Nicotine Intake in Adult Pod E-cigarette Users: Impact of User and Device Characteristics.

INTRODUCTION: This study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes. AIMS AND METHODS: In 2019-2020, people who use pod-mods in the San Francisco Bay Area completed questionnaires and provided a urine sample for analysis of total nicotine equivalents (TNE). The relationship between TNE and e-cigarette use, e-cigarette brands, e-liquid nicotine strength, e-cigarette dependence, and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as a measure of combustible cigarette exposure, were examined. RESULTS: Of 100 participants (64% male, 71% in the 18-34 age group, 45% white), 53 used JUUL primarily, 12 used Puff Bar primarily, and 35 used other brands, including Suorin; 48 participants reported current cigarette smoking. Participants most often reported use of e-liquid with 4.5%-6.0% nicotine (68%), fruit (35%), tobacco (28%), and menthol or mint flavors (26%), used e-cigarettes on 25.5 (SD = 6.3) days a month, 10.2 (SD = 14.2) times a day, and 40% used 1-2 pods/cartridges per week. In bivariate analysis, urinary TNE was higher with greater frequency (days used) and intensity (number of pods used) of e-cigarette use, e-cigarette dependence, and combustible cigarette use. In multivariable analysis, days of e-cigarette use in the last 30 days, number of pods used per week, and NNAL levels were significantly associated with TNE. There was no significant impact of e-liquid nicotine strength on TNE. CONCLUSIONS: Nicotine intake among people who used pod-mod e-cigarettes increased with e-cigarette consumption and e-cigarette dependence, but not with e-liquid nicotine strength. Our findings may inform whether FDA adopts a nicotine standard for e-cigarettes. IMPLICATIONS: The study examined how device and user characteristics influence nicotine intake among pod-mod e-cigarette users. Nicotine intake increased with frequency (days of e-cigarette use in past 30 days) intensity of use (number of pods used per day) and e-cigarette dependence but not with the flavor or nicotine concentration of the e-liquids. Regulation of nicotine concentration of e-liquids is unlikely to influence nicotine exposure among adult experienced pod-mod users.

Twenty-Four-Hour Cardiovascular Effects of Electronic Cigarettes Compared With Cigarette Smoking in Dual Users.

Background Cardiovascular safety is an important consideration regarding the benefits versus risks of electronic cigarette use (EC) for public health. The single-use cardiovascular effects of EC have been well studied but may not reflect effects of ad libitum use throughout the day. We aimed to compare the circadian hemodynamic effects as well as 24-hour biomarkers of oxidative stress, and platelet aggregation and inflammation, with ad libitum cigarette smoking (CS) versus EC versus no tobacco product use. Methods and Results Thirty-six healthy dual CS and EC users participated in a crossover study in a confined research setting. Circadian heart rate, blood pressure and plasma nicotine levels, 24-hour urinary catecholamines, 8-isoprostane and 11-dehydro-thromboxane B2, and plasma interleukin-6 and interleukin-8 were compared in CS, EC, and no nicotine conditions. Over 24 hours, and during daytime, heart rate and blood pressure were higher in CS and EC compared with no tobacco product conditions (P<0.01). Heart rate on average was higher with CS versus EC. Urinary catecholamines, 8-isoprostane, and 11-dehydro-thromboxane B2 were not significantly different, but plasma IL-6 and IL-8 were higher with both CS and EC compared with no tobacco product (P<0.01). Conclusions CS and EC had similar 24-hour patterns of hemodynamic effects compared with no tobacco product, with a higher average heart rate with CS versus EC, and similar effects on biomarkers of inflammation. EC may pose some cardiovascular risk, particularly to smokers with underlying cardiovascular disease, but may also provide a harm reduction opportunity for smokers willing to switch entirely to EC. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02470754.

A Mobile Health Intervention for Adolescents Exposed to Secondhand Smoke: Pilot Feasibility and Efficacy Study.

BACKGROUND: Secondhand smoke (SHS) exposure in children and adolescents has adverse health effects. For adolescents of lower socioeconomic status (SES), exposure is widespread, evidenced in the measurement of urinary cotinine, a major metabolite of nicotine. Direct intervention with exposed children has been proposed as a novel method, yet there is minimal evidence of its efficacy. Combining this approach with a mobile health (mHealth) intervention may be more time and cost-effective and feasible for adolescent populations. OBJECTIVE: In this pilot study, we assessed the feasibility and preliminary evidence of efficacy of a 30-day text message-based mHealth intervention targeted at reducing SHS exposure in adolescent populations of low SES. METHODS: For the study, 14 nonsmoking and nonvaping participants between the ages of 12-21 years exposed to SHS were enrolled. The intervention consisted of a daily text message sent to the participants over the course of a month. Text message types included facts and information about SHS, behavioral methods for SHS avoidance, or true-or-false questions. Participants were asked to respond to each message within 24 hours as confirmation of receipt. Feasibility outcomes included completion of the 30-day intervention, receiving and responding to text messages, and feedback on the messages. Efficacy outcomes included a reduction in urinary cotinine, accuracy of true-or-false responses, and participants' perceptions of effectiveness. RESULTS: Of the 14 participants that were enrolled, 13 completed the intervention. Though not required, all participants had their own cell phones with unlimited text messaging plans. Of the total number of text messages sent to the 13 completers, 91% (372/407) of them received on-time responses. Participant feedback was generally positive, with most requesting more informational and true-or-false questions. In terms of efficacy, 54% (6/11) of participants reduced their cotinine levels (however, change for the group overall was not statistically significant (P=.33) and 45% (5/11) of participants increased their cotinine levels. Of the total number of true-or-false questions sent across all completers, 77% (56/73) were answered correctly. Participants' ratings of message effectiveness averaged 85 on a scale of 100. CONCLUSIONS: In this pilot study, the intervention was feasible as the majority of participants had access to a cell phone, completed the study, and engaged by responding to the messages. The efficacy of the study requires further replication, as only half of the participants reduced their cotinine levels. However, participants answered the majority of true-or-false questions accurately and reported that the messages were helpful.

Comparison of Systemic Exposure to Toxic and/or Carcinogenic Volatile Organic Compounds (VOC) during Vaping, Smoking, and Abstention.

Comparisons of systemic exposure to toxicants during monitored cigarette smoking, electronic cigarette (e-cigarette) use, and abstention are needed to enhance our understanding of the risks of e-cigarette use (vaping). In a cross-over study, we measured 10 mercapturic acid metabolites of volatile organic compounds (VOCs) in 24-hour urine samples collected from 36 dual users (8 women) of e-cigarettes and cigarettes during 2 days of ad libitum vaping or cigarette-only use, and 2 days of enforced abstention. Concentrations of VOC metabolites were higher during smoking compared with vaping, except for the methylating agents' metabolite. The fold-difference in concentrations when smoking relative to vaping ranged from 1.31 (1.06-1.61; geometric mean, 95% confidence interval; 1,3-butadiene) to 7.09 (5.88-8.54; acrylonitrile). Metabolites of acrylamide [fold difference of 1.21 (1.03-1.43)] and benzene [1.46 (1.13-1.90)] were higher during vaping compared with abstention. The 1,3-butadiene and propylene oxide metabolites were higher in variable-power tank users compared with users of cig-a-likes. E-cigarettes expose users to lower levels of toxic VOCs compared with cigarette smoking, supporting their harm reduction potential among smokers. However, some e-cigarettes expose users to VOCs such as acrylamide, benzene, and propylene oxide, and may pose health risks to nonsmoking users. The results of our study will inform regulators in assessing e-cigarettes with respect to the balance between its potential harm reduction for adult smokers and risk to nonsmoking users.

Development and Piloting Testing of an Experimental Tobacco and Nicotine Product Marketplace.

INTRODUCTION: We describe the development and pilot testing of the experimental tobacco and nicotine product marketplace (ETM)-a method for studying tobacco and nicotine product (TNP) choices and use behavior in a standardized way. AIMS AND METHODS: The ETM resembles an online store populated with TNPs. Surveillance activities and data from a US representative survey and consumer reports were used to determine the most popular TNPs for inclusion in the ETM. Standardized information and videos demonstrating how to use the TNPs were provided. To test the feasibility of using the ETM, smokers (n = 119) underwent monitoring of usual brand cigarette smoking and other TNP use (Baseline Phase) followed by access to the ETM (ETM Phase) that included their usual brand cigarettes, e-cigarettes, moist snuff, snus, and nicotine replacement therapy. During the ETM Phase, participants were provided points based on their baseline TNP consumption to exchange for TNPs in the ETM. Participants were advised to exchange points for enough TNPs to last until their next visit and to refrain from using TNPs not obtained in the ETM. A subset of the participants (n = 62) completed a survey on their experience with the ETM. RESULTS: The majority of the participants stated they were comfortable with navigating the ETM (97%), it was easy to determine product characteristics (89%), and they were satisfied with the products included in the marketplace (85%). CONCLUSIONS: The ETM was well received by the vast majority of the participants and can be utilized by researchers to investigate a variety of TNP policy and regulatory science research questions. IMPLICATIONS: Patterns of TNP use are complex due to greater availability, marketing, and promotion of a diverse array of TNPs. Innovative methods are needed to experimentally study TNP choices and patterns. Through describing the development of the ETM, we provide researchers with a tool that can be readily adapted to studying a variety of phenomena challenging public health.

Urine Metabolites for Estimating Daily Intake of Nicotine From Cigarette Smoking.

INTRODUCTION: Accurate measurement of nicotine exposure from cigarette smoke is important in studying disease risk and level of dependence. Urine total nicotine equivalents, the molar sum of nicotine and six metabolites (NE7), accounts for more than 90% of a nicotine dose and is independent of individual metabolic differences. However, measuring NE7 is technically difficult and costly. We compared NE7, the gold standard of nicotine intake, with different combinations of fewer urinary nicotine metabolites. We also examined the impact of individual differences in nicotine metabolic rate, sex, and race on strength of association with NE7. METHODS: Urine samples from 796 daily smokers, who participated across five clinical studies, were assayed for nicotine and/or metabolites. Associations with NE7 were assessed by regression and Bland-Altman analyses. RESULTS: Overall, the molar sum of urine [cotinine + 3'-hydroxycotinine (3HC)] (NE2) and [nicotine + cotinine + 3HC] (NE3) were strongly correlated with NE7 (r = .97 and .99, respectively). However, in slow metabolizers NE2 was less predictive of NE7, whereas NE3 was equally robust. Urine total cotinine was also strongly correlated with NE7 (r = .87). CONCLUSIONS: Urine NE3 is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, whereas NE2 is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies. IMPLICATIONS: The molar sum of urine total nicotine, cotinine and 3HC (NE3) is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, and performs as well as measuring seven nicotine metabolites (NE7). The sum of cotinine and 3HC (NE2) is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies.

Differences in nicotine intake and effects from electronic and combustible cigarettes among dual users.

AIM: To describe systemic nicotine exposure and subjective effects of electronic cigarettes (e-cigarettes) in people who use both e-cigarettes and cigarettes (dual users), including within-subject comparisons of e-cigarette and cigarette use. DESIGN: Two-arm, counterbalanced cross-over study. Participants used their usual brand of e-cigarette or cigarette during a standardized session in a 2-week study. SETTING: Hospital research ward, San Francisco, CA, USA. PARTICIPANTS: Thirty-six healthy (eight women, 28 men) participants. MEASUREMENTS: Plasma nicotine was analyzed by gas chromatography-tandem mass spectrometry; nicotine withdrawal, urge to smoke and vape, affective states, craving, satisfaction and psychological reward were measured by standardized questionnaires. FINDINGS: Compared with cigarettes, average maximum plasma nicotine concentration (Cmax ) was lower with e-cigarettes [6.1 ± 5.5 ng/ml, mean ± standard deviation (SD) versus 20.2 ± 11.1 ng/ml, P < 0.001] and time of maximal concentration (Tmax ) was longer (6.5 ± 5.4 versus 2.7 ± 2.4 minutes, P < 0.001). Use of both products resulted in a reduction in the severity of withdrawal symptoms, negative affect and urge to use either product. E-cigarettes were less rewarding and satisfying and reduced craving to a lesser degree than cigarettes. We were not able to detect any differences in withdrawal symptoms, affective states and urge to smoke cigarettes between e-cigarette and cigarette use. CONCLUSION: Systemic nicotine exposure was, on average, lower with single use of e-cigarettes compared with cigarettes, and e-cigarettes were judged to be less satisfying and rewarding and reduced craving less than cigarettes.

The influence of nicotine metabolic rate on working memory over 6 hours of abstinence from nicotine.

BACKGROUND: A faster rate of nicotine metabolism has been associated with smoking more cigarettes, greater nicotine withdrawal symptoms, and lower smoking quit rates. However, the association between nicotine metabolic rate (NMR) and cognitive functioning during withdrawal has not been determined. METHODS: We compared cognitive function in 121 fast or slow nicotine metabolizers after smoking, and at 3 and 6 h of nicotine abstinence. Cognitive functioning was assessed using N-back working memory tests with outcomes of accuracy and processing speed. Participants smoked two cigarettes and then abstained from smoking for 6 h. N-back tests were administered after smoking (0 h) and at 3 and 6 h of nicotine abstinence. RESULTS: An effect of processing speed was found over time on the 2-back, in that participants had significantly longer average reaction times when the stimuli presented did not match the target letter. NMR was not significantly associated with the processing speed change over time. Within-race differences in working memory were evident in that Caucasian fast metabolizers had significantly poorer accuracy and processing speed. CONCLUSIONS: Minimal change in working memory over 6 h of nicotine abstinence was observed. Overall, NMR was not significantly associated with the change in processing speed, however Caucasian fast metabolizers displayed poorer accuracy and processing speed at discrete time points.

Twenty-four-hour subjective and pharmacological effects of ad-libitum electronic and combustible cigarette use among dual users.

BACKGROUND AND AIMS: Relative pharmacological effects of e-cigarettes and cigarettes during 24 hours of ad-libitum use have not been described. In this study, 24-hour blood plasma nicotine concentrations and 48-hour subjective effects with use of cigarettes and e-cigarettes were measured among dual users. DESIGN: Two-arm within-subject cross-over design with preferred e-cigarette or cigarette ad-libitum use over 48 hours. SETTING: Hospital research ward in San Francisco, California, USA. PARTICIPANTS: Thirty-six healthy dual users of e-cigarettes and cigarettes (n = 8, 25% females). MEASUREMENTS: Twenty-four-hour blood plasma nicotine and cotinine concentrations and 48-hour self-reported nicotine withdrawal symptoms and rewarding effects. FINDINGS: Analyses used analysis of variance (ANOVA)-based mixed models with order of product (e-cigarette or cigarette) and product type (combustible cigarette or type of e-cigarette) as fixed effects, and subject as a repeated effect. During a 24-hour period, e-cigarettes produced lower nicotine exposure than cigarettes for the majority of users, although 25% received more nicotine from e-cigarettes, which was predicted by more frequent e-cigarette use or greater dependence. Compared to cigarette smoking, nicotine exposure for variable-power tank users was similar, while cig-a-like (t(30)  = 2.71, P = 0.011, d = 0.745) and fixed-power tank users (t(30)  = 3.37, P = 0.002, d = 0.993) were exposed to less nicotine. Cigarettes were rated higher than e-cigarettes on some desirable subjective effects (e.g. psychological reward, t(322)  = 7.24 P < 0.001, d = 0.432), but withdrawal symptom reduction was comparable. No differences were found between e-cigarette types, but Bayes factors indicate that these measures were insensitive. CONCLUSIONS: During a 24-hour period in a hospital setting in the United States, nicotine exposure for dual users of e-cigarettes and cigarettes was similar when using cigarettes or variable-power tank devices only but was lower for those using cig-a-like or fixed-power devices only. Despite lower nicotine levels, all types of e-cigarette were effective in preventing withdrawal symptoms. E-cigarettes were rated less rewarding than cigarettes.

Biomarkers of Exposure for Dual Use of Electronic Cigarettes and Combustible Cigarettes: Nicotelline, NNAL, and Total Nicotine Equivalents.

INTRODUCTION: Dual use of electronic cigarettes (e-cigarettes) and combustible cigarettes is a major public health issue. It is generally accepted that exclusive e-cigarette use is less harmful than exclusive combustible cigarette use, but most e-cigarette users continue to smoke combustible cigarettes as well. To what extent the use of e-cigarettes reduces harm in people who continue to smoke combustible cigarettes has been debated. The aim of this study was to explore the utility of biomarkers as measures of dual use. METHODS: In two human studies of participants who used e-cigarettes only or both combustible cigarettes and e-cigarettes, we measured urine concentrations of the metabolites of nicotine (total nicotine equivalents) as well as two biomarkers of tobacco exposure: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen metabolite, and nicotelline, a tobacco alkaloid not found in significant concentrations in e-cigarette products. RESULTS: The presence of nicotine metabolites indicates either e-cigarette or combustible cigarette use. Nicotelline (half-life of 2-3 hours) indicates recent combustible cigarette use and NNAL (half-life of 10 days or more), indicates combustible cigarette use occurring within several weeks prior to sample collection. CONCLUSIONS: Nicotelline and NNAL are useful biomarkers for combustible tobacco use in users e-cigarettes. The application of these biomarkers provides a tool to help assess whether, or to what extent, dual use of e-cigarettes and combustible cigarettes reduces harm compared to sole use of combustible cigarettes. These biomarkers can also verify exclusive use of e-cigarettes over short (24 hour) or long (several week) time periods. IMPLICATIONS: To what extent dual use of e-cigarettes and combustible cigarettes reduce harm compared to smoking combustible cigarettes only is of considerable public health interest. We show that the levels of the minor tobacco alkaloid nicotelline and the nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are extremely low in electronic cigarette fluids. The urine biomarkers nicotelline and the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are indicative of cigarette smoking and can be used to assess recent and past smoking in dual users.

Effects of Nicotine Metabolic Rate on Cigarette Reinforcement.

INTRODUCTION: The rate of nicotine metabolism, estimated by the nicotine metabolite ratio (NMR), is an important determinant of tobacco dependence. This study investigated the effect of NMR on smoking behavior due to nicotine reinforcement during ad libitum smoking. AIMS AND METHODS: As part of a larger study, participants were stratified based on saliva NMR as fast and slow metabolizers. After smoking a cigarette and measuring nicotine blood concentrations, participants smoked as desired over a 90-minute period. Analysis included time to first cigarette, total number of cigarettes, total number of puffs, and weight of tobacco consumed. RESULTS: Sixty-one (48%) participants were fast metabolizers and 66 (52%) slow metabolizers by NMR. No significant differences were found regarding the smoking topography variables by NMR. Normal metabolizers by genotype (n = 79) had a shorter time to first cigarette than reduced metabolizers (n = 39; p = .032). Blacks smoked fewer cigarettes (p = .008) and took fewer total puffs (p = .002) compared with Whites. Among Whites, fast metabolizers by NMR had a shorter time to first cigarette compared with slow metabolizers (p = .014). Among fast metabolizers, Whites had, compared with Blacks, shorter latency to first cigarette (p = .003) and higher number of total puffs (p = .014) and cigarettes smoked (p = .014). Baseline cigarettes per day and nicotine elimination half-life significantly predicted topography outcomes. CONCLUSIONS: Saliva NMR did not predict cigarette reinforcement during a relatively brief period of ad libitum smoking. Differences were seen by race, with White fast metabolizers by NMR having shorter time to first cigarettes compared with slow metabolizers. IMPLICATIONS: After a 90-minute period of nicotine abstinence, NMR was not significantly associated with smoking reinforcement. Slow and fast metabolizers had similar time to first cigarette, number of cigarettes smoked, total number of puffs, and tobacco consumed; however, within-race differences show that within Whites, fast metabolizers had a faster time to first cigarette than slow metabolizers.

Sources and Biomarkers of Secondhand Tobacco Smoke Exposure in Urban Adolescents.

OBJECTIVE: In an urban adolescent population, we evaluated sources of exposure to secondhand smoke exposure (SHS), examined differences in exposure by race/ethnicity, age and sex, and determined the relationship between exposure source(s) and the biomarkers cotinine and NNAL. METHODS: Participants were recruited from a public hospital-based outpatient clinic in San Francisco, CA, USA. RESULTS: Of a sample of N = 298 adolescents screened, 235 were biologically confirmed to be exposed to tobacco smoke. Of those, N = 16 were active smokers and N = 219 were exposed to SHS; 91 (39%) were heavily SHS exposed (median cotinine = 0.76 ng/mL) and 128 (54%) had light SHS exposure (median cotinine = 0.11 ng/mL). Within those SHS exposed, the most common source of exposure was in a public area. No significant racial/ethnic differences were found, although African American adolescents were more likely to live in a home that allowed smoking. Older adolescents were more likely to be exposed across several difference sources, and females more likely to be exposed in a car and in public areas. Past 7-day exposure in the home, in a car, and current blunt use were significantly related to biomarkers of exposure. CONCLUSIONS: Urban adolescents are exposed to SHS across a variety of sources. Although exposure in a public area is most common, exposure in the home and in cars significantly influences tobacco biomarker levels. Interventions to reduce exposure would have the greatest impact in this population if they focused on reducing exposure in the home and in cars. History of blunt use is a strong determinant of tobacco exposure.

Quantitative biochemical screening for marijuana use and concordance with tobacco use in urban adolescents.

BACKGROUND: Assessing the prevalence and level of exposure (dose) of tobacco and marijuana use is important in studies of harm from use of these substances. We used biochemical analysis of urine to quantitatively assess exposure to nicotine and delta 9-tetrahydrocannabinol (THC) in adolescents receiving medical care in a public hospital METHODS: Participants were 686 adolescents between 12 and 21 years old seen at Zuckerberg San Francisco General Hospital between 2012 and 2014. Urine samples were assayed using high sensitivity liquid chromatographic assays for cotinine, a major metabolite of nicotine, and 11-nor-9-carboxy-delta 9-THC (THC-COOH), a major metabolite of THC. A commonly used immunoassay screen for THC-COOH was also performed. RESULTS: The THC-COOH immunoassay substantially underestimated THC exposure, as measured with the high sensitivity assay. THC use was detected in 25% of participants, with higher prevalence with increasing age and in non-Hispanic blacks. Active tobacco smokers had an 80% prevalence of THC use (odds ratio for cigarette smoking predicting THC use 13.2). Urine cotinine and THC-COOH were significantly correlated (r = 0.60). CONCLUSIONS: The use of a high sensitivity chromatographic urine assay provides a much more complete picture of adolescent tobacco use compared to a commonly used immunoassay. The immunoassay provides high specificity but moderate sensitivity. We confirm high concordance of tobacco and marijuana use and the high predictive value of cigarette smoking in predicting marijuana use, and provide novel data on the quantitative correlation between level of exposure to nicotine and THC. Quantitative screening of nicotine and THC exposure may enhance our understanding of addiction and harm from single and dual product use.

JUUL electronic cigarettes: Nicotine exposure and the user experience.

BACKGROUND: As of March 2019, JUUL electronic cigarettes are the most popular e-cigarette on the U.S. market, but little is known of nicotine exposure and dependence on JUUL and user experience. METHODS: JUUL users participated in a community-based study involving questionnaires, saliva collection and a qualitative interview. RESULTS: Fifteen participants were enrolled (80% male, 53% White) and had an average age of 29.8 (standard deviation = 10) years. Daily exposure to nicotine assessed via salivary cotinine was similar to those reported for other e-cigarette and tobacco cigarette users in general. The majority reported low to moderate nicotine dependence. Qualitative interview themes included: the importance of social networks in adoption and use of the product; device features such as small size and vapor cloud reinforced product use; the product provided satisfaction compared to a tobacco cigarette; and a perceived sense of addiction to the product. CONCLUSIONS: JUUL e-cigarettes expose users to levels of nicotine similar to other e-cigarettes but may be more satisfying due to unique device features. JUUL may be quite acceptable to tobacco cigarette smokers who are seeking to quit. However, it holds addictive potential and can reinforce long-term nicotine use.

Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence.

This study investigated the influence of the rate of nicotine metabolism, as indicated by the nicotine metabolite ratio (NMR), on tobacco dependence. We stratified 136 smokers on the basis of saliva NMR as fast (n = 65) and slow (n = 71) metabolizers. Two "loading cigarettes" were smoked after overnight, and a "reward cigarette" was smoked after 6 hours of daytime, abstinence. Blood nicotine concentrations, expired carbon monoxide, withdrawal/craving, and reward questionnaires were collected before/after smoking and during daytime abstinence. Compared with slow metabolizers, fast metabolizers had a shorter nicotine elimination half-life (P < 0.001), lower plasma nicotine concentrations (P < 0.001), and higher withdrawal/craving scores (P < 0.05) for most times during daytime abstinence, indicating that fast metabolizers are likely smoking more to relieve withdrawal symptoms (negative reinforcement). Reward/satisfaction scores were similar in fast and slow metabolizers, suggesting that faster nicotine metabolism, assessed by NMR, is not associated with greater positive reinforcement. CYP2A6 normal (n = 82) and reduced (n = 42) genotype predicted plasma nicotine concentrations but not withdrawal symptoms.

IQOS: examination of Philip Morris International's claim of reduced exposure.

BACKGROUND: New electronic heated tobacco products are being introduced in the global market and are gaining popularity. In 2016, Philip Morris International, Inc. (PMI) submitted a modified risk tobacco product (MRTP) application to the Food and Drug Administration (FDA) to market IQOS in the USA with claims of reduced exposure and reduced risk. METHODS: We examined PMI's MRTP application, specifically sections on aerosol chemistry and human exposure assessment, to assess the validity of PMI's claims of reduced exposure and risk. FINDINGS: PMI reported levels for only 40 of 93 harmful and potentially harmful constituents (HPHCs) on FDA's HPHC list in IQOS mainstream aerosol. All substances in PMI's list of 58 constituents (PMI-58) were lower in IQOS emissions compared with mainstream smoke of 3R4F reference cigarettes. However, levels of 56 other constituents, which are not included in the PMI-58 list or FDA's list of HPHCs, were higher in IQOS emissions; 22 were >200% higher and seven were >1000% higher than in 3R4F reference cigarette smoke. PMI's studies also show significantly lower systemic exposure to some HPHCs from use of IQOS compared with smoking combustible cigarettes. CONCLUSION: PMI's data appear to support PMI's claim that IQOS reduces exposure to HPHCs. However, PMI's data also show significantly higher levels of several substances that are not recognised as HPHCs by the FDA in IQOS emissions compared with combustible cigarette smoke. The impact of these substances on the overall toxicity or harm of IQOS is not known.

Comparison of Urine 4-(Methylnitrosamino)-1-(3)Pyridyl-1-Butanol and Cotinine for Assessment of Active and Passive Smoke Exposure in Urban Adolescents.

Background: Many adolescents are exposed to tobacco smoke, from either active smoking (CS) or secondhand smoke (SHS) exposure. Tobacco-specific biomarkers of exposure include cotinine (detects use in past 2-4 days) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; detects use for a month or longer). NNAL is expected to detect more intermittent tobacco exposure. We compared NNAL and cotinine as biomarkers of exposure to tobacco in urban adolescents and determined the optimal NNAL cutoff point to distinguish CS from SHS exposure.Methods: Surplus urine samples, collected from 466 adolescents attending pediatric well or urgent care visits at Zuckerberg San Francisco General Hospital in 2013 to 2014, were assayed for cotinine and NNAL.Results: Ninety-four percent of adolescents had measurable levels of NNAL compared with 87% for cotinine. The optimal NNAL cutoff point to distinguish CS from SHS was 9.6 pg/mL by latent class or 14.4 pg/mL by receiver-operating characteristic analysis. Cotinine and NNAL were strongly correlated, but the correlation slopes differed for active versus SHS-exposed adolescents. Among nonsmokers, NNAL levels were significantly higher in African American (median, 3.3 pg/mL) compared with other groups (0.9-1.9 pg/mL), suggesting greater exposure to SHS.Conclusions: Urine NNAL screening finds a large majority (94%) of urban adolescents are exposed to tobacco. African Americans are exposed to higher levels of SHS than other ethnic/racial groups.Impact: SHS is associated with significant medical morbidity in adolescents. Routine biochemical screening with NNAL or cotinine detects high prevalence of SHS exposure and should be considered as a tool to reduce SHS exposure in high-risk populations. Cancer Epidemiol Biomarkers Prev; 27(3); 254-61. ©2018 AACR.

Perceived nicotine content of reduced nicotine content cigarettes is a correlate of perceived health risks.

BACKGROUND: Reducing cigarette nicotine content may reduce smoking. Studies suggest that smokers believe that nicotine plays a role in smoking-related morbidity. This may lead smokers to assume that reduced nicotine means reduced risk, and attenuate potential positive effects on smoking behaviour. METHODS: Data came from a multisite randomised trial in which smokers were assigned to use cigarettes varying in nicotine content for 6 weeks. We evaluated associations between perceived and actual nicotine content with perceived health risks using linear regression, and associations between perceived nicotine content and perceived health risks with smoking outcomes using linear and logistic regression. FINDINGS: Perceived-not actual-nicotine content was associated with perceived health risks; compared with those perceiving very low nicotine, individuals who perceived low (ß=0.72, 95% CI 0.26 to 1.17), moderate (ß=1.02, 95% CI 0.51 to 1.53) or high/very high nicotine (ß=1.66, 95% CI 0.87 to 2.44) perceived greater health risks. Nevertheless, individuals perceiving low (OR=0.48, 95% CI 0.32 to 0.71) or moderate nicotine (OR=0.42, 95% CI 0.27 to 0.66) were less likely than those perceiving very low nicotine to report that they would quit within 1 year if only investigational cigarettes were available. Lower perceived risk of developing other cancers and heart disease was also associated with fewer cigarettes/day at week 6. CONCLUSIONS: Although the perception of reduced nicotine is associated with a reduction in perceived harm, it may not attenuate the anticipated beneficial effects on smoking behaviour. These findings have implications for potential product standards targeting nicotine and highlight the need to clarify the persistent harms of reduced nicotine combusted tobacco products.

Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms.

BACKGROUND: The FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction. METHODS: In this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures. RESULTS: Of the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p < .05); among those with CES-D scores ≥ 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D scores than those assigned to NNC cigarettes. Among those in the lowest nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores < 16 and no change in CES-D score for those with baseline CES-D scores ≥ 16. CONCLUSIONS: These findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms. IMPLICATIONS: This secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity.