- Email: [email protected]
A remarkable report card on progress in COPD
Perspectives
Book A remarkable report card on progress in COPD
www.thelancet.com Vol 370 September 1, 2007
television commercials for COPD drugs are a recent phenomenon. They may make some cringe, but make me beam; we’re finally getting some attention and public recognition for this important problem. I don’t know how long it will be before the acronym “COPD” will be as well recognised by the public as “AIDS” or “SARS”, but this recognition is all to the good.
“Instead of blaming COPD patients for their dirty little habit, we recognise the true addictive nature of cigarettes and put the blame where it belongs: on the tobacco companies.” Research into COPD has literally exploded. An only slightly scientific quantitative assessment of this is shown in the figure below. It plots the yearly citations identified as related to COPD on a PubMed search from 1987 to 2006. Note the steep increase: 613% over the 20-year period with a marked acceleration in the present
decade. Compare this with asthma, which presently has about twice the citations, but has increased by only 172% in the same period. Looked at one way, Chronic Obstructive Pulmonary Disease: A Practical Guide to Management is a report card on the progress all this research has brought us. The initial sections of the book on physiology draw strongly on ideas developed by the previous generation of physiologists, although supplemented with recent refinements. Physiology still has plenty to teach us about how to manage COPD. Lung mechanics, gas exchange, and muscle physiology yield important insights into the problems COPD patients face and suggest helpful strategies for symptom relief. But in section 3 we arrive at the heart of the recent research focus. Cell and molecular biology has revolutionised the way we think about this disease (as is the case for many other diseases); in particular, lung and associated systemic inflammation has been identified as a major mediator of damage not only in chronic
Chronic Obstructive Pulmonary Disease: A Practical Guide to Management Robert Stockley, Steve Rennard, Klaus Rabe, Bartolome Celli, eds. Blackwell Publishing, 2007. Pp 892. US$264·95, £165·00. ISBN 1-40512-289-7.
3000
2500 Number of COPD citations
The most remarkable thing about this book, I think, is that it was written at all. It is a weighty tome, tipping the scales at a little under 3 kg. The authorship can fairly be called stellar—the best minds of their generation in pulmonary medicine. And all 892 pages to examine our collected knowledge of a single disease entity: chronic obstructive pulmonary disease (COPD). How did COPD gain the respect that would support such an effort? I have been focusing almost exclusively on COPD for a little more than 20 years, but there aren’t too many like me. During the 1980s and early 1990s, I remember this COPD research as a lonely pursuit. The “big lung” organisations were loath to touch it. I distinctly recall attending a strategic planning meeting held by the American Lung Association and almost being hooted out of the room when I suggested that COPD should be included among the top three focus priorities (asthma, air pollution, and tuberculosis were the preferred choices). Pharmaceutical companies were also largely indifferent, allowing drugs designed for asthmatics to be adopted by COPD patients without much examination. Physicians, too, shared this lack of interest—feeling, I suspect, that smokers deserved their fate and that, besides, there wasn’t much that could be done for these elderly, yellow-fingered people. Part of the change has been one of perception. Instead of blaming COPD patients for their dirty little habit, we recognise the true addictive nature of cigarettes and put the blame where it belongs: on the tobacco companies. Our attitude towards COPD therapeutics has changed as well; we recognise that we can actually improve the lives of these patients with therapies at hand. In the USA,
2000
1500
1000
500
0 1985
1990
1995
2000
2005
2010
Year
Annual number of COPD citations in PubMed between 1987 and 2006
731
Perspectives
bronchitis, but in emphysema as well. The hope has been that, if we understand the genesis and consequences of inflammation, the road to better therapies will be cleared. There are 12 chapters that cover the breadth of cell and molecular biology topics of relevance to COPD and a substantial number of additional chapters on pathogenesis that have a strong emphasis on cell biology. The remarkable thing, of course, is that despite funnelling public funds for COPD research preferentially into cell and molecular biology pursuits for the past 20 years, these efforts have yielded no therapies we can offer to our patients. What do we have to offer? Our current mainstays
are bronchodilators, mainly using refined versions of drugs that have been around for a long, long time. For hypoxic and hypercapnic respiratory failure, we use supplemental oxygen and mechanical ventilatory support, respectively. Pulmonary rehabilitation is proving to be a highly effective (although currently poorly available) therapy; recent developments have served to cement its physiological base. Smoking cessation programmes now have the benefit of rational adjunctive pharmacological aids. Surgery is a viable option for only a minority of patients. What of the future? Both by public funding of research and through the efforts of the pharmaceutical industry, a number of avenues are
being explored: chronic antibiotics, antioxidants, anti-inflammatories, mucolytics, alveolar growth factors, and protease inhibitors. The payoff potential is big; COPD is a major killer, a major source of misery, and a major consumer of health-care dollars. All of this for a disease that would be rare, were it not for cigarette smoking. It would be nice to think that, after we win our battle against the tobacco interests, this book will be regarded by future generations as an interesting artifact. But, sadly, I wouldn’t bet on this happening any time soon; I’m afraid this excellent volume will find use for a number of editions.
Richard Casaburi [email protected]
In brief Book The story of fenoterol
Adverse Reactions: The Fenoterol Story Neil Pearce. Auckland University Press, 2007. Pp 239. NZ$40·00. ISBN 1-86940-374-4.
732
Vintage Papers from The Lancet, which was published a couple of years ago, is a wonderful anthology of some of the most influential articles that The Lancet published between 1823 and 2005. Selecting these articles was a challenging task for the editor, Ruth Richardson. However, one paper that Richardson did not include, but perhaps might have done, describes how fenoterol, a β agonist, was responsible for the increased mortality seen in young people with asthma in New Zealand during the 1980s (Lancet 1989; 333: 917–22). One of the authors of that study, Neil Pearce, has written a compelling book that describes the real-life events behind the identification of fenoterol as the causative agent behind the epidemic. Like all good thrillers, it contains a healthy dose of intrigue, conspiracy, deception, and perseverance in the face of adversity. For 10 years, starting in 1977, fenoterol had at least a 30% market share of β agonists in New
Zealand, but was not marketed to the same degree in other countries and was not licensed at all in the USA. At around the same time, New Zealand’s asthma mortality started to rise, reaching a death rate of 3·5 per 100 000 at the peak of the epidemic from 1977 to 1980, around three times the rate seen in other developed countries. But it took more than 10 years for epidemiologists to prove that the two were linked and it is this process that Pearce describes so expertly in his book. Pearce tells how New Zealand’s official body, the Asthma Task Force, dragged its heels over the epidemic. He also describes the tactics that Boehringer Ingelheim, the makers of the drug, used to convince doctors that Pearce and his team’s study was methodologically unsound and that the drug was safe. Even The Lancet comes out badly—according to Pearce, the editors at the time almost caved in to heavy industry pressure, in the form of commissioned peer-
review comments, and threatened to withdraw the paper, after acceptance, but before publication. Pearce wrote the first draft of the book soon after the controversy ended, in 1993, but he decided to wait 15 years before re-editing it because the original version was “too serious, too technical—and too angry”. Perhaps that was the right decision. But it seems a shame that such a wonderfully informative and well written book was in limbo for so long. Adverse Reactions: The Fenoterol Story should be considered essential reading for anyone interested in epidemiology. It also shows what can be achieved when a researcher with a real talent for writing takes it upon himself to describe his controversial work. There must be many hundreds of other stories out there, as yet unwritten, that deserve to be committed to paper so that others can learn from such collective mistakes.
James Butcher [email protected]
www.thelancet.com Vol 370 September 1, 2007
Book A remarkable report card on progress in COPD
www.thelancet.com Vol 370 September 1, 2007
television commercials for COPD drugs are a recent phenomenon. They may make some cringe, but make me beam; we’re finally getting some attention and public recognition for this important problem. I don’t know how long it will be before the acronym “COPD” will be as well recognised by the public as “AIDS” or “SARS”, but this recognition is all to the good.
“Instead of blaming COPD patients for their dirty little habit, we recognise the true addictive nature of cigarettes and put the blame where it belongs: on the tobacco companies.” Research into COPD has literally exploded. An only slightly scientific quantitative assessment of this is shown in the figure below. It plots the yearly citations identified as related to COPD on a PubMed search from 1987 to 2006. Note the steep increase: 613% over the 20-year period with a marked acceleration in the present
decade. Compare this with asthma, which presently has about twice the citations, but has increased by only 172% in the same period. Looked at one way, Chronic Obstructive Pulmonary Disease: A Practical Guide to Management is a report card on the progress all this research has brought us. The initial sections of the book on physiology draw strongly on ideas developed by the previous generation of physiologists, although supplemented with recent refinements. Physiology still has plenty to teach us about how to manage COPD. Lung mechanics, gas exchange, and muscle physiology yield important insights into the problems COPD patients face and suggest helpful strategies for symptom relief. But in section 3 we arrive at the heart of the recent research focus. Cell and molecular biology has revolutionised the way we think about this disease (as is the case for many other diseases); in particular, lung and associated systemic inflammation has been identified as a major mediator of damage not only in chronic
Chronic Obstructive Pulmonary Disease: A Practical Guide to Management Robert Stockley, Steve Rennard, Klaus Rabe, Bartolome Celli, eds. Blackwell Publishing, 2007. Pp 892. US$264·95, £165·00. ISBN 1-40512-289-7.
3000
2500 Number of COPD citations
The most remarkable thing about this book, I think, is that it was written at all. It is a weighty tome, tipping the scales at a little under 3 kg. The authorship can fairly be called stellar—the best minds of their generation in pulmonary medicine. And all 892 pages to examine our collected knowledge of a single disease entity: chronic obstructive pulmonary disease (COPD). How did COPD gain the respect that would support such an effort? I have been focusing almost exclusively on COPD for a little more than 20 years, but there aren’t too many like me. During the 1980s and early 1990s, I remember this COPD research as a lonely pursuit. The “big lung” organisations were loath to touch it. I distinctly recall attending a strategic planning meeting held by the American Lung Association and almost being hooted out of the room when I suggested that COPD should be included among the top three focus priorities (asthma, air pollution, and tuberculosis were the preferred choices). Pharmaceutical companies were also largely indifferent, allowing drugs designed for asthmatics to be adopted by COPD patients without much examination. Physicians, too, shared this lack of interest—feeling, I suspect, that smokers deserved their fate and that, besides, there wasn’t much that could be done for these elderly, yellow-fingered people. Part of the change has been one of perception. Instead of blaming COPD patients for their dirty little habit, we recognise the true addictive nature of cigarettes and put the blame where it belongs: on the tobacco companies. Our attitude towards COPD therapeutics has changed as well; we recognise that we can actually improve the lives of these patients with therapies at hand. In the USA,
2000
1500
1000
500
0 1985
1990
1995
2000
2005
2010
Year
Annual number of COPD citations in PubMed between 1987 and 2006
731
Perspectives
bronchitis, but in emphysema as well. The hope has been that, if we understand the genesis and consequences of inflammation, the road to better therapies will be cleared. There are 12 chapters that cover the breadth of cell and molecular biology topics of relevance to COPD and a substantial number of additional chapters on pathogenesis that have a strong emphasis on cell biology. The remarkable thing, of course, is that despite funnelling public funds for COPD research preferentially into cell and molecular biology pursuits for the past 20 years, these efforts have yielded no therapies we can offer to our patients. What do we have to offer? Our current mainstays
are bronchodilators, mainly using refined versions of drugs that have been around for a long, long time. For hypoxic and hypercapnic respiratory failure, we use supplemental oxygen and mechanical ventilatory support, respectively. Pulmonary rehabilitation is proving to be a highly effective (although currently poorly available) therapy; recent developments have served to cement its physiological base. Smoking cessation programmes now have the benefit of rational adjunctive pharmacological aids. Surgery is a viable option for only a minority of patients. What of the future? Both by public funding of research and through the efforts of the pharmaceutical industry, a number of avenues are
being explored: chronic antibiotics, antioxidants, anti-inflammatories, mucolytics, alveolar growth factors, and protease inhibitors. The payoff potential is big; COPD is a major killer, a major source of misery, and a major consumer of health-care dollars. All of this for a disease that would be rare, were it not for cigarette smoking. It would be nice to think that, after we win our battle against the tobacco interests, this book will be regarded by future generations as an interesting artifact. But, sadly, I wouldn’t bet on this happening any time soon; I’m afraid this excellent volume will find use for a number of editions.
Richard Casaburi [email protected]
In brief Book The story of fenoterol
Adverse Reactions: The Fenoterol Story Neil Pearce. Auckland University Press, 2007. Pp 239. NZ$40·00. ISBN 1-86940-374-4.
732
Vintage Papers from The Lancet, which was published a couple of years ago, is a wonderful anthology of some of the most influential articles that The Lancet published between 1823 and 2005. Selecting these articles was a challenging task for the editor, Ruth Richardson. However, one paper that Richardson did not include, but perhaps might have done, describes how fenoterol, a β agonist, was responsible for the increased mortality seen in young people with asthma in New Zealand during the 1980s (Lancet 1989; 333: 917–22). One of the authors of that study, Neil Pearce, has written a compelling book that describes the real-life events behind the identification of fenoterol as the causative agent behind the epidemic. Like all good thrillers, it contains a healthy dose of intrigue, conspiracy, deception, and perseverance in the face of adversity. For 10 years, starting in 1977, fenoterol had at least a 30% market share of β agonists in New
Zealand, but was not marketed to the same degree in other countries and was not licensed at all in the USA. At around the same time, New Zealand’s asthma mortality started to rise, reaching a death rate of 3·5 per 100 000 at the peak of the epidemic from 1977 to 1980, around three times the rate seen in other developed countries. But it took more than 10 years for epidemiologists to prove that the two were linked and it is this process that Pearce describes so expertly in his book. Pearce tells how New Zealand’s official body, the Asthma Task Force, dragged its heels over the epidemic. He also describes the tactics that Boehringer Ingelheim, the makers of the drug, used to convince doctors that Pearce and his team’s study was methodologically unsound and that the drug was safe. Even The Lancet comes out badly—according to Pearce, the editors at the time almost caved in to heavy industry pressure, in the form of commissioned peer-
review comments, and threatened to withdraw the paper, after acceptance, but before publication. Pearce wrote the first draft of the book soon after the controversy ended, in 1993, but he decided to wait 15 years before re-editing it because the original version was “too serious, too technical—and too angry”. Perhaps that was the right decision. But it seems a shame that such a wonderfully informative and well written book was in limbo for so long. Adverse Reactions: The Fenoterol Story should be considered essential reading for anyone interested in epidemiology. It also shows what can be achieved when a researcher with a real talent for writing takes it upon himself to describe his controversial work. There must be many hundreds of other stories out there, as yet unwritten, that deserve to be committed to paper so that others can learn from such collective mistakes.
James Butcher [email protected]
www.thelancet.com Vol 370 September 1, 2007