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Tobacco smoke is probably the most significant factor conducing to toxic xenobiotics exposure to humans. The aim of the study was to develop a rapid and sensitive method for the determination of selected nicotine metabolites in urine of tobacco smokers and passive smokers. The method for removing protein and extracting the metabolites involved the centrifugation of urine with acetonitrile. Cotinine, trans-3'-hydroxycotinine, and (2'S)-nicotine 1'-oxide in the supernatant were determined using the LC-Orbitrap-MS/MS technique, with the selected ion monitoring (SIM) and parallel reaction monitoring (PRM) modes used. The recovery of these analytes added to the urine samples ranged from 72% to 101%. Repeatability and reproducibility were less than 3.1% and 10.1%, respectively. The study was carried out among medical students. The group was selected as representatives of young people and who as future physicians should be more aware of the effects of nicotine use. Concentration levels of cotinine and trans -3'-hydroxycotinine determined in ng/mL in the urine of cigarette smokers were 70- and 58-fold higher, respectively, compared to passive smokers. Higher concentrations were recorded in the urine of those passively exposed to tobacco smoke than in non-smokers, confirming that passive exposure to tobacco smoke is not harmless to the human body. However, no significant differences were observed in the concentration of (1'S,2'S)-nicotine 1'-oxide in the samples of individuals from various groups.

Background: The US FDA announced its commitment to prohibiting menthol as a characterizing flavor in tobacco. The relationship between cigarette menthol and exposure to toxic substances in mainstream tobacco smoke is not well characterized., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015 to 2016 special sample were used to study markers of 26 harmful and potentially harmful constituents (HPHC) in tobacco smoke. These include urine metabolites of polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), and heavy metals in exclusive menthol (n = 162) and nonmenthol (n = 189) cigarette smokers. Urine metabolites of 7 PAHs, 15 VOCs, and 4 heavy metal biomarkers were compared by menthol status. Multivariable analyses were conducted on creatinine-adjusted concentrations., Results: There were no significant differences in cotinine levels or in 22 of 26 HPHCs. Among the urine metabolites of PAHs, the levels of 1-hydroxyphenanthrene were about 16% lower in menthol smokers. Among the urine metabolites of VOCs, menthol cigarette smokers presented significantly lower concentrations of acrylamide, N,N-dimethylformamide, and acrylonitrile. Menthol and nonmenthol smokers presented similar levels of heavy metals. Menthol did not affect the levels of cotinine and the nicotine metabolite ratio in urine., Conclusions: Menthol and nonmenthol cigarettes deliver similar levels of most HPHCs., Impact: Findings on toxicity are similar for menthol and nonmenthol cigarettes., (©2022 American Association for Cancer Research.)

Introduction: A majority of studies on tobacco smoke exposure and sleep quality have relied on self-reported smoking, resulting in potential exposure misclassification and biases related to self-report. The objective of this study was to investigate associations between urinary cotinine, a biological marker of tobacco smoke exposure, and sleep quality measures, including sleep duration, sleep continuity or efficiency, sleep satisfaction and alertness during normal waking hours., Methods: Using data on a national sample of 10 806 adults (aged 18-79 years) from the Canadian Health Measures Survey (2007-2013), we performed binary logistic regression analyses to estimate associations between urinary cotinine concentrations and sleep quality measures, while controlling for potential confounders. Additionally, we performed ordinal logistic regression to assess the association between urinary cotinine concentrations and increased number of sleep problems., Results: Overall, 28.7% of adult Canadian survey respondents had urinary cotinine concentrations above the limit of detection (LOD), nd the prevalence of each sleep problem ranged from 5.5% to 35.6%. Elevated urinary cotinine concentrations (quartile 4 vs.

Purpose: The aim is to study the effects of cigarette smoking on the structural and functional alterations of the macula in eyes of healthy young smokers., Methods: Cross-sectional clinical study included 100 active smokers (Group 1) and 100 age- and sex-matched healthy passive smokers (Group 2). All participants underwent a complete ophthalmologic assessment, axial length measurement, central corneal thickness measurement, spectral domain optical coherence tomography, and multifocal electroretinogram. Urine samples were collected to measure urinary levels of cotinine and creatinine with subsequent calculation of the cotinine creatinine ratio., Results: Central foveal thickness (255.62 ± 17.23 and 264.75 ± 17.35 μm, respectively, with P = 0.0003) and subfoveal choroidal thickness (377.48 ± 30.32 and 385.08 ± 21.10 μm, respectively, with P = 0.04) were significantly lower in active smokers than those of passive smokers. Retinal response density of ring 1 (31.08 ± 2.29 and 33.46 ± 3.83 nV/deg, respectively, with P < 0.001) and Ring 1 (R1) P1 amplitude (0.81 ± 0.07 and 0.95 ± 0.16 μV, respectively, with P < 0.001) were significantly lower, whereas R1 P1 latency (43.02 ± 0.97 and 40.39 ± 2.08 milliseconds, respectively, with P < 0.001) was significantly longer in active smokers than those of passive smokers. The mf-ERG ring ratios were significantly lower in the active smokers than those of passive smokers., Conclusion: In the absence of clinically apparent foveal toxicity, CFT, SFCT together with ring amplitude ratio could be used as good predictors of subclinical nicotine induced foveal changes.

Background: Most smoke-free legislation to reduce secondhand smoke (SHS) exposure exempts waterpipe (hookah) smoking venues. Few studies have examined SHS exposure in waterpipe venues and their employees., Methods: We surveyed 276 employees of 46 waterpipe tobacco venues in Istanbul, Moscow, and Cairo. We interviewed venue managers and employees and collected biological samples from employees to measure exhaled carbon monoxide (CO), hair nicotine, saliva cotinine, urine cotinine, urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and urine 1-hydroxypyrene glucuronide (1-OHPG). We estimated adjusted geometric mean ratios (GMR) of each SHS biomarker by employee characteristics and indoor air SHS measures., Results: There were 73 nonsmoking employees and 203 current smokers of cigarettes or waterpipe. In nonsmokers, the median (interquartile) range concentrations of SHS biomarkers were 1.1 (0.2, 40.9) µg/g creatinine urine cotinine, 5.5 (2, 15) ng/mL saliva cotinine, 0.95 (0.36, 5.02) ng/mg hair nicotine, 1.48 (0.98, 3.97) pg/mg creatinine urine NNAL, 0.54 (0.25, 0.97) pmol/mg creatinine urine 1-OHPG, and 1.67 (1.33, 2.33) ppm exhaled CO. An 8-hour increase in work hours was associated with higher urine cotinine (GMR: 1.68, 95% CI: 1.20, 2.37) and hair nicotine (GMR: 1.22, 95% CI: 1.05, 1.43). Lighting waterpipes was associated with higher saliva cotinine (GMR: 2.83, 95% CI: 1.05, 7.62)., Conclusions: Nonsmoking employees of waterpipe tobacco venues were exposed to high levels of SHS, including measurable levels of carcinogenic biomarkers (tobacco-specific nitrosamines and PAHs)., Implications: Smoke-free regulation should be extended to waterpipe venues to protect nonsmoking employees and patrons from the adverse health effects of SHS.

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

Tobacco smoking and exposure to tobacco secondhand smoke (SHS) can cause lung cancer. We determined uptake of NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone), a tobacco specific potent pulmonary carcinogen, in hookah smokers and non-smokers exposed to hookah tobacco SHS. We analyzed data from a community-based convenience sample of 201 of adult (aged ≥18 years) exclusive hookah smokers (n = 99) and non-smokers (n = 102) residing in San Diego County, California. Participants spent an average of three consecutive hours indoors, in hookah lounges or private homes, where hookah tobacco was smoked exclusively. Total NNAL [the sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides], the major metabolites of NNK, were quantified in spot urine samples provided the morning of and the morning after attending a hookah event. Among hookah smokers urinary NNAL increased significantly (p<0.001) following a hookah social event; the geometric mean doubled, from 1.97 to 4.16 pg/mg. Among non-smokers the increase was not significant (p = 0.059). Post hookah event urinary NNAL levels were highest in daily hookah smokers, and significantly higher than in non-daily smokers or non-smokers (GM: 14.96 pg/mg vs. 3.13 pg/mg and 0.67 pg/mg, respectively). For both hookah smokers and non-smokers, pre-to-post event change in urinary NNAL was not significantly different between hookah lounges and homes. We suggest posting health warning signs inside hookah lounges, and encouraging voluntary bans of smoking hookah tobacco in private homes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Data from National Health and Nutrition Examination Survey for 1999-2012 were used to evaluate factors that affect observed levels of blood cadmium (BCd) and urine cadmium (UCd) among former and current smokers aged 20-64 and ≥65 years. Adjusted levels (AGM) for BCd and UCd were higher among females as compared to males. The order of AGM for BCd by race/ethnicity for 20-64 years old was non-Hispanic white (NHW) < non-Hispanic black (NHB) and NHW > NHB for ≥65 years old. The order of AGMs for UCd for 20-64-year-old current smokers was NHW > NHB and NHW > NHB for former smokers. For 20-64-year-old current smokers, exposure to environmental tobacco smoke at home was associated with higher levels of BCd. Levels of both UCd and BCd increased with age, but the rate of increase was as much as seven times higher among ≥65 years old than 20-64 years old. For current smokers, the number of cigarettes smoked inside home was positively associated with the levels of BCd. For current smokers aged 20-64 years, the number of cigarettes smoked inside home was positively associated with the levels of UCd (p < 0.01), and the number of cigarettes smoked every day on the days they were smoked was also positively associated with the levels of UCd (p < 0.01). Among former smokers, levels of both UCd and BCd were positively associated (p < 0.1) with the number of cigarettes smoked per day at the time of quitting smoking and negatively associated with the time since smoking was quitted (p < 0.01).

The popularity of electronic cigarettes (e-cigarettes) is rapidly increasing in many countries. These devices are designed to imitate regular cigarettes, delivering nicotine via inhalation without combusting tobacco but currently, there is a lack of scientific evidence on the presence or absence of nicotine exposure. Such research relies on evidence from e-cigarette users urine samples. In this study, we aimed to determine the levels and compare the amount of nicotine to which e-cigarette users, cigarette smokers and passive smokers are exposed. Therefore, urine samples were collected from e-cigarette users, cigarette smokers, passive smokers, and healthy nonsmokers. The urinary cotinine levels of the subjects were determined using gas chromatography-mass spectrometry. The mean (±SD) urinary cotinine levels were determined as 1755 ± 1848 ng/g creatinine for 32 e-cigarette users, 1720 ± 1335 ng/g creatinine for 33 cigarette smokers and 81.42 ± 97.90 ng/g creatinine for 33 passive smokers. A significant difference has been found between cotinine levels of e-cigarette users and passive smokers (p < 0.05). There were no statistically significant differences between e-cigarette users and cigarette smokers (p > 0.05). This is a seminal study to demonstrate the e-cigarette users are exposed to nicotine as much as cigarette smokers.

The aims of this study were (1) to explore the behavioral and sociodemographic factors influencing urinary cotinine (COT-U) levels in active smokers and in environmental tobacco smoke (ETS)-exposed individuals, (2) to assess the specificity and sensitivity of the questionnaire for identifying active smokers and nonsmokers, and (3) to derive the upper reference value of COT-U in non-ETS exposed individuals. The COT-U levels of 495 adults (age range 18-69 years) who classified themselves as active smokers (29%) or as nonsmokers with (17%) or without (83%) ETS exposure were quantified by LC-MS-MS (quantification limit: 0.1µg/L, range of linearity: 0.1-4000µg/L). Median COT-U levels in these groups were 883, 1.38, and 0.39µg/L, respectively. Significant determinants of COT-U levels in active smokers were the number of cigarettes per day, type of smoking product, smoking environment, as well as time between the last cigarette and urine collection. Among ETS-exposed nonsmokers, significant determinants were living with smokers, being exposed to smoke at home, ETS exposure duration, as well as time between the last exposure and urine collection. When a 30-µg/L COT-U cut-off value was used to identify active daily smoking, the sensitivity and specificity of the questionnaire were 94% and 98%, respectively. For ETS exposure, the COT-U value of 1.78 (0.90 confidence interval 1.75-1.78) µg/L, corresponding to the 95th percentiles of the COT-U distribution in non-ETS-exposed participants, is proposed as upper reference value to identify environmental exposure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Data from National Health and Nutrition Examination Survey for 2005-2012 were used to study the trends and variability in the levels of urinary thiocyanate (u-SCN), perchlorate (u-P8), and nitrate (u-NO3) by gender, race/ethnicity, active smoking, and exposure to environmental tobacco smoke (ETS) at home for those aged 12-19 and ≥20years old. For those aged ≥20years, adjusted levels of u-SCN, u-P8, and u-NO3 (i) were lower for males than females (p<0.01), and (ii) were higher for non-Hispanic white (NHW) than non-Hispanic black (NHB) (p<0.01). Also, for those aged ≥20years NHB had higher adjusted levels than Mexican American (MA) for u-SCN (p<0.01) but NHB had lower adjusted levels than MA for u-P8 (p<0.01) and u-NO3 (p<0.01). For those aged 12-19years, adjusted levels of u-SCN, u-P8, and u-NO3 did not vary by gender (p>0.05), and adjusted levels of u-P8 and u-NO3 for NHB were lower than for NHW (p<0.01) as well as higher for NHB than MA for u-SCN (p<0.01) and lower for NHB than MA (p<0.01) for u-P8 and u-NO3. Among those aged ≥20years, active smoking was associated with higher adjusted levels of u-SCN (p<0.01) in a dose-response manner and active smoking was associated with lower adjusted levels of u-P8 (p<0.01) in a dose-response manner. Exposure to ETS was associated with higher adjusted levels of u-SCN (p=0.02) and lower adjusted levels of u-P8 (p<0.01) among ≥20years old. Adjusted levels of u-P8 decreased over 2005-2012 among both 12-19 (p<0.01) and ≥20years old (p=0.04). There was borderline increase in the adjusted levels of u-NO3 for those aged ≥20years (p=0.05) over 2005-2012., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of this study was to explore data from the DEMOCOPHES study population for Romania, Portugal and Poland, in order to assess smoking patterns and the extent of ETS exposure and compare the national study samples with reference to the respective anti-smoking laws. The subset of the DEMOCOPHES study sample consisted of 360 children and their mothers (120 in each of the three countries - Romania (RO), Portugal (PT) and Poland (PL). Smoking was assessed using a detailed questionnaire for the participants, which addresses both active and passive smoking. This assessment uses exposure-relevant questionnaire data, in particular on the home environment and residence, socio-demographic characteristics, lifestyle such as nutrition, smoking behavior, other exposure-relevant behavior and occupational history, as well as urinary cotinine and creatinine measurements. We performed general statistical analysis and innovative receiver operating characteristic (ROC) curve analyses. Smoking prevalence as evaluated by the questionnaire was generally high, and higher than official statistics, which suggests some under-reporting in the countries, particularly in Romania. Urinary cotinine levels provided biochemical confirmation of the high and similar smoking prevalence for the three countries. Concerning ETS exposure, Romania presented significantly higher levels, for children as well as for non-smoking mothers, with Portugal showing significantly lower levels. Compared to non-smoking mothers, the children showed relatively higher ETS exposure levels in all three countries. The established country-specific optimal cut-off values in urinary cotinine to distinguish smokers from non-smokers vary more than those to discriminate ETS exposure extent in non-smoking mothers and children. Although different between countries, these values are a valuable output to monitor effectiveness of both national antismoking laws and educational programs in the three countries. The findings of this study point to the urgent need for stronger, more effective and well enforced smoke-free legislation in the three countries., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The different role of prenatal and postnatal exposure to tobacco smoke in respiratory outcomes in infants has not yet been clearly established. Our objective is to assess the effects of these exposures on the risk of respiratory outcomes during the first year of life of infants from a Spanish multicenter cohort study. A total of 2506 women were monitored until delivery. About 2039 infants made up the final population. The outcomes were caused by the occurrence of the following: otitis, cough persisting for more than 3 weeks, lower respiratory tract symptoms (wheezing or chestiness), and lower respiratory tract infections (bronchitis, bronchiolitis, or pneumonia). The relationship between prenatal and postnatal exposure and health outcomes was explored using logistic regression analysis. Maternal smoking during pregnancy increased the odds for wheezing (OR: 1.41, 95% CI: 0.99-2.01) and chestiness (OR: 1.46, 95% CI: 1.03-2.01). Postnatal exposure from fathers was associated with otitis (OR: 1.25, 95% CI: 1.01-1.54). Passive exposure at work of non-smoking mothers during pregnancy was related to cough (OR: 1.62, 95% CI: 1.05-2.51). Exposure to tobacco smoke was related to a higher risk of experiencing respiratory outcomes in young infants. Prenatal exposure was that most clearly associated with the respiratory outcomes analyzed., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To explore the reach of a German population-based household sample using proactive recruitment and to test the efficacy of a behavioral change counseling intervention including feedback about children's urine cotinine level (CUCL)., Methods: A randomized controlled trial (2008-2010) was conducted in households with at least one child aged below 4years and at least one current smoker. The study area comprised of 3570 households. A screening assessment was provided in 2641 households; 1282 included one current smoker and 852 completed the study protocol. The intervention group (IG; n=428) received feedback about CUCL and up to two counseling sessions. The control group (CG; n=424) received a leaflet. Assessments were provided at baseline and 12-month follow-up. Heckman's selection model analysis was used to consider the detection limit of cotinine in urine (10ng/ml)., Results: CUCL below the detection limit in the IG was found in 43.2% at baseline and 44.6% at follow-up and in 44.8% of the CG at baseline and 47.2% at follow-up. The CUCL difference between follow-up and baseline was smaller in the CG than in the IG. The effect was not significant., Conclusions: Data revealed a high reach of the target population but failed to identify an intervention effect. Clinical Trial Registration www.clinicaltrials.gov (NCT00647413)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The objective of this clinical study was to investigate changes in levels of biomarkers of exposure (BOEs) in healthy Japanese male smokers who switched to a prototype heated cigarette (HC). This was a controlled, semi-randomized, open-label, residential study conducted in Japan. A total of 70 healthy Japanese male smokers were enrolled. Following enrollment, subjects smoked their usual brand of cigarette for 2days and were subsequently randomized either to an HC group or a 10mg tar conventional cigarette (CC10) group for four consecutive weeks. Levels of BOEs for ten selected cigarette smoke constituents (nicotine, carbon monoxide (CO), benzene, 1,3-butadiene, acrolein, hydrogen cyanide, crotonaldehyde, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK], pyrene, 4-aminobiphenyl), and urine mutagenicity were measured at several time points during the study period. At the end of the study period, except for blood carboxyhemoglobin, levels of BOEs for the other nine constituents and urine mutagenicity were significantly lower in the HC group compared to the CC10 group. These results suggest that exposure to most cigarette smoke constituents, except CO, can be reduced by switching from CC10 to HC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Comparison of the associations of maternal and mother's partner smoking with offspring outcomes is, in theory, a useful method for assessing whether there may be an intrauterine effect of tobacco exposure on these outcomes. However, this approach assumes that the effects of passive smoking from exposure to partner smoking during pregnancy are minimal. We evaluated this assumption using a biochemical measure of tobacco exposure in pregnant women., Methods: Cotinine levels taken during the first trimester of pregnancy were measured in a sample of 3928 women from the Avon Longitudinal Study of Parents and Children. Median cotinine values were compared across categories of smoking heaviness (cigarettes per day) of the women during the first trimester and in non-smoking women by the smoking heaviness of their partner., Results: Cotinine levels were substantially higher in women who smoked compared to non-smokers (range of medians across smoking heaviness categories: 900-5362 ng/ml versus 20 ng/ml, interquartile range (IQR) (0-63) for non-smokers). In contrast, cotinine levels in non-smoking women were only very weakly related to partner smoking status (range of medians in women with smoking partners: 34-69 ng/ml versus 12 ng/ml, IQR (0-48) in women with non-smoking partners)., Conclusions: Levels of tobacco exposure from partner smoking, as assessed by cotinine, were low in non-smoking pregnant women. This suggests that using mother's partner's smoking as a negative control for investigating intrauterine effects is valid., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Aims: Our objective was to evaluate the level of pregnant women's exposure to tobacco smoke by urinary cotinine testing at prenatal examinations, and to examine the effects of disclosing the results of urinary cotinine tests to pregnant women and their families on their smoking activities., Methods: A prospective cohort study was conducted, enrolling 420 pregnant women who attended prenatal examinations at five private clinics in Japan. Urinary cotinine testing and a questionnaire survey regarding smoking status were conducted in early, middle, and late pregnancy. Urinary cotinine values were measured semiquantitatively using NicCheck I test strips. The results of each urinary cotinine test were handed to the pregnant woman and shared with her family., Results: The percentages of urinary cotinine-positive subjects in middle and late pregnancy were significantly decreased compared with early pregnancy (P<0.001 each). Among the active smokers, there were no significant differences in the urinary cotinine-positive rates and the numbers of cigarettes among the three stages. In contrast, the urinary cotinine-positive rates in the passive smokers in late pregnancy were significantly lower than in early pregnancy (P=0.045) and those in non-smokers in middle and late pregnancy were also lower than in early pregnancy (P=0.001, P<0.001). The numbers of cigarettes smoked by persons close to the passive smokers in middle and late pregnancy were significantly lower than in early pregnancy (P<0.001)., Conclusions: The feedback of the urinary cotinine test results at prenatal examinations decreased the level of exposure of pregnant passive smokers and non-smokers to tobacco smoke., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Background: Indoor group water-pipe tobacco smoking, commonly referred to as water-pipe smoking (WPS), especially in coffee shops, has gained worldwide popularity. We performed a comprehensive laboratory and clinical evaluation of the acute effects of active and passive indoor group WPS., Methods: This comparative study evaluated pre- and post-30-min active and passive indoor group WPS. The outcome parameters were carboxyhemoglobin (COHb), nicotine, and cotinine levels; CBC count; and cardiorespiratory parameters. Exhaled breath condensate (EBC) cytokines and endothelial function (using the EndoPat device [Itamar Medical Ltd]) were measured only in active smokers. Statistical methods used were Student t test, Wilcoxon signed rank test, Fisher exact test, analysis of variance, and Newman-Keuls post hoc test where relevant., Results: Sixty-two volunteers aged 24.9±6.2 years were included; 47 were active smokers, and 15 were passive smokers. COHb level increased postactive WPS (active smokers, 2.0%±2.9% vs 17.6%±8.8%; P<.00001); six subjects (12.7%) had a >25% increase, and two subjects (4.2%) had a >40% increase. Plasma nicotine level increased postactive WPS (active smokers, 1.2±4.3 ng/mL vs 18.8±13.9 ng/mL; P<.0001); plasma cotinine and urinary nicotine and cotinine levels also increased significantly. EBC IL-4, IL-5, IL-10, IL-17, and γ-interferon decreased significantly with postactive smoking; endothelial function did not change. WPS was associated with adverse cardiorespiratory changes. In passive smokers, COHb level increased (0.8%±0.25% vs 1.2%±0.8%, respectively, P=.003) as did respiratory rate., Conclusions: One session of active indoor group WPS resulted in significant increases in COHb and serum nicotine levels (eightfold and 18-fold, respectively) and was associated with adverse cardiorespiratory health effects. The minor effects found in passive smokers suggest that they too may be affected adversely by exposure to WPS. The results call for action to limit the continuing global spread of WPS in coffee shops., Trial Registry: ClinicalTrials.gov; No.: NCT1237548; URL: www.clinicaltrials.gov.

Background: Central blood pressure (cSBP) is suggested to be a better predictor of cardiovascular risk than brachial BP. Although brachial BP levels among smokers have been reported to be the same or somewhat lower than those in nonsmokers, it is suggested that smoking might have a substantial impact on cSBP., Methods: We conducted a cross-sectional study to clarify the association of smoking habit with arterial tone and cSBP in a general population of 8557 participants using urinary cotinine levels as an objective marker of smoking intensity. Absolute pressure of the late systolic peak (SBP2) was obtained by calibrating the radial waveform with brachial systolic BP (bSBP) and considered to be the cSBP., Results: Confounding factor-adjusted mean pulse pressure amplification (PPa = bSBP-cSBP) was significantly smaller in habitual smokers (current, 9.3 ± 0.15; past, 10.2 ± 0.13; never, 10.6 ± 0.10 mmHg; p<0.001). Further, among smokers, PPa was linearly decreased with increasing urinary cotinine quartile (Q1, 10.9 ± 0.38; Q2, 10.9 ± 0.39; Q3, 10.4 ± 0.39; Q4, 9.7 ± 0.41 mmHg; p = 0.020). Multiple linear regression analysis identified both smoking habit (p = 0.003) and urinary cotinine levels (p = 0.008) as independent determinants of PPa. Urinary cotinine was also detected in a small fraction of never smokers (1.8%). These passive smokers showed a smaller PPa (passive smoker, 9.4 ± 0.4; never smoker, 10.4 ± 0.12 mmHg, p = 0.020) but not bSBP (122.7 ± 0.6, 123.1 ± 0.2 mmHg, p = 0.474)., Conclusions: Not only habitual smoking but also passive smoking had harmful effects on AIx and central BP. Our results strongly emphasize the importance of avoiding passive smoking to the prevention of cardiovascular risks of which the subject is likely unaware., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To examine smoking restrictions in households of children with cancer and their effect on biological measures of children's secondhand smoke exposure (SHSe)., Methods: A sample of 135 parents of nonsmoking children with cancer who lived with a smoker completed structured interviews., Results: Approximately 43% of families prohibited smoking in the home. Children living in homes that prohibited smoking had median cotinine levels that were 71% and 52% lower than did those from homes with no and partial restrictions., Conclusions: Parents should be directed to completely ban all smoking from the home and car to best protect their children from SHSe.

Background: Despite the low prevalence of daily smokers in Sweden, children are still being exposed to environmental tobacco smoke (ETS), primarily by their smoking parents. A prospective intervention study using methods from Quality Improvement was performed in Child Health Care (CHC). The aim was to provide nurses with new methods for motivating and supporting parents in their efforts to protect children from ETS exposure., Method: Collaborative learning was used to implement and test an intervention bundle. Twenty-two CHC nurses recruited 86 families with small children which had at least one smoking parent. Using a bundle of interventions, nurses met and had dialogues with the parents over a one-year period. A detailed questionnaire on cigarette consumption and smoking policies in the home was answered by the parents at the beginning and at the end of the intervention, when children also took urine tests to determine cotinine levels., Results: Seventy-two families completed the study. Ten parents (11%) quit smoking. Thirty-two families (44%) decreased their cigarette consumption. Forty-five families (63%) were outdoor smokers at follow up. The proportion of children with urinary cotinine values of >6 ng/ml had decreased., Conclusion: The intensified tobacco prevention in CHC improved smoking parents' ability to protect their children from ETS exposure.

Objectives: Measuring urinary cotinine is a popular and established method of biologically monitoring exposure to tobacco smoke. However, the lower detection limit of cotinine often impedes the evaluation of passive (second-hand) smoking and this, together with unconverted nicotine, does not reflect actual levels of exposure. Furthermore, a portion of the Japanese population might have decreased ability to metabolize nicotine. The present study was therefore carried out to validate the simultaneous analysis of total concentrations of free nicotine and cotinine and their glucuronides to determine actual levels of voluntary and involuntary exposure to cigarette smoke., Methods: Urine samples from 118 Japanese smokers and 117 non-smokers were analyzed using gas chromatography-mass spectrometry. Voluntary and involuntary smoking status was self-reported and workplace smoking restrictions were objectively evaluated., Results: The integrated sum of all concentrations showed 2.2- and 2.4-fold higher total levels (free and glucuronide) of nicotine and cotinine relative to the free levels. Median (quartiles) of total nicotine and cotinine were 1635 (2222) and 3948 (3512) ng/mL in smokers, and 3.5 (5.3) and 2.8 (4.2) ng/mL in non-smokers. Concentrations of urinary nicotine were higher than those of cotinine in 21 % of smokers and in 54 % of non-smokers. Nicotine and cotinine levels were significantly associated with a smoking habit, as well as being significantly associated with the workplace and home environments of non-smokers., Conclusions: The present method can monitor voluntary and involuntary exposure to tobacco smoke. Measuring total urinary nicotine levels might be useful for analyzing exposure to cigarette smoke among non-smokers.

Background: To date, no research exists on the role that different sources of exposure to second-hand smoke (SHS) have on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine uptake, assessed via urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cotinine concentrations of non-smoking pregnant women, nor the differences in NNAL concentrations among pregnant women who quit smoking in comparison to those who do not., Methods: As part of the 'Rhea' mother childbirth cohort in Crete, Greece, 1317 mother-child pairs were followed-up until delivery, while among a subsample, maternal urine was assessed for its NNAL (n=117) and cotinine concentrations (n=377)., Results: Pregnant women who continued to smoke during pregnancy were found to have geometric mean urinary NNAL concentrations of 0.612 pmol/ml, in comparison to the 0.100 pmol/ml of ex-smokers and 0.0795 pmol/ml of non-smokers exposed to SHS. Exposure to SHS in the home was associated with a 4.40 ng/ml increase in urinary cotinine levels, while reported exposure to SHS in cars was associated with an even higher (8.73 ng/ml) increase in cotinine concentrations and was strongly related to NNAL concentrations. Exposure to SHS in the workplace and in public places was also shown to increase cotinine and NNAL concentrations. The NNAL:cotinine ratio was found to be higher among pregnant women who were exposed to SHS but did not smoke (p<0.001)., Conclusions: Using cotinine levels as an indicator of NNK, exposure due to SHS during pregnancy leads to an underestimation of exposure to NNK uptake. Moreover, each source of exposure contributed to the increase in cotinine levels, indicating the importance of avoiding SHS exposure from any source.

Objective: Although medicine students express positive attitudes toward providing lifestyle counseling, they require more instruction in many areas of health behavior in order to be helpful to their patients. The presented study included the students' questionnaires analysis regarding their lifestyle and exposure to tobacco smoke. The aim of this study was to examine students' exposure to chosen xenobiotics by determination of selected biomarkers in urine samples, which underlay the basis for exposure assessment towards tobacco smoke., Materials and Methods: The investigated group consisted of first- and second-year medicine students from the Silesian Medical University (N = 133). Data obtained from a questionnaire survey was compared with the results of chosen biomarkers determined in urine samples. The analyses of the main nicotine metabolites were carried out firstly with use of ELISA, followed by the TLC technique with densitometry., Results: According to questionnaires, every third student examined was exposed to passive smoking. The mean concentration of the main nicotine metabolites determined by ELISA in urine samples of smoking students was 1293.52±396.70 μg/g creatinine. The results of the TLC analysis in the group of smoking students were as follows: for cotinine - 523.10±68.10 μg/g creatinine and for trans-3'-hydroxycotinine - 653.81±62.30 μg/g creatinine., Conclusions: Medicine students, regardless of their area of study, are a highly-exposed part of the population to tobacco smoke, not only actively but also passively. Tobacco smoke exposure can be assessed by ELISA as a screening method as well as by more specific TLC technique with densitometry.

Introduction: The causal relationship between tobacco smoking and a variety of cancers is attributable to the carcinogens that smokers inhale, including tobacco-specific nitrosamines (TSNAs). We aimed to assess the exposure to TSNAs in waterpipe smokers (WPS), cigarette smokers (CS), and nonsmoking females exposed to tobacco smoke., Methods: We measured 2 metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAl-Gluc) in the urine of males who were either current CS or WPS, and their wives exposed to either cigarette or waterpipe smoke in a sample of 46 subjects from rural Egypt., Results: Of the 24 current male smokers, 54.2% were exclusive CS and 45.8% were exclusive WPS. Among wives, 59.1% reported exposure to cigarette smoke and 40.9% to waterpipe smoke. The geometric mean of urinary NNAL was 0.19 ± 0.60 pmol/ml urine (range 0.005-2.58) in the total sample. Significantly higher levels of NNAL were observed among male smokers of either cigarettes or waterpipe (0.89 ± 0.53 pmol/ml, range 0.78-2.58 in CS and 0.21-1.71 in WPS) compared with nonsmoking wives (0.04 ± 0.18 pmol/ml, range 0.01-0.60 in CS wives, 0.05-0.23 in WPS wives, p = .000). Among males, CS had significantly higher levels of NNAL compared with WPS (1.22 vs. 0.62; p = .007). However, no significant difference was detected in NNAL levels between wives exposed to cigarette smoke or waterpipe smoke., Conclusions: Cigarette smokers levels of NNAL were higher than WPS levels in males. Exposure to tobacco smoke was evident in wives of both CS and WPS. Among WPS, NNAL tended to increase with increasing numbers of hagars smoked/day.

A modeling approach termed 'nicotine bridging' is presented to estimate exposure to mainstream smoke constituents. The method is based on: (1) determination of harmful and potentially harmful constituents (HPHC) and in vitro toxicity parameter-to-nicotine regressions obtained using multiple machine-smoking protocols, (2) nicotine uptake distributions determined from 24-h excretion of nicotine metabolites in a clinical study, and (3) modeled HPHC uptake distributions using steps 1 and 2. An example of 'nicotine bridging' is provided, using a subset of the data reported in Part 2 of this supplement (Zenzen et al., 2012) for two conventional lit-end cigarettes (CC) and the Electrically Heated Cigarette Smoking System (EHCSS) series-K6 cigarette. The bridging method provides justified extrapolations of HPHC exposure distributions that cannot be obtained for smoke constituents due to the lack of specific biomarkers of exposure to cigarette smoke constituents in clinical evaluations. Using this modeling approach, exposure reduction is evident when the HPHC exposure distribution curves between the MRTP and the CC users are substantially separated with little or no overlap between the distribution curves., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to nine selected harmful and potentially harmful constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic material in 160 male and female subjects smoking Marlboro cigarettes (6 mg tar, 0.5mg nicotine, and 7.0mg CO) at baseline. Subjects were randomized to continue smoking Marlboro cigarettes, or switch to using an Electrically Heated Cigarette Smoking System (EHCSS) smoking one of two EHCSS series-K cigarettes, the EHCSS-K6 cigarette (5mg tar, 0.3mg nicotine, and 0.6 mg CO) or the EHCSS-K3 cigarette (3mg tar, 0.2mg nicotine, and 0.6 mg CO), or switch to smoking Philip Morris One cigarettes (1mg tar, 0.1mg nicotine, and 2.0mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (p ≤ 0.05) for all determined HPHC including benzene and CO (the primary objectives), and urinary excretion of mutagenic material in the EHCSS-K6 (range -35.5 ± 29.2% to -79.4 ± 14.6% [mean ± standard deviation]), EHCSS-K3 (range -41.2 ± 26.6% to -83.1 ± 9.2%), and PM1 (range -14.6 ± 24.1% to -39.4 ± 17.5%) groups. The largest reductions in exposure occurred in the no-smoking group (range -55.4 ± 45.0% to -100.0 ± 0.0%)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; N=79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; N=237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke, excretion of mutagenic material in urine, and serum Clara cell 16-kDa protein (CC16) in 102 male and female Japanese subjects who smoked Marlboro Ultra Lights Menthol cigarettes (M4J(M); 4 mg tar and 0.3mg nicotine) at baseline. Subjects were randomized to continue smoking M4J(M), or switch to smoking either the Electrically Heated Cigarette Smoking System menthol cigarette (EHCSS-K6(M); 5mg tar and 0.3mg nicotine) or the Lark One menthol cigarette (Lark1(M); 1mg tar and 0.1mg nicotine), or to no-smoking. The mean decreases from baseline to Day 5/6 were statistically significant (p ≤ 0.05) for exposure to 10 of 12 cigarette smoke HPHC including the primary endpoint (carbon monoxide) and urinary excretion of mutagenic material in the EHCSS-K6(M) group (-12.3% to -83.4%). Smaller, but statistically significant reductions (p ≤ 0.05) occurred in the Lark1(M) group (-3.3% to -35.2%), with the exception of urinary mutagens. The largest mean reductions (all p ≤ 0.05) in exposure to cigarette smoke HPHC and excretion of mutagenic material occurred in the no-smoking group (-1.4% to -93.6%). Serum CC16, an indicator of lung epithelial injury, was not significantly different between groups., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A randomized, controlled, open-label parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic material in 72 male and female Korean subjects smoking Lark One cigarettes (1.0mg tar, 0.1mg nicotine, and 1.5mg CO) at baseline. Subjects were randomized to continue smoking Lark One cigarettes, or switch to an Electrically Heated Cigarette Smoking System (EHCSS) and EHCSS-K3 cigarette (3mg tar, 0.2mg nicotine, and 0.6 mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (all p<0.05) for 10 of 12 HPHC in mainstream cigarette smoke including CO (the primary objective) in the EHCSS-K3 group (range: -1.5% to -74.2%). Exposure to the other determined HPHC was not significantly different. In the Lark One group, the mean exposure to 6 of 12 HPHC in cigarette smoke was significantly (all p<0.05) decreased; however, exposure to CO was significantly increased. The largest mean reductions in biomarkers of exposure to HPHC occurred in smokers who switched to no-smoking (-3.4% to -98.9%). The mean excretion of mutagenic material was significantly decreased (p<0.05) in the EHCSS-K3 and no-smoking groups (-31.8% and -45.3%, respectively), and increased in the Lark One group (+31.5%)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to twelve selected harmful and potentially harmful constituents (HPHCs) in cigarette smoke and urinary excretion of mutagenic material in 128 male and female Japanese subjects smoking Marlboro cigarettes (6 mg tar, 0.5mg nicotine, and 7.0mg CO) at baseline. Subjects were randomized to continue smoking Marlboro cigarettes, or switch to the Electrically Heated Cigarette Smoking System (EHCSS) and smoke either the EHCSS-K6 (5mg tar, 0.3mg nicotine, and 0.6 mg CO) or the EHCSS-K3 (3mg tar, 0.2mg nicotine, and 0.6 mg CO) cigarette, or switch to smoking Lark One cigarettes (1mg tar, 0.1mg nicotine, and 2.0mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were statistically significant (p ≤ 0.05) for all cigarette smoke HPHC including CO (the primary objective) and excretion of mutagenic material in the EHCSS-K6 (range: -14.6% to -75.6%) and EHCSS-K3 (range: -9.8% to -73.0%) groups. Statistically significant reductions (all p ≤ 0.05) in exposure to ten cigarette smoke HPHC (range: -5.9% to -34.6%), but not urinary mutagenicity, were observed in the Lark One group. The largest mean reductions in exposure to HPHC (all p ≤ 0.01 level) occurred in the no-smoking group (range: -13.7% to -97.6%)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol plus its glucuronides (total NNAL), metabolites of the lung carcinogen NNK, and total cotinine, metabolites of nicotine, are biomarkers of active and passive cigarette smoking. We calculated the total NNAL:total cotinine (×10(3)) ratio in 408 passive (infants, children, and adults) and 1088 active smokers. The weighted averages were 0.73 (95% confidence interval 0.71, 0.76) for passive smokers and 0.07 (0.06, 0.08) for active smokers (p < 0.0001). These results demonstrate that cotinine measurements may underestimate exposure of passive smokers to the lung carcinogen NNK in second-hand cigarette smoke. The total NNAL:total cotinine (×10(3)) ratio may provide an improved biomarker for evaluating the health effects of passive smoking.

Objectives: Nitric oxide (NO) is a reactive gas generated by inflammatory cells and mucosal epithelial cells of the nose and paranasal sinuses and is an important mediator in nonspecific host defense against infectious agents. However, NO also mediates physiologic events such as vasodilation, mucus hypersecretion, and mucosal disruption that are associated with inflammatory conditions, and it is a regulator of ciliary beat frequency. In the present study, we hypothesized that lifestyle exposure to tobacco smoke, whether through active smoking or by inadvertent exposure to secondhand tobacco smoke, would result in higher detectable levels of nasal NO (nNO) than are found in well-documented nonsmokers., Methods: Nasal NO measurements were obtained concomitant with assays of urine cotinine from well-documented nonsmokers, active smokers, and individuals exposed by lifestyle to secondhand smoke. These parameters were statistically analyzed to determine whether increasing levels of tobacco smoke exposure yield higher concentrations of nNO., Results: Our results and subsequent statistical analyses imply that active smokers who exhibit high urine cotinine levels exhibit significant increases in nNO levels in comparison to both nonsmokers and nonsmokers exposed to secondhand smoke., Conclusions: There is an increased level of nNO associated with tobacco smoke exposure that may contribute to the inflammatory processes characteristic of disease pathogenesis in smokers.

Exposure to toxic metals during pregnancy may have detrimental effects on foetal development. We assessed the role of sociodemographic characteristics and active and passive smoking on blood concentrations of metals (As, Cd, Pb, Hg, Sb, U, Mn and Mo). Venous blood drawn from 50 pregnant women, randomly selected from the mother-child birth cohort 'Rhea'. Extensive questionnaire data on active and passive smoking were collected. Urinary cotinine was measured to validate self-reported exposure and non-smoking status. Smokers had higher concentrations of Cd (1.0 µg/L) as compared with non-smokers (0.29 µg/L, P < 0.001) and a tendency for higher As and Hg. Among non-smokers, blood As and Hg concentrations were also associated with exposure to passive smoking in public venues and the family home and to overall greater secondhand smoke (SHS) exposure (As: 0.97µg/L among heavy-exposed compared with 0.20 µg/L among the low-exposed, P < 0.05; Hg: 2.1 µg/L vs. 0.9 µg/L respectively, P < 0.05). Controlling for fish and seafood intake altered the statistical significance but not the direction of the above associations. Smoking was associated with higher Cd concentrations in pregnant women, although the association between passive smoking and elevated As and Hg concentrations was indicative, however inconclusive.

We examined the relationship between cotinine measures in follicular fluid (FF) and urine to inform our exposure assessment strategy for an ongoing epidemiological study of secondhand tobacco smoke (STS) exposure and early pregnancy loss. Among subjects undergoing in vitro fertilization (IVF), we compared cotinine levels in paired urine and FF samples from the same women and examined FF cotinine levels over time. We found a weak rank-order relationship (Spearman r<0.2) and poor agreement for classifying nonsmoking individuals as exposed to STS (sensitivity=0.29-0.71; specificity=0.35-0.72) between cotinine concentrations in FF and urine. We observed fair reliability (ICC=0.42-0.52) in FF cotinine concentrations from women undergoing multiple IVF cycles. If available, FF cotinine concentrations may be desired as a biomarker of low-level tobacco smoke exposure over urinary cotinine in studies of early reproduction. Collection of multiple FF samples for cotinine analysis may be needed to accurately represent long-term STS exposure., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: Cotinine is the most widely used biomarker to distinguish active versus passive smoking. However, there is an overlap in cotinine levels when comparing light or occasional smokers versus heavily exposed passive smokers. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. The aim of the study was to determine optimal cutoff points to discriminate active versus passive smokers and to compare sensitivity and specificity for the use of cotinine, NNAL, and the ratio of the NNAL/cotinine in urine., Methods: Cotinine and NNAL were measured in urine of 373 active smokers and 228 passive smokers., Results: Geometric mean cotinine levels were 2.03 ng/ml (interquartile interval: 0.43-8.60) and 1,043 ng/ml (658-2,251) and NNAL levels were 5.80 pg/ml (2.28-15.4) and 165 pg/ml (90.8-360) pg/ml in passive and active smokers, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 vs. 0.16, p < .01). The receiver operating characteristics analysis determined optimal cutoff points to discriminate passive versus active smokers: 31.5 ng/ml for cotinine (sensitivity: 97.1% and specificity: 93.9%), 47.3 pg/ml for NNAL (87.4% and 96.5%), and 0.74 x 10⁻³ for NNAL/cotinine ratio (97.3% and 87.3%)., Conclusions: Both urine cotinine and NNAL are sensitive and specific biomarkers for discriminating the source of tobacco smoke exposure. Cotinine is the best overall discriminator when biomarkers are measured while a person has ongoing exposure to tobacco smoke. NNAL because of its long half-life would be particularly useful when there is a delay between exposure and biomarker measurement. The NNAL/cotinine ratio provides similar sensitivity but poorer specificity at discriminating passive versus active smokers when compared with NNAL alone.

The nicotine metabolite cotinine is widely used to assess the extent of tobacco use in smokers, and secondhand smoke exposure in non-smokers. The ratio of another nicotine metabolite, trans-3'-hydroxycotinine, to cotinine in biofluids is highly correlated with the rate of nicotine metabolism, which is catalyzed mainly by cytochrome P450 2A6 (CYP2A6). Consequently, this nicotine metabolite ratio is being used to phenotype individuals for CYP2A6 activity and to individualize pharmacotherapies for tobacco addiction. In this paper we describe a highly sensitive liquid chromatography-tandem mass spectrometry method for determination of the nicotine metabolites cotinine and trans-3'-hydroxycotinine in human plasma, urine, and saliva. Lower limits of quantitation range from 0.02 to 0.1ng/mL. The extraction procedure is straightforward and suitable for large-scale studies. The method has been applied to several thousand biofluid samples for pharmacogenetic studies and for studies of exposure to low levels of secondhand smoke. Concentrations of both metabolites in urine of non-smokers with different levels of secondhand smoke exposure are presented., (© 2011 Elsevier B.V. All rights reserved.)

Unlabelled: Smoking cigarettes is very common among lactating women. The objective evaluation of an exposure to cigarette smoke is needed, as cotinine concentration. On many research a questionnaire is the only determinant of fact and intensification of smoking. The aim of this research was to establish a reliability of the questionnaire concerning cigarette smoking among lactating mothers by analyzing cotinine/creatinine ratio., Material and Methods: In 51 lactating mothers (participants of the research on oxidative stress in Obstetrics Departments on 3rd day post partum) during check-up visit, on 30th day post partum a questionnaire concerning smoking cigarettes before, during pregnancy and after childbirth, and amount of cigarettes smoked was made. Samples of matutinal urine were deep freezed in - 700 till cotinine was evaluated immunoenzymatically. Women were divided into groups: I of non-smokers (32 women), II of smokers (19 women). Statistical analysis was made by means of unparametric test U Mann-Whitney., Results: Average cotinine/creatinine ratio was 33,8 ng/mg in group I; 1275.9 ng/mg in group II. Specificity and sensitivity of data earned by virtue of statement of correspondents was 81% and 89%. Test of cotinine concentration in urine demonstrated 100% sensitivity and 94% specificity compared to the cotinine/creatinine ratio. Directly proportional relationship was stated between amount of cigarette smoked and concentration of cotinine in urine (55.9 ng/ ml cotinine/cigarette)., Conclusions: A questionnaire should not be the only method evaluating smoking among lactating women. The concentration of cotinine shows slightly lower specificity than cotinine/creatinine ratio. Both tests can be dealt equivalent.

Objectives: Cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are widely used biomarkers for tobacco-derived nicotine and the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. The discrepancy between cotinine levels in relation to disease risk comparing active versus passive smoking suggests a nonlinear tobacco smoke dose-response and/or that cotinine is not providing an accurate measure of exposure to the toxic constituents of secondhand tobacco smoke., Methods: Cotinine and NNAL were measured in the urine of 373 active smokers and 228 passive smokers., Results: Average cotinine levels were 1,155 (interquartile range, 703-2,715) for active smokers and 1.82 (0.45-7.33) ng/mg creatinine for passive smokers. Average NNAL levels were 183 (103-393) and 5.19 (2.04-11.6) pg/mg creatinine, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 × 10(3) versus 0.16 × 10(3), P < 0.0001)., Conclusions: Passive smoking is associated with a much higher ratio of NNAL/cotinine in the urine compared with active smoking., Impact: Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from secondhand smoke when compared with active smoking., (©2010 AACR.)

Background: The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its reduction product in the body, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are potent pulmonary carcinogens. We have measured total NNAL in the U.S. population of tobacco users and nonsmokers exposed to secondhand smoke., Methods: We measured total urinary NNAL (free NNAL plus its glucuronides following hydrolysis) by using a sensitive and specific high-performance liquid chromatography/tandem mass spectrometry method. We calculated the percentage above the limit of detection, the 50th through 95th percentiles, and in some cases, geometric means for groups classified by age, gender, and race/ethnicity., Results: Total urinary NNAL was measureable at or above its limit of detection (0.6 pg/mL) in 55% of the study participants, including 41% of nonsmokers. The population distribution of urinary NNAL included smoker and nonsmoker regions similar to the bimodal distribution of serum cotinine, and serum cotinine and total urinary NNAL were strongly correlated (r = 0.92; P < 0.001). Among nonsmokers, children had significantly higher concentrations of NNAL than did adults with the age of ≥20 years (P < 0.001)., Conclusions: Among National Health and Nutrition Examination Survey participants, total NNAL was found at measurable levels in the urine of 41% of nonsmokers and in 87.5% of those with substantial secondhand-smoke exposure (with serum cotinine concentrations of 0.1-10 ng/mL). Children with the age of 6 to 11 years had the highest NNAL concentrations among all nonsmokers., Impact: We describe for the first time the distribution of total urinary NNAL in the entire U.S. population, including smokers and nonsmokers. NNAL was detected in 41% of all nonsmokers., (©2010 AACR.)

Cigarette smoking constitutes one of the main sources of exposure to cancerogenic and procancerogenic xenobiotics in the human population. Smoking is not only a bad habit among adults but also among young people. Despite many anti-tobacco campaigns undertaken by European Union countries still the smoking percentage among young people is high and does not decrease in the recent years. Cigarettes smoking induces formation of reactive oxygen species and increases lipids peroxidation, which ultimately results in the production of MDA (malondialdehyde)--one of the oxidative stress biomarkers. Exposure to oxidative stress and the consequences of its influence can be measured by redox parameters monitoring. One of these methods is determination of total antioxidant activity by means of FRAP test (Ferric Reducing Antioxidant Power) in biological samples. The aim of this work was the evaluation of free radical processes increase related to tobacco smoke exposure by measurement of total antioxidant activity FRAP and MDA concentration in urine samples of medical students. In our study the authors'--designed questionnaire regarding the assessment of exposure to tobacco smoke and chosen xenobiotics was used. The investigated group included 134 students of 1-st and 2-nd year of study at Faculty of Medicine and Dentistry Division in Zabrze, Silesian Medical University. 85 students provided urine samples for further analysis. In the study group 40 students were active smokers and the control group consisted of 45 nonsmokers. The mean MDA concentrations in smoking students group were higher in comparison to the control group of non-smoking students. In the group of students exposed to second-hand smoke MDA concentrations were significantly higher in comparison to the group of students non-exposed to second hand smoke. The values of FRAP parameter were significantly higher for students who smoked in comparison with students non-exposed to tobacco smoke. Students exposed to second hand smoke had slightly higher FRAP values in comparison to smoking students. Exposure to tobacco smoke increased the intensity of free radical processes. Our study confirmed the harmful influence of second hand smoke that resulted in observed higher concentrations of determined biomarkers in the group of passive smoking students.

We assessed 12 urine metals in tobacco smoke-exposed and not exposed National Health and Nutrition Examination Survey participants. Our analysis included age, race/ethnicity, and poverty status. Gender and racial/ethnic differences in cadmium and lead and creatinine-adjusted and unadjusted data for group comparisons are presented. Smokers' had higher cadmium, lead, antimony, and barium levels than nonsmokers. Highest lead levels were in the youngest subjects. Lead levels among adults with high second-hand smoke exposure equaled smokers. Older smokers had cadmium levels signaling the potential for cadmium-related toxicity. Given the potential toxicity of metals, our findings complement existing research on exposure to chemicals in tobacco smoke.

Objective: To evaluate the impact of an indoor smoke-free bylaw in Toronto, Ontario, implemented June 2004., Methods: We used a pre-post comparison design to assess secondhand smoke (SHS) exposure among 79 eligible bar workers in Toronto, Ontario (bylaw enacted), and 49 eligible bar workers in a control community, Windsor, Ontario (no bylaw change), at four times: preban, and 1, 2, and 9 months postban., Results: SHS exposure time and urinary cotinine level were substantially reduced in Toronto bar workers immediately after the ban by 94% (from 7.8 to 0.5 hours) and 68% (from 24.2 to 7.8 ng/mL), respectively. The reduction was sustained throughout follow-up. There was no change among Windsor bar workers before and after the ban., Conclusions: Compliance with the ban was high, and the ban led to a substantial reduction in SHS exposure.

Background: Polycyclic aromatic hydrocarbons (PAHs) are compounds that are formed as a result of incomplete combustion of organic matter. The most common sources of PAHs are cigarette smoke, coal-fired utilities, steel plants, coke-oven plants, graphite electrode manufacturing plant, Söderberg aluminum electrolysis plant, vehicle exhaust, wood-burning ovens and fireplaces, and charcoal-grilled and smoked food. The aim of the study was to assess the exposure of smoking pregnant women to PAHs., Material and Methods: The study population consisted of 189 pregnant women from the Lódź voivodeship (province). Smoking status was assessed based on saliva cotinine level analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The cutoff point 10 ng/ml was adopted for saliva cotinine level. 1-hydroxypyrene (1-HP) concentration in urine sample was chosen as the biomarker of exposure to PAHs., Results and Conclusions: The mean concentration of 1-HP in urine of nonsmoking woman was 0.60 microg/g creatinine, whereas in smoking one 1.35 microg/g creatinine. Among the women with saliva cotinine level higher than 10 ng/ml, the mean concentration of 1-HP in urine was over twofold higher than that in women with cotinine level lower than 10 ng/ml after adjustment for the day of urine ample collection (ratio of geometric mean 2.3; 95% CI 1.7-3.0). The study confirmed a higher risk of exposure to PAHs in the group of women who smoke cigarettes during pregnancy as compared to nonsmoking women. It should be stressed that cigarette smoking is not the only source of exposure to PAHs.

The aim of the study was to evaluate the prenatal and postnatal child exposure to environmental tobacco smoke. The study population consisted of 83 women from Lodz, Poland among which detail questionnaire was conducted three times during pregnancy period. From all women included into the study the saliva sample was collected to verify smoking status in pregnancy. One year after delivery the second questionnaire was performed and urine sample from all children was collected. The cotinine level in saliva and urine was analyzed using Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS ESI+). About 22% of the children were expose to ETS during prenatal and 46% in postnatal period. Cotinine level in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 11.4 ng/ml; 95% CI 7.1-18.3) and exposed homes (GM 7.3 ng/ml; 95% CI 3.6-15.0) compared with non-exposed homes (GM 1.3 ng/ml; 95% CI 0.9-1.7) (p < 0.001). Children should be more protected from ETS exposure in prenatal and postnatal period.

The aim of this work was the assessment of the clinical condition, birth weight, frequency of premature birth and incidence of intrauterine growth restriction (IUGR) of the newborns whose mothers were active and passive smokers. This was a prospective study conducted in a group of 147 newborns born during the years 2003-2004 in the Princess Anna Mazowiecka Hospital, Warsaw, and hospitalized in the Neonatal and Intensive Care Department of Warsaw Medical University. Based on a questionnaire identifying the exposure to tobacco smoke and cotinine concentration in the mother's urine, the newborns were assigned to three groups: the newborns whose mothers were active smokers, the newborns whose mothers were passive smokers and the newborns of non-smoking mothers. There were no statistically significant differences in the Apgar score assessment at the 1st and 5th minute between the three groups of the newborns. Acid-base balance parameters (pH, BE) were also similar. The birth weight of the newborns of mothers who were active smokers was 325g lower than the birth weight of the newborns of non-smoking mothers. This difference was statistically significant p = 0.033. Maternal smoking in pregnancy was associated with an increased risk of deficit in birth weight 2.6 (1.0-6.9, CI 95%). In the group of the newborns whose mothers were active smokers, the incidence of lower birth weight (< 2500g) was also statistically significantly higher p = 0.01. There were no statistically significant differences in the incidence of premature birth and intrauterine growth restriction (IUGR).

In the course of epidemiologic studies on the health of preschool children in the Teplice and Prachatice districts of the Czech Republic, we have recorded the frequency of smokers in the families of the children under study and the exposure of the children to environmental tobacco smoke (ETS) by assaying urinary cotinine levels. Questionnaires were administered at the age of 3 years (children born 1994-1996) or 4.5 years (children born 1997-1998). Out of 1128 respondents, 35.6% of the mothers and 48.9% of their husbands/partners were smokers. Taking into account other adult smokers, 41.6% of children lived in households without smokers and 30.1% in households with one smoker. There were more smokers among both mothers and fathers in Teplice than in the Prachatice district (mothers: 41.1% vs. 28.5%, P=0.017; fathers: 50.8% vs. 46.5%, NS). Cotinine concentration in the urine was determined using a radioimmunoassay in 523 pairs of mothers and children at the age of 4.5 years. A level higher than 500 ng cotinine per mg creatinine (our cut-off for active smoking) was detected in 199 out of 523 mothers (38%). Using 20 ng/mg as the cut-off, 48.2% of 523 children were exposed to ETS. There were more ETS-exposed children in Teplice than in the Prachatice district (59.2% vs. 34.7%, P<0.001). When cotinine levels were measured in 479 of these children at the age of 6-7 years, the percentage of children exposed to ETS decreased to 36.5%. However, the difference between Teplice and Prachatice children persisted (44.6% vs. 27.8%). Our results suggest that in the Czech Republic, children under 5 years of age are significantly exposed to tobacco smoke and that more effective regulatory measures are needed to decrease the prevalence of smoking.

Of the few studies available regarding the effects of smoking on animals, most of them involve animals actively smoking through the use of a mask or tracheostomy. The present study investigated the effects of passive smoke exposure on domestic dogs. The sample comprised 30 Yorkshire terriers (18 males) ranging in age from 27 to 106 months (M = 38.6+/-15.8) and weighing 1.9-4.0 kg (M = 3.04+/-0.48). Half of the dogs came from homes where residents smoked at least 20 cigarettes/day for a minimum of 24 months, and the other half were from homes without smokers. All animals were subjected to bronchoalveolar lavage to determine cell populations and the presence of anthracosis in macrophage cytoplasm; in addition, a carinal biopsy was obtained. To characterize environmental cigarette smoke exposure, urinary cotinine was determined by an immunochromatographic assay. Cotinine was not detected in the urine of dogs not exposed to cigarette smoke, whereas exposed dogs tested positive. In dogs exposed to cigarette smoke, macrophage and lymphocyte populations were significantly increased (p<.05) and anthracosis was present in the cytoplasm of macrophages. The measurement of urinary cotinine by an immunochromatographic assay is an effective method that can be used to confirm environmental tobacco exposure. Cytological analysis of bronchoalveolar lavage fluid demonstrated airway alterations triggered by passive exposure to tobacco smoke in domestic animals.

Cadmium is a toxic, bioaccumulated heavy metal with a half-life of one to four decades in humans (CDC, 2005). Primary exposure sources include food and tobacco smoke. In our population-based study, a risk-factor interview was conducted as part of a breast cancer study for 251 randomly selected women living in Wisconsin (USA), aged 20-69 yr, and spot-urine specimens were also obtained. Urine collection kits were carefully designed to minimize trace element contamination during specimen collection and handling in each participant's home. Urine cadmium concentrations were quantified using inductively coupled plasma-mass spectrometry, and creatinine levels and specific gravity were also determined. Statistically significant increasing creatinine-adjusted urinary cadmium mean levels relative to smoking status (never, former, and current respectively) were observed. A difference in mean cadmium levels for nonsmokers who reported environmental tobacco smoke exposure during childhood or the recent past (approximately 2 yr prior to the interview) for exposure at home, at work, or in social settings compared to those who reported no exposure was not found.

An objective assessment of exposure to tobacco smoke may be accomplished by means of examining particular biomarkers in body fluids. The most common biomarker of tobacco smoke exposure is urinary, or serum, cotinine. In order to distinguish non-smokers from passive smokers and passive smokers from active smokers, it is necessary to estimate cotinine cut-off points. The objective of this article was to apply statistical distribution of urinary cotinine concentration to estimate cut-off points distinguishing the three above-mentioned groups. The examined group consisted of 327 volunteers (187 women and 140 men) who were ethnically homogenous inhabitants of the same urban agglomeration (Sosnowiec, Poland). The values which enabled differentiation of the examined population into groups and subgroups were as follows: 50 microg l(-1) (differentiation of non-smokers from passive smokers), 170 microg l(-1) (to divide the group of passive smokers into two subgroups: minimally and highly exposed to environmental tobacco smoke), 550 microg l(-1) (differentiation of passive smokers from active smokers), and 2100 microg l(-1) (to divide group of active smokers into two subgroups: minimally and highly exposed to tobacco smoke). The results suggest that statistical distribution of urinary cotinine concentration is useful for estimating urinary cotinine cut-off points and for assessing the smoking status of persons exposed to tobacco smoke.