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False positive result in study on hookah smoking and cancer in Kashmir: Measuring risk of poor hygiene is not the same as measuring risk of inhaling water filtered tobacco smoke all over the world

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The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.
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[*] Chaouachi K. False positive result in study on hookah smoking and cancer in Kashmir: measuring risk of
poor hygiene is not the same as measuring risk of inhaling water filtered tobacco smoke all over the world.
Br J Cancer. 2013 Apr 2;108(6):1389-90. doi: 10.1038/bjc.2013.98. Epub 2013 Mar 7.
http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc201398a.html
http://www.ncbi.nlm.nih.gov/pubmed/23470468
All users of the fashionable hookah across the world, except in rare cases, do change the water of the pipe
basin after each smoking session (or get it changed). This is a well-established fact as the following note a
physician in Nepal early wrote in the British Medical Journal shows: water is changed each time smoking is
carried out (Pande, 1962). As for the cancer risk, there is actually an extensive literature suggesting a null
or weaker association than the one usually measured when it comes to tobacco use in general (Chaouachi &
Sajid, 2010). Among others, let us cite an early study published in this very journal (Rakower & Fatal, 1962),
another one in India (Sanghvi,1981) and the most recent one in Punjab, Pakistan (Sajid et al, 2008).
Interestingly, the latter, which was carried out on the other side of the national border, actually represents
the same geographical, human and cultural environment as Kashmir in which the Dar et al study was
conducted (2012).
However, Dar et al.’s paper offers a false-positive result regarding hookah smoking. It is based on a serious
misinterpretation which could have easily been avoided if the authors had paid more attention to a recent
lung cancer study in the very same region, Kashmir, and a subsequent important clarification published by
its senior author (Koul et al, 2011; Koul & Chaouachi, 2011). None of the Kashmiri participants changed the
water after each session. A rarely-cited 84-page WHO Egyptian report on shisha smoking was quoted,
highlighting the filtering effect of water (Koul & Chaouachi, 2011). Amazingly, in a recent relevant review,
Maziak (2012) cites that very study in Kashmir while ignoring the above important clarification by Koul &
Chaouachi. Furthermore, because the setup (e.g., smoking mixture not described by Dar et al (2012)),
smoke chemistry and smoking behaviour of a Kashmiri hookah are completely different from those of the
fashionable shisha used these days in Washington or London, both Dar et al and Maziak in his biased review
extrapolate false-positive findings to the whole world. Such a wide confusion is also fuelled by the
widespread nominalist use of the ««waterpipe»» neologism since all water pipes of the world have almost
nothing in common but that name imposed one decade ago (Chaouachi & Sajid, 2010).
Yet, the water “detail” already led astray Maziak in a previous review when warning against aspergillosis. In
fact, the cited study (Szyper-Kravitz et al, 2001) showed that the patient had not changed the water of his
hookah for weeks. In sum, measuring a risk due to the blatant lack of primary hygiene (water, but also
suction hose) is one thing and measuring the real “corrected” risk (that of inhaling hookah smoke) is
something else. Similarly, the study on ESCC, opium and tobacco use in Iran cited by Dar et al, and on which
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we already commented (Chaouachi, 2009), may have simply measured the same lack of hygiene (water,
hose).
Another source of confusion in Dar et al.s study appears when its authors state that "hookah smokers seem
to be exposed to [as] many toxic compounds as cigarette smokers, citing exclusively for this purpose
studies by the US-American University of Beirut (US-AUB). First, the Kashmiri hookah is not the growingly
popular shisha targeted by antismoking research (different smoking product, chemistry, puffing, etc.). Then,
the cited experiments rely on machine smoking, not on human subjects. Cigarette smoking machines (used
for about 5 minutes at a pace of 1 puff/min. on average) have been widely criticised over the past half
century (including by the WHO) for greatly distorting the reality of actual human cigarette smoking. Quite
astoundingly, their use for hookah smoking “simulation” (about 60 minutes of puffs arbitrarily and
periodically drawn every 17s) has been virtually imposed to research for almost one decade now. Here, the
first unavoidable question is: where does the demonstrated relevance of the latter machine lie if the former
one (for much shorter periods) has failed?
Furthermore, the setup (cramming of the smoking mixture inside the bowl, its systematic charring with a
piece of charcoal kept in place over the same point for one full hour, etc.) represents at best a model about
how not to smoke a hookah (Chaouachi & Sajid, 2010).
Admitting (absurd hypothesis) that such a “protocol” were realistic, why did a German team find acrolein at
levels 66 times lower (6 times lower for formaldehyde and acetaldehyde) and benzo[a]pyrene 20 times
lower than in the studies by the US-AUB cited by Dar et al and Maziak? Yet, both used a shisha smoking
machine with similar parameters (notably, inter-puff time). The German scientists said they have “fully
validated [their] approach (Schubert et al, 2011b, 2012). In these conditions, is it scientifically acceptable
to hype this way the hazards of hookah smoking on a global scale?
The assessment of related biomarkers supports the need for questioning such methods as studies in the
USA, Germany and Pakistan show (Jacob et al, 2011; Schubert et al 2011a, 2012; Sajid et al, 2008). Biological
levels of blood nicotine and urine cotinine of shisha (with Moassel) users are generally similar to those
found in cigarette smokers after having smoked 1 single (2 at the most) cigarette(s), which obviously does
not mean that a hookah session is equivalent to smoking 20 cigarettes or more.
As for nitrosamines, polycyclic aromatic hydrocarbons, primary aromatic amines, carbonyls, etc., their
metabolites are generally found in very much lower quantities in shisha users than among cigarette smokers
(Schubert et al, 2011a, 2011b, 2012; Jacob et al, 2011). The German group even found no difference in
urinary NNAL between shisha smokers and non-smokers (Schubert et al, 2011b). As for urinary
concentrations of PAH metabolites, they were much less important in shisha smokers than in cigarette
smokers by factors ranging from about 1.5 to 5 (Jacob et al, 2011). From there, statements asserting “the
similarity of biological consequences of waterpipe and cigarette smoking” (Dar et al, 2012) are groundless.
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Finally, “systematic reviewsand “meta-analyses” have fallen prey to the same errors discussed above. Dar
et al cite one of them but ignore a methodological critique of such biased literature and the global
confusion it has contributed to fuel in this field of research (Chaouachi, 2011).
References
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Chaouachi K, Sajid KM (2010). A critique of recent hypotheses on oral (and lung) cancer induced by water
pipe (hookah, shisha, narghile) tobacco smoking. Med Hypotheses 74: 8436.
Doi:10.1016/j.mehy.2009.11.036
Chaouachi K (2009). Hookah, opium and tobacco smoking in relation to oesophageal squamous cell
carcinoma. Br J Cancer 100(6):1015
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7821(12)00152-X. doi: 10.1016/j.canep.2012.10.013. [Epub ahead of print]
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patient linked to Aspergillus contaminated marijuana smoking. Leuk Lymphoma 42:14337.
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the release of toxic carbonyls. Arch Toxicol. Jun 17 [Epub ahead of print]
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mainstream waterpipe smoke using liquid chromatography-electrospray ionization tandem mass
spectrometry. J Chromatogr A. 1218(33):5628-37
Schubert J, Hahn J, Dettbarn G, Seidel A, Luch A, Schulz TG (2011b). Mainstream smoke of the waterpipe:
Does this environmental matrix reveal as significant source of toxic compounds? Toxicol Lett. 205:279-84.
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Competing interests: I have no competing interests. I have never received direct or indirect funding, either
from pharmaceutical companies or the tobacco industry.
... There is a considerable number of studies that exhibit a weak understanding of the concept of spurious regression due to missing and dispelled variables. A study conducted in Indian Kashmir shows that a significant positive correlation between Nass chewing, hookah smoking, and many other habits with esophageal squamous cell carcinoma (ESCC) risk [9] does not necessarily mean that such a relationship truly exists between them [10]. This is because the original study failed to control for the 'water filtering factor' that was critical to the whole process. ...
... The phase ∅ 0 when is small. Ref. [10] adopted the definition of cointegration form [12] which is given as follows: In other words, the two-unit root series, i.e., Xt and Yt, are cointegrated if their linear combination Zt is stationary. ...
... These data are generated with pre-decided specifications, and the probability of spurious regression is being tested using classical methods and with the Ghouse equation. The two independent autoregressive non-stationary series are generated using Equation (10). Figure 1 given below is based on the results of Table 1. ...
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In conventional Econometrics, the unit root and cointegration analysis are the only ways to circumvent the spurious regression which may arise from missing variable (lag values) rather than the nonstationarity process in time series data. We propose the Ghouse equation solution of autoregressive distributed lag mechanism which does not require additional work in unit root testing and bound testing. This advantage makes the proposed methodology more efficient compared to the existing cointegration procedures. The earlier tests weaken their position in comparison to it, as they had numerous linked testing procedures which further increase the size of the test and/or reduce the test power. The simplification of the Ghouse equation does not attain any such type of error, which makes it a more powerful test as compared to widely cited exiting testing methods in econometrics and statistics literature.
... Overlooking the striking diversity of WFTSPs represents a serious ethical and methodological error since all water pipes (in two words) of the world have almost nothing in common but that ««waterpipe»» name arbitrarily imposed one decade ago [5]. From there, ««waterpipe»»-labelled clinical studies, or those carried out in a "real" "natural" environment, have generally mixed up different products used by the smokers: e.g., plain tobacco of the tumbak, ajamy or tutun type with the popular flavoured moassel (tabamel), etc (See Figs. 1, 2, 3). ...
... Yet, they do not realise, or simply wish to ignore, how biased are the corresponding procedures which led to the imposition of the puffing machine in question [6,7]. Indeed, it was recently stressed how two smoking machines, in two different laboratories from two different countries (Germany and Lebanon) could produce acrolein and benzo[a]pyrene levels 66 and 20 times different, respectively, in each case [5]. Yet, the two robots were set with similar (biased) parameters: notably an exaggerated inter-puff time interval of 17s/20s; the charcoal (non-natural) literally burning the flavoured smoking mixture instead of just heating it (because of its arbitrarily fixed position atop the bowl, for one full hour). ...
... Not only has the definition of an "epidemic" been revisited, as pointed out before, but also that of prevalence and psycho-pharmacological addiction as we will see further down. The answer to how such a global confusion, never witnessed before and elsewhere in the biomedical field [5], has been possible, certainly deserves a tentative answer; perhaps of a sociological nature [2]. In fact and with the benefit of hindsight, we can now state that a great number of researchers working on the hot issue of WFTSPs have got a poor grasp of the basics of tobacco science, not to mention of the everyday's life material culture of Asian and African societies. ...
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BACKGROUND: The traditional definition of an “epidemic” has been revisited by antismoking researchers. After 400 years, Doctors would have realized that one aspect of an ancient cultural daily practice of Asian and African societies was in fact a “global “epidemic””. This needed further investigation particularly if one keeps in his mind the health aspects surrounding barbecues. METHOD: Here, up-to-date biomedical results are dialectically confronted with anthropological findings, hence in real life, in order to highlight the extent of the global confusion: from the new definition of an “epidemic” and “prevalence” to the myth of “nicotine “addiction”” and other themes in relation to water filtered tobacco smoking pipes (WFTSPs). RESULTS: We found that over the last decade, many publications, -particularly reviews, “meta-analyses” and “systematic reviews”- on (WFTSPs), have actually contributed to fuelling the greatest mix-up ever witnessed in biomedical research. One main reason for such a situation has been the absolute lack of critical analysis of the available literature and the uncritical use of citations (one seriously flawed review has been cited up to 200 times). Another main reason has been to take as granted a biased smoking robot designed at the US American of Beirut whose measured yields of toxic chemicals may differ dozens of times from others' based on the same “protocol”. We also found that, for more than one decade, two other main methodological problems are: 1) the long-lived unwillingness to distinguish between use and misuse; 2) the consistent unethical rejection of biomedical negative results which, interestingly, are quantitatively and qualitatively much more instructive than the positive ones. CONCLUSION: the great majority of WFTSP toxicity studies have actually measured, voluntarily or not, their misuse aspects, not the use in itself. This is in contradiction with both the harm reduction and public health doctrines. The publication of negative results should be encouraged instead of being stifled. KEYWORDS: Electronic cigarette, harm reduction, hookah, narghile, public health,shisha, smoking, tobacco [NOTE: This article also offers a thorough response to all issues raised in the March 2015 (vol. 24, suppl. 1) issue of the "Tobacco Control" antismoking journal titled: "Waterpipe Tobacco Smoking: A Global Epidemic]
... We thank Chaouachi (2013) for his interest in our study (Dar et al, 2013). The first two paragraphs of his letter are on the potential role of changing the water of waterpipe basin. ...
... We agree with Chaouachi (2013) that cigarette-smoking machines may not be representative of exposure in waterpipe smokers. However, there is other evidence showing that waterpipe smokers are exposed to some harmful compounds present in tobacco, perhaps not as high levels as what have been reported with cigarette-smoking machines, but still at the levels significantly higher than non-smokers. ...
... However, there is other evidence showing that waterpipe smokers are exposed to some harmful compounds present in tobacco, perhaps not as high levels as what have been reported with cigarette-smoking machines, but still at the levels significantly higher than non-smokers. Chaouachi (2013) states 'Admitting (absurd hypothesis) that such a 'protocol' were realistic, why did a German team found acrolein at levels 66 times lower (6 times lower for formaldehyde and acetaldehyde) and benzo[a]pyrene 20 times lower than in the studies by the US-AUB cited by Dar et al and Maziak?'. This is correct, but Chaouachi (2013) does not state that the same German study detected five times higher formaldehyde levels during one waterpipe-smoking session when compared with one reference cigarette (Schubert et al, 2012), that the nicotine contents were 10 times higher and the levels of benzo[a]pyrene were 3 times higher in waterpipe smoke than in the reference cigarette, and that they found much higher nicotine and cotinine levels in the urine of waterpipe smokers than in urine of non-smokers (Schubert et al, 2011). ...
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... The World Health Organization (WHO) estimates that a hookah smoker may inhale 100 times the amount of smoke during one hookah session as is inhaled from one cigarette (WHO, 2005). Toxin concentrations have been shown to be lower in hookah (Chaouachi, 2013) and the chemical composition of the smoke differs depending on the type of hookah used (Chaouachi, 2009). Although some controversy exists to the amount of toxins in hookah smoke (Chaouachi, 2011), hookah smoke has been shown to contain tar, nicotine, and carbon monoxide (Katurji, Daher, Sheheitli, Saleh, & Shihadeh, 2010). ...
... If, on the one hand and for one decade now, the shisha (hookah, narghile) issue had not been the subject of a global confusion of concepts and methods never witnessed before nor elsewhere in the biomedical field (Chaouachi 2013), this would not have any great importance. However and on the other hand, the above sentence is unfortunately the one that heralds a critical article exposing a series of serious errors in relation to shisha smoking and oral cancer hypotheses, to be found in the very US-Syrian paper cited by the Tunisian team (Chaouachi and Sajid 2010). ...
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Background: Although cigarette smoking is an established risk factor for oesophageal squamous cell carcinoma (ESCC), there is little information about the association between other smoking and smokeless tobacco products, including hookah and nass, and ESCC risk. We conducted a case–control study in Kashmir Valley, India, where hookah smoking, nass chewing, and ESCC are common, to investigate the association of hookah smoking, nass use, and several other habits with ESCC. Methods: We recruited 702 histologically confirmed ESCC cases and 1663 hospital-based controls, individually matched to the cases for age, sex, and district of residence from September 2008 to January 2012. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Ever-hookah smoking (OR=1.85; 95% CI, 1.41–2.44) and nass chewing (OR=2.88; 95% CI, 2.06–4.04) were associated with ESCC risk. These associations were consistent across different measures of use, including intensity, duration, and cumulative amount of use, and after excluding ever users of the other product and cigarette smokers. Our results also suggest an increased risk of ESCC associated with ever-gutka chewing and -bidi smoking. However, the latter associations were based on small number of participants. Conclusion: This study shows that hookah and nass use are associated with ESCC risk. As prevalence of hookah use seems to be increasing among young people worldwide, these results may have relevance not only for the regions in which hookah use has been a traditional habit, but also for other regions, including western countries.
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Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world, including the United States, where it is especially popular among young people. Many perceive water pipe smoking to be less hazardous than cigarette smoking. We studied systemic absorption of nicotine, carbon monoxide, and carcinogens from one water pipe smoking session. Sixteen subjects smoked a water pipe on a clinical research ward. Expired carbon monoxide and carboxyhemoglobin were measured, plasma samples were analyzed for nicotine concentrations, and urine samples were analyzed for the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and polycyclic aromatic hydrocarbon (PAH) metabolite biomarker concentrations. We found substantial increases in plasma nicotine concentrations, comparable to cigarette smoking, and increases in carbon monoxide levels that are much higher than those typically observed from cigarette smoking, as previously published. Urinary excretion of NNAL and PAH biomarkers increased significantly following water pipe smoking. Absorption of nicotine in amounts comparable to cigarette smoking indicates a potential for addiction, and absorption of significant amounts of carcinogens raise concerns of cancer risk in people who smoke tobacco products in water pipes. Our data contribute to an understanding of the health impact of water pipe use.
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The literature about the causal relationship between lung cancer and tobacco smoking mostly concerns cigarettes. Hookah smoking is popular in the Kashmir valley of the Indian subcontinent, and is generally believed to be innocuous because of the passage of the smoke through water before inhalation. To determine the relationship of hookah smoking to lung cancer in Kashmir. In a case-control design, 251 cases of lung cancer and 500 age-matched controls were studied. A predefined questionnaire was administered through a personal interview regarding various smoking and dietary patterns and the results compared through statistical analyses. There were 194 (178 current) ever-smokers amongst the cases and 223 (134 current) amongst controls. Smokers had a 4.2 times risk of lung cancer compared to non smokers (OR 4.23, 95% CI 3.0-5.96, p < 0.0001). There were 120 hookah smokers amongst the cases and 100 amongst the controls and hookah smokers were nearly six times at risk for lung cancer as compared to nonsmokers (OR 5.83, (95% CI 3.95-8.60, p < 0.0001). Cigarette smokers were commoner amongst cases (46 vs 64 in controls; OR 3.49, 95% CI 2.18-5.60, p=0.000). The severity of smoking was associated with a higher risk of lung cancer (Chi-square 72.1, p 0.000).The practice of changing water of the hookah after each session proved non-existent. Hookah smoking is associated with a significantly higher risk for lung cancer in Kashmiri population, with about 6 fold elevated risk as compared to non-smoking controls.
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BACKGROUND: Although cigarette smoking is an established risk factor for oesophageal squamous cell carcinoma (ESCC), there is little information about the association between other smoking and smokeless tobacco products, including hookah and nass, and ESCC risk. We conducted a case–control study in Kashmir Valley, India, where hookah smoking, nass chewing, and ESCC are common, to investigate the association of hookah smoking, nass use, and several other habits with ESCC. METHODS: We recruited 702 histologically confirmed ESCC cases and 1663 hospital-based controls, individually matched to the cases for age, sex, and district of residence from September 2008 to January 2012. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Ever-hookah smoking (OR¼1.85; 95% CI, 1.41–2.44) and nass chewing (OR¼2.88; 95% CI, 2.06–4.04) were associated with ESCC risk. These associations were consistent across different measures of use, including intensity, duration, and cumulative amount of use, and after excluding ever users of the other product and cigarette smokers. Our results also suggest an increased risk of ESCC associated with ever-gutka chewing and -bidi smoking. However, the latter associations were based on small number of participants. CONCLUSION: This study shows that hookah and nass use are associated with ESCC risk. As prevalence of hookah use seems to be increasing among young people worldwide, these results may have relevance not only for the regions in which hookah use has been a traditional habit, but also for other regions, including western countries.
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In recent years waterpipe smoking has spread worldwide and emerged as global health issue. Yet only little is known on the composition of waterpipe smoke. Here, we present a study on the identification and quantification of primary aromatic amines (PAAs) in this complex environmental matrix. Smoking of the waterpipe was conducted with a smoking machine and particulate matter was collected on glass fiber pads. We developed a fast, simple and specific liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) approach to simultaneously detect 31 different PAAs in this matrix. The detection limits comprised a range of 0.45-4.50 ng per smoking session, represented by 2-aminobiphenyl and 3,4,5-trichloroaniline, respectively. Intra- and inter-day precision were determined and proved excellent. We detected 31.3 ± 2.2 ng aniline and 28.0 ± 1.6 ng 4,4'-oxydianiline in the smoke of one waterpipe session. The water in the bowl exerted a small but considerable filter effect on PAAs. The method worked-out showed excellent sensitivity and specificity and is thus highly suited for the determination of PAAs in mainstream waterpipe smoke.
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In recent years the number of waterpipe smokers has increased substantially worldwide. Here we report on the concentrations of tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) in waterpipe smoke and the analysis of selected biomarkers indicative for the body burden in waterpipe users. We further identify high amounts of unburned humectants (glycerol and propylene glycol) in the waterpipe smoke as main part of the so-called "tar" fraction. These results give cause for serious concern. For standardization we applied a machine smoking protocol. Smoke was collected on glass fiber filters and analyzed for nicotine, water, humectants, TSNAs, and PAHs. In addition, we determined carbon monoxide and found high amounts in the smoke being causative for high levels of carboxyhemoglobin (COHb) in the blood of smokers. In comparison to the reference cigarette 3R4F, the nicotine contents were 10-times higher, but TSNA levels were found lower in waterpipe smoke. This finding explained the low levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol detected in the urine of waterpipe smokers. Finally, the levels of benzo[a]pyrene were three times higher in waterpipe smoke compared to the reference cigarette. Altogether, the data presented in this study point to the health hazards associated with the consumption of waterpipes.