Total Nicotine Research Articles

Effect of Club cell secretory proteins on the association of tobacco smoke and PAH co-exposure with lung function decline: A longitudinal observation of Chinese coke oven workers.

Exposure to polycyclic aromatic hydrocarbons (PAH) and tobacco smoke is associated with epithelial damage and reduced lung function. Club cell secretory protein (CC16) is a known biomarker for lung epithelial cells. However, the potential relationships between PAH and tobacco smoke exposure, CC16 levels, and reduced lung function remain unclear. This longitudinal study aimed to explore the potential role of CC16 in the association of tobacco smoke and PAH co-exposure with lung function. We enrolled 313 workers from a coking plant in China in 2014 and followed them up in 2019. The concentrations of PAH and nicotine metabolites in urine were determined using high-performance liquid chromatography (HPLC) with a fluorescence detector and HPLC-tandem mass spectrometry, respectively. The plasma CC16 concentration was determined using an enzyme-linked immunosorbent assay. An analysis of the generalized estimating equation showed that each 1-unit increase in log-transformation of the last tertile of trans-3'-hydroxycotinine (3HC) was associated with a 3.30ng/ml decrease in CC16. Restricted cubic spline analysis revealed a significant nonlinear dose-effect association between cotinine (COT) and CC16 (Pnonlinear=0.018). In the low- CC16 subgroup, we found a significant association between total nicotine metabolites and forced vital capacity (FVC%) (β: 1.45, 95% CI: 2.87, -0.03), and the associations of nicotine (NIC), COT, and 3HC with FVC% were all of marginal significance. High levels of total hydroxyl polycyclic aromatic hydrocarbons (ΣOH-PAH) and NIC in the urine had an interactive effect on the decline of CC16 (P<0.05). Cross-lagged panel analysis indicated that the decrease in CC16 preceded the decrease in FVC%. CC16 mediated the association between elevated nicotine metabolites and decreased FVC% in the low- CC16 subgroup. CC16 plays an essential role in the association of PAH and tobacco smoke exposure with reduced lung function. Coke oven workers with low plasma CC16 levels are more likely to experience decreased lung function after tobacco smoke exposure.

Associations of biomarkers for exposure to tobacco smoke with lung cancer risk in Korea.

Nicotine metabolite ratio (NMR) can be used to predict total nicotine clearance. However, it is unknown whether NMR could be used as a marker of lung cancer risk. To evaluate the blood metabolites of nicotine relating to the risk of developing lung cancer and investigate the combined effects of NMR and cigarette per day on the risk of lung cancer. Among the 1,054 eligible subjects from the Korean Cancer Prevention Study-II biobank cohort, those with cotinine values below 0 ng/ml were excluded. Slow and fast metabolizer groups were defined using the median value of the NMR, calculated with the control group data, as the cut-point. The multivariable Cox proportional hazard models demonstrated that, the fast metabolizer group had a significantly higher risk of lung cancer than the slow metabolizer group (Adjusted HR: 2.02, 95% CI: 1.32-3.10). Fast metabolizers who smoked more than 15 cigarettes per day had an even higher risk of lung cancer (Adjusted HR: 3.51, 95% CI: 1.96-6.29) than the slow metabolizers who smoked less than 15 cigarettes per day. In summary, the NMR may be an effective marker for estimating tobacco-related disease risks such as lung cancer.

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

THE CHEST TOBACCO TREATMENT TOOLKIT: CHRONIC DISEASE MANAGEMENT, POINT-OF-CARE BIOCHEMISTRY ASSAYS, AND TITRATION OF TOBACCO TREATMENT MEDICATIONS INCREASES QUIT RATES

THE CHEST TOBACCO TREATMENT TOOLKIT: CHRONIC DISEASE MANAGEMENT, POINT-OF-CARE BIOCHEMISTRY ASSAYS, AND TITRATION OF TOBACCO TREATMENT MEDICATIONS INCREASES QUIT RATES

Market survey of disposable e-cigarette nicotine content and e-liquid volume

Inaccurate labels on some e-cigarette products have prompted calls for routine testing to monitor product label integrity. The objective of this study was to compare label statements of commercial disposable/non-chargeable e-cigarette products for nicotine concentration and e-liquid volume with analytically verified levels. Commercial e-cigarette samples were analyzed for nicotine concentration (N = 51), e-liquid volume and total nicotine content (N = 39). Twenty-three of the 51 samples analyzed for nicotine deviated from their label statements by more than ± 10%. Deviations ranged from -50.1% to + 13.9%. Thirty of the 39 samples analyzed for e-liquid volume deviated from their label statements by more than ± 10%. Deviations ranged from -62.1% to + 13.3%. Only one brand listed total nicotine on the label. In thirty-one of the 39 samples, calculated total nicotine amount in e-liquid deviated from the amounts calculated from the label metrics by more than ± 10%. Deviations ranged from -66.8% to -1.43%. These findings underscore the need for regulatory enforcement of manufacturing quality control and product labeling practices to optimize the harm reduction potential and consumer experience associated with the use of e-cigarette products.

A Comparison of Use Topography and Nicotine Pharmacokinetics Among Loose and Portioned Smokeless Tobacco Users.

Moist snuff smokeless tobacco (ST) products are available in the United States in both "loose" and "portioned" (ie, pouched) formats, but no published study to date has clinically evaluated the associations between ST format, use behavior, and nicotine exposure. Participants used their usual brand of ST (loose ST [n = 30] or portioned ST [n = 20]) during an experimental visit wherein use behavior and plasma nicotine pharmacokinetic parameters were measured following single use (first hour of the session) and ad libitum use (remaining 7 h of the session). Participants' ST products were chemically characterized prior to use for pH and nicotine content. The average amount per use (2.99 vs. 1.52 g; p = .005) and total amount used (11.45 vs. 5.4 g; p = .002) were significantly higher among the loose ST group. Maximum plasma nicotine concentration (Cmax; 33.4 vs. 19.1 ng/ml) and area under the nicotine concentration versus time curve (AUC) were significantly higher for the loose ST group for the first hour (1474.8 vs. 807.2 min* ng/ml; p = .003) and throughout the 8-hour session (15827.9 vs. 8155.3 min* ng/ml; p < .001). Significant associations were observed between free nicotine content and first use Cmax (rs = .488, loose ST group) and AUC0-1 h (rs = 0.448, loose ST group; rs = .441, portioned ST group). The loose ST group used more product and had a greater average deposition time per use than the portioned ST group. Nicotine exposure was more strongly associated with free nicotine content than total nicotine content. To our knowledge, the current investigation was the first study to date to clinically evaluate the associations between usual-brand smokeless format, use behavior, and nicotine exposure. We observed meaningful differences in use behavior and subsequent nicotine exposure between loose and portioned ST users. Further, we observed that nicotine exposure was more strongly associated with free nicotine content than total nicotine content.

Increased Levels of the Acrolein Metabolite 3-Hydroxypropyl Mercapturic Acid in the Urine of e-Cigarette Users.

Carcinogen and toxicant uptake by e-cigarette users have not been fully evaluated. In the study reported here, we recruited 30 e-cigarette users, 63 nonsmokers, and 33 cigarette smokers who gave monthly urine samples over a period of 4-6 months. Their product use status was confirmed by measurements of exhaled CO, urinary total nicotine equivalents, cyanoethyl mercapturic acid (CEMA), and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Urinary biomarkers of exposure to the carcinogens acrolein (3-hydroxypropyl mercapturic acid, 3-HPMA), benzene (S-phenyl mercapturic acid, SPMA), acrylonitrile (CEMA), and a combination of crotonaldehyde, methyl vinyl ketone, and methacrolein (3-hydroxy-1-methylpropyl mercapturic acid, HMPMA) were quantified at each visit. Data from subject visits with CEMA > 27 pmol/mL were excluded from the statistical analysis of the results because of possible unreported exposures to volatile combustion products such as secondhand cigarette smoke or marijuana smoke exposure; this left 22 e-cigarette users with 4 or more monthly visits and all 63 nonsmokers. Geometric mean levels of 3-HPMA (1249 versus 679.3 pmol/mL urine) were significantly higher (P = 0.003) in e-cigarette users than in nonsmokers, whereas levels of SPMA, CEMA, and HMPMA did not differ between these two groups. All analytes were significantly higher in cigarette smokers than in either e-cigarette users or nonsmokers. The results of this unique multimonth longitudinal study demonstrate consistent significantly higher uptake of the carcinogen acrolein in e-cigarette users versus nonsmokers, presenting a warning signal regarding e-cigarette use.

Disposable Puff Bar Electronic Cigarettes: Chemical Composition and Toxicity of E-liquids and a Synthetic Coolant.

The popularity of disposable fourth-generation electronic cigarettes (ECs) among young adults and adolescents has been increasing since the ban on flavored cartridge EC products such as JUUL. Although the constituents and toxicity of some cartridge-based fourth-generation ECs, such as JUUL, have been studied, limited data exist for other disposable ECs such as Puff. The purpose of this study was to determine flavor chemicals, synthetic coolants, and nicotine concentrations in 16 disposable Puff devices, evaluate the cytotoxicity of the different flavors from the Puff brand using in vitro assays, and investigate the health risks of synthetic coolants in EC products. Gas chromatography/mass spectrometry was used to identify and quantify chemicals in Puff EC fluids. One hundred and twenty-six flavor chemicals were identified in Puff fluids, and 16 were >1 mg/mL. WS-23 (2-isopropyl-N,2,3-trimethylbutyramide) was present in all products, and concentrations ranged from 0.8 to 45.1 mg/mL. WS-3 (N-ethyl-p-menthane-3-carboxamide) concentrations ranged from 1.5 to 16.4 mg/mL in 6/16 products. Nicotine concentrations ranged from 40.6 to 52.4 (average 44.8 mg/mL). All unvaped fluids were cytotoxic at dilutions between 0.1 and 10% in the MTT and neutral red uptake assays when tested with BEAS-2B lung epithelial cells. The cytotoxicity of Puff fluids was highly correlated with total chemical concentrations, nicotine, WS-23, both synthetic coolants, and synthetic coolants plus ethyl maltol. Lower concentrations of WS-23 than those in the fluids adversely affected cell growth and morphology. Concentrations of synthetic coolants exceeded levels used in consumer products. The margin of exposure data showed that WS-3 and WS-23 concentrations were high enough in Puff products to present a health hazard. Our study demonstrates that disposable Puff ECs have high levels of cytotoxic chemicals. The data support the regulation of flavor chemicals and synthetic coolants in ECs to limit potentially harmful health effects.

Abstract 5705: Identifying DNA methylation quantitative trait loci across multi-ethnic populations

Abstract Objective: To date, genome-wide association studies (GWAS), which are primarily conducted in Europeans, have identified a large number of validated DNA methylation quantitative trait loci (meQTLs) acting in both cis and trans. However, it is recognized that there are racial differences in genetic architectures such as allele frequencies and linkage equilibrium patterns, which may differentially influence DNA methylation levels. This points to a critical need to conduct a methylome wide association study (MWAS) to identify meQTLs across multiethnic populations including understudied African Americans (AAs), Latinos, Japanese Americans (JAs), and Native Hawaiians (NHs). Methods: We are performing a GWAS to identify meQTLs in blood leukocytes in a multiethnic population using data from the Multiethnic Cohort Study (MEC). In MEC, “genome-wide” germline genetic variants and DNA methylation levels of blood leukocytes have been measured using the Illumina 1M and MethEPIC array, respectively, for 372 AAs, 408 Latinos, 531 JAs, 319 NHs, and 406 European Americans who were current smokers at time of blood draw. Genotyped data has been imputed with 1000 Genomes phase 3 dataset. For DNA methylation data, standardized quality control (QC) and normalization have been performed. We adjusted for the following potential confounders at time of blood draw: age, sex, body mass index, estimated cell type composition variables, genetic principal components, smoking pack-years, and urinary total nicotine equivalents (a biomarker for internal smoking dose). A stringent Bonferroni-corrected threshold (P&amp;lt;5×10-8/(850,355×6) = 9.80×10-15) was used to define statistical significance. An independent dataset of MEC participants including 114 AAs, 142 Latinos, 286 JAs, 108 NHs, and 270 European Americans will be used to replicate the identified meQTLs. Results: Our preliminary analyses for identifying cis-meQTL SNPs (residing within 1 Mb upstream or downstream of a CpG site of interest) found 169,823 CpG sites (20.0%) are associated with at least one nearby genetic variant in AAs. Similarly, 284,371 CpG sites (33.4%) in JAs, 168,580 CpG sites (19.8%) in Latinos, 123,032 CpG sites (14.5%) in NHs, and 234,822 CpG sites (27.6%) in European Americans are significantly associated with at least one nearby genetic variant. In the pan-ethnic analyses including all five ethnic/racial groups, 193,743 CpG sites (23.0%) are associated with at least one nearby genetic variant. Conclusion: Our preliminary findings identified ethnic-specific and pan-ethnic cis-meQTL SNPs across a multiethnic population that includes understudied AAs, Latinos, JAs, NHs, along with European Americans. If replicated in independent datasets, these findings will significantly improve our understanding of genetic regulation of DNA methylation levels in these populations. Citation Format: Lang Wu, Xiequn Xu, Dalia Ghoneim, Kayla Kim, Alexandra Binder, Yesha Patel, Daniel O. Stram, Loïc Le Marchand, Sungshim L. Park. Identifying DNA methylation quantitative trait loci across multi-ethnic populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5705.

Exploring Potential for a Personalized Medicine Approach to Smoking Cessation With an American Indian Tribe.

A potential precision medicine approach to smoking cessation is tailoring pharmacotherapy to a biomarker known as the nicotine metabolite ratio (NMR). Little is known about the potential impact and acceptability of this approach for American Indian (AI) persons. Tribal-academic collaboration was formed and during 2019-2020 AI adults who smoke(N = 54) were recruited to (1) examine correlations between NMR, dependence, and smoking exposure; (2) assess the extent to which pharmacotherapy preference aligned with NMR-informed recommendations; (3) explore acceptability of NMR-informed pharmacotherapy selection. Participants provided samples for assessment of salivary NMR and urinary total nicotine equivalents (TNE) and completed a questionnaire that assessed cigarettes per day (CPD), Fagerstrom Test for Cigarette Dependence (FTCD), pharmacotherapy preference, and perceptions of NMR-informed pharmacotherapy selection. Significant positive correlations were observed between NMR and FTCD (r = 0.29;p = .0383) and its abbreviated version Heaviness of Smoking Index (HIS) (r = 0.28;p =.0426). Post-hoc analyses suggest that relationships between dependence and NMR were driven by time to first cigarette. Nonsignificant, but directionally consistent, relationships were observed between NMR and CPD (r = 0.21; p =0.1436) and TNE (r = 0.24;p = .2906). Most participants preferred nicotine replacement therapy (71%) over varenicline (29%) and preference for pharmacotherapy matched NMR-based recommendations in 54% of participants. NMR-informed pharmacotherapy selection was supported by 62% of participants. In a sample of AI adults who smoke, NMR was related to cigarette dependence and about one-half of participants' pharmacotherapy preference matched their NMR-informed recommendation. There was lower acceptability of NMR-informed approach in this sample of AI adults than prior studies among white or black/African American people who smoke. Relationships between NMR, dependence, and self-preference for pharmacotherapy suggest that NMR-informed pharmacotherapy selection may have potential for enhancing smoking quitting success in this Tribe. Lower acceptability of NMR-informed pharmacotherapy in this Tribe suggests that this approach may not be equitably utilized. Future work could include identifying community-driven solutions to mitigate precision medicine concerns.

Quantitative measurement of harmful and potentially harmful constituents, pH, and moisture content in 16 commercial smokeless tobacco products

Smokeless tobacco products expose adult and youth tobacco users to various addictive and carcinogenic constituents that can cause long-term nicotine dependence and oral cancers. In this study, nicotine, benzo[a]pyrene (B[a]P), N′-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acetaldehyde, crotonaldehyde, formaldehyde, moisture, and pH levels in 16 smokeless tobacco products were measured on a wet-weight basis (wwb). In addition, change in analytical variability with increasing replicate measurements was assessed. Total nicotine in the products varied from 6.2 to 35.5 mg/g. The percentage of total nicotine in the unprotonated form ranged from 0.1 to 62%; whereas, product moisture varied from 7.4 to 57%. The quantities of harmful and potentially harmful constituents (HPHCs) range from 0.46 to 179.9 ng/g for B [a]P, 270–12206 and 81–20716 ng/g for NNN and NNK, respectively, and 0.33–6.85 and 0.13–5.67 μg/g for acetaldehyde and formaldehyde, respectively. This study shows wide variation in smokeless tobacco product HPHC quantities. The results also show that analytical variability stabilizes after seven replicate measurements.

Association between Fathers' Use of Heated Tobacco Products and Urinary Cotinine Concentrations in Their Spouses and Children.

Heated tobacco products (HTPs) have become increasingly popular among smokers, especially among young adults in Japan in recent years. Assessments of secondhand tobacco smoke (SHS) exposure due to HTPs are scarce. The present study aimed to assess the urinary levels of total nicotine metabolites (TNMs) of non-smoking spouses and their children following SHS exposure due to their fathers’ use of HTPs. A total of 41 families including 129 participants were recruited between 2018 and 2021. The number of non-smoking spouses and children of the fathers who smoke combustion cigarettes, the fathers who use HTPs, and the fathers who are non-users or have never smoked was 27, 66, and 36, respectively. The urinary levels of TNMs, including cotinine (Cot) and 3′-hydroxycotinine (3-OHCot), were measured using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The spouses and children of fathers who use HTPs had significantly higher levels of TNMs in their urine compared to those with fathers who were non-smokers or non-users. The current study is the first to assess SHS exposure due to HTP use, and to suggest the importance of strategies to prevent exposure to SHS from HTP use in public places and educational strategies to protect non-smokers from secondhand HTP aerosol exposure in households and other private places.

Using complex behavior to understand brain mechanisms in health and disease.

Using complex behavior to understand brain mechanisms in health and disease.

Variability in Urinary Nicotine Exposure Biomarker Levels Between Waves 1 (2013-2014) and 2 (2014-2015) in the Population Assessment of Tobacco and Health Study.

To date, no studies have evaluated the consistency of biomarker levels in people who smoke over a long-time period in real-world conditions with a large number of subjects and included use behavior and measures of nicotine metabolism. We evaluated the variability of biomarkers of nicotine exposure over approximately a 1-year period in people who exclusively smoke cigarettes, including intensity and recency of use and brand switching to assess impact on understanding associations with product characteristics. Multivariate regression analysis of longitudinal repeated measures of urinary biomarkers of nicotine exposure from 916 adults in the Population Assessment of Tobacco and Health (PATH) Study with demographic characteristics and use behavior variables. Intraclass correlation coefficients (ICCs) were calculated to examine individual variation of nicotine biomarkers and the uncertainty of repeat measures at two time points (Waves 1 and 2). Age, race, and urinary creatinine were significant covariates of urinary cotinine. When including use behavior, recency, and intensity of use were highly significant and variance decreased to a higher extent between than within subjects. The ICC for urinary cotinine decreased from 0.7530 with no use behavior variables in the model to 0.5763 when included. Similar results were found for total nicotine equivalents. Urinary nicotine biomarkers in the PATH Study showed good consistency between Waves 1 and 2. Use behavior measures such as time since last smoked a cigarette and number of cigarettes smoked in the past 30 days are important to include when assessing factors that may influence biomarker concentrations. The results of this study show that the consistency of the nicotine biomarkers cotinine and total nicotine equivalents in spot urine samples from Waves 1 to 2 of the PATH Study is high enough that these data are useful to evaluate the association of cigarette characteristics with biomarkers of exposure under real-world use conditions.

Nicotine Exposure in the U.S. Population: Total Urinary Nicotine Biomarkers in NHANES 2015-2016.

We characterize nicotine exposure in the U.S. population by measuring urinary nicotine and its major (cotinine, trans-3′-hydroxycotinine) and minor (nicotine 1′-oxide, cotinine N-oxide, and 1-(3-pyridyl)-1-butanol-4-carboxylic acid, nornicotine) metabolites in participants from the 2015–2016 National Health and Nutrition Examination Survey. This is one of the first U.S. population-based urinary nicotine biomarker reports using the derived total nicotine equivalents (i.e., TNEs) to characterize exposure. Serum cotinine data is used to stratify tobacco non-users with no detectable serum cotinine (−sCOT), non-users with detectable serum cotinine (+sCOT), and individuals who use tobacco (users). The molar concentration sum of cotinine and trans-3′-hydroxycotinine was calculated to derive the TNE2 for non-users. Additionally, for users, the molar concentration sum of nicotine and TNE2 was calculated to derive the TNE3, and the molar concentration sum of the minor metabolites and TNE3 was calculated to derive the TNE7. Sample-weighted summary statistics are reported. We also generated multiple linear regression models to analyze the association between biomarker concentrations and tobacco use status, after adjusting for select demographic factors. We found TNE7 is positively correlated with TNE3 and TNE2 (r = 0.99 and 0.98, respectively), and TNE3 is positively correlated with TNE2 (r = 0.98). The mean TNE2 concentration was elevated for the +sCOT compared with the −sCOT group (0.0143 [0.0120, 0.0172] µmol/g creatinine and 0.00188 [0.00172, 0.00205] µmol/g creatinine, respectively), and highest among users (33.5 [29.6, 37.9] µmol/g creatinine). Non-daily tobacco use was associated with 50% lower TNE7 concentrations (p < 0.0001) compared with daily use. In this report, we show tobacco use frequency and passive exposure to nicotine are important sources of nicotine exposure. Furthermore, this report provides more information on non-users than a serum biomarker report, which underscores the value of urinary nicotine biomarkers in extending the range of trace-level exposures that can be characterized.

Increased acrolein-DNA adducts in buccal brushings of e-cigarette users.

DNA adducts are central in the mechanism of carcinogenesis by genotoxic agents. We compared levels of a DNA adduct of acrolein, a genotoxic carcinogen found in e-cigarette vapor, in oral cell DNA of e-cigarette users and non-users of any tobacco or nicotine product. e-Cigarette users and non-users visited our clinic once monthly for 6 months, and oral brushings and urine samples were collected. For this study, we analyzed oral cell DNA adducts from three monthly visits in e-cigarette users and non-users as confirmed by urinary cyanoethyl mercapturic acid and total nicotine equivalents. DNA was isolated from the oral brushings and analyzed by a validated liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry method for the acrolein DNA adduct 8R/S-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10-(3H)-one (γ-OH-Acr-dGuo). The median value of this DNA adduct in the e-cigarette users was 179 fmol/µmol dGuo (range 5.0 - 793 fmol/µmol dGuo) while that for non-users was 21.0 fmol/µmol dGuo (range 5.0 - 539 fmol/µmol dGuo), P = 0.001. These results demonstrate for the first time that e-cigarette users have elevated levels of a carcinogen-DNA adduct in their oral cells.

Changes in Biomarkers of Tobacco Exposure among Cigarette Smokers Transitioning to ENDS Use: The Population Assessment of Tobacco and Health Study, 2013-2015.

Limited data are available for how biomarkers of tobacco exposure (BOE) change when cigarette smokers transition to using electronic nicotine delivery systems (ENDS). Using biomarker data from Waves 1 (2013–2014) and 2 (2014–2015) of the PATH Study, we examined how mean BOE concentrations, including metabolites of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC) and metals, changed when 2475 adult smokers transitioned to using ENDS or quit tobacco products. Exclusive smokers who transitioned to dual use had a significant decrease in NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), but not nicotine metabolites, most PAHs, metals, or VOCs. Exclusive smokers who became dual users had significant reductions in total nicotine equivalents, NNAL, and 2CyEMA (acrylonitrile metabolite), but only in those who reduced cigarettes per day (CPD) by >=50%. Smokers who transitioned to exclusive ENDS use had significant reductions in most TSNAs, PAHs, and VOCs; however, nicotine metabolites did not decrease in dual users who became exclusive ENDS users. Smokers who quit tobacco use had significant decreases in nicotine metabolites, all TSNAs, most PAHs, and most VOCs. Cigarette smokers who became dual users did not experience significant reductions in most BOEs. Reductions were impacted by changes in CPD. However, transitioning from smoking to no tobacco or exclusive ENDS use was associated with reduced exposure to most BOEs measured. Future analyses could incorporate additional waves of PATH data and examine changes in biomarker exposure by ENDS device type and CPD.

Comparison of nicotine emissions rate, ‘nicotine flux’, from heated, electronic and combustible tobacco products: data, trends and recommendations for regulation

IntroductionTobacco smoking is a major cause of disease and premature death worldwide. While nicotine is recognised as the main addictive component in tobacco smoke, the total nicotine amount emitted (nicotine...

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries

Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 μM) than in MICs (31·1 μM) and LICs (25·2 μM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 μM) and MICs (11·3 μM) than in HICs (5·0 μM; ANCOVA p=0·0001). The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. Full funding sources are listed at the end of the paper (see Acknowledgments).

Associations of Smokeless Tobacco Use With Cardiovascular Disease Risk: Insights From the Population Assessment of Tobacco and Health Study.

Cigarette smoking is strongly associated with the development of cardiovascular disease (CVD). However, evidence is limited as to whether smokeless tobacco (ST) use is associated with CVD. Using data from 4347 adults in the Population Assessment of Tobacco and Health Study (2013-2014), we compared geometric mean concentrations of CVD-related harm biomarkers and biomarkers of exposure among exclusive ST users and exclusive cigarette smokers-in relation to recent nicotine exposure-and never tobacco users, adjusting for age, sex, race/ethnicity, income, body mass index, and CVD. Biomarker levels among exclusive ST users who were former established cigarette smokers were compared with exclusive cigarette smokers. Compared with cigarette smokers, ST users had significantly higher concentrations of total nicotine equivalents (TNE) but lower concentrations of inflammatory (high-sensitivity C-reactive protein, interleukin-6, intercellular adhesion molecule, fibrinogen) and oxidative stress (8-isoprostane) biomarkers (all p < .05). Biomarker levels among ST users were similar to never smokers. ST users who were former cigarette smokers had lower levels of inflammatory and oxidative stress biomarkers and biomarkers of exposure (cadmium, lead, 1-hydroxypyrene, acrylonitrile, and acrolein), compared with cigarettes smokers (p < .05), despite having higher TNE levels (p < .05). Among cigarette smokers, but not among ST users, inflammatory biomarkers and TNE were highly correlated. ST use is not associated with increases in biomarkers of CVD-related harm and exposure, compared with never smokers, despite exposure to nicotine at levels higher than those observed among cigarette smokers. These findings support the concept that increases in CVD risk among cigarette smokers is caused primarily by constituents of tobacco smoke other than nicotine. Despite having higher levels of nicotine and compared with exclusive cigarette smokers, exclusive ST users (including those who were former cigarette smokers) had significantly lower concentrations of inflammatory and oxidative stress biomarkers, comparable to levels observed among never tobacco users. These findings suggest that increases in CVD risk among cigarette smokers is caused primarily by tobacco constituents other than nicotine and that switching to ST is likely associated with lower CVD risk.