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AUTHOR COMMENTARIES - From Special Topics

Chronic Obstructive Pulmonary Disease (COPD) - Published: January 2010
Interview Date: February 2010
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Peter J. Barnes Peter J. Barnes
From the Special Topic of Chronic Obstructive Pulmonary Disease (COPD)

According to our Special Topics analysis of COPD research over the past decade, the work of Professor Peter J. Barnes ranks at #1 by both total citations and by total papers, based on 136 papers cited 6,156 times. Six of these papers also appear on the lists of the top 20 papers published in the past decade and the past two years.


In Essential Science IndicatorsSM from Thomson Reuters, Professor Barnes has 406 papers, the majority of which are classified under Clinical Medicine and Pharmacology & Toxicology, cited a total of 17,893 times between January 1, 1999 and October 31, 2009. He ranks among the top 100 scientists in the field of Clinical Medicine in this database. He has also been named a Highly Cited Researcher in Pharmacology and Clinical Medicine. Professor Barnes is the Head of Respiratory Medicine at the National Heart & Lung Institute of Imperial College London.

In this interview, he talks with ScienceWatch.com about his highly cited work as it relates to COPD.

 

  Would you tell us a bit about your educational background and research experiences?

I studied medicine at Cambridge and Oxford Universities in the UK and then trained as a respiratory specialist at Hammersmith Hospital in London. I first started to do research on the pharmacology of asthma, initially doing clinical studies, but then becoming involved in molecular and cellular research. I spent time at the University of California, San Francisco, doing research on receptors, and then became involved in translational research on my return to the UK. I took up my current post as Head of Respiratory Medicine at the National Heart & Lung Institute, now part of Imperial College London, in 1987, and since then have built up a large research group consisting of basic scientists and clinicians. Although our research was initially focused on asthma, we have gradually now changed towards COPD as the unmet needs are much greater in this disease.

  What first drew your interest to the field of COPD?

"COPD is a major global epidemic which represents one of the greatest unmet therapeutic needs in medicine and it is likely that there will be major academic and industrial investment in this disease in the future."

I have always been aware that COPD is a major clinical problem, but I only started to do research into COPD around 10 years ago. At that time very little was known about the underlying cellular and molecular mechanisms, so we started to use some of the research approaches that we had developed in asthma to look at the nature of the inflammatory response in COPD. A particular area of interest is why COPD inflammation is so resistant to the anti-inflammatory actions of corticosteroids, and we have now identified a molecular mechanism which is potentially reversible. The hope is that this research will lead to new treatments. In contrast to asthma, therapy for COPD is much less effective and there are no drugs that suppress the chronic inflammation and thus reduce progression and mortality of COPD.

  Your most-cited clinical paper in our analysis is the 2000 American Journal of Respiratory and Critical Care Medicine, "Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers," (Montuschi P, et al., 162[3]: 1175-7, September 2000). Would you tell us about this paper and why you think it has received citation attention?

We have been trying to develop non-invasive ways to measure inflammation in the lung and did a lot of work on exhaled nitric oxide in asthma, which is now being used clinically as a way to measure inflammation in asthmatic patients. However, this measurement does not work in COPD, so we developed a different approach, collecting exhaled breath condensate and measuring the concentration of inflammatory mediators.

We have been interested in oxidative stress for a long time, as it plays a key role in amplifying inflammation in COPD lung and in blocking the anti-inflammatory response to corticosteroids. 8-isoprostane is a relatively stable product of the effect of oxidative stress on arachidonic acid, so it has turned out to be a good biomarker of oxidative stress. We found that the concentrations of exhaled 8-isoprostane are elevated in patients with COPD and are related to disease severity, so this has proved to be a useful and simple way to quantify oxidative stress in the lungs.

  Many of your papers examine aspects of COPD and asthma. In general, how do these conditions compare?

Both asthma and COPD are common chronic diseases and both are increasing throughout the world. While both involve chronic inflammation of the respiratory tract there are obviously marked clinical differences. Asthma is characterized episodic airway obstruction and symptoms and usually starts early in life, whereas COPD occurs in much older patients and tends to have slowly progressive airway obstruction and symptoms. The inflammation differs markedly between asthma and COPD, with different cells, mediators, and consequences and, as I discussed earlier, there is a difference in response to corticosteroids.

However, more recently it has become clear that severe asthma is much more similar to COPD, with similarities in the inflammation and sharing a poor response to corticosteroids. Interestingly, studies of molecular genetics are now showing that severe asthma and COPD share several gene polymorphisms.

  Last year, you came out with a paper entitled "Systemic manifestations and comorbidities of COPD" in the European Respiratory Journal (Barnes PJ and Celli BR, 33[5]: 1165-85, May 2009). Would you tell our readers about this paper?

Although COPD involves inflammation of the respiratory tract and progressive airflow limitation due to small airway obstruction and to emphysema, it is now recognized that there are several systemic features that are associated with the disease, including skeletal muscle wasting, cachexia, depression, and osteoporosis. In addition, several diseases are commonly found in COPD patients as co-morbidities, including ischemic heart disease, cardiac failure, metabolic syndrome, and diabetes, all of which occur more commonly than can be accounted for by smoking. It is through that the inflammatory mediators in the peripheral lung of COPD patients may "spill over" into the circulation. These comorbid diseases worsen the prognosis of COPD and complicate its management.

  You are a part of the WHO/NIH GOLD Scientific Committee. Would you talk a little bit about your work with this group?

"In contrast to asthma, therapy for COPD is much less effective and there are no drugs that suppress the chronic inflammation and thus reduce progression and mortality of COPD."

The GOLD Initiative are the most commonly used guidelines for COPD management in the world. When they were started there was a need to develop easily accessible and clear guidelines for the management of COPD, and these guidelines are regularly updated. They have been adapted to fit in with available therapies in many different countries, and I think they have been of great value. The Scientific Committee reviews the peer-reviewed papers relating to COPD management twice a year and there is a yearly update of the guidelines. This is important as many new and important clinical trials on COPD are now being published.

  How far would you say COPD research has come in the past decade? Where do you see it going in the next 10 years?

I think there have been enormous advances in understanding the underlying disease mechanisms, although we still do not know why only a proportion of long-term cigarette smokers develop COPD. It is likely that this is genetically determined and it is now clear that many different genes might collectively predispose to COPD and to the phenotype of COPD that develops. It is now recognized that COPD also occurs in non-smokers, especially in developing countries, but we are only just beginning to study the effects of other causes of disease, such as exposure to biomass fuels. In terms of management, the major advance has been the introduction of long-acting bronchodilators, which improve symptoms.

However, there is still a need to find new drugs that reduce inflammation without significant side effects, and this is a very active area of research in academia and the pharmaceutical industry. Over the next 10 years it is likely that several novel targets will be identified for the development of effective anti-inflammatory therapies, including drugs that reverse corticosteroid resistance. It is likely that different clinical phenotypes of COPD will be more easily identified as they may require different therapeutic strategies.

Finally it is likely that new biomarkers of disease activity will be developed so that it is easier to diagnose and monitor COPD, as well as to select the most effective therapies. COPD is a major global epidemic which represents one of the greatest unmet therapeutic needs in medicine and it is likely that there will be major academic and industrial investment in this disease in the future.

Professor Peter J, Barnes FRS, FMedSci
Airway Disease Section
National Heart & Lung Institute
Imperial College London
London, United Kingdom

Peter J. Barnes's current most-cited paper in Essential Science Indicators, with 665 cites:

Leckie MJ, et al., "Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response," Lancet 356 (9248): 2144-8, 23 December 2000. Source: Essential Science Indicators from Clarivate Analytics.

Additional information:

KEYWORDS: ASTHMA, COPD, CELLULAR MECHANISMS, MOLECULAR MECHANISMS, INFLAMMATORY RESPONSE, CORTICOSTEROIDS, EXHALED NITRIC OXIDE, EXHALED BREATH CONDENSATE, OXIDATIVE STRESS, BIOMARKERS, 8-ISOPROSTANE, GENE POLYMORPHISMS, COMORBID DISEASES, GOLD INITIATIVE.

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Special Topics : Chronic Obstructive Pulmonary Disease (COPD) : Peter J. Barnes Interview - Special Topic of Chronic Obstructive Pulmonary Disease (COPD)