Researchers have identified a molecular mechanism that could explain why the common cold can bring on life-threatening asthma attacks.
Published today in Science Translational Medicine, the findings indicate this may be a potential target for new drugs that could be more effective than existing treatments.
Viruses that infect the airways are the most common cause of asthma attacks, accounting for 80-90 per cent of cases. The great majority of these are rhinoviruses, which are the predominant cause of the common cold.
Although illnesses caused by rhinoviruses are usually relatively mild for most people, they can also infect the lungs and, in people with respiratory diseases such as asthma, they can trigger severe attacks, sometimes leading to hospitalisation. The hallmark features of an asthma attack are inflammation and obstruction of the airways, and increased mucus production. These are all part of type-2 immune responses, which usually occur in response to allergies and parasitic infections. Until now it has been unclear how a rhinovirus infection can trigger such a response.
The new study, conducted at the Medical Research Council (MRC) & Asthma UK Centre in Allergic Mechanisms of Asthma at Imperial College London and King's College London, has confirmed that a small molecule or cytokine called IL-25 may play a central role in the effects of rhinoviruses on asthmatics. For the first time researchers have identified a possible sequence of biological events that could trigger these attacks.
The research shows that IL-25 is induced by rhinovirus infection, and is capable of instigating the production of other type-2 cytokines, creating a 'cascade' of these molecules which drives the type-2 immune response. Recent trials report that antibodies that block individual type-2 cytokines have modest therapeutic effects. The hope is that if scientists can target and block IL-25, this will stop the cascade 'higher up' and potentially produce a much greater therapeutic effect.
Dr Nathan Bartlett, Honorary Lecturer at the National Heart and Lung Institute, Imperial College London and joint lead author of the study said: "Our research has shown for the first time that the cells that line the airways of asthmatics are more prone to producing a small molecule called IL-25, which then appears to trigger a chain of events that causes attacks. By targeting this molecule at the top of the cascade, we could potentially discover a much-needed new treatment to control this potentially life-threatening reaction in asthma sufferers."
According to the World Health Organization, 235 million people suffer from asthma worldwide and asthma is the most common noncommunicable disease among children. In the UK, 5.4 million people are currently receiving treatment for asthma. That is one in every 12 adults and one in every 11 children.
The research team compared cells taken from the lungs of asthmatics to cells from healthy volunteers and demonstrated that, when infected with a rhinovirus, asthmatic lung cells produce around 10-fold higher levels of IL-25. To examine IL-25 expression directly in the airways the researchers then infected asthmatic and healthy volunteers with a rhinovirus and found that asthmatics had a higher level of IL-25 in nasal secretions.
By simulating asthma in mice and infecting them with a rhinovirus, the researchers discovered that increased IL-25 is associated with increased levels of other cytokines in the type-2 response, and that blocking IL-25 with an antibody decreases the levels of these other cytokines. These results suggest that IL-25 could be a target for possible treatments to prevent asthma attacks.
Professor Sebastian Johnston, from the National Heart and Lung Institute at Imperial College London, and joint lead author of the study, said: "Asthma attacks are still a huge healthcare problem. Existing medication containing inhaled steroids, are highly effective at controlling regular asthma symptoms, but during an attack the symptoms worsen and can lead to the patient going to hospital. This new study provides exciting results about potential ways to address this big unmet medical need. The next steps are to test blocking IL-25 in humans, and to investigate other possible pathways that could be important in asthma attacks and pool this knowledge to develop effective treatments." Professor Johnston is the Director of the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma and Asthma UK Clinical Chair.
Dr Samantha Walker, Director of Research and Policy at Asthma UK, said: "Excitingly, this research, although still at an early stage, could potentially lead to the development of new medicines to prevent life threatening asthma attacks. Years of research underfunding means that asthma still remains a relative mystery and the millions of people with asthma need more studies like this to bring us one step closer to new treatments. Promisingly we now have new technologies, talented asthma scientists and international collaborations with the potential to make life changing discoveries about asthma."
The study was funded by the MRC, Asthma UK, the National Institute for Health Research Imperial Biomedical Research Centre and Novartis Institute for Biomedical Research.
Reference: Beale et al. 'Rhinovirus induced IL-25 in asthma exacerbation drives type-2 immunity and allergic pulmonary inflammation.' Science Translational Medicine, 2014. doi/10.1126/scitranslmed.3009124
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Notes to editors:
1. The paper will be available after the embargo lifts at http://stm.
2. About 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 14,000 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 global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
3. About King's College London
King's College London is one of the top 20 universities in the world (2014/15 QS World University Rankings) and the fourth oldest in England. It is The Sunday Times 'Best University for Graduate Employment 2012/13'. King's has nearly 26,000 students (of whom more than 10,600 are graduate students) from some 140 countries worldwide, and more than 7,000 staff. The College is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
4. The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.
5. About Asthma UK
- Asthma UK is the UK's leading asthma charity. We're here to support people with asthma when they need us the most and fund world-leading research to find better treatments and ultimately a cure.
- Our goal is to prevent asthma attacks, especially those that result in death and emergency hospitalisation.
- The Asthma UK Helpline is open weekdays from 9am to 5pm on 0800 121 62 44.
- For more information about asthma please visit http://www.
asthma. org. uk
6. The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website.