John T. Bernert

Optimal Serum Cotinine Levels for Distinguishing Cigarette Smokers and Nonsmokers Within Different Racial/Ethnic Groups in the United States Between 1999 and 2004

Cotinine, a metabolite of nicotine, is widely used to distinguish smokers from nonsmokers in epidemiologic studies and smoking-cessation clinical trials. As the magnitude of secondhand smoke exposure declines because of proportionally fewer smokers and more clean-indoor-air regulations, the optimal cotinine cutpoint with which to distinguish smokers from nonsmokers is expected to change. The authors analyzed data on 3,078 smokers and 13,078 nonsmokers from the National Health and Nutrition Examination Survey for 1999-2004. Optimal serum cotinine concentrations for discriminating smokers from nonsmokers were determined using receiver operator characteristic curve analysis. Optimal cotinine cutpoints were 3.08 ng/mL (sensitivity = 96.3%, specificity = 97.4%) and 2.99 ng/mL (sensitivity = 86.5%, specificity = 93.1%) for adults and adolescents, respectively. Among adults, optimal cutpoints differed by race/ethnicity: They were 5.92 ng/mL, 4.85 ng/mL, and 0.84 ng/mL for non-Hispanic blacks, non-Hispanic whites, and Mexican Americans, respectively. Among adolescents, cutpoints were 2.77 ng/mL, 2.95 ng/mL, and 1.18 ng/mL for non-Hispanic blacks, non-Hispanic whites, and Mexican Americans, respectively. Use of the currently accepted cutpoint of 14 ng/mL overestimates the number of nonsmokers in comparison with the proposed new overall cutpoint of 3 ng/mL or the race/ethnicity-specific cutpoints of 1-6 ng/mL.

Households contaminated by environmental tobacco smoke: sources of infant exposures

Objectives: To examine (1) whether dust and surfaces in households of smokers are contaminated with environmental tobacco smoke (ETS); (2) whether smoking parents can protect their infants by smoking outside and away from the infant; and (3) whether contaminated dust, surfaces, and air contribute to ETS exposure in infants. Design: Quasi-experiment comparing three types of households with infants: (1) non-smokers who believe they have protected their children from ETS; (2) smokers who believe they have protected their children from ETS; (3) smokers who expose their children to ETS. Setting: Homes of smokers and non-smokers. Participants: Smoking and non-smoking mothers and their infants ⩽ 1 year. Main outcome measures: ETS contamination as measured by nicotine in household dust, indoor air, and household surfaces. ETS exposure as measured by cotinine levels in infant urine. Results: ETS contamination and ETS exposure were 5–7 times higher in households of smokers trying to protect their infants by smoking outdoors than in households of non-smokers. ETS contamination and exposure were 3–8 times higher in households of smokers who exposed their infants to ETS by smoking indoors than in households of smokers trying to protect their children by smoking outdoors. Conclusions: Dust and surfaces in homes of smokers are contaminated with ETS. Infants of smokers are at risk of ETS exposure in their homes through dust, surfaces, and air. Smoking outside the home and away from the infant reduces but does not completely protect a smoker’s home from ETS contamination and a smoker’s infant from ETS exposure.

Trends in the Exposure of Nonsmokers in the U.S. Population to Secondhand Smoke: 1988–2002

The objective of this study was to describe the exposure of nonsmokers in the U.S. population to secondhand smoke (SHS) using serum cotinine concentrations measured over a period of 14 years, from October 1988 through December 2002. This study consists of a series of National Health and Nutrition Examination Surveys (NHANES) measuring serum cotinine as an index of SHS exposure of participants. Study participants were individuals representative of the U.S. civilian, noninstitutionalized population, ≥ 4 years of age. We analyzed serum cotinine and interview data from NHANES obtained during surveys conducted during four distinct time periods. Our results document a substantial decline of approximately 70% in serum cotinine concentrations in non-smokers during this period. This decrease was reflected in all groups within the population regardless of age, sex, or race/ethnicity. The large decrease that we observed in serum cotinine concentrations suggests a substantial reduction in the exposure of the U.S. population to SHS during the 1990s. The exposure of nonsmokers to SHS represents an important public health concern. Our findings suggest that recent public health efforts to reduce such exposures have had an important effect, although children and non-Hispanic black nonsmokers show relatively higher levels of serum cotinine.

Variability and Predictors of Urinary Bisphenol A Concentrations during Pregnancy

Background Prenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy. Objective Our goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy. Methods We measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log10-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models. Results Geometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 μg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 μg/g) compared with those consuming no canned vegetables (GM = 1.6 μg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations. Conclusions These results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures.

Estimates of Nondisclosure of Cigarette Smoking Among Pregnant and Nonpregnant Women of Reproductive Age in the United States

Although clinic-based studies have used biochemical validation to estimate the percentage of pregnant women who deny smoking but are actually smokers, a population-based estimate of nondisclosure of smoking status in US pregnant women has not been calculated. The authors analyzed data from the 1999-2006 National Health and Nutrition Examination Survey and estimated the percentage of 994 pregnant and 3,203 nonpregnant women 20-44 years of age who did not report smoking but had serum cotinine levels that exceeded the defined cut point for active smoking (nondisclosure). Active smoking was defined as self-reporting smoking or having a serum cotinine concentration that exceeded the cut point for active smoking. Overall, 13.0% (95% confidence interval (CI): 8.8, 17.1) of pregnant women and 29.7% (95% CI: 27.3, 32.1) of nonpregnant women were active smokers. Nondisclosure was higher among pregnant active smokers (22.9%, 95% CI: 11.8, 34.6) than among nonpregnant smokers (9.2%, 95% CI: 7.1, 11.2). Among pregnant active smokers, nondisclosure was associated with younger age (20-24 years). Among nonpregnant active smokers, nondisclosure was associated with Mexican-American and non-Hispanic black race/ethnicity. Studies and surveillance systems that rely on self-reported smoking status are subject to underestimation of smoking prevalence, especially among pregnant women, and underreporting may vary by demographic characteristics.

Environmental tobacco smoke and pregnancy outcome.

Background: Recent reviews conclude that environmental tobacco smoke (ETS) leads to diminished birth weight. However, the threshold and magnitude of that effect is uncertain. We aimed to determine the magnitude and shape of the relations between ETS and various adverse pregnancy outcomes using a highly sensitive biochemical assay. Methods: Maternal serum specimens were collected from more than 3000 women enrolled in Californias prenatal screening program in 1992 and analyzed for cotinine. Information on pregnancy outcomes was obtained from live birth/fetal death records and hospital questionnaires. We conducted analyses on 2777 woman–live birth pairs and 19 woman–fetal death pairs in which the mother was presumed to be a nonsmoker (midtrimester cotinine levels ≤10 ng/mL). Results: In multiple logistic regression analyses, the odds ratios of fetal death, preterm delivery, and term-low birth weight were 3.4, 1.8, and 1.8, respectively, in the highest cotinine quintile (0.236–10 ng/mL), compared with the lowest quintile (<0.026 ng/mL). In adjusted linear models, there was a linear dose-dependent effect of log cotinine on mean birth weight (−109 g) and mean infant length (−0.84 cm) over the range of cotinine values. Linear relations were not found with respect to infant head circumference or the ratio of brain weight to body weight. Infants body mass index declined with exposures above approximately 0.5 ng/mL cotinine. We estimated that ETS levels at or above 0.05 ng/mL (experienced by 62% of the study population) accounted for 12% of all adverse outcomes. Conclusions: ETS exposure in pregnant women adversely affects pregnancy by increasing fetal mortality and preterm delivery at higher exposure levels and slowing fetal growth across all levels of ETS exposure.

Serum Fatty Acids and the Risk of Stroke

BACKGROUND AND PURPOSE To examine the relationship between serum fatty acids, which reflect dietary intake, and stroke, we conducted a nested case-control study of 96 men with incident stroke and 96 control subjects matched by age, clinical center, treatment group, and date of randomization who were enrolled in the Multiple Risk Factor Intervention Trial. METHODS After confirming the stability of the stored serum samples, we measured serum cholesterol ester and phospholipid fatty acid levels as the percentage of total fatty acids by gas-liquid chromatography and examined their association with incident stroke. Using stepwise conditional logistic regression that controlled for risk factors for stroke, we determined which fatty acids were independent correlates of stroke. RESULTS In univariate models, a standard deviation (SD) increase (1.37%) in phospholipid stearic acid (18:0) was associated with a 37% increase in the risk of stroke, whereas an SD increase (0.06%) in phospholipid omega-3 alpha-linolenic acid (18:3) was associated with a 28% decrease in the risk of stroke (all P < .05). Only alpha-linolenic acid in the cholesterol ester fraction was associated with the risk of stroke in multivariate models: an SD increase (0.13%) in the serum level of alpha-linolenic acid was associated with a 37% decrease in the risk of stroke (P < .05). Systolic blood pressure and cigarette smoking were also independently associated with stroke risk. CONCLUSIONS Our findings suggest that higher serum levels of the essential fatty acid alpha-linolenic acid are independently associated with a lower risk of stroke in middle-aged men at high risk for cardiovascular disease.

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 (eg, 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.

Exposure of casino employees to environmental tobacco smoke.

Environmental and medical evaluations were performed to evaluate occupational exposure to environmental tobacco smoke (ETS) among casino employees. Air concentrations of both nicotine and respirable dust were similar to those published in the literature for other non-industrial indoor environments. The geometric mean serum cotinine level of the 27 participants who provided serum samples was 1.34 nanograms per milliliter (ng/mL) (pre-shift) and 1.85 ng/mL (post-shift). Both measurements greatly exceeded the geometric mean value of 0.65 ng/mL for participants in the Third National Health and Nutrition Examination Survey (NHANES III) who reported exposure to ETS at work. This evaluation demonstrates that a sample of employees working in a casino gaming area were exposed to ETS at levels greater than those observed in a representative sample of the US population, and that the serum and urine cotinine of these employees increased during the workshift.

Carcinogen Exposure during Short-term Switching from Regular to “Light” Cigarettes

Objectives: “Light” cigarettes are extremely popular and are perceived by many smokers as less hazardous than higher-yield cigarettes. The objectives of this study were (a) to assess a battery of biomarkers of tobacco smoke exposure that includes tobacco smoke carcinogens, (b) to examine the behavioral nature of compensation, and (c) to examine the consistency of an individuals tobacco smoke exposure when smoking the same cigarette at different times. Methods: The study was a 3-week crossover study in which smokers smoked their usual cigarettes during weeks 1 and 3, and a light cigarette, with a machine-determined nicotine yield of about 50% of the usual cigarette, during week 2. Blood and urine biomarkers of exposure and subjective questionnaires were collected weekly. Results: Based on cotinine and carboxyhemoglobin levels, compensation averaged 78% and 83%, respectively. Urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-butanol, a metabolite of the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-butanone, and a number of polycyclic aromatic hydrocarbon metabolites was similar in all conditions. Compensation was accomplished both by smoking cigarettes more intensively and by smoking more cigarettes per day. Exposures to various tobacco smoke constituents while smoking the usual brand of cigarette in weeks 1 and 3 were highly correlated. Conclusion: Our findings support the idea that smokers compensate to a high degree when switched from their usual brand to a light cigarette. Short-term switching resulted in no significant reduction in carcinogen exposure. Our assessment, based on measures of biochemical exposures, supports the idea that switching to light cigarettes is unlikely to reduce the health risks of cigarette smoking.