Levels Of NNAL Research Articles

Analysis of urinary tobacco-specific nitrosamine 4- (methylnitrosamino)1-(3-pyridyl)-1- butanol (NNAL) and HPV infection in American women: National health and nutrition examination survey.

Tobacco-specific nitrosamines (TSNAs) are a group of toxic substances specific to tobacco. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. We aimed to examine the association between urinary tobacco-specific NNAL and HPV infection among American women. We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014 to collect details on their urinary NNAL, HPV infection status, and other essential variables. The association between dietary urinary NNAL and HPV infection status was analyzed by using a weighted multivariate logistic regression model, and stratified subgroup analysis. In total, 5197 participants aged 18-59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 22.0% and 19.1%, respectively. The highest quartile of NNAL(Q4) was more positively associated with low-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 1.83 (1.35,2.50), p<0.001). the highest quartile of NNAL(Q4) was more positively associated with high-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 2.20 (1.57,3.08), p < 0.001). In subgroup analyses, the positive correlation between urinary NNAL levels and low-risk HPV infection status was inconsistent in marital status and BMI (interaction p < 0.05). The positive association of urinary NNAL levels with high-risk HPV infection status was inconsistent in smoking and BMI. (interaction p < 0.05). Tobacco-specific NNAL levels positively correlate with high- and low-risk HPV. Future well-designed longitudinal studies are still needed to validate the effect of tobacco exposure on HPV infection by NNAL.

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

This study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes. 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. 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. 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. 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.

A Randomized, Controlled Study to Assess Biomarkers of Exposure in Adult Smokers Switching to Oral Nicotine Products.

This open-label, randomized, controlled, in-clinic, 6-parallel-group study evaluated changes in biomarkers of exposure (BoEs) to select harmful and potentially harmful constituents in adult smokers (N = 213) not planning to quit smoking. Adult smokers were randomized to continue smoking (CS), reduce smoking by 50% and dual use oral tobacco-derived nicotine (OTDN) products (VERVE chews/discs), stop smoking and exclusively use discs or chews, or stop using all tobacco products (NT). The primary objective compared 24-hour urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a biomarker for the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) in dual and exclusive use of discs and chews to continue smoking and NT on day 7. NNAL levels on day 7 were significantly lower (P < .05) among dual and exclusive users of discs/chews compared to continue smoking; median percent reductions were ≈30% and ≈73%, respectively. NNAL levels were not significantly different between those who used discs/chews and the NT group. Many of the additional secondary biomarkers of exposure were significantly lower in dual users (10/19) and exclusive users of discs/chews (17/19) compared to the continue smoking group. Overall, reductions in secondary biomarkers of exposure were greater in exclusive users than dual users. The 24-hour urinary nicotine equivalents were significantly lower (P < .05) among exclusive users of discs/chews compared to continue smoking. The discs/chews appeared to be well tolerated. These results demonstrate that while switching completely to discs/chews substantially reduces exposure to select harmful and potentially harmful constituents, dual use with 50% reduction in cigarette consumption also reduces exposure. oral tobacco-derived nicotine products like discs/chews may present a harm reduction opportunity for adult smokers, particularly those not intending to quit smoking.

Investigation of exposure biomarkers in human plasma following differing levels of tobacco-specific N-nitrosamines and nicotine in cigarette smoke

Tobacco-specific N-nitrosamines (TSNAs) are strong carcinogens widely found in tobacco products, environmental tobacco smoke, lake, and wastewater. The main objective of this study was to investigate the effects of cigarette smoke with different yields of TSNAs (NNK, NNN, NAT, NAB) and nicotine on the levels of biomarkers of exposure in smokers’ plasma. Three hundred healthy volunteers were recruited comprising 60 smokers of each of 3 mg, 8 mg and 10 mg ISO tar yield cigarettes and 60 smokers who smoked 10 mg, 8 mg, and 3 mg for 14 days sequentially and 60 non-smokers. All study participants were male, aged from 21 to 45 years old, and were recruited from a same unit in Hebei, China. We measured the levels of NNAL, NAT, NNN, NAB and cotinine in plasma from 240 smokers and 60 non-smokers using a novel method established by online two-dimensional solid phase extraction-liquid chromatography-tandem mass spectrometry. The results showed that NNAL, NAT, NNN, NAB and cotinine in the plasma of smokers smoking cigarette with low TSNAs and nicotine were lower than that with high TSNAs and nicotine. When smokers switched from higher to lower TSNA yields of cigarettes, their plasma NNAL, NAT, NNN, NAB levels significantly decreased. The plasma concentrations of NNAL were significantly correlated with those of cotinine, NNN, NAT and NAB for smokers (p < 0.001). Similarly, the plasma concentrations of cotinine were significantly correlated with those of NNN, NAT and NAB for smokers (p < 0.001). The plasma NNAL, NAT, NNN, NAB and cotinine levels for smokers were significantly higher than those for non-smokers. These findings suggested that the total NNAL, NNN, NAT, NAB and cotinine in plasma were valid and reliable biomarkers for human exposure to TSNAs and nicotine.

Gender differences in the association between biomarkers of environmental smoke exposure and developmental disorders in children and adolescents.

Effects of environmental tobacco smoke (ETS) exposure on children and adolescent health outcomes have been attracted more and more attention. In the present study, we seek to examine the gender-specific difference association of environmental smoke exposure biomarkers and developmental disorders in children and adolescents aged 6-15 years. US nationally representative sample collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 was enrolled (N = 4428). Developmental disorders (DDs) are defined as a positive answer to the question, "Does your child receive special education or early intervention services?" Serum cotinine and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were utilized as acute and chronic exposure biomarkers of ETS, respectively. Participants with serum cotinine >0.015 ng/mL were considered as with acute ETS exposure, and participants with creatinine-adjusted NNAL >0.0006 ng/mL were considered as with chronic ETS exposure. A survey logistic regression model was used to estimate the association between ETS exposure biomarkers and DDs. Additive interaction was utilized to examine the interaction of gender and biomarkers of ETS. Overall, approximately 9% of children were defined as DDs, and 65% of children had serum cotinine and urinary NNAL levels above the limit of detection. In the adjusted models, the association of ETS exposure biomarkers with DDs was only observed in girls. Girls with low cotinine levels and high urinary NNAL levels had 2.074 (95% CI: 1.012-4.247) and 1.851 (95% CI: 1.049-3.265) times higher odds of being DDs than those without ETS exposure, respectively. However, the effects of boys and NNAL exposure on DDs have additively interacted. Our findings first provided strong evidence for gender differences in the association between two tobacco metabolites and DDs in children, disclosing the public health implications and economic burdens of environmental tobacco smoke exposure.

Optimum Urine Cotinine and NNAL Levels to Distinguish Smokers from Non-Smokers by the Changes in Tobacco Control Policy in Korea from 2008 to 2018.

We examined the age- and sex-specific distributions of biomarkers of tobacco smoke exposure to determine the optimal cutoffs to distinguish smokers from non-smokers over the last 10 years in Korea, during which smoking prevalence and secondhand smoke (SHS) exposure declined due to changes in tobacco control policy. We analyzed data from the Korea National Health and Nutrition Examination Survey on creatinine-adjusted urinary cotinine (2008-2018; 33 429 adults: 15 653 males and 17 776 females) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; 2016-2018; 6337 adults: 3091 males and 3246 females). We determined the optimal cutoffs and confidence intervals (CIs) to distinguish smokers from non-smokers using receiver operator characteristic curve analysis and bootstrapping (1000 resamples). The optimal cutoff values of creatinine-adjusted urine cotinine and NNAL concentration were 20.9 ng/mg (95% CI: 20.8-21.0, sensitivity: 96.6%, specificity: 93.8%) and 8.9 pg/mg (95% CI: 8.8-8.9, sensitivity: 94.0%, specificity: 94.7%), respectively, in 2016-2018. The optimal cutoffs of both biomarkers increased with age and were higher in females than in males for NNAL concentration. In both sexes, the optimal cutoff of urine cotinine continuously declined over the study period. The optimal cotinine cutoff declined along with smoking prevalence and levels of SHS exposure due to enforcement of tobacco control policies, including smoke-free ordinances and tax increases. Monitoring of biomarkers of tobacco exposure appears necessary for verification of smoking status and regulatory use. Our results based on nationally representative data suggest that a large decrease in the optimal cutoff value of urine cotinine to distinguish smokers from non-smokers was caused by decreases in smoking prevalence and SHS exposure following enforcement of tobacco control policies over the last 10 years. We determined the optimal cutoff values of urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which were not previously reported in representative population in Asia, to enable more accurate estimation of exposure to tobacco smoke and proper assessment of disease risks. Gender- and age-specific differences in the optimal cutoffs require further study. Monitoring of biomarkers of tobacco smoke exposure seems necessary for verification of smoking status and regulatory use.

Carcinogenic and tobacco smoke-derived particulate matter biomarker uptake and associated healthcare patterns among children.

The objective was to assess the associations of child tobacco smoke exposure (TSE) biomarkers (urinary cotinine, NNAL, and nicotelline N-oxides) and parent-reported smoking and child TSE patterns with total hospital visits, pediatric emergency department (PED) visits, urgent care (UC), revisits, and hospital admissions among 0-9-year-olds. A convenience sample of PED/UC patients (N = 242) who presented to a large, US children's hospital who had baseline urine samples assayed for the TSE biomarkers of interest were included. Biomarker levels were log-transformed, and linear and Poisson regression models were built. The geometric means of child cotinine, creatinine-adjusted NNAL, and N-oxide levels were 11.2 ng/ml, 30.9 pg/mg creatinine, and 24.1 pg/ml, respectively. The mean (SD) number of daily cigarettes smoked by parents was 10.2 (6.1) cigarettes. Each one-unit increase in log-NNAL levels was associated with an increase in total UC visits (aRR = 1.68, 95% CI = 1.18-2.39) among 0-9-year-olds, while controlling for the covariates. Each one-unit increase in child log-NNAL/cotinine ratio (×103) values was associated with an increase in total hospital visits (aRR = 1.39, 95% CI = 1.10-1.75) and UC visits (aRR = 1.56, 95% CI = 1.14-2.13) over 6 months. Systematic screening for child TSE should be conducted during all hospital visits. The comprehensive assessment of TSE biomarkers should be considered to objectively measure young children's exposure. Higher levels of cotinine, a widely used tobacco smoke exposure biomarker, have been associated with higher healthcare utilization patterns among children. Less is known on the associations of carcinogenic and tobacco smoke-derived particulate matter biomarker uptake with child healthcare utilization patterns. This study assessed the associations of several biomarkers with healthcare utilization patterns among pediatric emergency department patients ages 0-9 years who lived with tobacco smokers. Higher urinary NNAL biomarker levels, in individual and ratio form with cotinine, increased children's risk for urgent care visits over 6 months. Higher parent-reported cumulative child tobacco smoke exposure increased children's risk for hospital admissions.

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

Transitions between e-cigarettes and cigarettes are common among tobacco users, but empirical evidence on the health outcomes of switching tobacco products is scarce. To examine changes in urinary biomarkers between baseline and 1-year follow-up among adult tobacco users switching between e-cigarettes and cigarettes. 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. 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). Within-participant changes in 55 urinary biomarkers of exposure (BOEs) to harmful and potentially harmful constituents were examined using multivariable regression models. 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. 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.

Assessing tobacco smoke exposure in pregnancy from self-report, urinary cotinine and NNAL: a validation study using the New Hampshire Birth Cohort Study

ObjectivesAccurate assessment of tobacco smoke exposure is key to evaluate its effects. We sought to validate and establish cut-offs for self-reported smoking and secondhand smoke (SHS) exposure during pregnancy using...

High Levels of the Carcinogenic Tobacco-Specific Nitrosamine NNAL and Associated Findings in Children of Smokers: A Case Series.

High levels of NNAL, the tobacco smoke exposure (TSE) biomarker of the carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicate future cancer risk. A prior study of smokers’ children revealed NNAL levels as high as active smokers. Therefore, we conducted a case series to examine the sociodemographics, TSE and clinical patterns, and other TSE biomarker levels in 9 children with extreme NNAL levels of >200 pg/ml to generate hypotheses and explore potential causes and implications. We identified 0 to 4-year-olds who presented to an emergency setting and lived with ⩾1 smoker who were part of a parental tobacco cessation trial (n = 461). Of these children, 52 had urinary NNAL, cotinine, and N-oxides results (n = 52). Nine children (17.3%) had NNAL levels >200 pg/ml, ranging from 206.4 to 1399.0 pg/ml (Median (Mdn) = 489.2 pg/ml; Interquartile Range (IQR) = 222.7-1289.3 pg/ml). The cotinine Mdn (IQR) was 38.5 (10.3-102.2) ng/ml and the N-oxides Mdn (IQR) = 93.8 (24.7-109.6) pg/ml. While all biomarker levels were alarmingly high, these young children would not have been flagged for very high cancer risk based on urinary cotinine levels alone. This underscores the critical role of comprehensive TSE biomarker measurement in capturing different TSE exposure patterns and assessing children’s future risk for cancer and other TSE-related morbidities.

Secondhand smoke exposure in school children in Malta assessed through urinary biomarkers

School children may be exposed to secondhand smoke (SHS) either at home, in transit or in social gatherings permitting smoking in their presence. Questionnaires about SHS often underestimate prevalence and extent of exposure. A more accurate tool is the use of biomarkers such as cotinine (COT) and trans-3′-hydrocycotinine (3HC) as biomarkers of SHS exposure, alongside 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a reduction product in the body of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), both potent carcinogens. We measured urinary COT, 3HC and total NNAL using sensitive and specific high-performance LC-MS/MS methods. The limit of quantification (LOQ) for each assay were 0.05 ng/mL, 0.1 ng/mL and 0.25 pg/mL respectively. The aim of this study was to evaluate the exposure to SHS of school children (9–11 years), from five public schools in the island of Malta, from questionnaire information about smoking at home and verify it by urinary biomarker data of COT, 3HC and NNAL. These biomarkers were measurable in 99.4%, 95.4% and 98.3% of the participating children respectively. From the children reporting smoking at home, 11% had a history of asthma and had COT, 3HC and NNAL geometric mean concentrations double compared to the non-asthmatic group. In has been confirmed that non-smokers exposed to SHS and THS have a higher NNAL/COT ratio than the group identified as smokers according to specific and defined COT threshold levels (despite the fact that a priori, the entire study group was composed of non-smokers). The implication of high measured levels of urinary NNAL in children should be of concern given its potency. A main effects multifactor ANOVA model was developed and the children's house and school locations and the smoking frequency were statistically significant to predict the levels of the three metabolites. For 3HC only, the status of the employment of the mother was also an important predictor.

Comparison of Levels of Three Tobacco Smoke Exposure Biomarkers in Children of Smokers.

Objectives: Cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and N-oxides are biomarkers of tobacco smoke exposure (TSE) used to assess short- and longer-term TSE. The objective of this study was to assess the associations between these TSE biomarkers, sociodemographics, parental smoking, and child TSE patterns among 0–17-year-olds. Methods: A convenience sample of 179 pediatric patients (mean (SD) age = 7.9 (4.3) years) who lived with ≥1 smoker and who had parental assessments completed and urine samples analyzed for the three TSE biomarkers of interest were included. Biomarker levels were log-transformed, univariate regression models were built and Pearson correlations were assessed. Results: In total, 100% of children had detectable levels of cotinine and >96% had detectable NNAL and N-oxide levels. The geometric means of cotinine, NNAL, and N-oxide levels were 10.1 ng/mL, 25.3 pg/mL, and 22.9 pg/mL, respectively. The mean (SD) number of daily cigarettes smoked by parents was 10.6 (6.0) cigarettes. Child age negatively correlated with urinary cotinine (r = −0.202, p = 0.007) and log NNAL levels (r = −0.275, p < 0.001). The highest log-cotinine levels were in children who were younger, of African American race, and whose parents had a lower education, an annual income ≤USD15,000, and no smoking bans. The highest log-NNAL and N-oxide levels were in children whose parents had a lower education, had no smoking bans, and were around higher numbers of cigarettes. Conclusion: Children of smokers who were younger, African American, and had no smoking bans had the highest TSE biomarker levels. Targeted interventions are needed to reduce TSE levels among high-risk children.

Home Smoking Bans and Urinary NNAL Levels to Measure Tobacco Smoke Exposure in Chinese American Household Pairs.

Home smoking bans can reduce tobacco smoke exposure, but little is known about the impact for Chinese American household pairs. In this study of 202 household pairs with low acculturation, 53.9% reported a home smoking ban, 31.7% had inconsistent reports, and 14.4% reported no ban. With decreasing home smoking ban enforcement, more nonsmokers had tobacco smoke exposure (66.1%–86.2%) as measured by the tobacco-specific nitrosamine biomarker urine NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol). Despite reported bans, about one-quarter of nonsmokers still reported tobacco smoke exposure at home (23.6%–30%) within the past 2 months and three-quarters reported outdoor exposure. In adjusted regression analyses of geometric mean NNAL ratios, nonsmokers in households with no ban had over two times higher levels than nonsmokers in households with a ban: adjusted log NNAL ratio = 2.70 (95% CI 1.21, 6.03). Higher smoker NNAL level and nonsmoker English fluency were also significantly associated with nonsmoker NNAL levels. Nonsmoker levels in households with an inconsistent ban were not significantly different compared to those with a ban. Although home smoking bans were generally associated with lower NNAL levels, tobacco smoke exposure in this immigrant population with low English proficiency was higher than that of the general population. From a health equity standpoint, there is a need for broader implementation and enforcement of comprehensive smoke-free policies.

Association between dual use of e-cigarette and cigarette and chronic obstructive pulmonary disease: an analysis of a nationwide representative sample from 2013 to 2018

BackgroundThe association between the dual use of electronic cigarette (e-cigarette) and conventional cigarettes (c-cigarette) and spirometry-defined chronic obstructive pulmonary disease (COPD) has not been studied thoroughly.MethodsA total of 47,217 participants were identified in the 2013–2018 Korea National Health and Nutrition Examination Survey; of them, 12,919 participants aged ≥ 40 who underwent spirometry and had no missing data were enrolled. Pulmonary function testing, urinary cotinine, and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels were compared between dual users, current smokers, former smokers, and non-users using complex sample linear regression analysis. The odds ratio (OR) for COPD was calculated using a complex sample logistic regression model after adjusting for covariates.ResultsAmong current e-cigarette users, approximately 85% of the participants used c-cigarette concurrently, and 1.3% of all the participants were dual users (2.3% in males and 0.1% in females). Both dual users and current smokers showed higher levels of urine cotinine and NNAL than non-users and former smokers. The weighted prevalence of COPD was the highest in dual users (13.8% for all participants and 14.1% for males). The multivariate-adjusted OR of COPD for male dual users, compared to non-users, was 3.46 (Ptrend < 0.001). The OR for COPD was 3.10 (Ptrend < 0.001) in middle-aged (40–64 years) and 3.70 (Ptrend < 0.001) in older (≥ 65 years) men. In females, the association was not observed and could not be precisely measured because of the small proportion of the smoking population.ConclusionsDual use of e-cigarette and c-cigarette is associated with COPD in males.

Sexual identity differences in biomarkers of tobacco exposure among women in a national sample

BackgroundSexual minority women are consistently at increased risk for tobacco use compared to heterosexual women. Neither biomarkers of nicotine exposure nor biomarkers of tobacco toxicant exposure have been examined by sexual identity. MethodsThis study used interview and biomarker data from women in the biomarker core sample of Wave 1 of the Population Assessment of Tobacco and Health (PATH) study (2013–2014; n = 4930). We examined associations of sexual identity with nicotine exposure (measured with urinary cotinine and TNE-2) and with tobacco-specific nitrosamines (measured with urinary NNAL). Multivariable regression modeling was used to examine these associations among the full biomarker core sample, among past 30-day tobacco users, and among exclusive established cigarette users before and after controlling for tobacco use quantity and intensity. ResultsIn the full biomarker sample of women, prior to adjusting for tobacco use quantity and intensity, bisexual women had significantly higher cotinine, TNE-2, and NNAL levels compared to heterosexual women. Among exclusive established cigarette users, gay/lesbian women had significantly higher NNAL compared to heterosexual women prior to adjusting for tobacco quantity and intensity. No differences by sexual identity were found after adjusting for tobacco use quantity and intensity. ConclusionsThis is the first study to demonstrate differences in biological markers of tobacco exposure by sexual identity among women in the U.S. This has important public health implications as greater exposure to both nicotine and to tobacco-specific nitrosamines are strongly linked to cancer risk.

Relationship Between Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol and Lung Cancer Risk in the General Population: A Community-Based Prospective Cohort Study.

No published studies have prospectively evaluated the association between urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels and lung cancer risk in the general population. Here, we conducted a prospective community-based cohort study in the Republic of Korea to evaluate the relationship between urinary NNAL levels and lung cancer risk using prediagnostic urine samples. This prospective cohort study was based on the Korean National Cancer Center Community Cohort. During the follow-up period, 173 primary lung cancer cases were identified. Total urinary NNAL levels were measured by liquid chromatography-tandem mass spectrometry, and data were analyzed using multivariable Cox proportional hazards regression models. The risk of lung cancer was significantly increased per unit of natural log-transformed urinary NNAL (HR, 1.27; 95% CI, 1.09–1.48), after adjusting for age, region, entry year into the cohort, education achievement, alcohol consumption status, BMI, smoking status, and urinary cotinine levels. Cox proportional-hazards models with NNAL quartiles also showed positive dose-response relationships with risk of lung cancer. A significantly increased risk of lung cancer was found in the fourth quartile of urinary NNAL levels (HR, 3.27; 95% CI, 1.37–7.79, P for trend < 0.01). After stratification with sex, the significant association remained in only men. Urinary NNAL levels are associated with the risk of lung cancer in the general population, and this association is independent from the quantification of cigarette smoking and nicotine uptake.

Differences in Levels of Biomarkers of Potential Harm Among Users of a Heat-Not-Burn Tobacco Product, Cigarette Smokers, and Never-Smokers in Japan: A Post-Marketing Observational Study.

IntroductionCigarette smoking is associated with the risk of certain diseases, but non-combustible products may lower these risks. The potential long-term health effects of the next-generation non-combustible products (heat-not-burn tobacco products (HNBP) or electronic vapor products) have not been thoroughly studied. The present study aimed to investigate the impact of biomarkers of potential harm (BoPH) of one of HNBP (a novel vapor product: NTV (novel tobacco vapor)), under the conditions of actual use.Aims and MethodsThis study was an observational, cross-sectional, three-group, multi-center study. Exclusive NTV users (NTV, n = 259), conventional cigarette smokers (CC, n = 100) and never-smokers (NS, n = 100) were enrolled. Biomarkers of tobacco smoke exposure (cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)) and BoPH including parameters of physical pulmonary functions relevant to smoking-related diseases were examined, and subjects answered a questionnaire on cough-related symptoms (J-LCQ) and health-related quality of life (SF-36v2®).ResultsLevels of cotinine, total NNAL and BoPH (high-density lipoprotein (HDL)-cholesterol, triglyceride, sICAM-1, WBC count, 11-DHTXB2, 2,3-d-TXB2, 8-epi-PGF2α, forced expiratory volume in 1 second (FEV1), % predicted value of FEV1 (%FEV1) and maximum midexpiratory flow (FEF25-75)) were significantly different in the NTV group as compared to levels in CC group (p < .05). Significantly higher levels of cotinine, total NNAL, and 2,3-d-TXB2, and lower levels of FEV1 and %FEV1, were observed among NTV users compared to the NS group.ConclusionIn a post-marketing study under actual use conditions, BoPH associated with smoking-related disease examined in exclusive NTV users were found to be favorably different from those of CC smokers, a finding attributable to a reduction in exposure to harmful substances of tobacco smoke.ImplicationsCigarette smoking is associated with an increased risk of pulmonary diseases like COPD, cardiovascular diseases, and certain cancers. There is a growing body of evidence that HNBP reduces the exposure associated with smoking and that there is a favorable change in BoPH. However, long-term effects regarding the relative health risks to HNBP users compared to CC smokers have not been examined. This study provides post-marketing data under actual use conditions of the effects on biomarkers of potential harm in NTV, one of HNBP, exclusive users compared to CC smokers and never-smokers. The evidence suggests that exclusive NTV users have favorable levels of BoPH compared to CC smokers, and that is result from a sustained reduction in exposure to harmful substances of tobacco smoke.

Association between Second-hand Smoke Exposure and Urinary NNAL Level in Korean Adolescents.

BackgroundThe 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers. Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents.MethodsThis cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels.ResultsThe mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively (P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58–4.53), 31.02 (9.46–101.74), and 1.89 (1.12–3.17) in boys; and 6.50 (3.22–13.11), 20.09 (7.08–57.04), and 3.94 (1.98–7.77) in girls, respectively.ConclusionSHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure. These findings remind us of the need to protect adolescents from SHS.

Comparing cotinine and NNAL verification of self-reported smoking status among lung cancer screening eligible population from the 2007–2014 National Health and Nutrition Examination Survey (NHANES)

Background: Biochemical verification of self-reported smoking status is not common among the population eligible for lung cancer screening (LCS). Methods: We used urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides) and serum cotinine as the gold standard to determine the validity and reliability of self-reported smoking status from the 2007–2014 National Health and Nutrition Examination Survey (NHANES). Results: We found 2.3% (n = 652, equivalent to 5.3 million weighted population) of adults eligible for LCS according to the current United States Preventive Services Task Force guideline. Self-reported current smoking status performed similarly against NNAL and cotinine: sensitivity [89.7% (95%CI: 84.9%–94.5%) vs. 89.5% (95%CI: 84.8%–94.3%)]; specificity [99.7% (95%CI: 99.2%–100.0%) vs. 100% (95%CI:100%–100%)]; positive predictive value (PPV) and negative predictive value (NPV) were 99.8% (95%CI:99.4%–100.0%) versus 100% (95%CI:100%–100%) and 85.3% (95%CI: 79.1%–91.5%) versus 85.1% (95%CI: 79.1%–1.0%), respectively; and Kappa [86.5% (95%CI:80.5%–92.5%) vs. 86.5% (95%CI:80.6%–92.3%)]. Performance measures were better among females than males; worst among the non-Hispanic white and best among other race/ethnicity group. The validity and reliability of self-reported smoking status increased with increasing cutpoint levels of both NNAL and cotinine. Conclusions: Self-reported smoking status among people who are at high risk of lung cancer is reasonably reliable. The difference between using NNAL and cotinine appears to be minimal.

Effects of smoking cessation on biological monitoring markers in urine

IntroductionUrinary nicotine and cotinine levels are often measured as biomarkers for tobacco smoke exposure. However, these biomarkers are not appropriate to evaluate the effects of quitting smoking for several days, because of their short half-lives. In this study, we focused on the changes in the urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels of 55 patients in a smoking cessation program, because of the long half-life. At the same time, urinary 7-methylguanine (m7Gua) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), as DNA damage markers of cigarette smoking, were also measured.ResultsIn the subjects who completed the quit-smoking program (18 subjects out of 55), the urinary nicotine and cotinine levels decreased to 1.7 and 0.2% at 8 weeks after the first visit to the clinic. By contrast, the NNAL levels decreased to 12.3% at 8 weeks after quitting smoking. During the same period, the urinary m7Gua levels significantly decreased, from 27.32 μg/mg creatinine to 14.17 μg/mg creatinine by the elimination of subjects who showed increased levels of NNAL during the smoking cessation program. The 8-OHdG levels were also reduced within the same period, but were not significantly different. From the all data analysis, the urinary levels of cotinine and NNAL positively correlated with the level of m7Gua.ConclusionsNNAL may be an appropriate exposure marker for evaluating the smoking status of patients in a smoking cessation program. The urinary cotinine and NNAL levels positively correlated with the m7Gua levels.