Geometric Mean Serum Cotinine Concentrations Confirm a Continued Decline in Secondhand Smoke Exposure among U.S. Nonsmokers-NHANES 2003 to 2018.

The objective of this study was to examine long-term trends in serum cotinine (COT) concentrations, as a measure of secondhand smoke (SHS) exposure, in U.S. nonsmokers using data from the National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2018. We analyzed NHANES serum COT results from 8 continuous NHANES 2 year cycles from 2003 to 2018 using a liquid chromatography−tandem mass spectrometry assay that has been maintained continuously at the Centers for Disease Control and Prevention (CDC) since 1992. Serum COT concentrations (based on the geometric means) among nonsmokers in the U.S. decreased by an average of 11.0% (95% confidence interval (CI) [8.8%, 13.1%]; p < 0.0001) every 2 year cycle. From 2003 to 2018, serum COT concentrations in U.S. nonsmokers declined by 55.0%, from 0.065 ng/mL in 2003−2004 to 0.029 ng/mL in 2017−2018 (p < 0.0001). Significant decreases in serum COT concentrations were observed in all demographic groups. While disparities between these groups seems to be shrinking over time, several previously observed disparities in SHS exposure remain in 2017−2018. Serum COT concentrations of the non-Hispanic Black population remained higher than those of non-Hispanic Whites and Mexican Americans (p < 0.0001). Additionally, serum COT concentrations were significantly higher for children aged 3−5 years than other age groups (p ≤ 0.0002), and men continued to have significantly higher serum COT concentrations than women (p = 0.0384). While there is no safe level of exposure to SHS, the decrease in serum COT concentrations in the U.S. population as well as across demographic groupings represents a positive public health outcome and supports the importance of comprehensive smoke-free laws and policies for workplaces, public places, homes, and vehicles to protect nonsmokers from SHS exposure.

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

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

Serum Concentrations of Cotinine and Trans-3'-Hydroxycotinine in US Adults: Results From Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative cohort of tobacco product users and nonusers. The study's main purpose is to obtain longitudinal epidemiologic data on tobacco use and exposure among the US population. AIMS AND METHODS: Nicotine biomarkers-cotinine (COT) and trans-3'-hydroxycotinine (HCT)-were measured in blood samples collected from adult daily tobacco users and nonusers during Wave 1 of the PATH Study (2013-2014; n = 5012; one sample per participant). Participants' tobacco product use and exposure to secondhand smoke were categorized based on questionnaire responses. Nonusers were subdivided into never users and recent former users. Daily tobacco users were classified into seven tobacco product use categories: exclusive users of cigarette, smokeless tobacco, electronic cigarette, cigar, pipe, and hookah, as well as polyusers. We calculated sample-weighted geometric mean (GM) concentrations of cotinine, HCT, and the nicotine metabolite ratio (NMR) and evaluated their associations with tobacco use with adjustment for potential confounders. RESULTS: The GMs (95% confidence intervals) of COT and HCT concentrations for daily tobacco users were 196 (184 to 208) and 72.5 (67.8 to 77.4) ng/mL, and for nonusers they were 0.033 (0.028 to 0.037) and 0.021 (0.018 to 0.023) ng/mL. Exclusive smokeless tobacco users had the highest COT concentrations of all user groups examined. The GM NMR in daily users was 0.339 (95% confidence interval: 0.330 to 0.350). CONCLUSIONS: These nationally representative estimates of serum nicotine biomarkers could be the basis for reference ranges characterizing nicotine exposure for daily tobacco users and nonusers in the US adult population. IMPLICATIONS: This report summarizes the serum nicotine biomarker measurements in Wave 1 of the PATH Study. We are reporting the first estimates of HCT in serum for daily tobacco users and nonusers in the noninstitutionalized, civilian US adult population; the first nationally representative serum COT estimates for daily exclusive users of different tobacco products and daily polyusers; and the first nationally representative estimate of the serum NMR in daily tobacco users by age, race/ethnicity, and sex.

Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

INTRODUCTION: The tobacco-specific nitrosamines (TSNAs) are an important group of carcinogens found in tobacco and tobacco smoke. To describe and characterize the levels of TSNAs in the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014), we present four biomarkers of TSNA exposure: N'-nitrosonornicotine, N'-nitrosoanabasine, N'-nitrosoanatabine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which is the primary urinary metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. METHODS: We measured total TSNAs in 11 522 adults who provided urine using automated solid-phase extraction coupled to isotope dilution liquid chromatography-tandem mass spectrometry. After exclusions in this current analysis, we selected 11 004 NNAL results, 10 753 N'-nitrosonornicotine results, 10 919 N'-nitrosoanatabine results, and 10 996 N'-nitrosoanabasine results for data analysis. Geometric means and correlations were calculated using SAS and SUDAAN. RESULTS: TSNA concentrations were associated with choice of tobacco product and frequency of use. Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was highest for smokeless tobacco users (993.3; 95% confidence interval [CI: 839.2, 1147.3] ng/g creatinine), followed by all types of combustible tobacco product users (285.4; 95% CI: [267.9, 303.0] ng/g creatinine), poly tobacco users (278.6; 95% CI: [254.9, 302.2] ng/g creatinine), and e-cigarette product users (6.3; 95% CI: [4.7, 7.9] ng/g creatinine). TSNA concentrations were higher in every day users than in intermittent users for all the tobacco product groups. Among single product users, exposure to TSNAs differed by sex, age, race/ethnicity, and education. Urinary TSNAs and nicotine metabolite biomarkers were also highly correlated. CONCLUSIONS: We have provided PATH Study estimates of TSNA exposure among US adult users of a variety of tobacco products. These data can inform future tobacco product and human exposure evaluations and related regulatory activities.

Biochemical Verification of Tobacco Use and Abstinence: 2019 Update.

BACKGROUND: The changing prevalence and patterns of tobacco use, the advent of novel nicotine delivery devices, and the development of new biomarkers prompted an update of the 2002 Society for Research on Nicotine and Tobacco (SRNT) report on whether and how to apply biomarker verification for tobacco use and abstinence. METHODS: The SRNT Treatment Research Network convened a group of investigators with expertise in tobacco biomarkers to update the recommendations of the 2002 SNRT Biochemical Verification Report. RESULTS: Biochemical verification of tobacco use and abstinence increases scientific rigor and is recommended in clinical trials of smoking cessation, when feasible. Sources, appropriate biospecimens, cutpoints, time of detection windows and analytic methods for carbon monoxide, cotinine (including over the counter tests), total nicotine equivalents, minor tobacco alkaloids, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol are reviewed, as well as biochemical approaches to distinguishing cigarette smoking from use of electronic nicotine delivery devices (ENDS). CONCLUSIONS: Recommendations are provided for whether and how to use biochemical verification of tobacco use and abstinence. Guidelines are provided on which biomarkers to use, which biospecimens to use, optimal cutpoints, time windows to detection, and methodology for biochemical verifications. Use of combinations of biomarkers is recommended for assessment of ENDS use. IMPLICATIONS: Biochemical verification increases scientific rigor, but there are drawbacks that need to be assessed to determine whether the benefits of biochemical verification outweigh the costs, including the cost of the assays, the feasibility of sample collection, the ability to draw clear conclusions based on the duration of abstinence, and the variability of the assay within the study population. This paper provides updated recommendations from the 2002 SRNT report on whether and how to use biochemical markers in determining tobacco use and abstinence.

Tobacco Use Classification by Inexpensive Urinary Cotinine Immunoassay Test Strips.

Urinary cotinine is one of the most commonly measured biomarkers reflecting recent exposure to nicotine. In some cases a simple qualitative dichotomization of smokers and non-smokers is all that is required. NicAlert® test strips have been evaluated for this purpose, but other recently introduced, inexpensive single-line test strips have not. In this study we evaluated two such strips with nominal cutoffs of 200 and 10 ng/mL. A total of 800 urine samples with known cotinine concentrations determined by an LC-MS-MS method were examined, including 400 urine samples ranging from 0.23 to more than 24,000 ng/mL by the 200 ng/mL strip, and 400 samples with concentrations <200 ng/mL by the 10 ng/mL cutoff strip. Both test strips performed well in these evaluations. Classification relative to LC-MS-MS by the 200 ng/mL strips had a sensitivity of 99.5% and specificity of 92%, with 95.8% accuracy. The 10 ng/mL strips had a sensitivity of 98.7% and specificity of 90.1%, with 93.3% accuracy. The positive predictive value for the 200 ng/mL strips was 92.6% and the negative predictive value was 99.5%. For the 10 ng/mL strips, the corresponding values were 85.4 and 99.2%, respectively. The prevalence of positive samples was 50% in the 200 ng/mL group, and 37% in the 10 ng/mL set. Each strip was read by two readers with an overall agreement of >98%. Our results suggest that these simple and inexpensive lateral flow immunoassay test strips can provide useful qualitative estimates of nicotine exposures for appropriate applications within the inherent limitations of sensitivity and precision of the immunoassay test strip format.

Collaborative Method Performance Study of the Measurement of Nicotine, Its Metabolites, and Total Nicotine Equivalents in Human Urine.

Background: Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements.Methods: This report presents the results from a method performance study involving 11 laboratories from 6 countries that are currently active in this area. Each laboratory assayed blind replicates of seven human urine pools at various concentrations on three separate days. The samples included five pools blended from smoker and nonsmoker urine sources, and two additional blank urine samples fortified with pure nicotine, cotinine, and hydroxycotinine standards. All laboratories used their own methods, and all were based on some form of liquid chromatography/tandem mass spectrometry.Results: Overall, good agreement was found among the laboratories in this study. Intralaboratory precision was good, and in the fortified pools, the mean bias observed was < + 3.5% for nicotine, approximately 1.2% for hydroxycotinine, and less than 1% for cotinine (1 outlier excluded in each case). Both indirect and direct methods for analyzing the glucuronides gave comparable results.Conclusions: This evaluation indicates that the experienced laboratories participating in this study can produce reliable and comparable human urinary nicotine metabolic profiles in samples from people with significant recent exposure to nicotine.Impact: This work supports the reliability and agreement of an international group of established laboratories measuring nicotine and its metabolites in urine in support of nicotine exposure studies. Cancer Epidemiol Biomarkers Prev; 27(9); 1083-90. ©2018 AACR.

Biomarkers of exposure to new and emerging tobacco delivery products.

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.

Temporal Trends of Secondhand Smoke Exposure: Nonsmoking Workers in the United States (NHANES 2001-2010).

BACKGROUND: The workplace is one of the major locations outside of the home for nonsmokers' exposure to secondhand smoke (SHS). New policies in many U.S. states and localities restrict or prohibit smoking in the workplace, and information on current trends in the exposure of nonsmokers to SHS across various occupational groups is therefore needed. OBJECTIVE: We evaluated temporal trends in SHS exposure among nonsmoking workers in the United States and identified those occupations with workers with the highest levels of SHS exposure. METHODS: We combined serum cotinine (sCOT) measurements and questionnaire data from five survey cycles of the National Health and Nutrition Examination Survey (NHANES: 2001-2010). Trends in SHS exposure by occupations were determined from percent changes and least-squares geometric means (LSGMs) of sCOT concentrations computed using sample-weighted multiple regression models. RESULTS: Between NHANES 2001-2002 and NHANES 2009-2010, LSGMs of sCOT levels had changed -25% (95% CI: -39, -7%) in nonsmoking workers. The largest decrease was identified among food preparation workers [-54% (95% CI: -74, -19%)], followed by white-collar [-40%, (95% CI: -56, -19%)] and blue-collar workers (-32%, 95% CI: -51, -5%). LSGMs of sCOT remained highest in food preparation workers in all survey cycles, but the gap between occupations narrowed in the latest survey cycle (2009-2010). For example, the gap in LSGMs of sCOT between food preparation and science/education workers dropped > 70% during 2000 to 2010. CONCLUSIONS: During the period from 2001 to 2010, the overall SHS exposure in nonsmoking workers declined with substantial drops in food preparation/service and blue-collar workers. Although disparities persist in SHS exposure, the gaps among occupations have narrowed. CITATION: Wei B, Bernert JT, Blount BC, Sosnoff CS, Wang L, Richter P, Pirkle JL. 2016. Temporal trends of secondhand smoke exposure: nonsmoking workers in the United States (NHANES 2001-2010). Environ Health Perspect 124:1568-1574; http://dx.doi.org/10.1289/EHP165.

Variation in nicotine intake among U.S. cigarette smokers during the past 25 years: evidence from NHANES surveys.

OBJECTIVE: To estimate changes in nicotine intakes among U.S. cigarette smokers from 1988 to 2012 with the National Health and Nutrition Examination Survey (NHANES). METHODS: NHANES provides data on nationally representative samples of cigarette smokers from the civilian noninstitutionalized U.S. population. A total of 4,304 smokers aged 20 years and older were studied in NHANES III 1988-1994 and 7,095 were studied in the continuous NHANES 1999-2012. We examined serum cotinine concentrations, daily cigarette consumption, and estimated nicotine intake per cigarette, with adjustment for sex, age, racial/ethnic background, level of education, and body mass index. RESULTS: There was little overall change in nicotine intake from smoking cigarettes either in the U.S. population as a whole or in major racial/ethnic subgroups during the 25-year period from 1988. Serum cotinine averaged 223.7ng/mL (95% confidence interval [CI] = 216.1-231.3) in 1988-1994, which was not significantly different from the adjusted mean of 219.2ng/mL (95% CI = 214.1-224.4) in 1999-2012. During the same period, average daily cigarette consumption declined substantially, from 17.3 (95% CI = 16.5-18.0) in 1988-1994 to 12.3 (95% CI = 11.0-13.6) by 2012. Cotinine per cigarette smoked increased by some 42% between 1988-1994 and 2011-2012, from a geometric mean of 12.4 (95% CI = 11.7-13.1) to 17.6 (95% CI = 16.1-19.2). CONCLUSIONS: Reductions in cigarette smoking prevalence since the late 1980s, changes in cigarette product design, and the widespread introduction of smoke-free policies have not had a significant impact on nicotine intakes among U.S. smokers. Reductions in cigarette consumption have been offset by increased nicotine intake per cigarette smoked.

Validation of a LC-MS/MS method for quantifying urinary nicotine, six nicotine metabolites and the minor tobacco alkaloids--anatabine and anabasine--in smokers' urine.

Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling--i.e., metabolite ratios. In addition, the minor tobacco alkaloids--anabasine and anatabine--can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides) and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme) that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1'-N-oxide, anatabine, and anabasine) are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76-99%), specificity, accuracy (0-10% bias) and reproducibility (2-9% C.V.) make this method ideal for large high through-put studies.

Comparison of creatinine and specific gravity for hydration corrections on measurement of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine.

BACKGROUND: Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was measured in all participants aged 6 years and older from the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey 2007-2008. The suitability of using creatinine or specific gravity for urinary NNAL correction in exposure assessment is examined in this study. METHODS: Effects of both specific gravity and creatinine correction on urinary NNAL among smokers were investigated with multiple linear regression models using either normalization or the fitting of creatinine and specific gravity in the model as covariates. RESULTS: When log-scaled NNAL was normalized by either creatinine or specific gravity, R(2) was slightly higher for creatinine than for specific gravity (R(2) = 0.1694 and 0.1439, for creatinine and specific gravity, respectively). When log-scaled NNAL was normalized by both factors, the R(2) was improved (R(2) = 0.2068). When specific gravity or creatinine was included as a covariate separately in the models, they were highly significant factors (P < 0.001, R(2) = 0.2226 and 0.1681 for creatinine and specific gravity, respectively). However, when both were included in the model as covariates, creatinine remained highly significant (P < 0.001), whereas the significance of specific gravity was eliminated (P = 0.4294). CONCLUSION: This study confirms significant relationships between NNAL concentrations and both urine creatinine and specific gravity. We conclude that creatinine is the more influential and preferred variable to account for urine dilution in tobacco-specific nitrosamine exposure assessment.

Can a minimal intervention reduce secondhand smoke exposure among children with asthma from low income minority families? Results of a randomized trial.

We report on the results of a low-intensity behavioral intervention to reduce second hand smoke (SHS) exposure of children with asthma from low income minority households in Los Angeles, California. In this study, 242 child/adult dyads were randomized to a behavioral intervention (video, workbook, minimal counseling) or control condition (brochure). Main outcome measures included child's urine cotinine and parental reports of child's hours of SHS exposure and number of household cigarettes smoked. Implementation of household bans was also considered. No differences in outcomes were detected between intervention and control groups at follow-up. Limitations included high attrition and low rates of collection of objective measures (few children with urine cotinine samples). There continues to be a need for effective culturally and linguistically appropriate strategies that support reduction of household SHS exposure among children with asthma in low income, minority households.

Assessing secondhand smoke using biological markers.

Secondhand smoke exposure (SHSe) is a known cause of many adverse health effects in adults and children. Increasingly, SHSe assessment is an element of tobacco control research and implementation worldwide. In spite of decades of development of approaches to assess SHSe, there are still unresolved methodological issues; therefore, a multidisciplinary expert meeting was held to catalogue the approaches to assess SHSe and with the goal of providing a set of uniform methods for future use by investigators and thereby facilitate comparisons of findings across studies. The meeting, held at Johns Hopkins, in Baltimore, Maryland, USA, was supported by the Flight Attendant Medical Research Institute (FAMRI). A series of articles were developed to summarise what is known about self-reported, environmental and biological SHSe measurements. Non-smokers inhale toxicants in SHS, which are mainly products of combustion of organic materials and are not specific to tobacco smoke exposure. Biomarkers specific to SHSe are nicotine and its metabolites (e.g., cotinine), and metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Cotinine is the preferred blood, saliva and urine biomarker for SHSe. Cotinine and nicotine can also be measured in hair and toenails. NNAL (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol), a metabolite of NNK, can be determined in the urine of SHS-exposed non-smokers. The selection of a particular biomarker of SHSe and the analytic biological medium depends on the scientific or public health question of interest, study design and setting, subjects, and funding. This manuscript summarises the scientific evidence on the use of biomarkers to measure SHSe, analytical methods, biological matrices and their interpretation.

A randomized trial of air cleaners and a health coach to improve indoor air quality for inner-city children with asthma and secondhand smoke exposure.

OBJECTIVE: To test an air cleaner and health coach intervention to reduce secondhand smoke exposure compared with air cleaners alone or no air cleaners in reducing particulate matter (PM), air nicotine, and urine cotinine concentrations and increasing symptom-free days in children with asthma residing with a smoker. DESIGN: Randomized controlled trial, with randomization embedded in study database. SETTINGS: The Johns Hopkins Hospital Children's Center and homes of children. PARTICIPANTS: Children with asthma, residing with a smoker, randomly assigned to interventions consisting of air cleaners only (n = 41), air cleaners plus a health coach (n = 41), or delayed air cleaner (control) (n = 44). MAIN OUTCOME MEASURES: Changes in PM, air nicotine, and urine cotinine concentrations and symptom-free days during the 6-month study. RESULTS: The overall follow-up rate was high (91.3%). Changes in mean fine and coarse PM (PM(2.5) and PM(2.5-10)) concentrations (baseline to 6 months) were significantly lower in both air cleaner groups compared with the control group (mean differences for PM(2.5) concentrations: control, 3.5 µg/m(3); air cleaner only, -19.9 µg/m(3); and air cleaner plus health coach, -16.1 µg/m(3); P = .003; and PM(2.5-10) concentrations: control, 2.4 µg/m(3); air cleaner only, -8.7 µg/m(3); and air cleaner plus health coach, -10.6 µg/m(3); P = .02). No differences were noted in air nicotine or urine cotinine concentrations. The health coach provided no additional reduction in PM concentrations. Symptom-free days were significantly increased [corrected] in both air cleaner groups compared with the control group (P = .03). CONCLUSION: Although the use of air cleaners can result in a significant reduction in indoor PM concentrations and a significant increase in symptom-free days, it is not enough to prevent exposure to secondhand smoke.

Measurement of nicotine, cotinine and trans-3'-hydroxycotinine in meconium by liquid chromatography-tandem mass spectrometry.

Nicotine (NIC), cotinine (COT) and trans-3'-hydroxycotinine (OHCOT) are the most prevalent and abundant tobacco biomarkers in meconium. We have developed and validated an accurate and precise method for the measurement of these analytes in meconium in which potassium hydroxide is used to digest the meconium sample, followed by solid phase extraction from the liquified sample. The precision of OHCOT, COT and NIC measurements (intra-day and inter-day) were 4.8-10.6%, 3.4-11.6% and 9.3-15.8%, respectively. Evaluation of accuracy indicated bias of -4.0, 2.0 and 0.8% for OHCOT at concentrations of 0.5, 2.5 and 7.5 ng/g. The accuracy estimates for COT at concentrations of 0.5, 2.5 and 7.5 ng/g are 4.0, 4.0 and 5.7%, respectively. For NIC at 2, 10 and 30 ng/g the accuracy was calculated to be 3.0, 5.0 and 5.1%, respectively. The linear range of standard solutions was 0.125-37.5 ng/mL for OHCOT and COT, and 0.75-150 ng/mL for NIC. This method was applied to the analysis of 374 meconium samples from infants of both smoking and nonsmoking mothers. Positive correlations with r(2)≥0.63 were observed between NIC and COT, COT and OHCOT, NIC and OHCOT, and NIC and (OHCOT+COT) in these samples.

Analysis of 4-aminobiphenyl in smoker's and nonsmoker's urine by tandem mass spectrometry.

The aromatic amine 4-aminobiphenyl (4-ABP) is present in tobacco smoke. In humans, it is also a known bladder carcinogen. We describe here a method for the quantification of total 4-ABP in urine using capillary gas chromatography/tandem mass spectrometry, with an effective detection limit in urine samples of approximately 0.87 pg/mL. We also examined the efficiency of chemical or enzymatic hydrolysis of urinary aromatic amine metabolites. Although we found acidic or basic hydrolysis effective, we found enzymatic hydrolysis (ß-glucuronidase with either Escherichia coli or Helix pomatia) ineffective. As part of this work, we also confirm the presence of N-acetyl-4-ABP and 4-ABP glucuronide in human urine samples from smokers. These metabolites have been reported in animal studies, but previously they have not been identified in human samples. These metabolites, however, were found to be unstable and thus infeasible for biomonitoring. The final validated urinary total 4-ABP assay was applied to the analysis of samples from smokers and nonsmokers, whose status was confirmed from cotinine EIA measurements. Among 41 confirmed nonsmokers, the geometric mean (95% CI) of 4-ABP concentration was 1.64 pg/mg creatinine (1.30-2.07). Conversely, in 89 smokers, the geometric mean of 4-ABP concentration was significantly greater, at 8.69 pg/mg creatinine (7.43-10.16), p < 0.001. Our results indicate that following tobacco smoke exposure, total urinary 4-ABP is a reliable biomarker for exposure to this carcinogen.

Environmental tobacco smoke exposure among casino dealers.

OBJECTIVE: This study quantified casino dealers' occupational exposure to environmental tobacco smoke (ETS). METHODS: We measured casino dealers' exposure to ETS components by analyzing full-shift air and preshift and postshift urine samples. RESULTS: Casino dealers were exposed to nicotine, 4-vinyl pyridine, benzene, toluene, naphthalene, formaldehyde, acetaldehyde, solanesol, and respirable suspended particulates. Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine increased significantly during an 8-hour work shift both with and without adjustment for creatinine clearance. Creatinine-unadjusted cotinine significantly increased during the 8-hour shift, but creatinine-adjusted cotinine did not increase significantly. CONCLUSIONS: Casino dealers at the three casinos were exposed to airborne ETS components and absorbed an ETS-specific component into their bodies, as demonstrated by detectable levels of urinary NNAL. The casinos should ban smoking on their premises and offer employee smoking cessation programs.

Comparison of serum cotinine concentration within and across smokers of menthol and nonmenthol cigarette brands among non-Hispanic black and non-Hispanic white U.S. adult smokers, 2001-2006.

BACKGROUND: The Food and Drug Administration (FDA) is examining options for regulating menthol content in cigarettes. There are many pharmacologic properties of menthol that may facilitate exposure to tobacco smoke, and it has been suggested that the preference for menthol cigarettes in black smokers accounts for their higher cotinine levels. OBJECTIVE: To assess cigarettes smoked per day-adjusted cotinine levels in relation to smoking a menthol or nonmenthol cigarette brand among non-Hispanic black and white U.S. adult smokers under natural smoking conditions. METHOD: Serum cotinine concentrations were measured in 1,943 smokers participating in the 2001 to 2006 National Health and Nutrition Examination Surveys (NHANES). The effect of smoking a menthol brand on cigarettes smoked per day-adjusted serum cotinine levels in these two populations was modeled by adjusting for sex, age, number of smokers living in the home, body weight, time since last smoked, and FTC (Federal Trade Commission)-measured nicotine levels. The 8- or 12-digit Universal Product Code (UPC) on the cigarette label was used to determine the cigarette brand and whether it was menthol. RESULTS: Smoking a menthol cigarette brand versus smoking a nonmenthol cigarette brand was not associated (P ≥ 0.05) with mean serum cotinine concentration in either black or white smokers. CONCLUSIONS: The higher levels of cotinine observed in black smokers compared with white smokers are not explained by their higher preference for menthol cigarette brands. IMPACT: Further studies like ours are needed to improve our ability to understand health consequences of future changes in tobacco product design.

Time course of nicotine and cotinine incorporation into samples of nonsmokers' beard hair following a single dose of nicotine polacrilex.

Hair nicotine and cotinine have been proposed as longer-term markers of exposure to secondhand smoke. In this study, we evaluated the rate and extent of nicotine and cotinine deposition into beard hair among six male nonsmokers following a single exposure to 4 mg of nicotine in Nicorette(®) (nicotine polacrilex) gum. We collected beard hair samples daily for 12 days following exposure and urine samples for 6 days after exposure. Using liquid chromatographic-tandem mass spectrometric analysis, we found that both nicotine and cotinine could be detected in beard samples within 24 h of the exposure and reached a maximum of about 71 pg nicotine and 47 pg cotinine/mg hair, respectively, within 1-2 days, followed by a gradual decline. Compared to beard hair concentrations, nicotine, cotinine, and hydroxycotinine were excreted in urine at much higher levels and also peaked on the day after exposure (mean ± SD urine cotinine = 300 ± 183 ng/mL). Our results confirmed that both nicotine and cotinine can be measured in beard hair samples following a single dose of nicotine. However, both the time-course and extent of deposition of these analytes in beard hair in this study differed from the results reported previously from a similar evaluation.