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We talk to Professor Ian Pavord, the newly appointed Statutory Chair in Respiratory Medicine. Professor Pavord recently joined the Nuffield Department of Clinical Medicine from the University Hospitals of Leicester NHS Trust.

Extracted from Issue 9, May 2014 OxfordMedSci News.

Tell us a little about the work in your group

Ian Pavord

We have been interested in measuring airway inflammation in patients with airway diseases (asthma, Chronic Obstructive Pulmonary Disease (COPD) and cough) for 20 years and have shown that a response to our most effective treatment, corticosteroids, is only seen in patients with eosinophilic airway inflammation ( Eosinophilic airway inflammation is not closely linked to symptoms or patterns of airway dysfunction, so our current approach to using corticosteroids based on an assessment of symptoms and lung function is flawed. We have shown that outcomes are much better when treatment is based on objective measures of eosinophilic airway inflammation. Our findings could be translated to ordinary clinical practice as simple tests, such as the concentration of nitric oxide in exhaled air and the number of eosinophils in peripheral blood provides a robust and accessible estimate of the presence of eosinophilic airway inflammation. Our main goal is to determine whether use of these tests in primary care and in emergency departments is feasible and results in improved outcomes.

What are the challenges and implications of your research?

Important outcomes such as deaths from asthma and hospital admissions due to COPD have not improved over the last decade despite a 3-fold increase in spending on drugs used to treat airway disease. Treatment adherence rates for inhaled steroids are poor, suggesting that patients are not convinced by the need for long-term treatment. We can address this unsatisfactory state of affairs by continuing to spend more money on treatments or by targeting treatment more effectively. We will champion the latter approach. We believe that it should be possible to better stratify preventable risk and discuss this with patients using simple biomarkers.

Progress with new drug discovery for airway disease has also been frustratingly slow. Many of our most promising new treatments have not progressed because of failed early phase clinical trials. A good example is mepolizumab, a monoclonal antibody that blocks IL-5 and selectively inhibits eosinophilic airway inflammation. We suspected that mepolizumab failed because of poor targeting of treatment and showed in a single centre investigator lead trial that the effects of treatment are impressive if treatment is given to patients with evidence of eosinophilic airway inflammation. These findings have been replicated in phase 2b and 3 studies and mepolizumab is now likely to be an important new treatment for severe eosinophilic airway disease.

How do you hope being at Oxford will help your work?

Nuffield Department of Medicine

One consequence of assessing airway disease thoroughly in large numbers of patients is that it helps identify potentially informative patterns of disease. My team described a number of previously unrecognised patterns of disease that look interesting and potentially tractable. One of my goals in Oxford is to investigate the mechanisms of these phenotypes, using the very considerable expertise in basic science and immunology available here.

Tell us about the key members of your department of Respiratory Medicine

We are a small but expanding department. Mona Bafadhel has moved with me from Leicester as a clinical Senior Lecturer and NIHR post-doctoral fellow. She has pioneered the use of the peripheral blood eosinophil count as a marker of corticosteroid responsive COPD and will be evaluating the use of this biomarker in everyday clinical practice. Luzheng Xue, a basic scientist and immunologist in Oxford, has joined the department and will be developing our laboratory techniques. Luzheng played a leading role in the development of CRTH2 antagonists, a class of drugs that might have utility in severe eosinophilic airway disease. Ling-Pei Ho is a clinician and basic science researcher with an established reputation in Oxford and beyond in interstitial lung disease and sarcoidosis. Naj Rahman leads a very successful Respiratory Clinical Trials unit and is a leading researcher in pleural diseases. Stacey is my PA and guide to all things important in Oxford and Samantha Thulborn has recently joined to lead development of laboratory airway assessments.

How did you get to where you are today?

I went to a comprehensive school in South Wales and from there read medicine at University College London and Westminster Hospital. I trained in General and Respiratory Medicine in the East Midlands and was a Consultant Physician at Glenfield Hospital in Leicester from 1995 and Honorary Professor from 2005 until 2013. I was very fortunate to be a visiting fellow at McMaster University in Canada where I learnt about new techniques to assess airway inflammation using induced sputum just before my consultant appointment. I was able to apply these measures in large numbers of patients in Leicester.