Toxicant exposure in cigarette reducers versus light smokers

Background: The extent of exposure to tobacco toxicants in smokers who have reduced their cigarette intake compared with smokers who are light smokers is relatively unknown. The goal of this study is to investigate the occurrence of compensatory smoking in reducers compared with light smokers by measuring toxicant exposure. Methods: Participants in two smoking reduction intervention studies (N=64) were selected for comparison with a group of light smokers (N=62) who smoked the same number of cigarettes as the reducers. A compensatory smoking score was defined (biomarker level for reducer/biomarker level for light smoker) and calculated for urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (total NNAL), metabolites of the tobaccospecific lung carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone, to measure the degree of smoking compensation in reducers when compared with the light smokers. Results: The mean level of creatinine-adjusted total NNAL for reducers was over twice that of light smokers even when they smoked about the same number of cigarettes per day. The difference of the mean total NNAL concentrations between light smokers and reducers was highly significant (P < 0.0001). Wide variability in total NNAL concentrations was also observed in reducers, with the extent of this variability between light smokers and reducers being significantly different (P=0.0005). The level of individual reduction was shown to be a consistent predictor of compensatory smoking r=0.50; adjusted Ps=0.002), with greater cigarette reduction associated with more compensation. Conclusions: Compensatory smoking limits the harm reduction value of decreased smoking of cigarettes

Review of epidemiologic data on the debate over smokeless tobacco's role in harm reduction

Some tobacco researchers have argued that the European Union should remove its ban on a form of low-nitrosamine smokeless tobacco referred to as Swedish 'snus'. This argument has developed in to an international debate over the use of smokeless tobacco as a measure of harm reduction for smokers. Leading authorities in the USA have firmly stated that there is no safe tobacco - a message which does not allow for any discussion of comparative tobacco risks. This commentary is intended to review the origin of the controversy over Swedish 'snus', to examine briefly the meta-analysis on cancer risks by Peter Lee and Jan Hamling (published in July in BMC Medicine) and to discuss the anticipated direction of the debate on tobacco-harm reduction in the USA. We anticipate that much of the debate will shift from the discussion of epidemiologic data to the discussion of the marketing, health communication and economics of smokeless tobacco. While the Food and Drug Administration's newly approved authority over tobacco will undoubtedly affect the smokeless products, it may not be the sole determinant of harm reduction's fate in the USA

Determinants of Salivary Cotinine among Smokeless Tobacco Users : A Cross-Sectional Survey in Bangladesh

INTRODUCTION: More than 80% of all smokeless tobacco (ST) products in the world are consumed in South Asia; yet little is known about their consumption behaviour, addictiveness, and toxic properties. This paper, for the first time, describes associations between salivary cotinine concentrations among ST users in Bangladesh and their socio-demographic characteristics and tobacco use behaviours. METHODS: In a survey of ST users in Dhaka, Bangladesh, we purposively recruited 200 adults who were non-smokers but consumed ST on a regular basis. In-person interviews were conducted to obtain information about socio-demographic and ST use behaviours, and saliva samples were collected to measure cotinine concentration. Simple and multiple linear regression analyses were conducted to test associations between the log transformed salivary cotinine concentration and other study variables. RESULTS: The geometric mean of cotinine concentration among ST users was 380ng/ml (GSD:2). Total duration of daily ST use in months had a statistically significant association with cotinine concentration. Other ST use characteristics including type and quantity of ST use, swallowing of tobacco juice, urges and strength of urges and attempts to cut down on tobacco use were not found to be associated with cotinine concentration in a multivariable model. CONCLUSION: This is the first report from Bangladesh studying cotinine concentration among ST users and it points towards high levels of addiction. This warrants effective tobacco control policies to help ST cessation and prevention

Measurement of nicotine withdrawal symptoms: linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) in Malay

<p>Abstract</p> <p>Background</p> <p>The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research.</p> <p>Methods</p> <p>A seven-member translation committee conducted the translation process using the following methodology: production of two independent forward translations; comparison and reconciliation of the translations; backward translation of the first reconciled version; comparison of the original WSWS and the backward version leading to the production of the second reconciled version; pilot testing and review of the translation, and finalization.</p> <p>Results</p> <p>Linguistic and conceptual issues arose during the process of translating the instrument, particularly pertaining to the title, instructions, and some of the items of the scale. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. Notable among these include expressions such as "irritability", "feeling upbeat", and "nibbling on snacks", which had to be replaced by culturally acceptable expressions. During cognitive debriefing and clinician's review processes, the Malay translated version of WSWS was found to be easily comprehensible, clear, and appropriate for the smoking withdrawal symptoms intended to be measured.</p> <p>Conclusions</p> <p>We applied a rigorous translation method to ensure conceptual equivalence and acceptability of WSWS in Malay prior to its utilization in research and clinical practice. However, to complete the cultural adaptation process, future psychometric validation is planned to be conducted among Malay speakers.</p

Suicidal Behavior and Depression in Smoking Cessation Treatments

BACKGROUND: Two treatments for smoking cessation--varenicline and bupropion--carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown. METHODOLOGY: From the FDA's Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug. RESULTS: Overall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8-10.4), and bupropion 2.9 (2.3-3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment. CONCLUSIONS: Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation

A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial

BACKGROUND: Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period. METHODOLOGY/PRINCIPAL FINDINGS: 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012). CONCLUSIONS: Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction. TRIAL REGISTRATION: Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616

Immunogenicity of a Promiscuous T Cell Epitope Peptide Based Conjugate Vaccine against Benzo[a]pyrene: Redirecting Antibodies to the Hapten

The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142–51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15–56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted

The Global Research Neglect of Unassisted Smoking Cessation: Causes and Consequences

Simon Chapman and Ross MacKenzie review the evidence and argue that health promotion messages should emphasize that the most successful method used by most ex-smokers is unassisted cessation

What potential has tobacco control for reducing health inequalities? The New Zealand situation

In this Commentary, we aim to synthesize recent epidemiological data on tobacco and health inequalities for New Zealand and present it in new ways. We also aim to describe both existing and potential tobacco control responses for addressing these inequalities. In New Zealand smoking prevalence is higher amongst Māori and Pacific peoples (compared to those of "New Zealand European" ethnicity) and amongst those with low socioeconomic position (SEP). Consequently the smoking-related mortality burden is higher among these populations. Regarding the gap in mortality between low and high socioeconomic groups, 21% and 11% of this gap for men and women was estimated to be due to smoking in 1996–99. Regarding the gap in mortality between Māori and non-Māori/non-Pacific, 5% and 8% of this gap for men and women was estimated to be due to smoking. The estimates from both these studies are probably moderate underestimates due to misclassification bias of smoking status. Despite the modest relative contribution of smoking to these gaps, the absolute number of smoking-attributable deaths is sizable and amenable to policy and health sector responses. There is some evidence, from New Zealand and elsewhere, for interventions that reduce smoking by low-income populations and indigenous peoples. These include tobacco taxation, thematically appropriate mass media campaigns, and appropriate smoking cessation support services. But there are as yet untried interventions with major potential. A key one is for a tighter regulatory framework that could rapidly shift the nicotine market towards pharmaceutical-grade nicotine (or smokeless tobacco products) and away from smoked tobacco