Environmental Tobacco Smoke and Tobacco Related Mortality - Essay Example

Title. Case Study: A seminal review of a publication in British Medical Journal (Enstrom JE, Kabat GC. BMJ, 2003; 326: 1057 – 1067). Abbreviations used: BMJ: British Medical Journal; CHD: Chronic Heart disease; COPD: Chronic obstructive pulmonary disease; ETS: Environmental Tobacco smoke; GCK: GC Kabat, the second author; JEE: JE Enstrom, the first author author; LC: Lung Cancer; NAD: Nicotinamide adenine dinucleotide; NADP: Nicotinamide adenine dinucleotide phosphate; RR: Rapid Response; Other abbreviations carry their usual significance. Introduction. Presently, tobacco smoking and its related disorders are the topics of intense research and debate the world over, perhaps representing one of the oldest scientific debates [1]. Reasons for this could be due to various governments of different countries the world over contemplating banning of smoking in public places, with Britain already having done so. Such a decision has adverse socio-economic, cultural and political consequences, given the fact that tobacco and related industry is a multi-billion dollar business employing millions of people. Any improper decision from the governments without proper reasoning causes loss of income to millions of households around the globe, irrespective of the fact whether those homes have smoking family members or not. Thus, every study involving the effects of tobacco smoke on smokers or passive smokers gains prominence and must be reviewed with utmost caution. Prior to reviewing or discussing any specific study, the following facts must be borne in the minds of the readers that: i. No study so far has directly implicated the effect of tobacco smoke on passive smokers, (although a few came close); ii. Whatever might be the type of the study, the conclusions are strongly associated with the affiliations of the researchers [2]; iii. Perhaps, one of the most misused/abused subjects in the field of biomedical research is (bio) statistics; iv. Biomolecules like Nicotinic Acid (Vitamin B3) {produced by the oxidation of nicotine}, Nicotinamide {amide derivative of nicotinic acid} Adenine Dinucleotide (NAD+) and NAD Phosphate (NADP+), both coenzymes, etc., are derivatives of nicotine, the major component of tobacco smoke; and v. Positive benefits of tobacco smoke and its condensate have been documented [3, 4]. Put simply, the exact role played by tobacco smoke on living cells or its effects on passive smokers is still a grey area in the field of life science. However, probably for economic reasons, extensive amount of research is spent on tobacco related studies. In this context, the publication of Enstrom (JEE) and Kabat (GCK) [5] chosen for case study gains prominence at least for the following two main reasons: i. The amount of patients studied/analysed (n = 118094); and ii. The long duration of the study – study period encompasses forty years. Additionally, the authors try to estimate the effect of environmental tobacco smoke (difficult to measure parameter) on passive smokers. While earlier attempts in similar directions have had their limitations, JEE & GCK have in part overcome the same by extending the follow-up for the participants, analysis of relation between environmental tobacco smoke and tobacco related diseases. Summary of the results of JEE & GCK. In the present paper, the personal lifestyles of never smokers were independent of spouse smoking status. Nevertheless, smoking status was found to be related to the three self-reported measures of exposure. Interestingly, the authors found that widowhood increased substantially with the level of smoking in the spouse, indicating a direct association of adverse effects of active smoking and mortality, a finding consistent with the earlier studies [6]. As can be expected with the changing times, the researchers found that the percentage of participants currently married as of 1999 declined substantially with the smoking status of the spouse. The authors attribute this decline to an increase in widowhood. Additionally, they found that smoking history strongly related to exposure to environmental tobacco smoke (ETS) as of 1999 for both men and women. In continuation, the authors acknowledge misclassification of the data, level of which might exaggerate the true level of misclassification, particularly in shot follow-ups. Perhaps the major finding of this epidemiology study by JEE & GCK is that they failed to find any significant relationship between ETS exposure and mortality associated with coronary heart disease (CHD), lung cancer (LC) and Chronic obstructive pulmonary disease (COPD) either in the short term follow-up or in the long–term. At best, an association was indicated only in the risks of COPD. However, an association was found only in active smokers. Based on their observations in active smokers and upon extrapolation of the results found in never smoker, the authors claim to have added to the existing scientific knowledge that no significant causal relationship exits between ETS and tobacco related mortality. However, JEE & GCK do not rule out the possibility of an association between ETS and other diseases, viz., COPD. The Aftermath. This particular article of JEE & GCK was published by British Medical Journal (BMJ) in the issue dated 17 May 2003. As with the journal they invited a ‘rapid response’ (RR) to the article [7]. By 19 April 2006, close to 157 RRs have been posted onto the journal’s website, majority of them responding within a week of the date of the publication. The responders ranged from nondescripts to big shots in the fields of epidemiology, statistics and the like to decision makers. Whereas the responses can be described as ranging from crap to stupid remarks to hinting at scandal, personal anecdotes and literal mudslinging, those that were sane hinted at the flaws in the study, with specific reference to the statistical analysis of the data. However, it must be noted that between 11 Dec 2003 and 3 July 2004, the responses were totally off-track and lacked ‘common sense’. In an attempt to answer a particular question posted on 11 Dec 2003, it became apparent that, a significant majority of the responders, perhaps, were not aware of the finer details of the publication of JEE & GCK. This situation makes the RR in the wake of the publication ‘a hysterical lynch mob on a witch hunting binge’. During the course of the debate, the Editors, of the journal, decided to upload the reviewers comments and the prepublication history [8] into the website. These decisions are laudable, go a long way in ensuring transparency, and in keeping, the slates clean on either side, in situation of controversy. Hope the same policy is adopted for other studies as well. There were also occasional clarifications from the authors in the due course of RRs. Whatever might be the case, let us review here and discuss the RRs. As already, stated, Britain recently passed laws concerning public smoking, and precisely for this reasons the article of JEE & GCK is significant. In this context, a comment titled “Give them enough rope” (posted on 17 May 2003) appears redundant. Because of Britain’s recent decision, it makes sense to publish these kinds of articles in a British journal. Such an effort kicks up a healthy debate in the target country as it has done now. A more matured response titled “Study objective flawed – fatally” was posted on 17 May 2003. The responder questions the study objective and continues to add that whereas during the first two decades of the study period the public was awash with ETS at home, in workplace, a point the authors chose to discount. Perhaps, if the Editors were to find a reason to reject the study, this would have been the reason. Subsequently, one of Editors, response titled “From hero to pariah in one easy jump” (posted on 18 May 2003), clarifies the journals stand and informs the responders that the journal is planning to post the prepublication history into the website. Furthermore, the Editor explains in brief how reviewing and editing of manuscripts is done. As the Editor has rightly put every publication has flaws in them, be it in the form of biased interpretation of the results or lack of appropriate technique to carry out precision experiments or others. The subtle flaws make the research tick; else, ‘Science’ would have been an extinct subject by now. Additionally, the authors of this particular response further clarifies that to reject the study simply because it was funded by the tobacco industry would have been a wrong decision. The Editor also highlights the considerable strengths of the study. With the prepublication history for this particular study being made available, the debate turned towards the ‘nexus’ between funding and flawed scientific studies. In this situation, the response titled “Environmental smoke paper requires further benefits from critical appraisal” (posted 19 May 2003) does a better job of reviewing the article. Their comment that they found the article difficult to interpret, data tables unhelpful, raises more questions than answered, assume significance when one casually browses through the study with preconceived notions. In a study of this magnitude, wherein massive work (at least with regard to documentation, collecting questionnaires and statistical analysis) is involved, there is bound to be a difficulty in interpreting the data. Hence, certain commonly accepted observations tend to be passed off as their findings also. For example, in the present case, an analysis was performed on active smokers with a biased view that they must find a correlation in this group with CHD, LC, COPD, etc., [the words ‘as expected…’ are indicative of a preconceived notion or are the authors under pressure not to challenge the earlier findings?]. {The journal statisticians reports also concur with this statement [8]}. Had the researchers done the analysis without any preconceived notions (easier said than done), they would have definitely come up with results that are even more explosive. Coming to the prepublication history and the reviewers comments, per se, both the reviewers agree on the importance of the study. Both of them concur on publishing the data and making it available to the public at large. Both of them suggest (major) revisions. Perhaps, presenting the data as was submitted originally by the authors would have been a better option (?). The original manuscript was rejected by the editorial advisory committee, which met on 11 Nov 2002. However, they decided to review a revised and shortened version of the manuscript (that was eventually accepted on 7 March 2003). Additionally, one should keep in mind that the statisticians reports did document their reservations. As on 19 April 2006, at least 30 online articles cite this particular article, irrespective of the fact whether it is in the positive note or not. Whatever might be the case, one thing is clear, this study represents a starting point for conducting more number of similar studies of the same magnitude in future. Such studies should plug the loopholes and flaws pointed in the RRs. Already one of the articles citing this article contradicts the findings of JEE & GCK [9]. An effective conclusion can only be arrived at after taking into account the results of all those studies {results of at least 30 (the statistically significant number) studies the world over}. Concluding remarks. Despite tobacco research being a topic of intensive research since the early 1900s, interestingly none of the studies could directly implicate ETS, passive smoke and their adverse effects on human health. Hence, the actual effects of tobacco continue to be a grey area in biomedical sciences. In addition, certain positive benefits to active smokers have been attributed [3, 4]. Perhaps, a possible answer for all these non-conclusive results lies in the observation that derivatives of Nicotine perform vital (life saving) functions in living organisms. This particular aspect has been overlooked by epidemiologists in the past. Hope they will at least include bio-chemical aspects in future rather than relying on rote statistics. Until then, the article by JEE & GCK remains to be the ‘gold standard’ / ‘bench mark’. Amon. References (in the order they appear in the text): 1. Schnonheur E. Beitrag zur statistik und klinik der lungentumoren. Z Krebsforsch, 1928; 27: 436 – 450; as cited by Smith GD. Effect of passive smoking on health. BMJ, 2003; 326: 1048 – 1049. 2. Barnes DE, Bero LA. Why review articles on the health effects of passive smoking reach different conclusions. JAMA, May 20, 1998; 279 # 19: 1566 – 1570. 3. Dandiya PC, Bhargava LP. The anti-parkinsonian activity of monoamine oxidase inhibitors and other agents in rats and mice. Arch Int Pharmacodyn Ther, 1968; 176 (1): 157 – 167. 4. Furusawa E, Ramanathan S, Suzuki N, Tani S, Furusa S. Antiviral activity of tobacco smoke condensate on encephalomyocarditis infection in smoke. Antimicrob Agents Chemother, 1973 April; 3 (4): 484 – 487. 5. Enstrom JE & Kabat GC. Environmental Tobacco smoke and tobacco related mortality in a prospective study of Californians, 1960 – 1998. BMJ, 2003; 326: 1057 – 1067. 6. A. Hammond EC. Smoking in relation to death rates of one million men and women. Natl Cancer Inst Monogr, 1966; 19: 127 – 204; B. Garfinkel L. Time trends in lung cancer mortality among non-smokers and a note on passive smoking. J Natl Cancer Inst, 1981; 66: 1061 – 1066; and C. Burns DM et al. The American cancer society cancer prevention study I: 12 year follow up of one million men and women. Smoking and Tobacco control monograph no. 8. Rockville, MD: US Dept. Health and Human Services, NIH, NCI, 1997: 113 – 304 (NIH Publication No. 97 – 4213) as cited in reference # 5. 7. RRs of reference # 5 can be accessed at – http://bmj.bmjjournals.com/cgi/eletters/326/7398/1057. 8. Prepublication history of reference # 5 at http://bmj.com/cgi/content/full/326/798/1057/DC1 9. Barnoya J, Glantz SA. Cardiovascular effects of second hand smoke: nearly as large as smoking. Circulation, May 24, 2005; 111 (20): 2684 – 2694. Read More