Scientists from King's College London and Imperial College London believe they have discovered a key element in the development of chronic asthma. Their research has been published in a new paper in the journal Proceedings of the National Academy of Sciences to explain why the structure and function of asthmatic airways are changed or ''remodelled'' and how this contributes to chronic asthma.
Remodelling occurs when the small airways in the lungs of people change gradually with time as their lungs respond to the presence of particles such as dust, pollen and mould in the air they breathe. These changes can also be compounded by viruses and bacteria.
Airway remodelling is apparent even in the lungs of young children with asthma, and can make the condition almost impossible to control. An important aspect of airway remodelling is changes to the muscle cells which line our airways. In people with asthma, these cells tend to multiply and become larger, increasing their ability to squeeze the airways and cause breathing difficulties. There is no known way of reversing airway remodelling once it has occurred.
Dr Elaine Vickers, Research Relations Manager at Asthma UK says: 'This research into the causes of asthma provides us with vital clues as to how such symptoms could be stopped and it has uncovered important information, which we hope will lead to the creation of effective new treatments for the millions of people in the UK affected by asthma symptoms.'
Professor Tak Lee, Head of the Division of Asthma and Allergy Research at King's, who led the research, comments: 'It is widely believed that this remodelling in Asthma is in large part responsible for the chronicity of the disease. There are many features responsible for remodelling but a key component of this process involves an increased amount of smooth muscle in the airways.'
Notes to Editors
This research was also supported by the Medical Research Council; the Dr Hadwen Trust for Humane Research; the Guy's and St Thomas' NHS Foundation Trust, King's College London National Institute for Health Research Biomedical Research Centre, and Asthma UK.
These experiments have shown that cells derived from asthmatic patients are very abnormal. The recent work by researchers from the MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London and Imperial College London has found for the first time a unifying mechanism that may account for many features of this aspect of the remodelling process.
Professor Tak Lee and colleagues have focused their attention on the movement of calcium in and out of muscle cells because calcium is the most plentiful mineral in the human body and it regulates many cellular activities. They believe that they have discovered a key reason why muscle cells in the lungs of people with asthma become over-sensitive.
The amount of calcium in muscle cells is controlled by a series of channels and pumps that either increase or decreased calcium levels. One of these pumps is called SERCA2. It relaxes muscle cells by pumping calcium out of the main body of the cell, the cytoplasm, and into an internal compartment called the sarcoplasmic reticulum.
The Asthma UK and Dr Hadwen Trust for Humane Research-supported scientists studied muscle cells from the airways of people with moderate asthma, who experience daily asthma symptoms and need both preventer and reliever inhalers to keep their symptoms under control. The scientists compared these cells to those from people who either had asthma or didn't have asthma at all. They discovered that in people with moderate asthma SERCA2 levels were reduced, lowering the cells' capacity to remove calcium from the cytoplasm. They also found that if they removed SERCA2 from the cells of people who didn't have asthma, these cells started to behave more like asthma cells.
These discoveries suggest that a lack of SERCA2 in airway muscle cells play an important role in causing asthma symptoms. Professor Lee suggests that replacing SERCA2 in these cells might be an effective way of creating new asthma treatments to reduce asthma symptoms and prevent the long term lung changes which can make some people's asthma almost impossible to control.
Dr Sebastien Farnaud, Science Director at the Dr Hadwen Trust for Humane Research says: 'This is a really exciting development in asthma research because it brings us a step further to replacing potentially misleading animal models with more human-relevant approaches that could hasten the development of more appropriate and effective treatments.'
For media interviews please contact Professor Jeremy PT Ward, Head of Department of Physiology & Professor of Respiratory Cell Physiology, Division of Asthma, Allergy and Lung Biology at King's College London on: 0780 316 3258
King's College London
King's College London is one of the top 25 universities in the world (Times Higher Education 2008) and the fourth oldest in England. A research-led university based in the heart of London, King's has more than 21,000 students from nearly 140 countries, and more than 5,700 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.
King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: www.kingshealthpartners.org.
Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 13,000 students and 6,000 staff of the highest international quality.
Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy. Website: www.imperial.ac.uk
Asthma UK
Asthma UK is the charity dedicated to improving the health and well-being of the 5.4 million people in the UK whose lives are affected by asthma.
For up-to-date news on asthma, information and publications, visit the Asthma UK website asthma.org.uk.
Kickasthma.org.uk is Asthma UK's interactive website for children and young people with asthma. The site offers support and advice and includes an asthma dictionary, problem page, games and a messageboard.
For independent and confidential advice on asthma, call the Asthma UK Adviceline, which is staffed by asthma nurse specialists. It is open weekdays from 9am to 5pm on 0800 121 62 44. Or email an asthma nurse at asthma.org.uk/adviceline.
For further information, contact the Asthma UK media office on 020 7786 4949 or at mediaoffice@asthma.org.uk.
The Dr Hadwen Trust for Humane Research
The Dr Hadwen Trust for Humane Research is the UK's leading non-animal medical research charity funding the development of advanced techniques to replace the use of animals in human disease research. For further information contact the Dr Hadwen Trust press office on mobile 07989 972 423 or wendy@drhadwentrust.org
Journal
Proceedings of the National Academy of Sciences