Tobacco-based Products Research Articles

Health risk assessment of lead and cadmium exposure from food and snuff in Pakistani population

BackgroundSmokeless tobacco (SLT) is a tobacco-based product consumed without burning or smoking. Snuff, commonly known as naswar, is a widely used SLT product in Pakistan. This study is designed to investigate the concentrations of lead (Pb) and cadmium (Cd) in snuff and their associated health risks to consumers. MethodsBlood samples from snuff consumers and non-consumers were analyzed for Pb and Cd concentrations. Additionally, samples of drinking water and wheat flour were also analyzed for Pb and Cd. Health risk assessments were calculated using hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) for Pb and Cd. ResultsSnuff consumers had significantly higher blood-Pb and blood-Cd levels compared to non-consumers. Approximately 38.5 % of snuff consumers were found to exceed blood-Pb levels from the safe limits (10 µg dL⁻¹) of the World Health Organization (WHO), while 48.9 % of snuff consumers were found to exceed blood-Cd levels from the WHO safe range of 0.03–0.12 µg dL⁻¹. Snuff samples contained Pb and Cd concentrations ranging from 5.3 to 22.4 µg g⁻¹ and 0.5–2.2 µg g⁻¹, respectively. Drinking water and wheat flour samples were found within the safe limits for Pb and Cd concentration, suggesting snuff as the primary source of exposure. Health risk assessments indicated elevated HQ values, for Pb (38.9 %) and Cd (14.3 %) detected in snuff, surpassing the safe HQ threshold of 1. Concerning ILCR from snuff, values for Pb were within the acceptable range, but alarmingly 100 % of samples for Cd exceeded the safe limits of USEPA (1.0×10⁻⁴), indicating a significant cancer risk in snuff users. ConclusionThis study highlights the exceeded Pb and Cd concentrations in snuff as well as also reporting significant carcinogenic and non-carcinogenic health risks to consumers. These findings emphasized the urgent need for regulatory bodies to ensure the safety of snuff before selling in the market. Public Health Professionals should also initiate educational campaigns to raise awareness among consumers and manufacturers about various health risks associated with the snuff.

Identification of Terpene-Related Biosynthetic Gene Clusters in Tobacco through Computational-Based Genomic, Transcriptomic, and Metabolic Analyses

Terpenes and terpenoids contribute aroma and flavor that influence consumer preferences in selecting plant-based products. Computational identification of biosynthetic gene clusters (BGCs) in plants can pave the way for future biosynthetic genetic engineering. Using integrative genomic, transcriptomic, and metabolic pathway annotation analyses, 35 BGCs were identified in tobacco with high confidence. Among the 35 BGCs identified, 7 were classified as terpene biosynthesis-related BGCs. Two BGCs found on C13 and C14 chromosomes belonged to terpene and saccharide-terpene biosynthetic classes that were only 93 Mb and 189 Kb apart, respectively. Other clusters have lengths ranging from 120 Kb (Cluster 9) to 1.6 Mb (Cluster 18). Each cluster contained five (Cluster 21) to twenty genes (Cluster 32), and the number of terpene synthase genes present in the clusters also varied from one (Clusters 18 and 21) to eight (Cluster 32). Gene expression profiling using diurnal and topping transcriptome datasets identified co-expressing genes within modules and varying levels of expression among modules as represented by the normalized enrichment score measured in each module. The positions pinpointed from these computational analyses will allow for the more efficient modifications of specific genes and BGCs for the development of tobacco-based products with improved aroma and flavor.

59P Prognostic impact of HPV status evaluation in head and neck squamous cell carcinomas

Worldwide, head and neck carcinomas represent the seventh most common cancer, with known risk factors such as alcohol consumption, use of various tobacco-based products, and infection with high-risk human papillomavirus (HR-HPV). Association with HPV infection has already been proven to represent an indicator of a better outcome for patients with oropharyngeal squamous cell carcinomas (SCC) only. This paper aimed to highlight the prognostic value of the HPV status in all head and neck squamous cell carcinomas (SCC), independent of the location, evaluated using both immunohistochemical (IHC) and molecular techniques, and to assess the p16 marker (clone 16P04, JC2) value for predicting HPV.

Analysis of Crassostrea Virginica Protein Metal Complexes after Exposure to Toxic Environmental Pollutant Cadmium

Cadmium is a metal found in the parts per million of the earth’s crust, and it has been shown to have toxic effects on various plants, animals and humans. Exposure to cadmium occurs mainly through use of tobacco‐based products or industrial pollution. Once ingested, it is observed to take 20 to 30 years for cadmium concentration to reduce in half, which means it is difficult to clear from the body. A protein that is involved in the detoxification of harmful metals in cells is metallothionein. Having a strong binding affinity to divalent metals, metallothioneins allow cells to shuttle cadmium and other toxic metals away from important biological processes. Our current research aims to determine the effects of cadmium on the proteins within Crassostrea Virginica (oysters) living in the Chesapeake Bay area and how fast these changes occur. After homogenizing oyster samples and testing the amount of total protein, the protein structural differences will be analyzed using circular dichroism spectroscopy and Western blot techniques with metallothionein and other proteins as well. The quantification of cadmium uptake in oysters and final destinations of cadmium within protein complexes of samples will also be examined. Knowing the impacts of this heavy metal on oysters is directly useful for increasing insights into the toxic effects from industrialization on our ecosystem, as well as elucidating the functional aspects of macromolecular complexes containing cadmium.

Nicotine products relative risk assessment: a systematic review and meta-analysis

Background: Nicotine products have been the subject of considerable innovation over the past few decades. While the health risks of combustible cigarettes and most tobacco-based products are well characterized, there is less clarity regarding newer nicotine products, and how they compare with the traditional forms. Methods: In this study, we have developed a relative risk hierarchy (RRH) of 13 nicotine products based on systematic review of the scientific literature and analysis of the best available evidence. In total, 3980 publications were identified and screened, with 320 studies being carried through to the final analysis. The health risk data for each product was extracted and the level assessed. The products were analyzed in terms of their toxin emissions and epidemiological data, which were combined on an arbitrary scale from 0 to 100 (low to high risk) to derive a combined risk score for each nicotine product. Results: Combustible tobacco products dominate the top of the RRH, with combined risk scores ranging from 40 to 100. The most frequently consumed products generally score highest. Dipping and chewing tobacco place considerably lower on the hierarchy than the combustible products with scores of 10 to 15, but significantly above heat-not-burn devices and snus, which score between 3 and 4. The lowest risk products have scores of less than 0.25 and include electronic cigarettes, non-tobacco pouches and nicotine replacement therapy. Conclusions: The RRH provides a framework for the assessment of relative risk across all categories of nicotine products based on the best available evidence regarding their toxin emissions and the observed risk of disease development in product users. As nicotine products continue to evolve, and more data comes to light, the analyses can be updated to represent the best available scientific evidence.

What will Happen in the World of COPD 2030?

2030 may seem to be a long way into the future, but it's not. We live in a world of relentless rapid change in modern medicine and our approach to our patients with chronic diseases such as chronic obstructive pulmonary disease (COPD) will need to evolve at speed. This review looks at what may occur in society and medicine that will influence the way we manage COPD. The article is the opinion of the authors and is based upon current research at the cutting edge of management with a degree of gazing into a dimly lit crystal ball. COPD is a current epidemic, and this is likely to continue. Legislative efforts to reduce smoking will continue and hopefully accelerate, but this will not be globally accepted or successful. Technological advances will occur that will lead to miniaturization and the rise of near patient testing. This itself will enable a personalised approach to management with the ability to measure rapidly biomarkers which will direct therapy. The blood eosinophil is the most promising of these and is available now. New developments in the identification of disease clusters and phenotypes will also enhance a more personalised approach. Through both these epidemiological studies and also new developments in the understanding of basic mechanisms it is hoped that in the future patients will be given treatments that may fundamentally change the prognosis of COPD. Small molecule and antibody directed therapies may, if given early enough, stop and even possibly reverse the effects of COPD on cells and organs. Of course, the most important step which is achievable now is to ban all tobacco-based products from the world.

Analytical Determination of Nicotine and Tar Levels in Various Dokha and Shisha Tobacco Products.

In the Middle East, there is no precise data and literature on tobacco-based products, such as dokha and shisha. The proposed study aims to quantify the levels of nicotine and tar in different kinds of dokha and shisha products that are sold in the local marketplace. The amount of nicotine in dokha and shisha products can be quantitatively determined using a combination of the "kissling" and "silicotungstic acid" method proposed by Robert M. Chapin. The tar residue from the smoke sample was collected on a glass wool placed before the stopcock (tap) of a separatory funnel as the smoke passes through the inlet of an electronically controlled vacuum pump. The nicotine levels in dokha and shisha samples ranged from 23.83 to 52.80 mg/g and 0.80 to 20.52 mg/g, respectively. The nicotine level varies between different tobacco products. It varies from 0.5 to 19.5 mg/g in cigarettes, from 10.3 to 23.1 mg/g in snuff tobacco, from 11 to 18 mg/g in electronic cigarettes and from 2.9 to 16.6 mg/g in chewing tobacco. The tar levels in the dokha and shisha samples ranged from 21.6 to 45.02 mg/g and 1.68 to 11.87 mg/g, respectively. Smokers are at a high risk of getting lung cancer, chronic obstructive pulmonary disease, emphysema and coronary artery disease owing to the high levels of nicotine and tar present in dokha and shisha tobacco products. These findings contradict the widespread belief among teenagers that dokha and shisha tobacco products are safer alternatives to cigarettes.

In vitro exposure systems and dosimetry assessment tools for inhaled tobacco products: Workshop proceedings, conclusions and paths forward for in vitro model use.

In 2009, the passing of the Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 4-6 April 2016, the Institute for In Vitro Sciences, Inc. (IIVS) convened a workshop conference entitled, In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products, to bring together stakeholders representing regulatory agencies, academia and industry to address the research priorities articulated by the FDA CTP. Specific topics were covered to assess the status of current in vitro smoke and aerosol/vapour exposure systems, as well as the various approaches and challenges to quantifying the complex exposures in in vitro pulmonary models developed for evaluating adverse pulmonary events resulting from tobacco product exposures. The four core topics covered were: a) Tobacco Smoke and E-Cigarette Aerosols; b) Air-Liquid Interface-In Vitro Exposure Systems; c) Dosimetry Approaches for Particles and Vapours/In Vitro Dosimetry Determinations; and d) Exposure Microenvironment/Physiology of Cells. The 2.5-day workshop included presentations from 20 expert speakers, poster sessions, networking discussions, and breakout sessions which identified key findings and provided recommendations to advance these technologies. Here, we will report on the proceedings, recommendations, and outcome of the April 2016 technical workshop, including paths forward for developing and validating non-animal test methods for tobacco product smoke and next generation tobacco product aerosol/vapour exposures. With the recent FDA publication of the final deeming rule for the governance of tobacco products, there is an unprecedented necessity to evaluate a very large number of tobacco-based products and ingredients. The questionable relevance, high cost, and ethical considerations for the use of in vivo testing methods highlight the necessity of robust in vitro approaches to elucidate tobacco-based exposures and how they may lead to pulmonary diseases that contribute to lung exposure-induced mortality worldwide.

The Use of Human 3D Reconstructed Airway Cultures for Tobacco Product Evaluation: Precision Low-Volume Exposures at the Apical Site

Abstract With a mandate to evaluate the dynamics of pulmonary exposure to inhaled materials such as tobacco-based products, researchers are employing complex, human, three-dimensional pulmonary models. Human reconstructed airway (RHuA) tissues present a platform that more closely resembles airways in vivo. Grown at the air–liquid interface (ALI), RHuA tissues offer apical and basal compartments that allow flexibility in modeling physiologically relevant exposures and provide sampling location-specific results. Various instruments can produce smoke/aerosols (including that from e-cigarette) and expose tissues at the apical surface, but the quantitation of materials deposited remains a challenge. Alternatively, a solution containing solubilized materials can be applied through a pipette, but this less physiologically relevant method may adversely impact the tissue. We have tested the HP D300 digital dispenser as a means to deliver patterned picoliter amounts of dimethyl sulfoxide-based material (including t...

E-Cigarettes and Potential Implications for Plastic Surgery.

The use of tobacco-based products, most notably cigarettes, is related directly to wound healing problems and poorer outcomes in plastic surgery. Current abstracts have highlighted the potential complications from nicotine, specifically following plastic surgery in patients who choose to smoke. Recently, products that use electricity to vaporize liquid nitrogen have been gaining popularity. New rules were recently proposed that would give the federal government authority over electronic cigarettes. However, the health-related issues surrounding e-cigarettes are still largely unknown or misunderstood. These issues also extend to their impact on surgical procedures, notably their effect on plastic surgical procedures that rely heavily on the vascularity of either the host wound bed or the replacement tissue.

Aktivitas Integrated Marketing Communications Terhadap Brand Image Untuk Industri Rokok Kelas Mild

The cigarette industry in Indonesia has evolved from a traditional industry to be one of the important manufacturing sectors in terms of value added, employment and government revenue. On the other hand, aside from increasing social welfare, the government also has a moral responsibility particularly for raising public awareness of their health. Draft of Government Regulation regarding tobacco based-product as an addictive substance expressly prohibits the advertising, promotion and sponsorship of products containing tobacco. In the industry of mild class cigarette, the level of competition gets tighter where many cigarette companies conduct their integrated marketing communication activities in creative ways. This research is aimed at determining the effect of Integrated Marketing Communication variables on Brand Image of mild class cigarette companies in Bandung region. This research type is descriptive and verification research. The method used is survey descriptive method i.e collecting data on the research object by taking a sample of the population. Questionnaires are used as the principal means of collecting data. The positive coefficient shows that there is a positive relationship between the integrated marketing communications with brand image. As t count > t table (7.748> 1.965), H0 is rejected. Thus, it is found that there is a significant influence of integrated marketing communications on brand image.

Abstract 2354: Nasal gene expression reflects the physiologic response to potentially reduced exposure products

Abstract Rationale Potentially reduced exposure products (PREPs) are tobacco-based products that may yield lower toxicant levels as compared to traditional cigarettes thereby possibly mitigating tobacco-exposure related harm. Due to their increasing popularity, there is an urgent need to develop approaches for evaluating the biological impact of these products to determine their potential health risks. We have shown that gene expression profiling of intra- and extra-thoracic airway epithelium can serve as an indicator of physiological responses to cigarette smoke exposure. Our goal here is to establish whether this same approach might identify similarities and differences in the response to reduced exposure tobacco products. We therefore examined longitudinal gene-expression alterations upon switching from traditional cigarettes to a lower nicotine product (Xodus) in readily collected nasal epithelium and compared these transcriptomic alterations to those associated with smoking-cessation. Methods Nasal epithelial brushings were obtained from 13 active smokers who switched to Xodus cigarettes for 6 weeks and then were tobacco abstinent for the next 18 weeks. Nasal brushings were obtained at baseline and at 4, 6, 16, and 24-weeks. Alveolar carbon monoxide levels were used to confirm cigarette use at baseline, 4 and 6 weeks and tobacco abstinence at 16 and 24 weeks. RNA from the nasal brushings was processed and hybridized to Affymetrix Human Gene 1.0 ST Arrays. Gene expression alterations at each time point were identified using a mixed model ANOVA. Results Alterations in the expression levels of 161 genes were associated with either switching to PREPs or with complete smoking cessation (FDR<0.2). For a minority of genes, Xodus usage resulted in decreased expression levels that further decreased upon smoking cessation. These genes were primarily involved in xenobiotic metabolism (P<0.05). The majority of genes altered by smoking cessation time points do not change upon switching to this PREP product. Conclusion Our data indicate that some of the gene expression differences induced by switching to the PREP product are intermediate between traditional cigarette smoking and tobacco abstinence whereas majority of gene expression remain unaltered with Xodus use. These data suggest that the PREP product may only constitute partially reduced exposure. Our study further suggests that the nasal epithelium can serve as a minimally invasive tool to measure responses to alternative tobacco products and may ultimately serve as a biomarker to evaluate the potential disease risks associated with these products. Citation Format: Kahkeshan Hijazi, Bozena Bomalysz, Katrina Steiling, Ji Xiao, Gang Liu, Yuriy Alekseyev, Martine Dumas Yves, Louise A. Hertsgaard, Joni Jensen, Rachel Isaksson Vogel, Dorothy Hatsukami, George O'Connor, Daniel R. Brooks, Jennifer Beane, Avrum Spira. Nasal gene expression reflects the physiologic response to potentially reduced exposure products. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2354. doi:10.1158/1538-7445.AM2014-2354

Comparison of Tobacco-Containing and Tobacco-Free Waterpipe Products: Effects on Human Alveolar Cells

In recent years, a class of products marketed as "tobacco-free" alternatives for the "health conscious user" has become widely available for waterpipe (hookah, narghile, or shisha) smoking. Their adoption may be in part driven by regulations banning tobacco smoking in public places and by an increasing awareness of the hazards of waterpipe tobacco smoking. Although these products are presented in advertising as a "healthier" choice, very little is known about their health effects. In this study, we compared the effects of smoke generated with tobacco-free and conventional tobacco-derived products on human alveolar cells. Smoke was generated with a smoking machine that precisely mimicked the puffing behavior of 15 experienced waterpipe smokers when they used conventional waterpipe tobacco products of their choice and flavor-matched tobacco-free products. Human alveolar epithelial cells (A549) were treated with particulate matter sampled from the smoke, and the effects on cell cycle, proliferation, and doubling time were measured during the subsequent 72hr. We found that smoke from both types of waterpipe products markedly reduced cell proliferation, caused cell cycle arrest at G0/G1, and increased cell doubling time. There were no significant differences across product in any measure. Tobacco-free and tobacco-based waterpipe products exert substantial and similar deleterious effects on human lung cells. This study adds to the nascent evidence base indicating that except for exposure to nicotine and its derivatives, use of tobacco-free waterpipe products does not present a reduced health risk relative to the use of conventional tobacco-based products.

Abstract 4030: Nasal gene expression reflects the physiologic response to alternate tobacco products.

Abstract Rationale: Potentially reduced exposure products (PREPs) are tobacco-based products that may reduce exposure to the toxins found in tobacco and thereby potentially reduce tobacco-exposure related harm. There is an urgent need to develop approaches for evaluating the biological impact of these products to determine their potential health risks. We have shown that gene expression profiling of intra- and extra-thoracic airway epithelium can serve as an indicator of physiological responses to cigarette smoke exposure. Our goal here is to establish whether this same approach might identify similarities and differences in the response to reduced exposure tobacco products. We therefore sought to determine whether the gene-expression alterations upon switching from traditional cigarettes to reduced nicotine product (0.09 mg nicotine yield XODUS) could be detected in readily collected nasal epithelium. Methods: Nasal epithelial brushings were obtained from 13 active smokers who switched to XODUS cigarettes for 6 weeks and then became cigarette free for the remaining 18 weeks. Nasal brushings were obtained at baseline and at 4, 6, 16, and 24-weeks. Self-report was used to determine cigarette use at baseline, 4 and 6 weeks,and self-report and alveolar CO verified cigarette abstinence at 16 and 24 weeks. RNA from the nasal brushings was processed and hybridized to Gene 1.0 ST Arrays. Gene expression alterations at each time point were identified using a linear mixed effects model among a set of 78 genes that we previously found to be altered following smoking cessation. Results: The expression levels of 17 of the 78 smoking cessation-associated genes changed when individuals switched from usual brand cigarettes to Xodus for 6 weeks (P<0.05). XODUS usage resulted in expression levels intermediate between the normal smoking and no smoking time points for several of these genes including CYP1A1 and CYP1B1. These genes were enriched in biological categories including steroid hormone biosynthesis. Conclusion: Our data suggests that some of the gene expression differences induced by switching to the PREP product are intermediate between normal cigarette smoking and cigarette abstinence, consistent with the idea that these products result in reduced exposure. Our study further demonstrates that the nasal epithelium can serve as a minimally invasive tool to measure the responses to alternative tobacco products and can be leveraged to understand the underlying biological mechanisms that are similar and different from smoking-cessation. Citation Format: Kahkeshan Hijazi, Bozena Malyszko, Katrina Steiling, Xiaohui Zhang, Gang Liu, Yuriy Alekseyev, Ji Xiao, Martine Dumas, Louise Hertsgaard, Joni Jenson, Cindy Rohde, Rachel Isaksson, Dorothy Hatsukami, Stephen Hecht, Daniel Brooks, Marc Lenburg, Avrum Spira. Nasal gene expression reflects the physiologic response to alternate tobacco products. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4030. doi:10.1158/1538-7445.AM2013-4030

Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a “healthy” tobacco-free alternative

Tobacco smoking using a waterpipe (narghile, hookah, shisha) has become a global epidemic. Unlike cigarette smoking, little is known about the health effects of waterpipe use. One acute effect of cigarette smoke inhalation is dysfunction in autonomic regulation of the cardiac cycle, as indicated by reduction in heart rate variability (HRV). Reduced HRV is implicated in adverse cardiovascular health outcomes, and is associated with inhalation exposure-induced oxidative stress. Using a 32 participant cross-over study design, we investigated toxicant exposure and effects of waterpipe smoking on heart rate variability when, under controlled conditions, participants smoked a tobacco-based and a tobacco-free waterpipe product promoted as an alternative for “health-conscious” users. Outcome measures included HRV, exhaled breath carbon monoxide (CO), plasma nicotine, and puff topography, which were measured at times prior to, during, and after smoking. We found that waterpipe use acutely decreased HRV (p<0.01 for all measures), independent of product smoked. Plasma nicotine, blood pressure, and heart rate increased only with the tobacco-based product (p<0.01), while CO increased with both products (p<0.01). More smoke was inhaled during tobacco-free product use, potentially reflecting attempted regulation of nicotine intake. The data thus indicate that waterpipe smoking acutely compromises cardiac autonomic function, and does so through exposure to smoke constituents other than nicotine.

Does switching to a tobacco-free waterpipe product reduce toxicant intake? A crossover study comparing CO, NO, PAH, volatile aldehydes, “tar” and nicotine yields

Waterpipe (hookah, narghile, shisha) use has become a global phenomenon, with numerous product variations. One variation is a class of products marketed as “tobacco-free” alternatives for the “health conscious user”. In this study toxicant yields from waterpipes smoked using conventional tobacco-based and tobacco-free preparations were compared. A human-mimic waterpipe smoking machine was used to replicate the puffing sequences of 31 human participants who completed two double-blind ad libitum smoking sessions in a controlled clinical setting: once with a tobacco-based product of their choosing and once with a flavor-matched tobacco-free product. Outcome measures included yields of carbon monoxide, nitric oxide, volatile aldehydes, nicotine, tar, and polycyclic aromatic hydrocarbons. Smoke from both waterpipe preparations contained substantial quantities of toxicants. Nicotine yield was the only outcome that differed significantly between preparations. These findings contradict advertising messages that “herbal” waterpipe products are a healthy alternative to tobacco products.

US smokers' reactions to a brief trial of oral nicotine products

BackgroundIt has been suggested that cigarette smokers will switch to alternative oral nicotine delivery products to reduce their health risks if informed of the relative risk difference. However, it is important to assess how smokers are likely to use cigarette alternatives before making predictions about their potential to promote individual or population harm reduction.ObjectivesThis study examines smokers' interest in using a smokeless tobacco or a nicotine replacement product as a substitute for their cigarettes.MethodsThe study included 67 adult cigarette smokers, not currently interested in quitting, who were given an opportunity to sample four alternative oral nicotine products: 1) Camel Snus, 2) Marlboro Snus, 3) Stonewall dissolvable tobacco tablets, and 4) Commit nicotine lozenges. At visit 1, subjects were presented information about the relative benefits/risks of oral nicotine delivery compared to cigarettes. At visit 2, subjects were given a supply of each of the four products to sample at home for a week. At visit 3, subjects received a one-week supply of their preferred product to see if using such products reduced or eliminated cigarette use.ResultsAfter multiple product sampling, participants preferred the Commit lozenges over the three smokeless tobacco products (p = 0.011). Following the one week single-product trial experience, GEE models controlling for gender, age, level of education, baseline cigarettes use, and alternative product chosen, indicated a significant decline in cigarettes smoked per day across one week of single-product sampling (p < 0.01, from 11.8 to 8.7 cigarettes per day), but no change in alternative product use (approximately 4.5 units per day). Biomarkers of exposure showed no change in cotinine, but a 19% reduction in exhaled CO (p < 0.001).ConclusionsFindings from this study show that smokers, who are currently unwilling to make a quit attempt, may be willing to use alternative products in the short term as a temporary substitute for smoking. However, this use is more likely to be for partial substitution (i.e. they will continue to smoke, albeit at a lower rate) rather than complete substitution. Of the various substitutes offered, smokers were more willing to use a nicotine replacement product over a tobacco-based product.

Estimating Preventable Fractions of Disease Caused by a Specified Biological Mechanism: PAHs in Smoking Lung Cancers as an Example

Epidemiology textbooks often interpret population attributable fractions based on 2 x 2 tables or logistic regression models of exposure-response associations as preventable fractions, i.e., as fractions of illnesses in a population that would be prevented if exposure were removed. In general, this causal interpretation is not correct, since statistical association need not indicate causation; moreover, it does not identify how much risk would be prevented by removing specific constituents of complex exposures. This article introduces and illustrates an approach to calculating useful bounds on preventable fractions, having valid causal interpretations, from the types of partial but useful molecular epidemiological and biological information often available in practice. The method applies probabilistic risk assessment concepts from systems reliability analysis, together with bounding constraints for the relationship between event probabilities and causation (such as that the probability that exposure X causes response Y cannot exceed the probability that exposure X precedes response Y, or the probability that both X and Y occur) to bound the contribution to causation from specific causal pathways. We illustrate the approach by estimating an upper bound on the contribution to lung cancer risk made by a specific, much-discussed causal pathway that links smoking to a polycyclic aromatic hydrocarbon (PAH) (specifically, benzo(a)pyrene diol epoxide-DNA) adducts at hot spot codons at p53 in lung cells. The result is a surprisingly small preventable fraction (of perhaps 7% or less) for this pathway, suggesting that it will be important to consider other mechanisms and non-PAH constituents of tobacco smoke in designing less risky tobacco-based products.

FAIRCHILD AND COLGROVE RESPOND

We appreciate the thoughtful comments and concerns of Giovino, who was intimately involved in the Institute of Medicine’s (IOM’s) assessment of the scientific basis for tobacco harm reduction. We did not state, nor did we intend to imply, that the IOM report was primarily about less hazardous cigarettes. Further, we took care to describe the report as “endorsing harm reduction only ‘as a component of a comprehensive national tobacco control program that emphasizes abstinence-oriented prevention and treatment.’ ” We recognize that the term “safer cigarette” is problematic. But our purpose in the article was to analyze the historical evolution of public health thinking about “safer” products. The belief that such products were possible was central to that history, as was the use of the term “safer cigarettes.” We believe that others who, like us, are interested in how broadly the public health community defines harm reduction in the coming years and what place tobacco products will occupy within that framework will appropriately read the IOM report as stating the need to face squarely the challenge of tobacco-based products.

EXPLORING THE FACTORS THAT INFLUENCE THE UPTAKE OF BOTANICAL INSECTICIDES BY FARMERS: A CASE STUDY OF TOBACCO-BASED PRODUCTS IN NIGERIA

This paper presents the results of extensive experience in the development and promotion of tobacco-based insecticides for the control of field crop pests in Igalaland, Nigeria. A non-governmental organization (NGO), the Diocesan Development Services (DDS), became involved in the development of tobacco-based insecticides in the early 1990s, and facilitated a series of ‘on-farm’ trials between 1997 and 2000 designed to test the effectiveness of such insecticides for two crops that are particularly vulnerable to pest attack in Igalaland: cowpea (Vigna unguiculata) and maize (Zea mays). The results suggest that even crude tobacco formulations had a significant benefit on cowpea and maize yields relative to the absence of pest control, although commercial insecticides were more effective. However, while having advantages of cost and availability over commercial insecticides, tobacco-based products appear to have serious internal and external disadvantages that limit their widespread use, and some of these are discussed. It is concluded that while technical efficacy of botanicals is an important element, there are others such as the logistics of production and preparation that need to be considered. A better understanding of the balance between these factors and how context-specific they may be is required in order to maximize their adoption by farmers under ‘resource-poor’ conditions.