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Rapid Responses: Rapid Responses published:
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“Single Patient Based Medicine” versus EBM.
- Sergio Stagnaro (16 May 2003)
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Tobacco Smoke Pollution
- Georgina Lovell (17 May 2003)
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what controversy?
- JOnathan P. Krueger (22 May 2003)
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George Davey Smith declaration of no competing interests
- Norbert Hirschhorn (27 May 2003)
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Response to myself, Re: George Davey Smith
- Norbert Hirschhorn (29 May 2003)
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A Retraction
- Norbert Hirschhorn (30 May 2003)
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Earlier longer version of this editorial
- Rajendra Kale (6 June 2003)
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases Via Erasmo Piaggio 23/8, 16037 Riva Trigoso (Genoa) Italy
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Sirs, Notoriously the impact of environmental tobacco smoke on health remains under dispute. In my opinion, this issue will last controversial for long time, untill we shall decide to consider not only EBM, but also, as I suggest unheeded, SPBM, i.e., “Single Patient Based Medicine”. In fact, although unfortunately overlooked all around the world, Biophysical Semeiotics Constitutions do really exists, as I referred in my earlier Rapid Response http://bmj.com/cgi/eletters/324/7348/0/h#22477, as well as on my HONCode site 233736, http://digilander.libero.it/semeioticabiofisica; Biophysical-Semeiotic Constitutions). Certainly, in individuals whithout Oncological Terrain (Constitution) cancer will surely not occur, even in lasting presence of passive tobacco smoke. In a few word, we can now-a-day easily recognize at the bed-side subjects with particular constitution(s), who can be involved by defined diseases under environmental tobacco smoke. Therefore, statements such as “A substantial increased risk of chronic obstructive pulmonary disease could result from exposure to environmental tobacco smoke” are valid if we can precisely examine the “single” subject presenting with well-defined inherited predispositions, evaluated properly by means of Biophysical Semeiotics. For example, there is convincing evidene that cigarette smoking is a risk factor for type 2 diabetes. Cigarette smoking has been consistently associated with a relatively small byt significantly increased risk of type 2 diabetes in both men (2) and women (3) in large prospective cohort studies. However, only individuals with both “diabetic “ and “dyslipidemic” biophysical-semeiotic constitutions can suffer from diabetes mellitus type 2, as allows me to state a 46-year-long clinical experience (4, 5). 1) Smith GD. Effect of passive smoking on health BMJ 2003;326:1048- 1049 (17 May) 2) Rimmm EB., Chan J., Stampfer MJ., et al. Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men. BMJ 1995; 310 555- 559. 3) Rimmm EB., Manson JE., Stampfer MJ., et al. A prospective study of cigarette smoking and the risk of diabetes in women. Am.J Public Health 1993; 83:211-214. 4) Stagnaro S., Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. letter [PubMed –indexed for MEDLINE]. 5) Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986. Competing interests: None declared |
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Georgina Lovell, author, You Are The Target (Big Tobacco: Lies, Scams - Now The Truth) Vancouver, Canada
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"Environmental Tobacco Smoke" is, first off, a term coined by the tobacco industry to minimize the severity of the by-product of smokers. Score one for the tobacco industry. My mother lived with a smoker for a few months short of 50 years - a smoker, my father died of lung cancer months before their golden wedding anniversary. Score two for the tobacco industry. My mother and we live daily with her emphysema - caused by exposure to tobacco smoke pollution (well, that's if her team of doctors are to be believed). Other risk factors and the remote possibility she has alpha 1- antitrypsin type of emphysema were eliminated. She has no history of exposure to vinyl chloride, no family history of COPD and no other predisposing factors aside from living with a smoking spouse - something Enstrom and Kabat claim to be inconsequential - to have resulted in this devastating condition causing her to suffocate, slowly, to death. I will tell her of the tobacco-funded conclusions that living with a smoking spouse (who did not know what the tobacco companies kept secret about the harm caused by exposure to tobacco smoke pollution) did not cause her to become semi-invalid, her very life dependent on plastic tubing attached to a cylinder of oxygen. I will also advise my mother she is "statistically insignificant" the next time I find it necessary to call an ambulance to administer requisite care when she has collapsed, because her tobacco-smoke damaged lungs no longer breathe for her. Her care and medications cost the government of British Columbia over $1,000 each month. I can only hope administrators will be gratified to hear exposure to tobacco smoke pollution is not responsible for this inconvenient expense. Despite your cover, your editorial and your article, nobody of discretion can ever be expected to believe tobacco smoke pollution is harmless. Score three for the tobacco industry. Competing interests: None declared |
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JOnathan P. Krueger, private capacity 94566
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For 50 years, the tobacco industry conspired to "create the appearance of scientific controversy where there was none" on smoking and health. "Scientists disagree"; "studies are inconclusive"; "not proven"; "merely statistical" -- the industry pushed this PR for decades, long after any real controversy had ended in the scientific community. The goal for the industry was "keep doubt alive". Now the industry is doing the same thing with secondhand smoke. And you are helping. You are saying there is controversy. There is not. Let's be blunt: what controversy? I know of exactly two scientists outside the tobacco industry and tobacco industry funding who think secondhand smoke doesn't cause disease. That's not a "controversy". Any more than two scientists who believe HIV isn't the cause of AIDS makes it somehow "controversial" that HIV causes AIDS. The overwhelming consensus of the scientific community is there is sufficient scientific evidence to conclude that this product causes the same diseases in its customers and those closest to them. That is the conclusion of every major review of the scientific literature, and of virtually every major scientific, health, and medical organization. WHO, IARC, EPA, NCI, all agree: the product causes cancer, heart disease, and lung disease, in its customers and in bystanders. The scientific evidence establishes this. There is no controversy in the scientific community: secondhand smoke kills. It's time for you to publish that fact here: there is no controversy here. There is a poor study which fails to detect what other studies have. Or else you must use the same standards and say that it's "controversial" whether HIV causes AIDS. Competing interests: None declared |
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Norbert Hirschhorn, independent consultant 1044 Chapel Street #502, New Haven CT 06510 USA
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Professor George Davey Smith wrote the cautious editorial accompanying the now-famous article by Enstrom and Kabat on passive smoking (1) (2). While one of the latter authors admitted some link to the tobacco industry, Professor Davey Smith declared none. However, George Davey Smith was a grantee from the Council for Tobacco Research (on cervical cancer and human papillomavirus) in 1993 (3). The connection may be remote; yet I find puzzling that an epidemiologist of his standing would declare, in the face of current and overwhelming evidence, that "controversy still exists." (1) Enstrom J, Kabat G. Environmental tobacco smoke and tobacco related mortality in a prospective study of Californians, 1960-98. BMJ 2003;326:1057-61. (2) Davey Smith G. Effect of passive smoking on health [.] More information is available, but the controversy still exists. BMJ 2003;326:1048-1049. (3)"CTR Grant Application Cards (Alphabetical)." 3 June 1993. www.tobaccodocuments.org. Bates No.: 60135419-60136530, at -5736. Accessed 27 May 2003. Competing interests: I am a paid consultant to the World Health Organization on tobacco industry documents |
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Norbert Hirschhorn, independent consultant 1044 Chapel Street #502, New Haven CT 06510 USA
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I have just come across the well-considered article by Professor George Davey Smith, whose most cogent statement (followed by firm evidence)is, "The review of the evidence linking passive smoking to lung cancer risk produced by the tobacco industry sponsored working group is of limited use as a scientific document." (1) Professor Davey Smith's review of the Enstrom-Kabat article is now all the more puzzling. (1) Davey Smith G, Phillips AN. Passive smoking and health: should we believe Philip Morris's "experts"? BMJ 1996;313:929-933. Competing interests: I am a paid consultant to the World Health Organization on tobacco industry documents |
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Norbert Hirschhorn, independent consultant 1044 Chapel Street #502, New Haven CT 06510 USA
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Professor George Davey Smith has written to me privately with emphatic assurance that he has never received money from the tobacco industry, an assurance I accept. I was therefore wrong to imply that his editorial was in any way influenced by anything but his own objective analysis (1). I should have contacted Professor Davey Smith personally first for confirmation, and for this discourtesy I apologize. (1) Hirschhorn N. George Davey Smith declaration of no competing interests. BMJ Rapid Response, 27 May 2003. Competing interests: I am a paid consultant to the World Health Organization on tobacco industry documents. |
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Rajendra Kale, Editorials editor BMJ
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We had asked the author to shorten an earlier longer version of this editorial, which he had submitted to us. We are posting the earlier version (unedited) as a rapid response. Rajendra Kale
--- (Competing interests: None declared by the author) Passive smoking: will we ever know the truth?
Department of Social Medicine
In 1928 Schönherr presented a lung cancer case-series from Chemnitz and discussed the contribution of smoking to the disease[1]. He noted that none of the small number of cases among women occurred in smokers, but concluded that these cancers could have been caused by the inhalation of their husband's smoke. Thus passive smoking was identified as a potential cause of lung cancer at the same time as active smoking was first formally studied as a putative cause. While the issue of personal smoking and lung cancer is now resolved, the impact of environmental tobacco smoke (ETS) remains highly controversial[2] [3]. Partly this is because of technical issues related to measurement error, confounding and the identification of small risks in epidemiological studies, as Enstrom and Kabat discuss in their paper in this week's BMJ. However it also reflects the large investment by the tobacco industry in keeping this issue from closure, through the funding of research, review articles, commentaries and methodological critiques from "scientists" who, unsurprisingly, generally seem to reach the conclusion that the evidence regarding any causal effect of ETS is limited, and that the profits of their paymasters (and thus the source of their rewards) should not be interfered with. The study by Enstrom and Kabat has considerable relevance for the debate on the health effects of passive smoking. Given the small risks associated with ETS exposure, meta-analysis has played an important role in demonstrating an apparent adverse effect on lung cancer, coronary heart disease (CHD) and chronic obstructive pulmonary disease (COPD). The consistent elevated risks associated with ETS in these meta-analyses are, however, potentially influenced by publication bias, with small negative studies being less likely to get published (and thus into the public domain) than positive studies[4]. A controversial issue in this regard relates to a tobacco industry funded analysis of the American Cancer Society's first Cancer Prevention Study (ACS I)[5]. This has not generally been included in published meta-analyses, although it would contribute by far the largest number of events - and thus statistical power - to such an analysis. The main argument advanced by the meta-analysts who have not included the study in their reviews is that the published ACS I analysis was not presented in a format that allowed for the combination of equivalent effect estimates across studies. Enstrom and Kabat have analysed the California sub-sample of the ACS I, with considerable additional follow-up, and have presented the data in a format that allows inclusion in future meta-analyses. They also present data that give a handle on the degree to which misclassification of ETS exposure may dilute the association with mortality. They interpret their findings as null, although, inevitably, statistical uncertainty remains. Indeed they may over-emphasise the negative nature of their findings. With respect to chronic obstructive pulmonary disease (COPD) - plausibly related to ETS exposure - the estimates based on the most accurately classified exposure groups give relative risks of 1.80 in men and 1.57 in women. These are said to be non-significant, but combining them - and there is no good evidence that ETS exposure has a different effect for men and women - gives a relative risk of 1.65 (95% confidence intervals 1.0-2.73). A substantial increased risk of COPD could result from ETS exposure. Despite this, it is certain that this paper will be hailed as demonstrating that the detrimental effect of passive smoking has been overstated, and controversy will continue. What are the issues? Confounding is clearly important, with ETS exposed individuals in many situations being likely to display adverse profiles in relation to socio- economic position and health-related behaviors. The ACS I was established in 1959, when smoking was much less related to such factors than it is currently within the US, as is evident from Enstrom and Kabat paper. It could be argued that this is why smaller - if any - ETS-associated risks are seen in the first compared to the second American Cancer Society study (ACS II)[6]. In ACS II, with participants recruited in 1982, women exposed to ETS had less education than those unexposed, as opposed to the lack of any such gradient in ACS I. Similarly amongst men in the 1982 cohort there was little education gradient, whilst amongst men in the 1959 cohort the exposed group had more education than the unexposed group. These figures reflect a changing social gradient in smoking amongst men and women over time. Socio-economic confounding in ACS II would lead to over-estimation of the effect of ETS, whereas there is relatively little confounding in ACS I, and what confounding there is could lead to under-estimation of the ETS effects. The findings of the two studies are, in some respects, in line with this - in ACS II exposure to ETS was associated with increased risk of coronary heart disease mortality, while this is not seen in ACS I. Misclassification is a key issue in studies of passive smoking. It is not being married to a smoker - the indicator of ETS exposure utilized in the Enstron and Kabat paper - that leads to disease, rather it is the inhalation of ETS. As an indicator of ETS exposure the smoking status of spouses is a highly approximate measure. This will lead to the ETS- associated risk being under-estimated. Conversely misclassification of confounders can lead to statistical adjustment failing to fully account for confounding, leaving apparently "independent" elevated risks that are residually confounded[7]. Methods of statistically correcting for misclassification in both the exposure of interest and in confounders exist, but they are highly dependant upon the validity of assessments of measurement imprecision7 , which renders them a highly unsatisfactory method for resolving such issues. In the passive smoking field the tobacco industry has eagerly discussed measurement error that would lead to the effect of passive smoking being over estimated, and rely on the work of its consultants in this regard[8], while ignoring misclassification that would lead to underestimation of the strength of the ETS-disease association2. A second approach to evaluating the risks of passive smoking is to assess the exposure to known carcinogens produced by ETS. Tobacco industry consultants have repeatedly suggested that levels of such exposures are to low to be of concern, with even a heavily exposed passive smoker inhaling much less than the equivalent of one cigarette a day2. However the amount of exposure to the 4,000+ compounds within cigarette smoke differs between passive and active smokers, since sidestream and mainstream smoke have different compositions. Tobacco-specific nitrosamine 4-(methylnitrosamino) -1-(3-pyridyl)-1-butanone (NNKs) is metabolized and metabolites excreted in urine, and levels in non-smoking women married to smokers are about 6% of those of their spouses (and 8 times higher in women not married to smokers)[9]. Given the strength of relationship between active smoking and, say, lung cancer, exposure to 6% of the dose that is received by an active smoker could easily produce the level of risk associated with passive smoking[10]. However the exact factors in cigarette smoke responsible for its detrimental health consequences are not fully understood and thus these forms of calculation are highly approximate. Given the considerable problems with measurement imprecision, confounding and the small predicted excess risks associated with passive smoking, conventional observational epidemiology is somewhat limited in addressing this issue. Randomised controlled trials of exposure to ETS will clearly not be carried out, but it may be possible to improve understanding through a form of natural experiment: "Mendelian Randomisation"[11]. Genetic polymorphisms that are associated with poor detoxification of tobacco smoke carcinogens have been identified. The distribution of these polymorphisms in the population will not be related to the same behavioural in socioeconomic confounders that ETS exposure is currently associated with. Amongst people unexposed to such carcinogens there is no reason to believe that the polymorphisms would be related to lung cancer risk. However amongst the ETS-exposed a decrease in the ability to detoxify the carcinogens should be related to increased lung cancer risk, if ETS exposure is responsible for increased lung cancer risk. Indeed one study suggested that a null (non-functional) variant for one such detoxification enzyme, GSTM1, was associated with an increased risk of lung cancer in non-smoking women exposed to ETS, but not in non-exposed non-smoking women[12]. However a later study failed to confirm this finding[13], reflecting one limitation of Mendelian Randomisation, which is that large sample sizes are required to produce robust results. However this is a promising strategy if we really want to know whether passive smoking increases the risk of various diseases. Enstrom and Kabat's study demonstrates yet again the huge elevated risks for lung cancer, COPD and - to a lesser extent - coronary heart disease, seen among active smokers. Why, then, is there interest in passive smoking? It is obvious that smokers have large potential health gains from quitting. Several commercially sensitive reasons particular to passive smoking exist. First, legal action against tobacco companies for compensation with respect to health damaging consequences of active smoking are opposed on the grounds that smokers should have known of the risks. The same cannot be said of those involuntarily exposed to other people's smoke. Second, adverse health consequences of passive smoke encourage smoking bans in work places and other public spaces, which would lead to reduced cigarette sales. Both strictures imposed on smoking and the effectiveness of health promotion may increase if it is shown that those that have no say in their exposure to tobacco smoke are being made sick. The financial interests in this regard make it unlikely that the debate about passive smoking and health will go away. REFERENCES 1 Schnönherr E. Beitrag zur Statistik und Klinik der Lungentumoren. Z Krebsforsch 1928;27:436-50. 2 Davey Smith G, Phillips AN. Passive smoking and health: should we believe Philip Morris's "experts"? BMJ 1996;313:929-33. 3 Bayer R, Colgrove J. Science, politics, and ideology in the campaign against environmental tobacco smoke. Am J Public Health 2002;92:949-954. 4 Vandenbroucke JP. Passive smoking and lung cancer: a publication bias? BMJ 1988;296:391-392. 5 LeVois ME, Layard MW. Publication bias in the environmental tobacco smoke/coronary heart disease epidemiologic literature. Regulatory Toxicology and Pharmacology 1995;21:184-191. 6 Steenland K, Thun M, Lally C, Heath C. Environmental tobacco Smoke and Coronary Heart Disease in the American cancer Society CPS-II Cohort. Circulation 1996;94:622-628. 7 Phillips AN, Davey Smith G. How independent are independent effects? Relative risk estimation when correlated exposures are measured imprecisely. J Clin Epidemiol 1991;44:1223-31. 8 Lee PN, Forey VA. Misclassification of smoking habits as a source of bias in the study of environmental tobacco smoke and lung cancer. Statistics in Medicine 1996;15:591-605. 9 Andersen KE, Carmella SG, Bliss RL, Murphy L. Metabolites of a tobacco- specific Lung carcinogen in nonsmoking women exposed to environmental tobacco smoking. Journal of the National Cancer Institute 2001;93(5):378- 381) 10 Taylor R, Cumming R, Woodward A, Black M. Passive smoking and lung cancer: a cumulative meta-analysis. Australian and New Zealand Journal of Public Health 2001;25(3):203-211. 11 Davey Smith G, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiology 2003;32:1-22. 12 Bennett WP, Alavanja MCR, Blomeke B, Vähäkangas KH, Castrén K, Welsh JA, Bowman ED, Khan MA, Flieder DB, Harris CC. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. Journal of the National Cancer Institute 1999;91(23):2009-2014. 13 Malats N, Camus-Radon AM, Nyberg F, Ahrens W, Constantinescu V, Mukeria A, Benhamou S, Batura-gabryel H, bruske-Hohfeld I, Simonato L, Menezes A, Lea S, Lang M, Boffeta P. Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism. Cancer Epidemiology, Biomarkers & Prevention 2000;9:827833. Competing interests: None declared |
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