James L. Pirkle

Biologic monitoring (i.e., biomonitoring) is used to assess human exposures to environmental and workplace chemicals. Urinary biomonitoring data typically are adjusted to a constant creatinine concentration to correct for variable dilutions among spot samples. Traditionally, this approach has been used in population groups without much diversity. The inclusion of multiple demographic groups in studies using biomonitoring for exposure assessment has increased the variability in the urinary creatinine levels in these study populations. Our objectives were to document the normal range of urinary creatinine concentrations among various demographic groups, evaluate the impact that variations in creatinine concentrations can have on classifying exposure status of individuals in epidemiologic studies, and recommend an approach using multiple regression to adjust for variations in creatinine in multivariate analyses. We performed a weighted multivariate analysis of urinary creatinine concentrations in 22,245 participants of the Third National Health and Nutrition Examination Survey (1988-1994) and established reference ranges (10th-90th percentiles) for each demographic and age category. Significant predictors of urinary creatinine concentration included age group, sex, race/ethnicity, body mass index, and fat-free mass. Time of day that urine samples were collected made a small but statistically significant difference in creatinine concentrations. For an individual, the creatinine-adjusted concentration of an analyte should be compared with a "reference" range derived from persons in a similar demographic group (e.g., children with children, adults with adults). For multiple regression analysis of population groups, we recommend that the analyte concentration (unadjusted for creatinine) should be included in the analysis with urinary creatinine added as a separate independent variable. This approach allows the urinary analyte concentration to be appropriately adjusted for urinary creatinine and the statistical significance of other variables in the model to be independent of effects of creatinine concentration.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

<h3>Objective.</h3> —To describe trends in blood lead levels for the US population and selected population subgroups during the time period between 1976 and 1991. <h3>Design.</h3> —Two nationally representative cross-sectional surveys and one cross-sectional survey representing Mexican Americans in the southwestern United States. <h3>Setting/Participants.</h3> —Participants in two national surveys that included blood lead measurements: the second National Health and Nutrition Examination Survey, 1976 to 1980 (n=9832), and phase 1 of the third National Health and Nutrition Examination Survey, 1988 to 1991 (n=12119). Also, Mexican Americans participating in the Hispanic Health and Nutrition Examination Survey, 1982 to 1984 (n=5682). <h3>Results.</h3> —The mean blood lead level of persons aged 1 to 74 years dropped 78%, from 0.62 to 0.14 μmol/L (12.8 to 2.8 μg/dL). Mean blood lead levels of children aged 1 to 5 years declined 77% (0.66 to 0.15 μmol/L [13.7 to 3.2 μg/dL]) for non-Hispanic white children and 72% (0.97 to 0.27 μmol/L [20.2 to 5.6 μg/dL]) for non-Hispanic black children. The prevalence of blood lead levels 0.48 μmol/L (10 μg/dL) or greater for children aged 1 to 5 years declined from 85.0% to 5.5% for non-Hispanic white children and from 97.7% to 20.6% for non-Hispanic black children. Similar declines were found in population subgroups defined by age, sex, race/ethnicity, income level, and urban status. Mexican Americans also showed similar declines in blood lead levels of a slightly smaller magnitude over a shorter time. <h3>Conclusions.</h3> —The results demonstrate a substantial decline in blood lead levels of the entire US population and within selected subgroups of the population. The major cause of the observed decline in blood lead levels is most likely the removal of 99.8% of lead from gasoline and the removal of lead from soldered cans. Although these data indicate major progress in reducing lead exposure, they also show that the same sociodemographic factors continue to be associated with higher blood lead levels, including younger age, male sex, non-Hispanic black race/ ethnicity, and low income level. Future efforts to remove other lead sources (eg, paint, dust, and soil) are needed but will be more difficult than removing lead from gasoline and soldered cans. (<i>JAMA</i>. 1994;272:284-291)

OBJECTIVE: To estimate the extent of exposure of the US population to environmental tobacco smoke and the contribution of the home and workplace environment to environmental tobacco smoke exposure. DESIGN: Nationally representative cross-sectional survey including questionnaire information from persons aged 2 months and older (n=16818) and measurements of serum cotinine (a metabolite of nicotine) from persons aged 4 years and older (n=10642). SETTING/PARTICIPANTS: Participants in the Third National Health and Nutrition Examination Survey, October 25, 1988, to October 21, 1991. RESULTS: Of US children aged 2 months to 11 years, 43% lived in a home with at least 1 smoker, and 37% of adult non-tobacco users lived in a home with at least 1 smoker or reported environmental tobacco smoke exposure at work. Serum cotinine levels indicated more widespread exposure to nictoine. Of non-tobacco users, 87.9% had detectable levels of serum cotinine. Both the number of smokers in the household and the hours exposed at work were significantly and independently associated (P<.001, multiple regression t test) with increased serum cotinine levels. Serum cotinine levels of children, non-Hispanic blacks, and males indicated that these groups had higher exposure to environmental tobacco smoke. Dietary variables showed no consistent association with serum cotinine levels, and dietary contribution to serum cotinine level, if any, appeared to be extremely small. CONCLUSIONS: The high proportion of the population with detectable serum cotinine levels indicates widespread exposure to environmental tobacco smoke in the US population. Both the home and workplace environments significantly contribute to environmental tobacco smoke exposure in the United States.