[Chronic diarrhoea and weight loss secondary to nicotine use in an adolescent]. / Cas clinique. Diarrhée chronique et perte pondérale suite à la consommation de nicotine chez un adolescent.

Chronic diarrhoea is described as diarrhoea lasting more than 4 weeks. The underlying causes are multiple and the diagnostic orientation depends on several anamnestic and clinical elements. The basic work-up includes biology and stool analysis. We present the case of a 14-year-old adolescent with chronic diarrhoea and weight loss for several months. Extensive complementary analyses were performed, all being totally negative. A careful repeated clinical history revealed that the patient had a significant nicotine intake, confirmed by a urine cotinine test. Withdrawal led to a resolution of the symptomatology. Nicotine consumption in the form of nicotine replacement products among young people is increasing rapidly. Nicotine has multiple health effects, including neurological, gastrointestinal and immune adverse effects.

La diarrhée chronique est décrite comme une diarrhée qui dure plus de 4 semaines. Les étiologies sont multiples et l'orientation diagnostique dépend de plusieurs éléments anamnestiques et cliniques. La mise au point de base comprend une biologie et une analyse de selles. Nous présentons le cas d'un adolescent de 14 ans avec diarrhée chronique et perte pondérale depuis plusieurs mois. Un bilan complémentaire extensif est réalisé et revient totalement négatif. C'est en répétant l'anamnèse qu'une consommation nicotinique non négligeable est mise en évidence chez le patient, confirmée par un dosage élevé de cotinine urinaire. Le sevrage a permis une résolution de la symptomatologie. La consommation de nicotine sous forme de produits de substitution nicotinique chez les jeunes est en forte augmentation. La nicotine a de multiples effets négatifs sur la santé, notamment neurologiques, gastrointestinaux et immunitaires.

Dual-Function Platform Based on Postsynthetic Functionalization of a Water-Stable Hydrogen-Bonded Organic Framework: Ratiometric Sensing of Nicotine and Cotinine and Dynamic Anticounterfeiting for Information Encryption.

Nicotine and its major metabolite cotinine are widely used as markers of tobacco smoke abstinence as well as indicators of active smoking levels and the assessment of passive inhalation of tobacco smoke in nonsmokers. Therefore, using an easy-to-prepare sensing platform that can provide a rapid, highly sensitive response for the simultaneous detection of salivary nicotine levels and urinary cotinine levels is especially crucial for helping heavy cigarette smokers quit smoking and protecting public health. Hydrogen-bonded organic frameworks, as a novel class of porous crystalline materials, show immense potential for functional modification and optical sensing. Herein, a new HOF was prepared by a simple solvent evaporation method, and a dual-emitting material Eu(bpy)@HOF-215(1) was obtained by the postsynthetic modification of HOF by lanthanide luminescent complexes, which maintains favorable structural stability and introduces the characteristic emitting of Eu, allowing use as a ratiometric fluorescent sensor for salivary nicotine and urinary cotinine, with a limit of detection of nicotine of 0.045 µM in saliva and a limit of detection of cotinine of 0.591 µM in urine. Furthermore, luminescent inks based on HOF-215 have been fabricated based on the photoresponse variations of 1 to NIC and COT, which enables the multilevel encryption and decryption of information, in a dynamic and recyclable process. This work not only synthesizes a novel blue HOF but also provides a representative successful case of a dual-function platform for simultaneous application to ratiometric sensing and dynamic anticounterfeiting.

Biomarkers of Toxic Exposure and Oxidative Stress Among U.S. Adult Users of Premium Cigar Versus Other Cigar Subtypes: 2013-2019.

INTRODUCTION: Cigars are currently the second-highest-used combustible tobacco product among U.S. adults, but knowledge about health effects of premium cigars versus other cigar subtype use is limited. AIMS AND METHODS: This study analyzed the biospecimen data (n = 31 875) from Waves 1-5 of the Population Assessment of Tobacco and Health Study, collected during 2013-2019. Multivariable generalized estimation equations, accounting for within-person clustering, were conducted to examine differences in urine biomarkers of exposure (BOE) from five classes of harmful and potentially harmful constituents along with a biomarker of oxidative stress (urine 8-isoprostane) among exclusive users of premium cigars versus other exclusive cigar subtypes (ie, non-premium large cigars, cigarillos, and filtered cigars), cigarettes, and non-tobacco users. RESULTS: In comparison to non-tobacco users, exclusive premium cigar users had higher geometric mean concentrations of the nicotine metabolite cotinine (5.8 vs. 0.5ng/mg, p < .0001), tobacco-specific nitrosamine (TSNA) (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL): 7.8 vs. 1.3pg/mg, p < .0001), and volatile organic compound (VOC) (N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA, acrylonitrile): 4.7 vs. 1.6ng/mg, p < .0001). Exclusive premium cigar users were less likely to be daily users than other tobacco user groups and had comparable BOEs with exclusive non-premium large cigar users but generally lower BOEs than exclusive cigarillo, filtered cigar, and cigarette smokers. Daily exclusive premium cigar users had similar nicotine and TSNA exposure but lower exposure to polycyclic aromatic hydrocarbons and volatile organic compounds than exclusive cigarillo and filtered cigar users. CONCLUSIONS: Premium cigar use exhibits different exposure to toxicants from other cigar subtype users. Regulations of premium cigars need to formalize product definition and take the population's health effects into consideration. IMPLICATIONS: This population study provides important information on BOE and potential harm with premium cigar use and its potential health effects. At present, premium cigars appear to pose a relatively low overall population health risk due to low frequency of use. However, future regulation of other tobacco products might change the landscape of premium cigar use and alter the overall health impact.

Improving Wastewater-Based Tobacco Use Estimates Using Anabasine.

In wastewater-based epidemiology (WBE), nicotine metabolites have been used as biomarkers for monitoring tobacco use. Recently, the minor tobacco alkaloids anabasine and anatabine have been suggested as more specific biomarkers for tobacco use since nicotine use can be from both tobacco and non-tobacco sources. This study aimed to provide an in-depth evaluation of the suitability of anabasine and anatabine as WBE biomarkers of tobacco and subsequently estimate their excretion factors for WBE applications. Pooled urine (n = 64) and wastewater samples (n = 277), collected between 2009 and 2019 in Queensland, Australia, were analyzed for nicotine and its metabolites (cotinine and hydroxycotinine), as well as anabasine and anatabine. Anabasine performed as the better biomarker, showing a similar per capita load in pooled urine (2.2 ± 0.3 µg/day/person) and wastewater samples (2.3 ± 0.3 µg/day/person), while the per capita load of anatabine in wastewater was 50% higher than its load in urine. It is estimated that 0.9 µg of anabasine was excreted per cigarette smoked. Triangulation of tobacco sales data and tobacco use estimated from either anabasine or cotinine showed that anabasine-based estimates were 5% higher than sales data, while cotinine-based estimates were between 2 and 28% higher. Our results provided concrete evidence to confirm the suitability of anabasine as a specific biomarker for monitoring tobacco use by WBE.

Impact of Genetic Variants in the Nicotine Metabolism Pathway on Nicotine Metabolite Levels in Smokers.

BACKGROUND: Nicotine metabolism is a major factor in nicotine dependence, with approximately 70% to 80% of nicotine metabolized to cotinine in Caucasians. Cotinine formation is catalyzed primarily by CYP2A6, which also converts cotinine to trans-3'-hydroxycotinine (3HC). The goal of the present study was to examine the effects of CYP2A6 deficiency on nicotine metabolism profiles in vivo and the importance of genetic variants in nicotine-metabolizing enzyme genes on urinary nicotine metabolites levels. METHODS: Urine samples from 722 smokers who participated in the Singapore Chinese Health Study were analyzed using UPLC-MS/MS to detect nicotine and eight of its urinary metabolites, and a total of 58 variants in 12 genes involved in nicotine metabolism were investigated in 475 of these subjects with informative genotyping data. RESULTS: Urine samples stratified by the ratio of 3HC/cotinine exhibited a 7-fold increase in nicotine-N'-oxide, a 6-fold increase in nicotine-Glucuronide (Gluc), and a 5-fold decrease in 3HC-Gluc when comparing the lower versus upper 3HC/cotinine ventiles. Significant (P < 0.0001) associations were observed between functional metabolizing enzyme genotypes and levels of various urinary nicotine metabolites, including CYP2A6 genotype and levels of nicotine, nicotine-Gluc, nicotine-N'-oxide and 3HC, UGT2B10 genotype and levels of cotinine, nicotine-Gluc and cotinine-Gluc, UGT2B17 genotype and levels of 3HC-Gluc, FMO3 genotype and levels of nicotine-N'-oxide, and CYP2B6 genotype and levels of nicotine-N'-oxide and 4-hydroxy-4-(3-pyridyl)-butanoic acid. CONCLUSIONS: These data suggest that several pathways are important in nicotine metabolism. IMPACT: Genotype differences in several nicotine-metabolizing enzyme pathways may potentially lead to differences in nicotine dependence and smoking behavior and cessation.

Trends in Urinary Biomarkers of Exposure to Nicotine and Carcinogens Among Adult e-Cigarette Vapers vs Cigarette Smokers in the US, 2013-2019.

This study assesses temporal trends of biomarkers among adult nicotine and nonnicotine e-cigarette users and cigarette smokers.

Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer.

The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in levels of DNA adducts in oral cells of cigarette smokers would be related to these differing risks of lung cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry to quantify 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, 1) and the lipid peroxidation-related DNA adduct 1,N6-etheno-dAdo (εdAdo, 2) in DNA obtained by oral rinse from 101 Native Hawaiians, 101 Whites, and 79 Japanese Americans. Levels of urinary biomarkers of nicotine, acrolein, acrylonitrile, and a mixture of crotonaldehyde, methyl vinyl ketone, and methacrolein were also quantified. Whites had significantly higher levels of γ-OH-Acr-dGuo than Japanese Americans and Native Hawaiians after adjusting for age and sex. There was no significant difference in levels of this DNA adduct between Japanese Americans and Native Hawaiians, which is not consistent with the high lung cancer risk of Native Hawaiians. Levels of εdAdo were modestly higher in Whites and Native Hawaiians than in Japanese Americans. The lower level of DNA adducts in the oral cells of Japanese American cigarette smokers than Whites is consistent with their lower risk for lung cancer. The higher levels of εdAdo, but not γ-OH-Acr-dGuo, in Native Hawaiian versus Japanese American cigarette smokers suggest that lipid peroxidation and related processes may be involved in their high risk for lung cancer, but further studies are required.

Urinary Nicotine Metabolites and Self-Reported Tobacco Use Among Adults in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

INTRODUCTION: The Population Assessment of Tobacco and Health (PATH) Study is a longitudinal cohort study on tobacco use behavior, attitudes and beliefs, and tobacco-related health outcomes, including biomarkers of tobacco exposure in the U.S. population. In this report we provide a summary of urinary nicotine metabolite measurements among adult users and non-users of tobacco from Wave 1 (2013-2014) of the PATH Study. METHODS: Total nicotine and its metabolites including cotinine, trans-3'-hydroxycotinine (HCTT), and other minor metabolites were measured in more than 11 500 adult participants by liquid chromatography tandem mass spectrometry methods. Weighted geometric means (GM) and least square means from statistical modeling were calculated for non-users and users of various tobacco products. RESULTS: Among daily users, the highest GM concentrations of nicotine, cotinine and HCTT were found in exclusive smokeless tobacco users, and the lowest in exclusive e-cigarette users. Exclusive combustible product users had intermediate concentrations, similar to those found in users of multiple products (polyusers). Concentrations increased with age within the categories of tobacco users, and differences associated with gender, race/ethnicity and educational attainment were also noted among user categories. Recent (past 12 months) former users had GM cotinine concentrations that were more than threefold greater than never users. CONCLUSIONS: These urinary nicotine metabolite data provide quantification of nicotine exposure representative of the entire US adult population during 2013-2014 and may serve as a reference for similar analyses in future measurements within this study. IMPLICATIONS: Nicotine and its metabolites in urine provide perhaps the most fundamental biomarkers of recent nicotine exposure. This report, based on Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study, provides the first nationally representative data describing urinary nicotine biomarker concentrations in both non-users, and users of a variety of tobacco products including combustible, e-cigarette and smokeless products. These data provide a urinary biomarker concentration snapshot in time for the entire US population during 2013-2014, and will provide a basis for comparison with future results from continuing, periodic evaluations in the PATH Study.

Exposure to polycyclic aromatic hydrocarbons and nicotine, and associations with sperm DNA fragmentation.

BACKGROUND: Tobacco smoking has been reported to cause DNA fragmentation and has been suggested to cause mutations in spermatozoa. These effects have been ascribed to the action of polycyclic aromatic hydrocarbons (PAH) present in the smoke. Simultaneously, DNA fragmentation has been associated with mutagenesis. OBJECTIVE: The aim of this study was to investigate whether levels of urinary biomarkers of PAH and nicotine exposure were associated with sperm DNA fragmentation. METHODS: In the urine of 381 men recruited from two cohorts of young men (17-21 years old) from the general Swedish population, the PAH metabolites 1-hydroxypyrene and 2-hydroxyphenanthrene, as well as the nicotine metabolite cotinine, were measured. The sperm DNA fragmentation index (DFI) was analysed using the sperm chromatin structure assay. Associations between the DFI, and PAH metabolite levels as continuous variables as well as in quartiles, were studied by general linear models adjusted for abstinence time. A similar analysis was carried out for cotinine levels, according to which the men were categorised as "non-smoking" (n = 216) and "smoking" (n = 165). RESULTS: No association was found between levels of any of the three biomarkers and DFI, either as a continuous variable (p = 0.87-0.99), or when comparing the lowest and the highest quartiles (p = 0.11-0.61). The same was true for comparison of men categorised as non-smoking or smoking (DFI 11.1% vs. 11.8%, p = 0.31). DISCUSSION: We found no evidence of PAH or nicotine exposure to be associated with DFI, which does not exclude that these exposures may have other effects on sperm DNA. CONCLUSION: In these young men, levels of biomarkers of nicotine and PAH exposure were not associated with DFI.

Biomarkers of Exposure and Biomarkers of Potential Harm in Adult Smokers Who Switch to e-Vapor Products Relative to Cigarette Smoking in a 24-week, Randomized, Clinical Trial.

INTRODUCTION: Long-term health effects of e-vapor products (EVPs) are not well-established. We compared biomarkers of exposure (BoE) to select harmful and potentially harmful constituents and biomarkers of potential harm (BoPH) in adult smokers who switched to EVPs versus continued smoking for 24 weeks. METHODS: Adult smokers (n = 450, >10 cigarettes per day for ≥10 years) were randomly assigned to continue smoking (control) or switch to one of two cartridge-based EVPs (test 1: classic; test 2: menthol, 4% nicotine). BoE and BoPH were measured at baseline and 12 weeks. The results presented here are from a subset of 150 control and EVP subjects (switchers with exhaled carbon monoxide <8 ppm and <10% baseline cigarettes per day) followed for 24 total weeks. RESULTS: Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and carboxyhemoglobin were significantly reduced (p < .0001) in tests 1 and 2 at 24 weeks. Urinary nicotine equivalents were not statistically significantly different between the control and EVP groups. At week 24, statistically significant reductions (p < .05) were observed for white blood cell counts, 11-dehydrothromboxane ß2, and sICAM in both test groups, and there were several significant changes in measures of pulmonary function. High-density lipoprotein cholesterol and 8-epi-prostaglandin-F2α were directionally favorable in both EVP groups versus control. CONCLUSIONS: We demonstrate that significant reductions of selected harmful and potentially harmful constituents in EVP aerosol results in significant reductions in BoEs and favorable changes in BoPHs after switching to EVPs for 24 weeks. These changes approached those reported for smoking cessation, suggesting that switching to exclusive use of the EVPs may be less harmful than continuing smoking. IMPLICATIONS: Cigarette smoking causes serious diseases. Switching from cigarettes to a noncombustible product is a potential harm reduction pathway for adult smokers unable or unwilling to quit. Long-term health effects of e-vapor products (EVPs) compared with continued smoking have not been extensively studied. We present biomarker of exposure evidence on select harmful and potentially harmful constituents and biomarkers of potential harm related to inflammation and oxidative stress in adult smokers switching to two EVPs. This study demonstrates significant reductions in biomarkers of exposure (except for nicotine) accompanied with favorable changes in various biomarkers of potential harm, including pulmonary function. The totality of evidence suggests that exclusive EVP use may present lower health risks compared with smoking cigarettes.

Exposure to Toxicants Associated With Use and Transitions Between Cigarettes, e-Cigarettes, and No Tobacco.

Importance: Transitions between e-cigarettes and cigarettes are common among tobacco users, but empirical evidence on the health outcomes of switching tobacco products is scarce. Objectives: To examine changes in urinary biomarkers between baseline and 1-year follow-up among adult tobacco users switching between e-cigarettes and cigarettes. Design, Setting, and Participants: This cohort study used data from wave 1 (baseline, September 2013 to December 2014) and wave 2 (1-year follow-up, October 2014 to October 2015) of the Population Assessment of Tobacco and Health Study. A subset of the probability sample of US adults who voluntarily provided biospecimens at 2 waves was analyzed. Participants were divided into 3 mutually exclusive groups at baseline: exclusive cigarette smokers, exclusive e-cigarette users, and dual users. Data analysis was performed in 2021. Exposures: Harmful and potentially harmful constituents included nicotine metabolites, tobacco-specific nitrosamines (TSNAs; including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Main Outcomes and Measures: Within-participant changes in 55 urinary biomarkers of exposure (BOEs) to harmful and potentially harmful constituents were examined using multivariable regression models. Results: Among 3211 participants (55.6% women, 68.3% White, 13.2% Black, and 11.8% Hispanic) at baseline, 21.9% of exclusive cigarette users, 42.8% of exclusive e-cigarette users, and 62.1% of dual users changed product use at follow-up (all percentages are weighted). There was a significant reduction in urine concentrations of TSNAs, PAHs, and VOCs when users transitioned from exclusive cigarette to exclusive e-cigarette use, with a 92% decrease in NNAL, from a mean of 168.4 pg/mg creatinine (95% CI, 102.3-277.1 pg/mg creatinine) to 12.9 pg/mg creatinine (95% CI, 6.4-25.7 pg/mg creatinine; P < .001). A similar panel of BOEs decreased when dual users transitioned to exclusive e-cigarette use; NNAL levels decreased by 96%, from a mean of 143.4 pg/mg creatinine (95% CI, 86.7-237.0 pg/mg creatinine) to 6.3 pg/mg creatinine (95% CI, 3.5-11.4 pg/mg creatinine; P < .001). Nicotine metabolites, TSNAs, PAHs, and VOCs significantly increased when baseline exclusive e-cigarette users transitioned to exclusive cigarette use or dual use. Switching from exclusive cigarette use to dual use was not associated with significant decreases in BOEs. Conclusions and Relevance: This national cohort study provides evidence on the potential harm reduction associated with transitioning from exclusive cigarette use or dual use to exclusive e-cigarette use. e-Cigarettes tend to supplement cigarettes through dual use instead of cessation at the population level. Continuous monitoring of BOE at the population level and assessment of BOE change by product transition are warranted, as well as defined adverse health outcomes.

Comprehensive metabolic study of nicotine in equine plasma and urine using liquid chromatography/high-resolution mass spectrometry for the identification of unique biomarkers for doping control.

Nicotine is classified as a stimulant, and its use is banned in horse racing and equestrian sports by the International Federation of Horseracing Authorities and the Fédération Équestre Internationale, respectively. Because nicotine is a major alkaloid of tobacco leaves, there is a potential risk that doping control samples may be contaminated by tobacco cigarettes or smoke during sample collection. In order to differentiate the genuine doping and sample contamination with tobacco leaves, it is necessary to monitor unique metabolites as biomarkers for nicotine administration and intake. However, little is known about the metabolic fate of nicotine in horses. This is the first report of comprehensive metabolism study of nicotine in horses. Using liquid chromatography/electrospray ionization high-resolution mass spectrometry, we identified a total of 17 metabolites, including one novel horse-specific metabolite (i.e., 4-hydroxy-4-(3-pyridyl)-N-methylbutanamide), in post-administration urine samples after nasoesophageal administration of nicotine to three thoroughbred mares; eight of these compounds were confirmed based on reference standards. Among these metabolites, N-hydroxymethylnorcotinine was the major urinary metabolite in equine, but it could only be tentatively identified by mass spectral interpretation due to the lack of reference material. In addition, we developed simultaneous quantification methods for the eight target analytes in plasma and urine, and applied them to post-administration samples to establish elimination profiles of nicotine and its metabolites. The quantification results revealed that trans-3'-hydroxycotinine could be quantified for the longest period in both plasma (72 h post-administration) and urine (96 h post-administration). Therefore, this metabolite is the most appropriate monitoring target for nicotine exposure for the purpose of doping control due to its long detection times and the availability of its reference material. Further, we identified trans-3'-hydroxycotinine as a unique biomarker allowing differentiation between nicotine administration and sample contamination with tobacco leaves.

Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes.

OBJECTIVE: To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes. METHODS: We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment. RESULTS: Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89). CONCLUSIONS: Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00388297.

Study on the daily Ad Libitum smoking habits of active Korean smokers and their effect on urinary smoking exposure and impact biomarkers.

INTRODUCTION: Understanding interactions of smoking topography with biomarkers of exposure to tobacco is essential for accurate smoking risk assessments. METHODS: In this study, the smoking topography and the levels of tobacco smoke exposure urinary biomarkers of a sample of active Korean smokers were quantified and measured. The results were used to investigate the effect of daily activities and smoking time on the smoking topography. Moreover, correlations between the smoking topography parameters and biomarkers were assessed. RESULTS: No significant effect of either the daily activities or time on the smoking topography of the subjects were observed. Synchronic correlations of the cigarette consumption per day (CPD) and the average flow per puff with both urinary cotinine and trans-3'-hydroxycotinine were significant. For the urinary nicotine metabolites, the peak levels appeared when the CPD was over 19 cigarettes per day and the average puff velocity was between 35 and 45 ml/s. Nevertheless, when the average flow was over 60 ml/s, the levels of cotinine and trans-3'-hydroxycotinine significantly dropped. CONCLUSIONS: The findings of this study may be beneficial for further smoking risk assessments with contributions of both the smoking topography and biomarkers to provide current smokers with applicable cession programs.Clinical significanceSmoking habits and levels of urinary biomarkers of Korean smokers are investigated.People with a higher dependency on nicotine smoke cigarettes with slower puffs.Effects of daily activities or time on smoking topography were not significant.Correlations between smoking topography and urinary biomarkers were significant.Peak biomarker levels were observed under certain smoking topography conditions.

Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke.

Prevalence of smoking is higher in Alaska Native and American Indian (ANAI) populations living in Alaska than the general US population. Genetic factors contribute to smoking and cessation rates. The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. ANAI (N = 151) people trying to quit smoking were recruited. DNA samples were genotyped for CYP2A6 variants *1X2A, *1B, *2, *4, *9, *10, *12, and *35. Multiple nicotine metabolites were measured in plasma and urine samples, including cotinine and 3'-hydroxycotinine used to determine CYP2A6 activity (e.g., nicotine metabolite ratio [NMR]). We calculated summary statistics for all of the genotypes and metabolites and assigned CYP2A6 activity scores based on known information. We studied the association of CYP2A6 variants with the NMR and smoking histories. The overall frequency of the CYP2A6*1B gain of function allele was high in the ANAI versus non-ANAI populations in other studies. Both *4 null and *9 decrease of function alleles had frequencies similar to previous studies of ANAI populations. In a multivariate analysis, the genotype-inferred CYP2A6 activity score was associated with both plasma and urine NMR (p value = 8.56E-08 and 4.08E-13, respectively). Plasma NMR was also associated with duration of smoking (p value < 0.01) but not urinary total nicotine equivalents uncorrected for creatinine (TNE9uc ) or biological sex. Urine NMR was significantly associated (p value < 0.01) with TNE9uc . Variation in NMR in this ANAI population is explained in part by CYP2A6 genetic variation.

Exposure to Nicotine and Toxicants Among Dual Users of Tobacco Cigarettes and E-Cigarettes: Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

INTRODUCTION: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure.

Nicotine, Cotinine, and Tobacco-Specific Nitrosamines Measured in Children's Silicone Wristbands in Relation to Secondhand Smoke and E-cigarette Vapor Exposure.

INTRODUCTION: Simple silicone wristbands (WB) hold promise for exposure assessment in children. We previously reported strong correlations between nicotine in WB worn by children and urinary cotinine (UC). Here, we investigated differences in WB chemical concentrations among children exposed to secondhand smoke from conventional cigarettes (CC) or secondhand vapor from electronic cigarettes (EC), and children living with nonusers of either product (NS). METHODS: Children (n = 53) wore three WB and a passive nicotine air sampler for 7 days and one WB for 2 days, and gave a urine sample on day 7. Caregivers reported daily exposures during the 7-day period. We determined nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) concentrations in WB, nicotine in air samplers, and UC through isotope-dilution liquid chromatography with triple-quadrupole mass spectrometry. RESULTS: Nicotine and cotinine levels in WB in children differentiated between groups of children recruited into NS, EC exposed, and CC exposed groups in a similar manner to UC. WB levels were significantly higher in the CC group (WB nicotine median 233.8 ng/g silicone, UC median 3.6 ng/mL, n = 15) than the EC group (WB nicotine median: 28.9 ng/g, UC 0.5 ng/mL, n = 19), and both CC and EC group levels were higher than the NS group (WB nicotine median: 3.7 ng/g, UC 0.1 ng/mL, n = 19). TSNAs, including the known carcinogen NNK, were detected in 39% of WB. CONCLUSIONS: Silicone WB show promise for sensitive detection of exposure to tobacco-related contaminants from traditional and electronic cigarettes and have potential for tobacco control efforts. IMPLICATIONS: Silicone WB worn by children can absorb nicotine, cotinine, and tobacco-specific nitrosamines, and amounts of these compounds are closely related to the child's urinary cotinine. Levels of tobacco-specific compounds in the silicone WB can distinguish patterns of children's exposure to secondhand smoke and e-cigarette vapor. Silicone WB are simple to use and acceptable to children and, therefore, may be useful for tobacco control activities such as parental awareness and behavior change, and effects of smoke-free policy implementation.

Challenges associated with quantification of selected urinary biomarkers of exposure to tobacco products.

Tobacco use, of which cigarette smoking is the most common, is a global health concern and is directly linked to over 7 million premature deaths annually. Measurement of the levels of tobacco-related biomarkers in biological matrices reflects human exposure to the chemicals in tobacco products. Nicotine, nicotine metabolites, anatabine, and anabasine are specific to tobacco and nicotine containing products. However, as nicotine and its metabolites are ubiquitous in the environment, background contamination during sample preparation can occur, making the quantification of target analytes challenging. The main purpose of the present study was to examine quality control measures needed in the determination of urinary nicotine, nicotine metabolites, anatabine, and anabasine. Urine samples (n = 75) and NIST standard reference materials SRM 3671 and SRM 3672 were analysed. A one-step extraction procedure using cold acetone was used in this study, which involved no additional clean up. The blank matrices investigated included synthetic urine prepared with HPLC-grade water, synthetic urine prepared with Milli-Q water, and bovine urine. By adopting strategies for minimizing the background levels, very low detection limits for all the target analytes ranging from 0.025 ng/mL for 3-hydroxycotinine to 0.634 ng/mL for nicotine, were achieved. Recoveries ranged between 67% and 118% with RSD values below 20%. Intra-day and inter-day precisions were in the range of 1.1-11.7% and 4.8-25.2%, respectively. The levels of all target analytes were higher in daily smokers than in non-smokers, with the largest difference observed for 3-hydroxycotinine. No difference was observed in the levels of target analytes between individuals who were former smokers, who never smoked or who were exposed to environmental tobacco smoke (ETS), except for total nicotine equivalents (TNE), which was significantly higher in non-smokers exposed to environmental tobacco smoke compared with study participants who never smoked. The results obtained from SRM 3671 and SRM 3672 could inform a potential certification of additional biomarkers of exposure to tobacco products in those standard reference materials.

Exposure to tobacco smoke measured by urinary nicotine metabolites increases risk of p16/Ki-67 co-expression and high-grade cervical neoplasia in HPV positive women: A two year prospective study.

BACKGROUND: Human papillomavirus (HPV) is considered the strongest epidemiologic risk factor for cervical cancer. However, it is not a sufficient cause given the high prevalence of transient infections. We examined the relationship between exposure to tobacco smoke, measured using urinary nicotine metabolite concentrations, and p16/Ki-67 co-expression in cervical smears and subsequent risk of developing CIN2+/CIN3+ lesions in HPV positive women. METHODS: This prospective longitudinal study enrolled women presenting to colposcopy with cytological abnormalities LSIL/ASCUS at the National Maternity Hospital, Dublin. Women gave a urine sample which was used to perform the Nicotine Metabolite Assay (Siemens). HPV positive (HC2) cervical smears were stained by immunocytochemistry for p16/Ki-67 (CINtec PLUS, Roche). Two year follow-up data, including histological diagnosis, was collected for each woman. Crude and adjusted odds ratios were calculated using logistic regression to investigate associations between tobacco smoke, p16/Ki-67 positivity and CIN2+/CIN3 + . RESULTS: In total, 275 HPV positive women were included. Women with nicotine metabolite concentrations above 500 ng/mL, indicative of smoking, were classified as smokers. Smokers were at an increased risk of testing positive for p16/Ki-67 (OR 1.678; 1.027-2.740) and CIN2+ and CIN3+ (OR 1.816; 1.107-2.977 and OR 2.453; 1.200-5.013) in compared to non-smokers. In p16/Ki-67 positive women, smoking further increased their risk of CIN2+/CIN3+ (OR 2.290; 1.017-5.159 and OR 3.506 (1.534-8.017). CONCLUSION: HPV positive women exposed to tobacco smoke are at a higher risk of testing positive for p16/Ki-67 co-expression. Risk of high-grade disease is almost doubled in women who are exposed to tobacco smoke.

Mechanistic Insight into a Novel Ultrasensitive Nicotine Assay Base on High-Efficiency Quenching of Gold Nanocluster Cathodic Electrochemiluminescence.

Monitoring nicotine concentrations in human fluids is extremely crucial owing to the harmful effect of nicotine on human health. Herein, it is shown that nicotine could quench the cathodic electrochemiluminescence (ECL) of gold nanoclusters (AuNCs) with high efficiency. The ECL quenching mechanism of nicotine was studied in detail using various experimental tools and theoretical calculations. It was concluded that the strongly oxidizing intermediate SO4•-, produced from K2S2O8, could oxidized nicotine, resulting in ECL emission quenching. On the basis of this high-efficiency ECL quenching of the AuNCs/K2S2O8 system, a recyclable, ultrasensitive, and selective ECL sensing platform for nicotine detection was proposed. Even in the absence of any complex signal amplification techniques, the ECL sensor for nicotine detection showed an unprecedentedly low detection limit of 7.0 × 10-13 M (S/N = 3) and a wide linear range over 8 orders of magnitude. Most remarkably, it could be successfully used for nicotine detection in human urine samples. This is expected to promote the investigations and applications on nicotine-related diseases. We believe that the proposed ECL platform can hold great prospects for commercialization in biomedical fields and tobacco industries.