Understanding asthma and chronic obstructive pulmonary disease by Professor Peter Barnes MAE#
Professor Peter Barnes MAE tells us about his career highlights and the effect of COVID-19 on his research.
Professor Peter Barnes
About Peter Barnes#
Peter Barnes is Professor of Medicine at the National Heart and Lung Institute
and Honorary Consultant Physician at Royal Brompton Hospital, London. He has worked as a respiratory scientist for over 40 years and was Head of Respiratory Medicine at Imperial College from 1987 to 2017. He has been the most highly cited respiratory researcher in the world over the last 30 years (h-index = 185) and recently ranked as 4th most highly cited researcher in the world across all areas. He is a Fellow of the Royal Society and the Academy of Medical Sciences. He was elected a Member of Academia Europaea in 2012.
The interview#
Professor Barnes, how did you first become interested in studying respiratory diseases?
“I was keen to practice general medicine but it was impossible to obtain a consultant post without doing some research, which I was initially reluctant to do. I had originally been interested in neurology and neuroscience, but it was difficult to obtain a training post in this field, so I went into respiratory medicine as I was offered a research post at Hammersmith Hospital in London looking at the pharmacology of asthma. I had enjoyed respiratory medicine as a junior doctor as it was closer to general medicine than most specialties. My reservations about doing research were rapidly dispersed and I became fascinated in my research project on the neural and hormonal control of the airways in asthma, particularly as I had suffered from mild asthma as a child. I worked in the renowned Department of Clinical Pharmacology at the Royal Postgraduate Medical School, led by Professor Sir Colin Dollery and I was very fortunate to have an excellent mentor in Professor Neil Pride who was a world expert in respiratory physiology and an inspirational researcher. I have found research in respiratory medicine to be fascinating, as there are so many unanswered questions in common complex diseases, such as asthma and COPD, which have been my main areas of research.”
in London looking at the pharmacology of asthma. I had enjoyed respiratory medicine as a junior doctor as it was closer to general medicine than most specialties. My reservations about doing research were rapidly dispersed and I became fascinated in my research project on the neural and hormonal control of the airways in asthma, particularly as I had suffered from mild asthma as a child. I worked in the renowned Department of Clinical Pharmacology at the Royal Postgraduate Medical School, led by Professor Sir Colin Dollery and I was very fortunate to have an excellent mentor in Professor Neil Pride who was a world expert in respiratory physiology and an inspirational researcher. I have found research in respiratory medicine to be fascinating, as there are so many unanswered questions in common complex diseases, such as asthma and COPD, which have been my main areas of research.”
As an international leader in diseases like asthma and COPD, can you give us the highlights of your research findings?
“After my initial research on the role of cholinergic nerves, adrenaline and neuropeptides in regulating airway function in asthma, I focused on the mechanisms of inflammation in asthma and the role of cytokines as mediators of chronic inflammation. I explored the cellular and molecular mechanisms of steroids in asthma and showed that by binding to glucocorticoid receptors, they were able to suppress inflammation in asthma by altering the structure of DNA to turn off the production of molecules that cause inflammation.
Elucidating this mechanism led to an understanding of why some patients with severe asthma and patients with COPD fail to respond effectively to steroids. This led to the discovery of new drugs are able to reverse steroid-resistance.
One area of research that has now become useful in clinical practice is the finding that nitric oxide (NO) gas levels are elevated in the breath of asthmatic patients as a result of eosinophilic inflammation and that this is reduced by inhaled steroids. Measuring NO in breath has not become a routine test for measuring inflammation in asthmatic airways and monitoring the effects of treatments.
More recently I have focused understanding inflammatory mechanisms in COPD as there are no effective anti-inflammatory treatments to reduce progression of this common disease. We have found that cellular senescence in COPD as a result of accelerated lung ageing causes the release of inflammatory mediators and elucidating the molecular pathways of cellular senescence has identified several novel targets for therapy that we are now exploring, Since these same pathways are seen in common comorbidities of COPD (such as cardiovascular disease) and may spread form the lung by extracellular vesicles, it is possible that a single therapeutic intervention may not only stop COPD progression, but also treat associated comorbid diseases. This is a very exciting prospect that may revolutionize the management of mutimorbidity of the elderly in the future.”
Elucidating this mechanism led to an understanding of why some patients with severe asthma and patients with COPD fail to respond effectively to steroids. This led to the discovery of new drugs are able to reverse steroid-resistance.
One area of research that has now become useful in clinical practice is the finding that nitric oxide (NO) gas levels are elevated in the breath of asthmatic patients as a result of eosinophilic inflammation and that this is reduced by inhaled steroids. Measuring NO in breath has not become a routine test for measuring inflammation in asthmatic airways and monitoring the effects of treatments.
More recently I have focused understanding inflammatory mechanisms in COPD as there are no effective anti-inflammatory treatments to reduce progression of this common disease. We have found that cellular senescence in COPD as a result of accelerated lung ageing causes the release of inflammatory mediators and elucidating the molecular pathways of cellular senescence has identified several novel targets for therapy that we are now exploring, Since these same pathways are seen in common comorbidities of COPD (such as cardiovascular disease) and may spread form the lung by extracellular vesicles, it is possible that a single therapeutic intervention may not only stop COPD progression, but also treat associated comorbid diseases. This is a very exciting prospect that may revolutionize the management of mutimorbidity of the elderly in the future.”
Can you tell us how your research has translated into better treatments for patients suffering from these debilitating diseases?
“Our early work highlighted the role of the nervous system in these diseases, and explained why bronchodilators make breathing easier in patients with COPD by relaxing the muscles in the lungs. Our work on airway inflammation in asthma led to much earlier use of inhaled steroids in the treatment of asthma and these drugs have now become the mainstay of asthma management across all severities of asthma. Our research on the interactions between steroids and long-acting beta-agonists has led to the development of combination inhalers that are now very commonly used to treat asthma and COPD. The development of exhaled NO to assess asthma has led to better management of this disease and has proved to be very useful in monitoring whether patients are taking adequate doses of Inhaled steroids – poor compliance with taking regular inhaled steroids has been a major barrier to improving asthma symptoms in real world settings. As indicated above, we are now looking for new treatments for COPD that may more effectively reduce symptoms and also prevent disease progression. I am optimistic that this research will lead to new therapies, either by repurposing existing treatments. or by finding drugs against novel targets linked to senescence. “
How is the COVID-19 pandemic impacting your research? What challenges do you have to overcome and which opportunities can you see?
“The COVID-19 pandemic is having a profound effect on research at the moment. As clinical studies have been disrupted and we are not able to do any laboratory based research. We have regular virtual research meetings to discuss results, how to write up the manuscripts and to plan future work. Isolation at home provides more time to think, so time is not entirely wasted although it is very frustrating as there are so many key experiments we want to continue! More basic research into the interaction of the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome-related coronavirus) in epithelial cells may give us new insights into the mechanisms of exacerbations of asthma and COPD and provide new and unexpected treatments for the future.”
The interview was published 27th August 2020 and conducted by the Academia Europaea Cardiff Knowledge Hub.
For further information please contact AECardiffHub@cardiff.ac.uk.
.For further information please contact AECardiffHub@cardiff.ac.uk
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