Commentary: Cigarette dependence in menthol and non-menthol young adult cigarette smokers.

FDA's Proposed Final Rule to ban menthol cigarettes asserts that "menthol cigarettes contribute to greater nicotine dependence in youth and young adults than non-menthol cigarettes." However, none of the publications referenced included young adults. To provide empirical evidence on the subject, we examine smoking frequency and Heaviness of Smoking Index (HSI) dependence among 2,194 young adult (ages 18-25 years) menthol and non-menthol smokers from 31 online survey samples. Unpaired t-tests examined if daily smoking or the proportion of daily smokers who are low or high dependence on the HSI vary by menthol cigarette smoking status. Young adult menthol smokers were less likely to be daily smokers than young adult non-menthol smokers. There were no differences in the percentages of daily menthol and non-menthol smokers categorized as low or high dependence on the HSI. Smoking menthol cigarettes, therefore, does not appear to be associated with greater cigarette dependence among young adults than smoking non-menthol cigarettes.

Heaviness of smoking index in menthol and non-menthol smokers.

BACKGROUND: It has been hypothesized that menthol in cigarettes increases dependence. Several studies suggest that menthol and non-menthol smokers have similar or lower levels of dependence, but those studies are not without limitations. The Heaviness of Smoking Index (HSI) is a widely accepted, validated measure of cigarette dependence. OBJECTIVES: This report aims to provide further evidence regarding dependence among menthol and non-menthol smokers, as indicated by daily smoking and as measured by the HSI. METHODS: Survey data from 27,131 adult smokers were analyzed to compare the percent of menthol and non-menthol smokers who are daily smokers, and the percentage who are low or high HSI dependence. Logistic regressions were also conducted to determine if menthol use predicts daily smoking, and low or high dependence after controlling for demographic differences. RESULTS: Comparisons among weighted samples of adult smokers demonstrate that menthol smokers were consistently more likely to be non-daily smokers, more likely to be in the low dependence category, and less likely to be in the high dependence category on the HSI as compared to non-menthol smokers. Logistic regression confirmed that when controlling for age, gender, race/ethnicity, and education, relative to non-menthol smokers, menthol smokers had no difference in odds of being in the low dependence HSI category and significantly lower odds of being a daily smoker, and of being in the high dependence category. CONCLUSIONS: These analyses support the conclusion that, based on the HSI, menthol smokers are not more cigarette dependent than non-menthol smokers, and may be less dependent.

Measures of dependence in menthol and nonmenthol smokers - A comprehensive narrative review.

Introduction. More than a decade ago, concerns were raised that menthol in cigarettes might enhance addiction to smoking. This article provides a comprehensive review of published studies examining cigarette dependence among menthol and nonmenthol smokers. The purpose of the review is to evaluate the scientific evidence to determine if menthol increases cigarette dependence. Materials and Methods. The published literature was searched in 2019 for studies that provide evidence on cigarette dependence among menthol compared to nonmenthol smokers. Included in this review are published studies that compare menthol and nonmenthol smokers based on widely accepted and validated measures of dependence, or other established predictors of dependence (age of smoking initiation [first cigarette]/age of progression [regular/daily smoking]) and indicators of dependence (smoking frequency, cigarettes smoked per day, time to first cigarette after waking, night waking to smoke, smoking duration). Results and Conclusion. Based on a review of the available studies, including those with adjusted results and large representative samples, reliable and consistent empirical evidence supports a conclusion that menthol smokers are not more dependent than nonmenthol smokers and thus menthol in cigarettes does not increase dependence.

A Well-Mixed Computational Model for Estimating Room Air Levels of Selected Constituents from E-Vapor Product Use.

Concerns have been raised in the literature for the potential of secondhand exposure from e-vapor product (EVP) use. It would be difficult to experimentally determine the impact of various factors on secondhand exposure including, but not limited to, room characteristics (indoor space size, ventilation rate), device specifications (aerosol mass delivery, e-liquid composition), and use behavior (number of users and usage frequency). Therefore, a well-mixed computational model was developed to estimate the indoor levels of constituents from EVPs under a variety of conditions. The model is based on physical and thermodynamic interactions between aerosol, vapor, and air, similar to indoor air models referred to by the Environmental Protection Agency. The model results agree well with measured indoor air levels of nicotine from two sources: smoking machine-generated aerosol and aerosol exhaled from EVP use. Sensitivity analysis indicated that increasing air exchange rate reduces room air level of constituents, as more material is carried away. The effect of the amount of aerosol released into the space due to variability in exhalation was also evaluated. The model can estimate the room air level of constituents as a function of time, which may be used to assess the level of non-user exposure over time.

Predictors, indicators, and validated measures of dependence in menthol smokers.

This article presents a comprehensive review of the menthol cigarette dependence-related literature and results from an original analysis of the Total Exposure Study (TES), which included 1,100 menthol and 2,400 nonmenthol adult smokers. The substantial scientific evidence available related to age of first cigarette, age of regular use, single-item dependence indicators (smoking frequency, cigarettes per day, time to first cigarette, night waking to smoke), smoking duration, numerous validated and widely accepted measures of nicotine/cigarette dependence, and our analysis of the TES do not support that menthol smokers are more dependent than nonmenthol smokers or that menthol increases dependence.

Cigarettes with different nicotine levels affect sensory perception and levels of biomarkers of exposure in adult smokers.

INTRODUCTION: Few clinical studies involving cigarettes have provided a comprehensive picture of smoke exposure, test article characterization, and insights into sensory properties combined. The purpose of these pilot studies was to determine whether cigarettes with different levels of nicotine but similar tar levels would affect sensory experience or smoking behavior so as to significantly alter levels of selected biomarkers of exposure (BOE). METHODS: In 2 confined, double-blind studies, 120 adult smokers switched from Marlboro Gold cigarettes at baseline to either 1 of 2 lower nicotine cigarettes or 1 of 2 higher nicotine cigarettes and then to the other cigarette after 5 days. Urinary excretion of exposure biomarkers (nicotine equivalents [NE], total and free 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL], 1-hydroxypyrene, and 3-hydroxypropyl mercapturic acid) as well as carboxyhemoglobin and plasma cotinine were measured at baseline, Day 5, and Day 10. Daily cigarette consumption was monitored and sensory characteristics were rated for each cigarette. RESULTS: With higher nicotine yield, urine NE, urine total NNAL, and plasma cotinine increased while nonnicotine BOE decreased without changes in cigarette consumption. In contrast, with lower nicotine yield, urine NE, urine total NNAL, and plasma cotinine dropped while nonnicotine BOE and cigarettes per day increased. Higher nicotine cigarettes were rated harsher and stronger than at baseline while lower nicotine cigarettes were less strong. All 4 test cigarettes were highly disliked. CONCLUSIONS: These studies demonstrate that abrupt increases or decreases in nicotine and the resulting sensory changes impact BOE through changes in intensity or frequency of smoking.

Factors affecting exposure to nicotine and carbon monoxide in adult cigarette smokers.

Exposure to cigarette smoke among smokers is highly variable. This variability has been attributed to differences in smoking behavior as measured by smoking topography, as well as other behavioral and subjective aspects of smoking. The objective of this study was to determine the factors affecting smoke exposure as estimated by biomarkers of exposure to nicotine and carbon monoxide (CO). In a multi-center cross-sectional study of 3585 adult smokers and 1077 adult nonsmokers, exposure to nicotine and CO was estimated by 24h urinary excretion of nicotine and five of its metabolites and by blood carboxyhemoglobin, respectively. Number of cigarettes smoked per day (CPD) was determined from cigarette butts returned. Puffing parameters were determined through a CreSS® micro device and a 182-item adult smoker questionnaire (ASQ) was administered. The relationship between exposure and demographic factors, smoking machine measured tar yield and CPD was examined in a statistical model (Model A). Topography parameters were added to this model (Model B) which was further expanded (Model C) by adding selected questions from the ASQ identified by a data reduction process. In all the models, CPD was the most important and highest ranking factor determining daily exposure. Other statistically significant factors were number of years smoked, questions related to morning smoking, topography and tar yield categories. In conclusion, the models investigated in this analysis, explain about 30-40% of variability in exposure to nicotine and CO.

A comprehensive evaluation of the toxicology of cigarette ingredients: aromatic and aliphatic alcohol compounds.

CONTEXT: Various aromatic and aliphatic alcohol compounds are found in tobacco and tobacco smoke. OBJECTIVE: A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing eight aromatic and aliphatic alcohol compounds that were added individually to experimental cigarettes at three different levels. The lowest target inclusion level was 100 ppm and the highest level was 24,400 ppm. MATERIALS AND METHODS: Mainstream smoke from each of the cigarette types was evaluated using analytical chemistry and assays to measure in vitro cytotoxicity (neutral red uptake) and Salmonella (five strains) mutagenicity. For three of the compounds (benzyl alcohol, propyl paraben, and rum flavor), 90-day smoke inhalation studies with 6-week recovery periods were also performed using rats. RESULTS: Inclusion of eugenol produced several dose-related reductions in concentrations of selected smoke constituents. Cytotoxicity and mutagenicity were unaffected by any of the test ingredients, except for dose-related reductions in cytotoxicity of the gas vapor phase produced by the inclusion of eugenol. The three smoke inhalation studies showed a few sporadic differences between the groups and there were no differences in the patterns of recovery for any of the ingredients. CONCLUSIONS: Despite using exaggerated inclusion levels of the eight aliphatic and aromatic alcohol compounds in experimental cigarettes, there was minimal toxicological response, which is consistent with published reports of studies using mixtures of compounds added to tobacco.

Relationship between biomarkers of cigarette smoke exposure and biomarkers of inflammation, oxidative stress, and platelet activation in adult cigarette smokers.

BACKGROUND: Cigarette smoking is a risk factor for several diseases, including cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, but the role of specific smoke constituents in these diseases has not been clearly established. METHODS: The relationships between biomarkers of potential harm (BOPH), associated with inflammation [white blood cell (WBC), high sensitivity C-reactive protein (hs-CRP), fibrinogen, and von Willebrand factor (vWF)], oxidative stress [8-epi-prostaglandin F(2α) (8-epiPGF(2α))] and platelet activation [11-dehydro-thromboxin B(2) (11-dehTxB(2))], and machine-measured tar yields (grouped into four categories), biomarkers of exposure (BOE) to cigarette smoke: nicotine and its five metabolites (nicotine equivalents), 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (total NNAL), carboxyhemoglobin, 1-hydroxypyrene, 3-hydroxypropylmercapturic acid, and monohydroxybutenyl-mercapturic acid, were investigated in 3,585 adult smokers and 1,077 nonsmokers. RESULTS: Overall, adult smokers had higher levels of BOPHs than nonsmokers. Body mass index (BMI), smoking duration, tar category, and some of the BOEs were significant factors in the multiple regression models. Based on the F value, BMI was the highest ranking factor in the models for WBC, hs-CRP, fibrinogen, and 8-epiPGF(2α), respectively, and gender and smoking duration for 11-dehTxB(2) and vWF, respectively. CONCLUSIONS: Although several demographic factors and some BOEs were statistically significant in the model, the R(2) values indicate that only up to 22% of the variability can be explained by these factors, reflecting the complexity and multifactorial nature of the disease mechanisms. IMPACT: The relationships between the BOEs and BOPHs observed in this study may help with the identification of appropriate biomarkers and improve the design of clinical studies in smokers.

The relationship between nicotine dependence scores and biomarkers of exposure in adult cigarette smokers.

BACKGROUND: Tobacco dependence is a multidimensional phenomenon. The Fagerström Test for Nicotine Dependence (FTND) is a widely administered six-item questionnaire used as a measure of nicotine dependence. It has been suggested that this test may not represent the entire spectrum of factors related to dependence. Also the relationship of this test with biomarkers of exposure to cigarette smoke has not been extensively studied. METHODS: Data from a multi-center, cross-sectional, ambulatory study of US adult smokers (the Total Exposure Study, TES) was analyzed. The FTND score and a number of additional questions related to smoking behavior, from an adult smoker questionnaire (ASQ) completed by 3585 adult smokers in the TES were analyzed. The 24-h urine nicotine equivalents, serum cotinine and blood carboxyhemoglobin were measured as biomarkers of exposure (BOE) to nicotine and carbon monoxide. Cigarette butts returned were collected during the 24-h urine collection period. RESULTS: The FTND showed moderate correlations with BOE, while selected questions from ASQ although statistically significant, had weaker correlations. FTND scores showed substantially weaker correlations without the question about cigarettes smoked per day (CPD). CPD and time to first cigarette (TTFC) had the most impact on BOE. CONCLUSION: Additional questions from ASQ did not appear to contribute towards refining the FTND test. The correlation of the FTND scores with nicotine and carbon monoxide seems to be primarily driven by CPD. CPD and TTFC were the most important factors correlating with exposure.

Biomarkers of potential harm among adult smokers and nonsmokers in the total exposure study.

INTRODUCTION: There is overwhelming medical and scientific consensus that cigarette smoking causes lung cancer, heart disease, emphysema, and other serious diseases in smokers. In the Total Exposure Study, 29 biomarkers of potential harm (BOPH) were measured in a cross-sectional sample of 3,585 adult smokers (AS) and 1,077 nonsmokers (NS). The BOPH included markers of oxidative stress, inflammation, platelet activation, endothelial function, lipid metabolism, hematology, metabolism, the cardiovascular system, lung function, kidney function, and liver function. METHODS: Multiple stepwise regression was used to examine the effect of demographic factors (age, gender, body mass index [BMI], and race) and smoking (number of cigarettes smoked per day or nicotine equivalents [NE] per 24 hr and smoking duration) on each BOPH. RESULTS: As compared with NS, AS had >10% higher levels of 8-epi-prostaglandin F(2α) (8-epi-PG F(2α), 42%), 11-dehydrothromboxane B2 (11-DHTB, 29%), white blood cell (WBC) count (19%), high-sensitivity C-reactive protein (15%), triglycerides (16%), and alkaline phosphatase (11%) and had 18% lower total bilirubin. Multiple stepwise regression revealed that although NE (milligrams per 24 hours) was statistically significant for 18 of the 29 BOPH, it was the most important factor only for WBCs and 11-DHTB. Smoking duration was the most important factor for forced expiratory volume in 1 second. In contrast, BMI was the most important factor for 12 BOPH. CONCLUSIONS: These results contribute to the understanding of the relationship between tobacco smoking and potential biological effects.

Does dual use jeopardize the potential role of smokeless tobacco in harm reduction?

INTRODUCTION: The use of smokeless tobacco as part of a strategy to reduce the harm from cigarette smoking is a topic of debate within the tobacco control and public health communities. One concern voiced regarding endorsement of such a tactic is the possibility of actually increasing harm should current smokers adopt dual cigarette/smokeless tobacco use (dual use), which could lead to unintended consequences by perpetuating cigarette smoking, diminishing tobacco cessation, or increasing tobacco-related harm. METHODS: Here, we review the available literature on health effects and trajectories of use among dual users from a variety of U.S. and European epidemiological studies. RESULTS: These data suggest that there are not any unique health risks associated with dual use of smokeless tobacco products and cigarettes, which are not anticipated or observed from cigarette smoking alone. Furthermore, studies show that dual users smoke fewer cigarettes than exclusive smokers, and studies of tobacco use patterns over time (tobacco use trajectory data) indicate that dual users are more likely than exclusive cigarette smokers to cease smoking. CONCLUSIONS: Overall, the concern about dual use appears to be contradicted by the evidence in the literature that dual use of smokeless tobacco and cigarettes may result in reduction in smoking-related harm as smoking intensity is decreased and smoking cessation increases.

The relationship between smoking machine derived tar yields and biomarkers of exposure in adult cigarette smokers in the US.

UNLABELLED: Comprehensive data on human exposure to smoke constituents from different machine-measured tar yield cigarettes is limited. METHODS: This study used a stratified, cross-sectional, multi-center design to estimate biomarkers of exposure (BOE) from nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene, CO, acrolein, and 1,3-butadiene and their relationship to tar yield categories of cigarette in adult smokers in the U.S. 3625 adults smokers were enrolled into four tar categories < or =2.9 mg (T1), 3.0-6.9 mg (T2), 7.0-12.9 mg (T3), and > or =13.0mg (T4). Biomarkers were measured in blood (carboxyhemoglobin, 4-aminobiphenyl-hemoglobin (4-ABP-Hb)-adducts, serum cotinine) and 24h urine (nicotine and five metabolites, calculated as nicotine equivalents (NE), NNAL, 1-OH-pyrene, 3-HPMA, MHBMA and DHBMA). Data were analyzed using analysis of covariance (ANCOVA). RESULTS: Tar was a significant factor for most biomarkers in the ANCOVA models. The largest least square mean differences between tar categories was 35% for NE per day, 28% for NE per cigarette, 36% for serum cotinine, 42% for NNAL per day, 29% for NNAL per cigarette, 26% for 1-OHP, 24% for COHb, 14% for 3-HPMA and 40% for 4-ABP-Hb. Variability in BOE ranged from 41% to 154% CV. CONCLUSIONS: There was a statistically significant effect of machine-measured tar yield on most BOE, which were generally lower with lower tar yield.

Evaluation of biomarkers of exposure to selected cigarette smoke constituents in adult smokers switched to carbon-filtered cigarettes in short-term and long-term clinical studies.

Cigarette smoke is a complex aerosol that includes a gas vapor phase and a particulate phase. Inclusion of activated carbon in the cigarette filter can reduce some of the gas-phase smoke constituents implicated as toxicologically relevant. The present study evaluated exposure to selected gas-phase constituents when adult smokers switched to prototype cigarettes with a highly activated carbon filter. Smokers (N = 160) in two separate studies were randomized to continue to smoke conventional cigarettes (either a 6-mg or 11-mg FTC tar product), to smoke test cigarettes containing carbon filters (comparable tar levels), or to stop smoking. After completing 8 days in controlled smoking conditions (short-term studies), smokers had the option to continue in 24-week long-term ambulatory studies with unrestricted smoking. Urinary excretion of mercapturic acid metabolites of 1,3-butadiene, acrolein, and benzene; nicotine and five of its metabolites, total NNAL, and 1-hydroxypyrene were measured at baseline in the conventional cigarette group, in all groups in the short-term studies, and every 4 weeks in the long-term studies. In the short-term studies, statistically significant reductions (>70%, p<.001) in gas-phase biomarker levels were observed in the test cigarette group for both tar level products compared with the conventional cigarette group. These reductions were similar to those observed in the stop-smoking groups. The reductions continued consistently (p<.001) throughout the long-term studies. Switching to test cigarettes minimally affected the particulate-phase biomarkers. Statistically significant and consistent reductions in selected gas vapor phase biomarkers were observed when smokers switched to activated carbon filter cigarettes.

Short-term clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers.

This randomized, controlled, forced-switching, open-label, parallel-group, single-center study in 100 male and female adult smokers evaluated 12 biomarkers of tobacco smoke exposure. We measured exposure to the following smoke constituents: nicotine, pyrene, tobacco-specific nitrosamines, three aromatic amines, carbon monoxide, benzene, acrolein, crotonaldehyde, and 1,3-butadiene. After baseline exposure determination, adult smokers of a conventional cigarette (CC) were switched to an electrically heated cigarette smoking system (EHCSS, Series K), continued smoking the CC, or stopped smoking (No-smoking) for 8 days in a controlled, confined, clinical setting. In the EHCSS group, the mean decrease from Baseline to Day 8 in the biomarkers of exposure ranged from 16% to 77% at Day 8 compared to Baseline. After adjusting for the residual effect (carryover effects due to long elimination half-life and non-tobacco confounding sources of exposure), the mean percent decrease from Baseline for all 12 biomarkers ranged from 47% to 90%. In conclusion, switching for 8 days from a conventional cigarette to the EHCSS substantially reduced exposure of adult smokers to several constituents of both the particulate and gas phases of cigarette smoke.

Environmental tobacco smoke (ETS) evaluation of a third-generation electrically heated cigarette smoking system (EHCSS).

This sub-study of a randomized, controlled, forced-switching, open-label, parallel-group, clinical study compared environmental tobacco smoke (ETS) produced when 60 male and female adult smokers switched to a third-generation electrically heated cigarette smoking system (EHCSS), continued to smoke a conventional cigarette (CC), or stopped smoking (No-smoking). Concentrations of air constituents including respirable suspended particulate (RSP), carbon monoxide (CO), ammonia and total volatile organic compounds (TVOCs) and ETS markers including solanesol-related particulate matter (Sol-PM), ultraviolet absorbing particulate matter (UVPM), fluorescent particulate matter (FPM), nicotine and 3-ethenyl pyridine (3-EP) were measured in a ventilated, furnished conference room over a 2-h period on separate occasions for each smoking condition. When the EHCSS was used, concentrations of CO and most ETS markers were in the same range as during no-smoking. Concentrations of ammonia were reduced by 41% and concentrations of other selected constituents of ETS were reduced by 87-99% in the air of a room in which EHCSS cigarettes were smoked as compared to concentrations in the same room when conventional cigarettes were smoked. Switching from conventional cigarette smoking to the EHCSS resulted in substantial reductions in concentrations of several markers of environmental tobacco smoke.

12-week clinical exposure evaluation of a third-generation electrically heated cigarette smoking system (EHCSS) in adult smokers.

This randomized, controlled, forced-switching, open-label, parallel-group, single-center study in 90 male and female adult smokers evaluated six biomarkers of tobacco smoke exposure over a 12-week period of unrestricted smoking in the participants' normal life setting. Baseline biomarker levels were measured, then participants were randomly assigned to switch to an electrically heated cigarette smoking system (EHCSS, Series K) or to continue smoking a conventional cigarette (CC) of similar tar yield (Federal Trade Commission method) for 12 weeks. Compared to Baseline, adult smokers who switched to the EHCSS for 12 weeks in their normal life setting had significantly reduced nicotine equivalents (-33%), total NNAL (a biomarker for NNK, -63%), 1-OHP (a surrogate biomarker for polycyclic aromatic hydrocarbons, -38%), carboxyhemoglobin (a biomarker for carbon monoxide, -23%), 3-HPMA (a biomarker for acrolein, -25%) and S-PMA (a biomarker for benzene, -49%), whereas exposure was stable in the CC control group.

Tobacco and psychiatric dual disorders.

Smoking is a leading cause of morbidity and premature mortality in the United States. The relationship between tobacco smoking and several forms of cancer, heart disease, stroke, chronic lung disease, and other medical diseases is well recognized and accepted. Recent epidemiological studies are now focusing on the link between tobacco use and psychiatric diseases. Experts now suggest that in the differential diagnosis of "smoker," depression, alcohol dependence, and schizophrenia are highest on the list. Studies are also focusing on the role of secondhand tobacco exposure, either in utero or during childhood, in the risk of dual disorders. Prenatal exposure may alter gene expression and change the risk for a variety of life-long psychiatric diseases, e.g., ADD/ADHD, antisocial personality disorders, substance use disorders, and major depression. Considerable time and effort have been devoted to studying the link between smoking and depression and also schizophrenia. We will focus on less well-studied areas in tobacco use and psychiatric dual disorders (including eating disorders), prenatal and early childhood secondhand smoke (SHS) exposure, and the relationship to the genesis of these dual disorders.

Weight gain during substance abuse treatment: the dual problem of addiction and overeating in an adolescent population.

Obesity and substance abuse during adolescence have reached epidemic proportions, and both are among the leading major public health problems in the United States. There is a significant amount of weight and Body Mass Index (BMI) gain in adolescent ex-addicts during supervised and confirmed abstinence from drugs and alcohol. The primary purpose of this secondary data analysis was to examine the effectiveness of two interventions implemented to address weight management in residential facilities treating adolescent substance use disorders. The secondary purpose was to establish if the outcome was a function of mandated smoking cessation and prescribed psychotropic medications. The results of the study suggest adolescents experienced weight gain in all groups, however there was no interaction effect for smokers and those adolescents on psychotropic medication for either outcome variable.