment of international growth charts for pulmonary function in young children. (Funded by Asthma UK)
- A multi-centre study to determine phenotypic and genotypic relationships between asthma, sleep-disordered breathing, pain and acute chest syndrome in children with Sickle Cell Disease (The SAC study: NHLBI funded)
- Identification of early changes in lung structure and function and airwayinflammation in young children with asthma. (Funded by Asthma UK)
- Longitudinal assessments of lung function and clinical status in children with CF, from birth through to school age. (London Cystic Fibrosis Collaboration (LCFC) funded by the CF Trust)
- Early detection of lung disease in infants with CF diagnosed by newborn screening, structure- function relationships (Funded by GOSH Children’s Charities)
- Effect of altitude on cardio-respiratory function and sleep patterns in healthy children (See Smiths Medical Young Everest Study for more details)
Higher Degree Students
The unit always has a number of students undertaking research degrees in the field of respiratory physiology. These currently include
- Dr Amit Gupta (Characterising the nature and severity of lung disease in infants born extremely preterm, year 5)
- Jane Kirkby (Application and interpretation of lung function in children with airways obstruction, year 4)
- Lena Thia (Lung function and structure in infants with cystic fibrosis one year after diagnosis through newborn screening, year 2)
- Rachel Bonner (Ethnic differences in lung function, body size, shape and composition during childhood, year 1)
Recent awards include
- Dr Sanja Stanojevic (PhD awarded 2009) for her work on developing international growth charts for lung function in young children
- Dr Sanja Stanojevic has also recently won the prestigious European Respiratory Society 'Paediatric Respiratory Research Award' for outstanding contributions to the field, which was awarded as a special symposium at the ERS meeting in September 2011
- Professor Janet Stocks has also been recently awarded the 'Paediatric Assembly: Lifetime Achievement Award 2011' for her achievements in the Paediatric Respiratory field, as the special symposium at the ERS meeting in September 2011.
Involvement in International Scientific Organisations
Several members of the respiratory physiology theme are active in a number of scientific and professional organisations, including the European Respiratory Society (ERS) and American Thoracic Society (ATS) and the Association of Respiratory Technicians and Physiologists (ARTP: Ms Jane Kirkby), where they have responsibility for developing national and international guidelines and standards for topics such as lung function reference values, multiple breath inert gas washout and the application and interpretation of lung function tests in very young children.
Lead Contact: Dr Eleanor Main
We are working towards improving physiotherapy treatments for patients suffering from cardio-respiratory conditions by:
- Evaluating therapeutic effects of different techniques in specific populations using robust and sensitive outcome measures
- Understanding how good clinical decisions are made and increasing benefit and minimising risk in treatments involving critically ill patients
- Investigating the physiological basis of different components of airway clearance techniques as well as unforeseen consequences of such treatments.
- To improve the therapeutic benefits of physiotherapy and minimise the potential for any harm or risk to patients undergoing such treatments
- To better understand the physiological basis for traditional therapeutic strategies and physiotherapy interventions and their role in current policy and practice
- To develop and use sensitive and appropriate outcome measures and improve the evidence base for cardio-respiratory physiotherapy
- To understand how the process of clinical reasoning and decision making can differentiate expert from novice physiotherapy practitioners, and use this knowledge to pre-empt training requirements
- Characterisation of treatment profiles, including timing, magnitude and repeatability, patterns and hand surface pressure area of forces applied during physiotherapy
- Safety and efficacy of on-call and weekend physiotherapy treatments
- Measures of clinical decision making and evaluation of physiotherapy interventions and techniques purported to improve clinical outcomes
- Development of novel monitoring techniques (including Lung Clearance Index, Electric Impedance Tomography and Novel Pliance pressure mats) to evaluate the efficacy of different therapeutic interventions
Evaluation of current key issues in Cardiorespiratory Physiotherapy, including:
- The effects of intermittent positive pressure breathing on regional lung ventilation
- The relative benefits and limitations of ventilator versus manual hyperinflation
- Factors influencing change in peak expiratory flow during chest physiotherapy
- Consensus on the physiotherapy management of asymptomatic infants with cystic fibrosis
- PIF / PEF flow relationship and two phase gas liquid interaction
- Oxygen delivery systems on exercise performance in patients who are hypoxaemic on activity
- The importance of preoperative physiotherapy for adults undergoing upper gastrointestinal surgery in terms of postoperative pulmonary complications
- The use of abdominal binders for improving peak expiratory flow during chest wall vibrations in ventilated patients
- Validated tools for diagnosing chronic hyperventilation syndrome
- Optimising critical care rehabilitation programmes
Babies and children may experience pain as a result of illness or its treatment.
Evidence for effective pain management is increasing, particularly for the management of pain after surgery.
Ongoing research is required to more fully understand how the nervous system processes pain, particularly in early development, in order to determine the most effective and safest analgesic treatments for children of different ages.
In addition, the best ways to assess pain, particularly in young pre-verbal or communication-impaired children are being evaluated. We also work with other specialist teams to improve the understanding and multidisciplinary management of children with chronic pain.
Members of the Portex Unit Pain Research Group are involved in laboratory and clinical research investigating the effects, assessment and management of pain throughout childhood.
The research questions have frequently arisen from the team’s clinical experience in acute and chronic pain management, and our aim is to translate research findings into improvements in clinical practice.
- Publications can also be found via the UCL Discovery website
Lauriane Harrington (UCL MSci Natural Sciences 2010) has won the ENP Photo Competition 2011 (www.paris-neuroscience.fr) for her picture ‘From the opium poppy to the opioid receptor’. Lower image represents staining for mu opioid receptor in the adult spinal cord following exposure to morphine in early life. Supervisor: S Walker
- Understanding pain processing during postnatal development
- Exploration of the impact of developmental age on the mechanisms and efficacy of analgesia
- Investigation of the potential long-term effects of pain and different forms of injury in early life
- Improving the assessment and measurement of pain
- Evaluating current evidence, and development and implementation of guidelines for the management of acute procedural and postoperative pain
- Evaluation of treatment strategies for chronic pain in children and adolescents
- Mechanisms, presentation and treatment of neuropathic pain
- Efficacy and toxicity of spinally administered analgesia
- Mechanisms and impact of long-term sensory changes following surgical injury in early life
- Developmental opioid pharmacology
- Risk factors for opioid-related side-effects
- Changes in sensory processing and coping strategies in children with chronic pain
Lead Contact: Dr Mark Peters
Severe infection or injury requiring intensive care are the most common reasons for admission to Great Ormond Street Hospital and the most common causes of death in childhood.
In the last 10 years, progress has been made in the care of these cases that has resulted in dramatic improvements in survival.
Intensive care medicine is characterised by complex disease processes in which there is a dynamic interaction between an insult or injury and the subsequent host response.
The Critical Care Group investigates these responses with international clinical studies and a basic science programme into cellular adhesion, cytokine balance, platelets and fibrinolysis in inflammation, ischaemia reperfusion injury and the role of the innate immune system in systemic inflammation.
- To increase the understanding of the pathophysiology of the systemic inflammatory response to infection or injury in critically ill children
- To develop new therapeutic strategies for the systemic inflammatory response to infection or injury in critically ill children
- A multi-centre randomised controlled trial to determine the effectiveness of different central venous catheters in the prevention of blood stream infection in the paediatric intensive care unit
- Haemodynamics and therapeutics of Shock in Children and Neonates
- Novel therapies for Pulmonary Hypertension of the Newborn
- Genetic control of platelet count during critical illness
- A multi-centre randomised controlled study of glycaemic control in critically ill children
- Mathematical model of intra-cranial pressure and therapeutics in severe paediatric head injury
- Mechanisms of ischaemic-preconditioning in humans
- Role of the protein C pathway in necrotising enterocolitis
- Genetic risk factors for the systemic inflammatory response following infection or trauma
- UK paediatric intensive care outcome study
- Alteration in mitochondrial functions with age in critical illness
- Hereditary surfactant protein B deficiency: genetic analysis for mutations in the SP-B gene
- The effect of glutamine on liver metabolism during sepsis in infants and children
Lead contact: Dr Paul Aurora
Respiratory illness is the single most common cause of paediatric admission to NHS hospitals, accounting for 25% of neonatal deaths and 10% of all infant deaths. One child in ten is affected by asthma, while cystic fibrosis (CF) is the most common lethal inherited condition in the United Kingdom.
The paediatric respiratory service at GOSH encounters a large number of rare clinical conditions and research projects have been established to look in detail at the pathophysiology, clinical course, effective therapy and functional impairments in some of these conditions.
In addition, the Portex Unit has an outstanding record for the development and validation of lung function tests for use in infants and young children, and the application of these measurements in epidemiological and clinical research studies, and the respiratory medicine service collaborates closely with this work.
Finally, the hospital is home to many world class paediatric speciality services, and the respiratory unit collaborates closely with numerous research projects in other patient groups. In particular, collaborative research with the paediatric cardiothoracic transplant service is currently very active. Dr P Aurora is the academic lead for the department, but all senior staff are actively involved in the department’s research programme.
- To increase the understanding of the pathophysiology of lung disease in children
- To develop new therapeutic strategies for lung disease in children
Current and Recent Projects
- Longitudinal monitoring of very young children diagnosed with CF, with the aim of developing new outcome measures for the detection of early lung disease, and then utilising these outcome measures in therapeutic trials. Much of this ground-breaking research is part of a pan-London collaboration, and is co-ordinated through the Portex Unit.
- Longitudinal study of young children with asthma, and correlation of subtle physiological change with evidence of inflammation and structural change. The aim of this work is to develop a better understanding of the pathophysiology of early childhood asthma, with the aim of developing and refining new treatments. As with the CF work, this research is part of a developing multicentre collaboration, and co-ordinated through the Portex Unit.
- Establishment of a national registry for children with rare 'Orphan' lung disease
- A longitudinal study of the impact of viral infections following lung transplantation. This multicentre international study is funded by the National Institutes of Health (NIH) in the US
- A multicentre international study of the impact of paediatric lung transplantation on health related quality of life in CF. This study is also funded by the NIH.
- Comparison of urokinase versus primary video-assisted thoroscopic surgery for the treatment of empyema in children. (3 yr study). This is the only prospective evidence based study to guide treatment in this disease. By recommending urokinase treatment in children with these conditions there is the potential saving to the NHS of £1.2 million.
- The treatment of upper airway obstruction secondary to Pierre-Robin sequence with nasopharygeal airways
- Ciliary function in children following lung transplantation (joint work with the University of Leicester)
- Signalling pathways of macrolide antibiotics
- Assessing the impact of hypoxia in children with cystic fibrosis
- The impact of gastro-oesophageal reflux upon outcomes following lung transplantation, and how to best measure and treat this complication
- Lung transplantation in high risk children with severe pulmonary hypertension and children with CF with unusual infections
- Measurement of non-invasive markers of inflammation on the intensive care unit
- Physiological and structural lung disease in children with connective tissue disease
- Physiological and structural lung disease in children following stem cell transplantation
- 8-isoprostane and exhaled nitric oxide in children with atopic dermatitis
- Stem cell engraftment in the human and mouse lung
- Assessment of body composition in cystic fibrosis
- Assessing the role of vitamins D and K on bone disease in cystic fibrosis
- The use of inhaled dry powdered mannitol in cystic fibrosis
- The effect of hypoxia in sickle cell disease
Current and Recent Higher Degree Submissions
The unit always has a number of students undertaking research degrees. These are usually medical trainees, but also occasionally trainees from other disciplines. Recent submissions & awards include
- Dr Samatha Sonnappa (PhD thesis awarded 2009) for her work on lung function abnormalities in preschool children with asthma
Involvement in National and International Scientific and Professional Organisations
Members of the department are active in a number of scientific and professional organisations, where they have responsibility for stimulating collaborative research, and developing agreed standards for both research and clinical practice.
These organisations include the British Paediatric Respiratory Society (Dr C Wallis), the Association of Respiratory Technicians and Physiologists (Mrs E Fettes), the European Respiratory Society (Dr P Aurora), and The International Society of Heart and Lung Transplantation (Dr P Aurora).
Lead Contact: Dr Mike Sury
Our main theme is to minimise the risk, stress and discomfort for children requiring anaesthesia and sedation. Our work involves improving the care for children not only having major surgery in the operating theatres but also for those having minor procedures outside the operating theatre environment. We have expertise in the development, assessment and investigation of new techniques and we are working to improving practice both locally and nationally. We collaborate closely with Pain Research and all our sibling research groups.
- To eliminate the pain, discomfort and risk of surgery
- To assess conscious level and avoid both inadequate and excessive anaesthesia drug doses
- To better understand the pathogenesis of both pre and post-operative distress
- To develop new techniques, technologies and management strategies that will improve outcome following anaesthesia and sedation
- To assess new technology in infants and small children
- Anaesthesia - investigation of markers of conscious level in infants and small children
- Cardiac Anaesthesia – minimising risk in pulmonary hypertension
- Neurosurgical anaesthesia – management of major haemorrhage
- Sedation – development of short acting techniques for painless imaging and endoscopy
- Anxiety management – identification and management of severe preoperative anxiety
- Resuscitation – working towards evidence based guidelines
- Airway management – assessment of a new laryngoscope
- Assessment of new technology – continuous non-invasive blood pressure
- Safety – implementation and assessment of national check-lists for surgery
Page last modified on 19 jun 14 14:49