- Email: [email protected]
The story of fenoterol
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
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