Ian Pavord: Asthma
Ian Pavord's research in to airway inflammation has resulted in mepolizumab being identified as an effective inhibitor of eosinophilic inflammation and asthma attacks. Mepolizumab is currently in Phase III clinical trials and if found to be effective could be a promising treatment for certain asthma patients.
Q: How big a problem is asthma?
IP: Asthma is a big problem. 5-10% of children and adults have a diagnosis of asthma and require treatment. Asthma is a common cause of hospital admission particularly in the winter when it contributes to the winter bed crisis that many hospitals have. Unlike many other chronic health conditions the key outcomes in asthma are not improving or have stopped improving over the last 10 years, so hospitalisation rates for adults and death due to acute, severe asthma have both plateaued over the last 10 years, so I would say that it is a significant problem.
Q: What are the different types of inhalers and what do they do?
IP: Well they are broadly in two categories: relievers, which are often blue inhalers and ease the symptoms of asthma but don't deal with the underlying cause of the symptoms (airway inflammation), and preventers, which are usually brown or purple and deal with the airway inflammation, which is the basis of many of the problems that asthma patients have.
Q: How is your research helping the development of new treatments?
IP: We're interested in measuring airway inflammation and have developed a number of relatively simple techniques that help us to get a better feel for the nature of lower airway inflammation. We've been applying these measurements to patients with asthma for 20 years, or more, now. Our findings have been in many respects very surprising in that it had been assumed that the symptoms as measures of lung function that we usually use in clinical practice to base treatment decisions on are, in fact, not that closely related to either the nature or the severity of airway inflammation. So, they are probably not the best basis on which to decide which patient needs anti-inflammatory treatment, who should have more or who should have less. We feel that objective measures of airway inflammation are a much better basis for making key decisions about anti-inflammatory treatment.
Q: What are the most important lines of research that have developed in the past 5-10 years?
IP: As a result of the new understanding of the relationship between airway inflammation and symptoms, and particularly our discovery that one of the major clinical manifestations of uncontrolled inflammation is an increased risk of asthma attacks, has been the development of much more specific inhibitors of eosinophilic inflammation. Now these drugs had been trialled in asthma 10 or more years ago, with very disappointing findings but when we investigated the effects of a selective inhibitor of eosinophilic airway inflammation (mepolizumab) in patients who we knew had eosinophilic inflammation and we looked at the main clinical outcomes associated with the airway inflammation (asthma attacks), we were able to show that mepolizumab was very effective and this drug is now undergoing Phase III clinical trials and is likely to become a viable treatment option for an important subgroup of patients with asthma. So that's one very important area.
I think that there's a wide-spread realisation now that the drugs that we have in the future are not going to work well in all patients and one of the big clinical challenges is going to be identifying the right patient for the right drug, a process that we call phenotyping patients and phenotype-specific treatments, and that is very much my area of interest. We've had some success in that area.
Q: Why is your research important and why should we put money in to it?
IP: Asthma is one of the most common chronic diseases and the outcomes are not improving in the way that they are for other chronic conditions. It is also a very important condition for the UK – we have some of the highest incidences and the worst outcomes from asthma of any country. The existing drugs that we have available to treat asthma are largely British drugs that were invented in the UK and are manufactured by British pharmaceutical companies so this is a particularly important subject for a UK PLC and we need the next generation of effective treatments.
Q: How does your research fit in to translational medicine within the department?
IP: One of the effects of measuring airway inflammation in a large number of patients is that one begins to recognise the particular patterns of disease in patients that haven't been recognised before. Some of these patterns look so characteristic that it looks to be possible that we should be able to understand the pathogenesis and develop better and more specific treatments. One of the things that attracted me to come to Oxford was that I had identified these groups of patients but didn't have any obvious way to move on with investigation and understanding of pathogenesis and I felt that it might be possible here to connect these interesting groups of patients to very clever immunologists and basic scientists and really begin to dissect out what was happening and work out when there are other opportunities to intervene, to the benefit of the patient. That's one of the areas that I hope to achieve effective translational research. I'm very much at the patient –side but I hope to connect patients to scientists and I think that's really what we have got to do. We've got a big opportunity in Oxford, in the Nuffield Department of Medicine, because of the way that things have been set up to do that effectively.