Trends and Associations of Past-30-Day Cigar Smoking in the U.S. by Age, Race/Ethnicity, and Sex, NSDUH 2002-2020.

Cigar smoking remains a public health issue in the United States (U.S.), with a heterogeneous prevalence based on sociodemographic characteristics. Nationally representative data suggest changes in cigar smoking over time, with some evidence for sociodemographic differences. Using data from the 2002-2019 National Survey on Drug Use and Health (NSDUH), the prevalence of past-30-day cigar smoking was examined overall and stratified by sociodemographic characteristics; joinpoint regression examined the trends. Logistic regression analyses identified the correlates of cigar smoking using 2020 NSDUH data. From 2002 to 2004, the prevalence of cigar smoking remained stable (5.33-5.73%), but declined from 2004 to 2019 (5.73-4.29%). Cigar smoking declined in some periods between 2002-2019 among the non-Hispanic White, Hispanic, ages 12-17, ages 18-20, ages 21-25, age ≥ 35, and male subgroups, but remained unchanged among the non-Hispanic Other, ages 26-34, and female subgroups. Cigar smoking increased among non-Hispanic Black persons overall from 2002 to 2019 (6.67-8.02%). Past-30-day cigarette smoking and drug or alcohol use disorder was associated with an increased likelihood of cigar use, while female sex was associated with a decreased likelihood of cigar use, across all age groups. Though a decline in the prevalence of past-30-day cigar smoking is seen in the general population, the same is not evident among all sociodemographic subgroups. Our findings have the potential to inform tobacco cessation efforts within clinical practice, as well as regulatory efforts to reduce cigar use.

Stagnant daily smoking prevalence between 2008 and 2019 among Black and Hispanic adults with serious psychological distress.

BACKGROUND: Racial/ethnic minority status and mental illness independently drive inequity in cigarette smoking and related morbidity. Racial/ethnic minority groups suffer a disproportionate burden of tobacco-related diseases. People with serious mental illness (SMI) smoke at up to 7 times the rate of the general population. There is a need to quantify smoking prevalence and trends among people at the intersection of both groups. METHODS: This study analyzes 2008-2019 data from the National Survey on Drug Use and Health. Linear time trends of daily smoking prevalence were assessed among people with serious psychological distress (SPD; marker for SMI) and people without SPD reporting White, Black, Hispanic, and Other race/ethnicity using logistic regression, with survey year as the predictor. Models with year-by-smoking status interaction terms and F-tests assessed differential time trends. RESULTS: The prevalence of daily smoking among people without SPD decreased over time among people reporting White (aOR=0.96, p<0.001), Black (aOR=0.96, p<0.001), Hispanic (aOR=0.95, p<0.001), and Other (aOR=0.97, p=0.002) race/ethnicity. Among people with SPD, the smoking prevalence decreased among people with White race/ethnicity (aOR=0.95, p<0.001), with no significant changes among people of Black, Hispanic, and Other race/ethnicity. CONCLUSIONS: Smoking among people with SPD who report Black and Hispanic race/ethnicity has not changed significantly in the past 11 years, despite decreasing among non-SPD and White groups. People who are Black/Hispanic and people with SPD struggle to quit smoking, which is amplified intersectionally. Tailored interventions may be a better mechanism to reduce barriers to smoking cessation in this population.

Effects of advertising features on smokers' and non-smokers' perceptions of a reduced nicotine cigarette modified risk tobacco product.

INTRODUCTION: Research is needed to determine the impact of marketing on perceptions and use of reduced nicotine content (RNC) cigarettes, particularly as US regulators have permitted the sale of an RNC cigarette modified risk tobacco product (MRTP) that seeks further authorisation to advertise using modified risk claims. This study examined the effects of two advertising elements (product name and disclaimer content) on perceptions of an RNC cigarette MRTP. METHODS: Adult participants (n=807, 28.7% smokers, 58.2% male, 74.2% non-Latinx white) completed an online MTurk survey. Participants were randomised to view one of six RNC cigarette advertisements, using a 2×3 between-subject factorial design to manipulate product name ('Moonlight' vs 'Moonrise') and disclaimer content (industry-proposed: 'Nicotine is addictive. Less nicotine does NOT mean a safer cigarette' vs focused: 'Less nicotine does NOT mean a safer cigarette' vs no content), then completed recall and product perception questionnaires. RESULTS: All participants who viewed the industry-proposed disclaimer (vs no content) perceived greater addiction risk (p's<0.05). Non-smokers who viewed this disclaimer also perceived greater health risks and held fewer false beliefs (p's<0.05). Smokers who viewed Moonlight (vs Moonrise) ads perceived lower health risks (p<0.05). CONCLUSIONS: Disclaimer content may effectively inform consumers about addiction risk of a new RNC cigarette MRTP, and further inform non-smokers about health risks. This element, however, had little effect on perceived health risks among smokers, among whom the Moonlight product name was associated with health risk misperceptions similar to the banned 'light' descriptor.

Early Changes in Puffing Intensity When Exclusively Using Open-Label Very Low Nicotine Content Cigarettes.

INTRODUCTION: In response to reducing cigarette nicotine content, people who smoke could attempt to compensate by using more cigarettes or by puffing on individual cigarettes with greater intensity. Such behaviors may be especially likely under conditions where normal nicotine content (NNC) cigarettes are not readily accessible. The current within-subject, residential study investigated whether puffing intensity increased with very low nicotine content (VLNC) cigarette use, relative to NNC cigarette use, when no other nicotine products were available. AIMS AND METHODS: Sixteen adults who smoke daily completed two four-night hotel stays in Charleston, South Carolina (United States) in 2018 during which only NNC or only VLNC cigarettes were accessible. We collected the filters from all smoked cigarettes and measured the deposited solanesol to estimate mouth-level nicotine delivery per cigarette. These estimates were averaged within and across participants, per each 24-h period. We then compared the ratio of participant-smoked VLNC and NNC cigarette mouth-level nicotine with the ratio yielded by cigarette smoking machines (when puffing intensity is constant). RESULTS: Average mouth-level nicotine estimates from cigarettes smoked during the hotel stays indicate participants puffed VLNC cigarettes with greater intensity than NNC cigarettes in each respective 24-h period. However, this effect diminished over time (p < .001). Specifically, VLNC puffing intensity was 40.0% (95% CI: 29.9, 53.0) greater than NNC puffing intensity in the first period, and 16.1% (95% CI: 6.9, 26.0) greater in the fourth period. CONCLUSION: Average puffing intensity per cigarette was elevated with exclusive VLNC cigarette use, but the extent of this effect declined across four days. IMPLICATIONS: In an environment where no other sources of nicotine are available, people who smoke daily may initially attempt to compensate for cigarette nicotine reduction by puffing on individual cigarettes with greater intensity. Ultimately, the compensatory behavior changes required to achieve usual nicotine intake from VLNC cigarettes are drastic and unrealistic. Accordingly, people are unlikely to sustain attempts to compensate for very low cigarette nicotine content.

Multiple Tobacco Product Use Conceptual Framework: A 2021 Update on Evidence.

INTRODUCTION: One-third of adults in the United States who use tobacco regularly use two or more types of tobacco products. As the use of e-cigarettes and other noncombusted tobacco products increases-making multiple tobacco product (MTP) use increasingly common-it is essential to evaluate the complex factors that affect product use. AIMS AND METHODS: In this update to our 2019 conceptual framework, we review and evaluate recent literature and expand the model to include ways in which MTP use may be affected by market factors such as the introduction of new products and socioenvironmental factors like marketing and advertising. RESULTS AND CONCLUSIONS: MTP use patterns are complex, dynamic, and multiply determined by factors at the level of individuals, products, situations or contexts, and marketplace. Substitution, or using one product with the intent of decreasing use of another, and complementarity, or using multiple products for different reasons or purposes, explain patterns in MTP use. Moreover, substitution and complementarity may inform our understanding of how market changes targeted at one product, for instance, new product standards, bans, product pricing, and taxation, affect consumption of other tobacco products. New data from natural experiments and novel laboratory-based techniques add additional data and expand the framework. IMPLICATIONS: A substantial proportion of people who use tobacco use more than one product. This review synthesizes and evaluates recent evidence on the diverse factors that affect MTP use in addition to expanding our framework. Our review is accompanied by suggested research questions that can guide future study.

Appeal, subjective effects, and relative reinforcing effects of JUUL that vary in flavor and nicotine content.

The U.S. Food and Drug Administration has the authority to regulate characteristics of electronic nicotine delivery systems (ENDS). Prior research indicates that regulation of certain characteristics of these products may have an effect on their appeal and use. Policies that affect appeal and use of ENDS are relevant to attempts to reduce use among young people-including young adults-but are also relevant to adults who use these products as harm reduction tools. Using a novel concurrent choice task, we evaluated the relative reinforcement of JUUL brand ENDS products that varied in flavor (n = 8) and nicotine (n = 8) among samples of young adults who use JUUL. Findings suggest that restricting JUUL flavor to tobacco-only results in decreased appeal, while reducing the nicotine content of JUUL pods to 3%-from the conventional 5%-does not have an effect on product appeal. Findings also validate a novel methodology for delivering fixed doses of ENDS vapor within the context of a task that assesses the relative reinforcement of ENDS products with varying characteristics. This methodology can be applied to assessing the relative reinforcing effects of a wide variety of tobacco products with varied characteristics. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cross-Sectional Associations of Multiple Tobacco Product Use with Depressive and Anxiety Symptoms among Young Adult E-Cigarette Users.

BACKGROUND: Tobacco users with mental health conditions are a vulnerable population in tobacco research, yet few studies have evaluated the association of depressive and anxiety symptoms with multiple tobacco product (MTP) use among young adult electronic cigarette (ENDS) users. METHODS: Cross-sectional survey data on U.S. young adult past 30-day ENDS users (N = 2348) were collected via Amazon MTurk from May-July 2019. Binary logistic regressions evaluated the association of tobacco use pattern (exclusive ENDS use, ENDS + one other tobacco product [OTP; dual use], ENDS + two or more OTPs [poly-use]) with depressive (PHQ-9) and anxiety (GAD-7) symptoms. Among MTP users (n = 1736), we evaluated the association of ENDS use relative to OTP use and same-day MTP use with depressive and anxiety symptoms. RESULTS: The sample included 26% exclusive ENDS, 27% dual, and 47% poly-users. We observed a gradient-relationship for depressive and anxiety symptoms: poly-users had greater odds of depressive and anxiety symptoms compared to dual users (aOR = 1.86 [95%CI:1.50-2.30] and aOR = 1.61 [95%CI:1.30-2.01], respectively), and dual users had greater odds of depressive and anxiety symptoms compared to exclusive ENDS users (aOR = 1.42 [95%CI:1.11-1.81] and aOR = 1.56 [95%CI:1.20-2.02], respectively). MTP users who used ENDS more often than OTPs (vs. less often than OTPs) had greater odds of depressive (aOR = 1.38 [95%CI:1.06-1.80]) and anxiety (aOR = 1.37 [95%CI:1.04-1.79]) symptoms. CONCLUSIONS: The majority of young adult past 30-day ENDS users in this sample reported OTP use. Future research on MTP use should distinguish between dual and poly-use. Tobacco prevention efforts for young adults with mental health symptoms are needed.

Risk Perceptions of Low Nicotine Cigarettes and Alternative Nicotine Products across Priority Smoking Populations.

BACKGROUND: As the U.S. Food and Drug Administration considers a low nicotine product standard for cigarettes, it is important to examine how people who smoke, especially individuals from priority populations disproportionately affected by smoking, perceive low nicotine content (LNC) cigarettes and their relative risk perceptions of alternative nicotine delivery system (ANDS) products, including e-cigarettes and snus, and medicinal nicotine. METHODS: Data are from Wave 4 (2016-2017) of the adult Population Assessment of Tobacco Use and Health (PATH) Study. We examined respondents' absolute risk perceptions about nicotine, LNC cigarettes, ANDS products and medicinal nicotine; their relative risk perceptions of LNC cigarettes and ANDS products compared to conventional cigarettes; and their relative risk perceptions of medicinal nicotine compared to ANDS products. RESULTS: The majority of respondents across priority smoking populations indicated snus, e-cigarettes, and LNC cigarettes were 'about the same' level of harmfulness or addictiveness as conventional cigarettes. The majority of respondents indicated e-cigarettes to be 'about the same' harmfulness as medicinal nicotine. CONCLUSIONS: Our study indicates that adults who smoke cigarettes generally have misperceptions about the harms of nicotine and the relative risks of ANDS products and such misperceptions exist regardless of their racial/ethnic identity, sexual orientation, and gender identity.

Impact of nicotine reduction in cigarettes on smoking behavior and exposure: Are there differences by race/ethnicity, educational attainment, or gender?

BACKGROUND: Lowering nicotine in cigarettes may reduce smoking prevalences; however, it is not known whether an immediate or gradual reduction in nicotine is the optimal approach for all population groups. OBJECTIVES: We examined whether the optimal approach to nicotine reduction depended on the education, gender, or race of people who smoke and whether the optimal approach differentially benefited people who smoke based on their education, gender, or race. METHODS: Secondary analysis was conducted on a randomized clinical trial (N = 1250) comparing (1) immediate reduction from 15.5 to 0.4 mg of nicotine per gram of tobacco(mg/g);(2) gradual reduction to 0.4 mg/g;(3) control group with normal nicotine cigarettes(15.5 mg/g). Outcomes included cigarettes per day(CPD), carbon monoxide(CO), total nicotine equivalents(TNE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides(NNAL), phenanthrene tetraol(PheT), N-Acetyl-S-(2-cyanoethyl)-l-cysteine(CEMA). Data were analyzed as area under the curve(AUC). RESULTS: Results were presented by education (High school[HS] or less n = 505, more than HS n = 745), gender (males n = 701, females n = 549), and race (Black participants n = 373,White participants n = 758). Regardless of education, gender, and race, CPD, CO, TNE, NNAL, PheT, and CEMA were lower in immediate versus gradual nicotine reduction. Comparing immediate versus the control, outcomes were lower for all subgroups; however, the magnitude of the effect for TNE varied by race. Specifically, geometric mean of the AUC of TNE in immediate versus gradual was 49 % lower in Black participants and 61 % lower in White participants (p-value = 0.047). CONCLUSIONS: Immediately reducing nicotine in cigarettes has the potential to benefit people who smoke across lower and higher educational attainment, male and female gender, and Black and White race.

Reactions to reduced nicotine content cigarettes in a sample of young adult, low-frequency smokers.

RATIONALE: Reducing nicotine content in cigarettes to ≤ 2.4 mg per g of tobacco [mg/g] reduces smoking behavior and toxicant exposure among adult daily smokers. However, cigarettes with similar nicotine content could support continued experimentation and smoking progression among young adults who smoke infrequently. OBJECTIVES: This study evaluated the threshold for nicotine in cigarettes that produces reactions associated with smoking progression in a sample of young adults who smoke infrequently. METHODS: Young adults (n = 87, 18-25 years, 49% female) using tobacco products ≤ 15 days per month completed three counterbalanced, double-blinded sessions, each measuring positive and negative subjective reactions to fixed doses of smoke from investigational cigarettes containing one of three different nicotine contents: normal (NNC; 15.8 mg/g); very low (VLNC; 0.4 mg/g); and intermediate (INC; 2.4 mg/g). In a final session, participants chose one of the cigarettes to self-administer. RESULTS: Post-cigarette breath carbon monoxide was greater for VLNC than for NNC (p < 0.001). Positive reactions were greater for NNC than INC (p < 0.001) and for INC than VLNC (p = 0.001). Negative reactions were greater for NNC than INC and VLNC (both p < 0.001); INC and VLNC did not differ. Cigarette choices did not differ from an even distribution (43% NNC, 25% INC, 32% VLNC), but choice for NNC or INC was associated with higher ratio of positive to negative reactions during the NNC and INC fixed dose sessions, respectively (p < 0.001). CONCLUSIONS: Reducing nicotine content will likely lower the abuse liability of cigarettes for most young, low-frequency smokers. Additional work is needed to determine if compensatory smoking may lead to increased toxicant exposure, and if a subset of individuals choosing lower nicotine cigarettes may continue to smoke regardless of nicotine content.

Experiences With Smoking Cessation Attempts and Prior Use of Cessation Aids in Smokers With HIV: Findings From a Focus Group Study Conducted in Durham, North Carolina.

Cigarette smoking remains disproportionately prevalent and is increasingly a cause of death and disability among people with HIV (PWH). Many PWH are interested in quitting, but interest in and uptake of first-line smoking cessation pharmacotherapies are varied in this population. To provide current data regarding experiences with and perceptions of smoking cessation and cessation aids among PWH living in Durham, North Carolina, the authors conducted five focus group interviews (total n = 24; 96% African American) using semistructured interviews. Interviews were recorded, transcribed, coded, and thematically analyzed. Major themes included ambivalence and/or lack of interest in cessation; presence of cessation barriers; perceived perceptions of ineffectiveness of cessation aids; perceived medication side effects; and conflation of the harms resulting from use of tobacco products and nicotine replacement therapy. Innovative and effective interventions must account for the aforementioned multiple barriers to cessation as well as prior experiences with and misperceptions regarding cessation aids.

Cessation classification likelihood increases with higher expired-air carbon monoxide cutoffs: a meta-analysis.

BACKGROUND: Expired-air carbon monoxide (CO) is commonly used to biochemically verify smoking status. The CO cutoff and CO monitor brand may affect the probability of classifying smokers as abstinent, thus influencing conclusions about the efficacy of cessation trials. No systematic reviews have tested this hypothesis. Therefore, we performed a meta-analysis examining whether the likelihood of smoking cessation classification varied due to CO cutoff and monitor brand. METHODS: Eligible studies (k = 122) longitudinally assessed CO-verified cessation in adult smokers in randomized trials. Primary meta-regressions separately assessed differences in quit classification likelihood due to continuous and categorical CO cutoffs (Low, 3-4 parts per million [ppm]; [SRNT] Recommended, 5-6 ppm; Moderate, 7-8 ppm; and High, 9-10 ppm); exploratory analyses compared likelihood outcomes between monitor brands: Bedfont and Vitalograph. RESULTS: The likelihood of quit classification increased 18% with each 1 ppm increase above the lowest cutoff (3 ppm). Odds of classification as quit significantly increased between each cutoff category and High: 261% increase from Low; 162% increase from Recommended; and 150% increase from Moderate. There were no differences in cessation classification between monitor brands. CONCLUSIONS: As expected, higher CO cutoffs were associated with greater likelihood of cessation classification. The lack of CO monitor brand differences may have been due to model-level variance not able to be followed up in the present dataset. Researchers are advised to report outcomes using a range of cutoffs-including the recommended range (5-6 ppm)-and the CO monitor brand/model used. Using higher CO cutoffs significantly increases likelihood of quit classification, possibly artificially elevating treatment strategies.

An Evaluation of Potential Unintended Consequences of a Nicotine Product Standard: A Focus on Drinking History and Outcomes.

INTRODUCTION: A nicotine product standard reducing the nicotine content in cigarettes could improve public health by reducing smoking. This study evaluated the potential unintended consequences of a reduced nicotine product standard by examining its effects on (1) smoking behaviors based on drinking history; (2) drinking behavior; and (3) daily associations between smoking and drinking. METHODS: Adults who smoke daily (n = 752) in the United States were randomly assigned to smoke very low nicotine content (VLNC) cigarettes versus normal nicotine content (NNC; control) cigarettes for 20 weeks. Linear mixed models determined if baseline drinking moderated the effects of VLNC versus NNC cigarettes on Week 20 smoking outcomes. Time-varying effect models estimated the daily association between smoking VLNC cigarettes and drinking outcomes. RESULTS: Higher baseline alcohol use (vs no use or lower use) was associated with a smaller effect of VLNC on Week 20 urinary total nicotine equivalents (ps < .05). No additional moderation was supported (ps > .05). In the subsample who drank (n = 415), in the VLNC versus NNC condition, daily alcohol use was significantly reduced from Weeks 17 to 20 and odds of binge drinking were significantly reduced from Weeks 9 to 17. By Week 7, in the VLNC cigarette condition (n = 272), smoking no longer predicted alcohol use but remained associated with binge drinking. CONCLUSIONS: We did not support negative unintended consequences of a nicotine product standard. Nicotine reduction in cigarettes generally affected smoking behavior for individuals who do not drink or drink light-to-moderate amounts in similar ways. Extended VLNC cigarette use may improve public health by reducing drinking behavior. IMPLICATIONS: There was no evidence that a VLNC product standard would result in unintended consequences based on drinking history or when considering alcohol outcomes. Specifically, we found that a very low nicotine standard in cigarettes generally reduces smoking outcomes for those who do not drink and those who drink light-to-moderate amounts. Furthermore, an added public health benefit of a very low nicotine standard for cigarettes could be a reduction in alcohol use and binge drinking over time. Finally, smoking VLNC cigarettes may result in a decoupling of the daily associations between smoking and drinking.

Support for a nicotine reduction policy among participants enrolled in a 20-week trial of very low nicotine content cigarettes.

INTRODUCTION: The Food and Drug Administration is considering a policy to drastically reduce the allowable nicotine content of cigarettes. The current study examined whether the policy implementation approach, i.e., either immediately reducing nicotine content to very low levels or gradually reducing nicotine content over an extended period, influences policy support among people who smoke cigarettes. METHODS: Adults who smoked daily were randomly assigned (double-blind) to an immediate nicotine reduction condition (0.4 mg/g nicotine cigarettes), a gradual nicotine reduction condition (15.5 to 0.4 mg/g), or a control condition (15.5 mg/g) for 20 weeks. Participants were asked if they would "support or oppose a law that reduced the amount of nicotine in cigarettes, to make cigarettes less addictive." Logistic regression analyses assessed if policy support was affected by treatment condition, demographic covariates, interest in quitting, and subjective cigarette effects. RESULTS: At Week 20 (N = 957 completers), 60.4% of participants supported the policy, 17.4% opposed, and 22.2% responded "Don't know." Policy support did not differ by treatment condition. Support was greater among those interested in quitting (OR = 3.37, 95% CI = 2.49, 4.55). Support was lower among males (OR = 0.49, 95% CI = 0.37, 0.67), those with greater dependence scores (OR = 0.92, 95% CI = 0.86, 0.99) and participants aged 18-24 (OR = 0.53, 95% CI = 0.28, 0.99). No other covariates were associated with policy support. CONCLUSIONS: The majority of participants supported a nicotine reduction policy. The implementation approach, immediate or gradual reduction, did not affect policy support. Participants interested in quitting smoking were more likely to support a nicotine reduction policy.

Cigarette Smoking and Cessation-Related Interactions With Health Care Providers in the Context of Living With HIV: Focus Group Study Findings.

ABSTRACT: Smoking is disproportionately prevalent among people living with HIV (PLWH) compared with the general population. We conducted five focus groups (n = 24) using semi-structured interview guides to explore perceptions and experiences of smoking and cessation-related interactions with health care providers among smokers with HIV. Major themes included a limited understanding of how smoking affects illness among PLWH and minimal discussion about cessation with providers. Findings highlight the need to educate smokers with HIV about the known impacts of smoking on illness among PLWH and to facilitate greater discussion of cessation between providers and smokers with HIV. Prior experiences with smoking cessation medications and desire for additional information regarding these medications should be considered when implementing medication regimens in research and clinical settings.

The United States National Cancer Institute's Coordinated Research Effort on Tobacco Use as a Major Cause of Morbidity and Mortality among People with HIV.

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease. IMPLICATIONS: This Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population.

The Impact of Exclusive Use of Very Low Nicotine Cigarettes on Compensatory Smoking: An Inpatient Crossover Clinical Trial.

BACKGROUND: The FDA is considering a mandated reduction in the nicotine content of cigarettes. Clinical trials have been limited by non-study cigarette use (noncompliance), which could mask compensation. The goal of this study was to assess whether compensation occurs when smokers provided with very low nicotine cigarettes cannot access normal nicotine cigarettes. METHODS: In a within-subjects, crossover design, current smokers (n = 16) were confined to a hotel for two 4-night hotel stays during which they were only able to access the research cigarettes provided. The hotel stays offered normal nicotine cigarettes or very low nicotine content (VLNC) cigarettes, in an unblinded design, available for "purchase" via a study bank. RESULTS: In the context of complete compliance with the study cigarettes (n = 16), there was not a significant increase during the VLNC condition for cigarettes smoked per day, expired carbon monoxide, or N-acetyl-S-(cyanoethyl)-l-cysteine (cyanoethyl-MA, metabolite of acrylonitrile). There was a significant nicotine × time interaction on urine N-acetyl-S-(3-hydroxypropyl)-l-cysteine (hydroxypropyl-MA, metabolite of acrolein), driven by an increase in the VLNC condition during the first 24 hours. By the end of the VLNC condition, there was no evidence of compensation across any measure of smoking or smoke exposure. CONCLUSIONS: Among current smokers who exclusively used VLNC cigarettes for 4 days, there was no significant compensatory smoking behavior. IMPACT: These data, combined with the larger body of work, suggest that a mandated reduction in nicotine content is unlikely to result in an increase in smoking behavior to obtain more nicotine.

Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers.

BACKGROUND: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers. METHODS: Secondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers. NMR was modeled continuously in secondary analysis. RESULTS: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant. CONCLUSIONS: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers. IMPACT: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco-related disease.