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.
Essential Science IndicatorsSM from
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 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: 1175-7, September 2000). Would
you tell us about this paper and why you think it has received
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
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:
1165-85, May 2009). Would you tell our readers about this
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
"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
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
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
Essential Science Indicators from
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.