Urinary NNAL Research Articles

Association of Urinary Biomarkers of Tobacco Exposure with Lung Cancer Risk in African American and White Cigarette Smokers in the Southern Community Cohort Study.

After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans. In a nested case-control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk. TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10-1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03-1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL. Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years. Urinary NNAL, TNE, and Cd concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.

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.

Exposure to Tobacco-Specific Nitrosamines Among People Who Vape, Smoke, or do Neither: A Systematic Review and Meta-Analysis.

Smoking exposes people to high levels of Tobacco-Specific Nitrosamines (TSNAs), which include potent carcinogens. We systematically reviewed TSNA exposure between people smoking, vaping, and doing neither. Databases were searched between August 2017-March 2022, using vaping-related terms. Peer-reviewed articles reporting TSNA metabolites (NNAL, NNN, NAB, and NAT) levels in bio-samples among adults exclusively vaping, exclusively smoking, or doing neither were included. Where possible, meta-analyses were conducted. Of 12 781 identified studies, 22 were included. TSNA levels fell substantially when people who smoke switched to vaping in longitudinal studies and were lower among people who vaped compared to smoked in cross-sectional studies. Levels of TSNAs were similar when comparing people who switched from smoking to vaping, to those who switched to no use of nicotine products, in longitudinal studies. Levels were higher among people who vaped compared to people who neither vaped nor smoked in cross-sectional studies.When comparing people who vaped to smoked: pooled urinary NNAL was 79% lower across three randomized controlled trials and 96% lower across three cross-sectional studies; pooled NAB was 87% lower and NAT 94% lower in two cross-sectional studies. When comparing people who neither vaped nor smoked to people who vaped, pooled urinary NNAL was 80%, NAB 26%, and NAT 27% lower in two cross-sectional studies. Other longitudinal data, and NNN levels could not be pooled. Exposure to all TSNAs was lower among people who vaped compared to people who smoked. Levels were higher among people who vaped compared to people who neither vaped nor smoked. As well as TSNAs, there are many other toxicant exposures from smoking and vaping that can increase the risk of disease. However, it is likely that the reduced exposure to TSNAs from vaping relative to smoking reduces the risk to health of those who use vaping products to quit smoking. Future high-quality research, with robust definitions of exclusive vaping and smoking, and accounting for TSNAs half-lives, is needed to fully assess exposure to TSNAs among people who vape.

Urinary tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cognitive functioning in older adults: The National Health and Nutrition Examination Survey 2013-2014.

Tobacco contains carcinogens called tobacco-specific nitrosamines. Among the tobacco-specific nitrosamines, is nicotine-derived nitrosamine ketone (NNK) which produces the metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). We aimed to examine the association between urinary tobacco-specific NNAL and cognitive functioning among older adults. A total of 1673 older adults aged ≥60 years from the National Health and Nutrition Examination Survey 2013-2014 were included. Urinary tobacco-specific NNAL was analyzed in the laboratory. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD-WL) immediate and delayed memory tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on means and standard deviations of the cognitive test scores. Multivariable linear regression models were constructed to examine the independent association between quartiles of urinary tobacco-specific NNAL and cognitive test-specific and global cognition z-scores controlling for age, sex, race/ethnicity, education level, depressive symptoms, body mass index, systolic blood pressure, urinary creatinine, hypertension, diabetes, alcohol use, and smoking status. About half of the participants (mean age 69.8 years) were female (52.1%), non-Hispanic White (48.3%), and completed some college and above (49.7%). Multivariable linear regression results showed that participants in the 4th quartile (highest quartile) of urinary NNAL, compared with those in the 1st quartile (lowest quartile), had lower DSST z-scores (β= -0.19; 95% CI: -0.34 - -0.04). Tobacco-specific NNAL was negatively associated with processing speed, sustained attention, and working memory in older adults.

Diagnostic Performance Evaluation of the Novel Index Combining Urinary Cotinine and 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Smoking Status Verification and Usefulness for Trend Monitoring of Tobacco Smoking Exposure.

During the last decade in Korea, urinary cotinine concentrations in non-current smokers have decreased, making it difficult to distinguish secondhand smoke (SHS) exposure from nonsmokers because of overlapping values between non-current smokers with and without SHS exposure. Additionally, the importance of smoking status verification to avoid misclassification is increasing with the increased use of e-cigarettes. We developed a novel index combining urinary cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and evaluated its diagnostic performance for the classification of smoking status using the KNHANES VII dataset. A total of 10,116 and 5575 Korean participants aged >19 years with measured urinary cotinine concentrations were enrolled in a training set and validation set, respectively. When using 4.0 as the cutoff value for distinguishing current smokers from non-current smokers, urinary cotinine∙NNAL showed a better diagnostic performance than urinary cotinine or urinary NNAL. Among e-cigarette users, urinary cotinine∙NNAL showed more accurate classification rates than urinary NNAL. Furthermore, urinary cotinine∙NNAL had measurable values in non-current smokers, whereas urinary cotinine had unmeasurable values in one-fourth of all participants. This study shows that urinary cotinine∙NNAL might be a useful biomarker for smoking status verification and trend monitoring of tobacco smoking exposure with increased use of e-cigarettes.

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.

Assessment of passive human exposure to tobacco smoke by environmental and biological monitoring in different public places in Wuhan, central China.

Passive exposure to tobacco smoke is a global public health problem, while there are few data on public place monitoring and general population exposure assessment in central China. This study aimed to examine the levels of airborne nicotine (n=256) in ten kinds of different public places in Wuhan, central China, and assess short-term and long-term smoke exposure in 340 non-smokers aged 18-67 who worked in these public places using tobacco biomarkers [i.e., cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), respectively]. The highest median concentration of airborne nicotine (17.0μg/m3) was observed in internet cafes, approximately 304-fold of the lowest value found in nurseries (55.9ng/m3). Among the other studied public places, restaurants had the highest median concentrations (ng/m3) of airborne nicotine (3,120), followed by subway stations (810), hotels (624), government officess (286), middle schools (269), health institutions (268), public institutions (190), and primary schools (140). Urinary cotinine and NNAL were found in almost all the participants, and the highest concentrations were found in non-smokers from the internet cafes [specific gravity (SG)-corrected urinary median concentrations: 23.1ng/mL, geometric mean (GM): 24.1ng/mL, range: 0.62-1679ng/mL] for cotinine and 104pg/mL (GM: 97.6pg/mL, range: 32.3-236pg/mL) for NNAL, respectively]. Urinary cotinine concentrations in male non-smokers (median: 2.02ng/mL) were significantly higher than those in female non-smokers (1.44) (P<0.01). Participants aged 18-27 were detected with the highest urinary cotinine and NNAL concentrations. Urinary cotinine and NNAL concentrations were significantly correlated with daily and monthly working hours, respectively. Besides, a positive correlation was observed between log-transformed urinary concentrations of cotinine and NNAL (r=0.32, P<0.001). This is the first time to report matched data on airborne nicotine and urinary cotinine/NNAL among employees in different public places. This study demonstrated ubiquitous exposure to environmental tobacco smoke in the studied public places.

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 Secondhand Smoke and a Tobacco-Specific Carcinogen in Non-Smokers.

BackgroundThe International Agency for Research on Cancer classifies 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as a known carcinogen. This study aimed to investigate the association between exposure to secondhand smoke (SHS) and NNAL concentrations in non-smokers.MethodsThis was a cross-sectional study based on data from the 2016 to 2018 Korea National Health and Nutrition Examination Survey. Urine NNAL concentrations were categorized into tertiles of 3,615 study participants who were non-smokers. All sampling and weight variables were stratified, and analyses to account for the complex sampling design were conducted.ResultsThe overall, male, and female percentages of SHS exposure among non-smokers were 22.4%, 29.2%, and 20.4%, respectively. The geometric means of urine NNAL concentrations were 1.896±0.098 pg/mL and 1.094±0.028 pg/mL in the SHS exposure and non-exposure groups, respectively. After adjusting for confounding variables, in the total group, the geometric mean of urine NNAL concentrations was significantly higher in the SHS exposure group than in the SHS non-exposure group (adjusted P-value <0.001). Compared with the non-exposure group, the adjusted odds ratios (95% confidence intervals) for the highest NNAL tertile group of overall SHS exposure in the total, men, and women groups were 2.44 (1.95–3.05), 1.65 (1.08–2.53), and 2.73 (2.11–3.52), respectively, after full adjustment.ConclusionThe urine NNAL concentration in the SHS exposure group was significantly higher than that in the non-exposure group. Exposure to SHS was associated with a higher risk of elevated urine NNAL concentrations in non-smokers.

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...

Cigarette Smoke Exposure and Acute Respiratory Distress Syndrome in Sepsis: Epidemiology, Clinical Features, and Biologic Markers.

Rationale: Cigarette smoke exposure is associated with an increased risk of developing acute respiratory distress syndrome (ARDS) in trauma, transfusion, and nonpulmonary sepsis. It is unknown whether this relationship exists in the general sepsis population. Furthermore, it is unknown if patients with ARDS have differences in underlying biology based on smoking status. Objectives: To assess the relationship between cigarette smoke exposure and ARDS in sepsis and identify tobacco-related biomarkers of lung injury. Methods: We studied a prospective cohort of 592 patients with sepsis from 2009 to 2017. Plasma cotinine and urine NNAL [urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol] were measured to categorize smoking status. Plasma biomarkers of inflammation and lung injury were measured, including in a smaller cohort of trauma patients with ARDS to increase generalizability. Measurements and Main Results: Passive and active smoking were associated with increased odds of developing ARDS in patients with sepsis. Among patients with sepsis and ARDS, active cigarette smokers were younger and had lower severity of illness than nonsmokers. Patients with ARDS with cigarette smoke exposure had lower plasma levels of IL-8 (P = 0.01) and sTNFR-1 (soluble tumor necrosis factor 1; P = 0.01) compared with those without exposure. Similar biomarker patterns were observed in blunt trauma patients with ARDS. Conclusions: Passive and active smoking are associated with an increased risk of developing ARDS in patients with pulmonary and nonpulmonary sepsis. Among patients with ARDS, those with cigarette smoke exposure have less systemic inflammation, while active smokers also have lower severity of illness compared with nonsmokers, suggesting that smoking contributes to biological heterogeneity in ARDS.

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.

Tobacco-use behavior and toxicant exposure among current dual users of electronic cigarettes and tobacco cigarettes.

Electronic cigarette (e-cigarette) use continues to grow with most users reporting concurrent cigarette smoking, but few studies have focused on tobacco use and toxicant exposure among naturalistic dual-using populations. This controlled clinical laboratory study examined how dual versus exclusive use of e-cigarettes and cigarettes and no tobacco/nicotine affected behavioral, physiological, and subjective measures among current dual users. Twenty-two participants identifying as cigarette (≥ 10 cigarettes per day [CPD]) and e-cigarette (≥ 3 days/week) users of "cig-a-like" e-cigarettes completed four 5-day outpatient conditions, which differed by their own brand of products used ad libitum: (a) cigarette and e-cigarette (dual), (b) cigarette-only, (c) e-cigarette-only, and (d) no tobacco/nicotine. Primary outcomes included daily tobacco use, expired air carbon monoxide (CO), and urinary cotinine and NNAL. Linear mixed models with pairwise comparisons (Bonferroni corrected) were performed (p < .05). CPD did not differ significantly between dual and cigarette-only use, but e-cigarette use and liquid consumed increased significantly during e-cigarette-only relative to dual use. Relative to dual use, expired air CO did not differ during cigarette-only and was significantly lower during e-cigarette-only use. Urinary cotinine was significantly lower during e-cigarette-only use relative to dual and cigarette-only use, while urinary NNAL did not differ between the nicotine-containing conditions. In summary, among current dual users, e-cigarettes in combination with cigarettes did not reduce CPD relative to exclusive cigarette use or toxicant exposure relative to exclusive use of either product. However, exclusive e-cigarette use did reduce CO and cotinine, highlighting the benefits of cigarette cessation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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.

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.

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.

Effect of an electronic nicotine delivery system with 0, 8, or 36 mg/mL liquid nicotine versus a cigarette substitute on tobacco-related toxicant exposure: a four-arm, parallel-group, randomised, controlled trial

Electronic nicotine delivery systems (ENDSs) are used by some smokers to reduce cigarette consumption, but their effectiveness is uncertain. We aimed to examine the extent to which ENDSs or a non-nicotine cigarette substitute influence tobacco-related toxicant exposure and cigarette consumption in smokers interested in smoking reduction. We did a four-arm, parallel-group, randomised controlled trial at two sites in the USA (Penn State University, Hershey, PA, and Virginia Commonwealth University, Richmond, VA). We enrolled adults aged 21-65 years who smoked more than nine cigarettes per day (for at least the past year), with exhaled CO of more than 9 parts per million at screening, who were not currently using an ENDS, and who were interested in reducing smoking but not quitting. Participants were randomised (site-specific with allocation concealment; 1:1:1:1) to receive either a cartomiser-based, pen-style ENDS (eGo-style) paired with 0, 8, or 36 mg/mL liquid nicotine (participants and researchers masked to concentration) or a non-ENDS cigarette-shaped plastic tube that delivered no nicotine or aerosol (cigarette substitute; unmasked) for 24 weeks. Conditions were chosen to reflect a range of nicotine delivery including none (cigarette substitute and 0 mg/mL ENDS), low (8 mg/mL), and cigarette-like (36 mg/mL), and all conditions were paired with smoking reduction instructions. The primary outcome was concentration of the tobacco-specific carcinogen metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; urinary total) collected at randomisation and at 4, 12, and 24 weeks. Multiple imputation with and without covariate adjustment was used in addition to sensitivity analyses. This trial is registered with ClinicalTrials.gov, NCT02342795. Between July 22, 2015, and Nov 16, 2017, 684 individuals were screened and 520 (76%) were enrolled and randomised. 188 (36%) of 520 participants were lost to follow-up by week 24; attrition did not differ by study group (39 [30%] of 130 in the cigarette substitute group, 56 [43%] of 130 in the ENDS with 0 mg/mL nicotine group, 49 [38%] of 130 in the ENDS 8 mg/mL group, and 44 [34%] of 130 in the ENDS 36 mg/mL group). Urinary total NNAL at 24 weeks in the ENDS with 36 mg/mL nicotine group was 210·80 pg/mg creatinine (95% CI 163·03-274·42) compared with 346·09 pg/mg creatinine (265·00-455·32) in the cigarette substitute group (p=0·0061). No other significant differences between groups were observed for any time point for urinary total NNAL. Serious adverse event frequency was similar across groups (12 events in 12 participants [9%] in the ENDS with 36 mg/mL nicotine group, seven events in six participants [5%] in the 8 mg/mL group, 11 events in ten participants [8%] in the 0 mg/mL group, and 13 events in 13 participants [10%] in the cigarette substitute group), and all of these were deemed unrelated or unlikely to be related to study product use. There was one death between randomisation and 24 weeks (suicide; in the ENDS with 0 mg/mL nicotine group). Use of an ENDS with cigarette-like nicotine delivery can reduce exposure to a major pulmonary carcinogen, NNAL, even with concurrent smoking. Future ENDS trials should involve products with well characterised nicotine delivery, including those with nicotine delivery approaching that of a cigarette. National Institutes of Health, US Food and Drug Administration.

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.

A new method for the simultaneous determination of urinary NNAL and cotinine concentrations using HILIC-MS/MS coupled with PRiME HLB SPE

Urinary cotinine and NNAL are the biomarkers of tobacco smoke exposure and tobacco specific nitrosamines (TSNAs), respectively. A new method for the simultaneous analysis of them by hydrophilic interaction liquid chromatography tandem mass (HILIC-MS/MS) combined with PRiME HLB solid phase extraction (SPE) was developed. The sample matrix was removed effectively with PRiME HLB SPE and HILIC separation. The linearities were good in a range of 5.00-3.00 × 103 ng/L for NNAL and 0.200-4.00 × 102 μg/L for cotinine. The method detection limit of NNAL (0.0580 ng/L) was better than that in other literatures, and 0.0240 μg/L for cotinine. Recoveries were 91.6-110% and 88.7-113% with relative standard deviations of 3.78-9.12% and 0.120-1.15% for NNAL and cotinine, respectively. 29 urine samples were detected by the established method. The contents of NNAL and cotinine were 0.590-66.7 ng/g·Cr and 2.86-1.34 × 103 μg/g·Cr, respectively. Moreover, the results showed that urinary NNAL and cotinine were significantly positive correlation, even in passive smokers.

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.