The Clinical Laboratory Is an Integral Component to Health Care Delivery : An Expanded Representation of the Total Testing Process.

OBJECTIVES: Developing an expanded representation of the total testing process that includes contemporary elements of laboratory practice can be useful to understanding and optimizing testing workflows across clinical laboratory and patient care settings. METHODS: Published literature and meeting reports were used by the coauthors to inform the development of the expanded representation of the total testing process and relevant examples describing its uses. RESULTS: A visual representation of the total testing process was developed and contextualized to patient care scenarios using a number of examples covering the detection of blood culture contamination, use of next-generation sequencing, and pharmacogenetic testing. CONCLUSIONS: The expanded representation of the total testing process can serve as a model and framework to document and improve the use of clinical testing within the broader context of health care delivery. This representation recognizes increased engagement among clinical laboratory professionals with patients and other health care providers as essential to making informed decisions. The increasing use of data is highlighted as important to ensuring quality, appropriate test utilization, and sustaining an efficient workflow across clinical laboratory and patient care settings. Maintaining a properly resourced and competent workforce is also featured as an essential component to the testing process.

Effective Access to Laboratory Test Results: A Health Equity Issue that Enhances Diagnostic Excellence.

Access to laboratory test results through patient portals is a health equity issue for patients with limited English proficiency (LEP), particularly for Spanish-speaking patients, the largest minority group in the USA. Gaps ranging from linguistic, cultural, and socioeconomic disparities to lack of systematic approaches (e.g., implementation of specific support protocols, policies) are among the identified factors that limit LEP patients' access to patient portals. This paper summarizes initiatives healthcare providers, laboratory professionals, and portal developers can use to address disparities that affect >26 million LEPs while improving their health equity.

Optimal Cutoff Concentration of Urinary Cyanoethyl Mercapturic Acid for Differentiating Cigarette Smokers From Nonsmokers.

INTRODUCTION: Cotinine is a widely used biomarker for classifying cigarette smoking status. However, cotinine does not differentiate between the use of combustible and noncombustible tobacco products. The increasing use of noncombustible tobacco drives the need for a complementary biomarker for distinguishing cigarette smokers from users of noncombustible tobacco products. AIMS AND METHODS: We evaluated the urinary acrylonitrile metabolite, 2CyEMA, as a biomarker of exposure to cigarette smoke in the US population-representative data from the National Health and Nutritional Examination Survey (NHANES). Smoking status was categorized based on the recent tobacco use questionnaire. The receiver operating characteristic (ROC) curve analysis was performed to identify optimal cutoff concentrations by maximizing Youden's J index. The area under the curve (AUC) was used to compare 2CyEMA effectiveness with respect to serum cotinine. RESULTS: The overall cutoff concentration for the classification of cigarette smokers from nonsmokers was 7.32 ng/ml with high sensitivity and specificity (≥0.925). When stratified by demographic variables, the cutoff concentrations varied among subgroups based on age, sex, and race/Hispanic origin. Non-Hispanic Blacks had the highest cutoff concentration (15.3 ng/ml), and Hispanics had the lowest (4.63 ng/ml). Females had higher cutoff concentrations (8.80 ng/ml) compared to males (6.10 ng/ml). Among different age groups, the cutoff concentrations varied between 4.63 ng/ml (21-39 years old) and 10.6 ng/ml (for ≥60 years old). We also explored the creatinine adjusted cutoff values. CONCLUSIONS: 2CyEMA is an effective biomarker for distinguishing cigarette smokers from nonsmokers (users of noncombustible tobacco products or nonusers). IMPLICATIONS: Distinguishes smokers from noncombustible tobacco product users.

Characterization of the association between cigarette smoking intensity and urinary concentrations of 2-hydroxyethyl mercapturic acid among exclusive cigarette smokers in the National Health and Nutrition Examination Survey (NHANES) 2011-2016.

BACKGROUND: 2-Hydroxyethyl mercapturic acid (2HEMA, N-acetyl-S-(2-hydroxyethyl)-L-cysteine) is a urinary metabolite of several volatile organic compounds including acrylonitrile and ethylene oxide, which are found in cigarette smoke. METHODS: We measured 2HEMA concentrations in urine specimens collected during the National Health and Nutrition Examination Survey (2011-2016) from eligible participants aged >12 years (N = 7,416). We developed two multiple linear regression models to characterize the association between cigarette smoking and 2HEMA concentrations wherein the dependent variable was 2HEMA concentrations among participants who exclusively smoked cigarettes at the time of specimen collection and the independent variables included sex, age, race/ethnicity, creatinine, diet, and either cigarettes smoked per day (CPD) or serum cotinine. RESULTS: We detected 2HEMA in 85% of samples tested among exclusive cigarette smokers, and only 40% of specimens from non-smokers. When compared to exclusive cigarette smokers who smoked 1-9 CPD, smoking 10-19 CPD was associated with 36% higher 2HEMA (p < 0.0001) and smoking >19 CPD was associated with 61% higher 2HEMA (p < 0.0001). Additionally, 2HEMA was positively associated with serum cotinine. CONCLUSIONS: This study demonstrates that cigarette smoking intensity is associated with higher urinary 2HEMA concentrations and is likely a major source of acrylonitrile and/or ethylene oxide exposure.

Associations between Biomarkers of Exposure and Lung Cancer Risk among Exclusive Cigarette Smokers in the Golestan Cohort Study.

Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case-control study examining baseline levels and subsequent lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean biomarker concentrations for 28 matched cases and 52 controls for the correlation of biomarker levels among controls and for adjusted odds' ratios (ORs) for lung cancer incidence by biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and opium use. Lung cancer cases had higher average levels of most biomarkers including total nicotine equivalents (TNE-2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA). Lung cancer risk increased with concentration for several biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55), N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for opium use. Concentrations of many biomarkers were higher at the baseline for participants who subsequently developed lung cancer than among the matched controls. Odds of lung cancer were higher for several biomarkers including with adjustment for smoking exposure for some but not with adjustment for opium use.

Biomonitoring of volatile organic compounds (VOCs) among hairdressers in salons primarily serving women of color: A pilot study.

Hairdressers are exposed to volatile organic compounds (VOCs), many of which have been linked to acute and chronic health effects. Those hairdressers serving an ethnic clientele may potentially experience disproportionate exposures from frequent use of products containing VOCs or different VOC concentrations contained in products which are marketed to the specific needs of their clientele. However, no biomonitoring studies have investigated occupational exposures in this population. In the present pilot study, we sought to characterize concentrations and exposure determinants for 28 VOC biomarkers in post-shift urine samples among 23 hairdressers primarily serving an ethnic clientele. VOC biomarker concentrations among hairdressers of color were compared to concentrations among a comparison group of 17 office workers and a representative sample of women participating in the U.S. National Health and Nutrition Examination Survey. VOC biomarkers were detected in all hairdressers with higher concentrations observed among hairdressers serving a predominantly Black versus Latino clientele, and among hairdressers overall versus office workers and women in the U.S. general population. Median biomarker concentrations for acrolein,1,3-butadiene, and xylene in hairdressers were more than twice as high as those observed among office workers. Median concentrations for 1-bromopropane, acrolein and 1,3-butadiene were more than four times higher among all hairdressers compared to those reported among women in the U.S. general population. Select salon services (e.g., sister locs, flat ironing, permanent hair coloring, permanent waves or texturizing, Brazilian blowout or keratin treatment, etc.) were also associated with higher VOC biomarker concentrations among hairdressers. This pilot study represents the first biomonitoring analysis to characterize VOC exposures among women hairdressers of color and to provide evidence that this occupational population may experience elevated VOC exposures compared to women in the U.S. general population. Results from our study represent an important first step in elucidating occupational VOC exposures in this understudied occupational group. Larger studies among a racially and ethnically diverse cohort of hairdressers are warranted to confirm our findings and inform future exposure interventions in this understudied occupational population.

Harmonization of acronyms for volatile organic compound metabolites using a standardized naming system.

Increased interest in volatile organic compound (VOC) exposure has led to an increased need for consistent, systematic, and informative naming of VOC metabolites. As analytical methods have expanded to include many metabolites in a single assay, the number of acronyms in use for a single metabolite has expanded in an unplanned and inconsistent manner due to a lack of guidance or group consensus. Even though the measurement of VOC metabolites is a well-established means to investigate exposure to VOCs, a formal attempt to harmonize acronyms amongst investigators has not been published. The aim of this work is to establish a system of acronym naming that provides consistency in current acronym usage and a foundation for creating acronyms for future VOC metabolites.

Method for Accurate Quantitation of Volatile Organic Compounds in Urine Using Point of Collection Internal Standard Addition.

A method to achieve accurate measurement of unmetabolized volatile organic compounds (VOCs) in urine was developed and characterized. The method incorporates a novel preanalytical approach of adding isotopically labeled internal standard (ISTD) analogues directly to the collection container at the point of collection to compensate for analyte loss to the headspace and the collection container surfaces. Using this approach, 45 toxic VOCs ranging in water solubility and boiling point were evaluated and analyzed by headspace solid-phase microextraction/gas chromatography-mass spectrometry. Results show that urine VOCs could be equally lost to the container headspace as to the container surface suggesting similarity of these two regions as partition phases. Surface adsorption loss was found to trend with compound water solubility. In particular, with no headspace, more nonpolar VOCs experienced substantial losses (e.g., 48% for hexane) in a standard 120 mL urine cup at concentrations in the low- and sub-ppb range. The most polar VOCs evaluated (e.g., tetrahydrofuran) showed no significant loss. Other commonly practiced methods for urine sample collection and analysis such as aliquoting, specimen freezing, and use of surrogate ISTD were found to significantly bias results. With this method, we achieved errors ranging from -8.0 to 4.8% of spiked urine specimens. Paired urine and blood specimens from cigarette smokers were compared to assess this method.

Assessment of Serum Concentrations of 12 Aldehydes in the U.S. Population from the 2013-2014 National Health and Nutrition Examination Survey.

Aldehydes are known carcinogens and irritants that can negatively impact health. They are present in tobacco smoke, the environment, and food. The prevalence of aldehyde exposure and potential health impact warrants a population-wide study of serum aldehydes as exposure biomarkers. We analyzed 12 aldehydes in sera collected from 1843 participants aged 12 years or older in the 2013-2014 National Health and Nutrition Examination Survey. Several aldehydes were detected at high rates, such as isopentanaldehyde (99.2%) and propanaldehyde (88.3%). We used multiple linear regression models to examine the impact of tobacco smoke and dietary variables on serum concentrations of isopentanaldehyde and propanaldehyde. Although 12 serum aldehydes were analyzed and compared to tobacco smoke exposure, only isopentanaldehyde and propanaldehyde showed any significant association with tobacco smoke exposure. Survey participants who smoked 1-10 cigarettes per day (CPD) had 168% higher serum isopentanaldehyde and 28% higher propanaldehyde compared with nonusers. Study participants who smoked 11-20 CPD had higher serum isopentanaldehyde (323%) and propanaldehyde (70%). Similarly, study participants who smoked >20 CPD had 399% higher serum isopentanaldehyde and 110% higher serum propanaldehyde than nonexposed nonusers. The method could not, however, differentiate between nonexposed nonusers and nonusers exposed to secondhand smoke for either of these two aldehydes. No dietary variables were consistently predictive of serum isopentanaldehyde and propanaldehyde concentrations. This report defines baseline concentrations of serum aldehydes in the U.S. population and provides a foundation for future research into the potential health effects of aldehydes. In addition, this study suggests that tobacco smoke is a significant source of exposure to some aldehydes such as isopentanaldehyde and propanaldehyde.

Exposure to 1,3-Butadiene in the U.S. Population: National Health and Nutrition Examination Survey 2011-2016.

1,3-Butadiene is a volatile organic compound with a gasoline-like odour that is primarily used as a monomer in the production of synthetic rubber. The International Agency for Research on Cancer has classified 1,3-butadiene as a human carcinogen. We assessed 1,3-butadiene exposure in the U.S. population by measuring its urinary metabolites N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (34HBMA), N-acetyl-S-(1-hydroxymethyl-2-propenyl)-L-cysteine (1HMPeMA), N-acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine (2HBeMA), and N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (4HBeMA). Urine samples from the 2011 to 2016 National Health and Nutrition Examination Survey were analysed for 1,3-butadiene metabolites using ultrahigh-performance liquid chromatography/tandem mass spectrometry. 34HBMA and 4HBeMA were detected in >96% of the samples; 1HMPeMA and 2HBeMA were detected in 0.66% and 9.84% of the samples, respectively. We used sample-weighted linear regression models to examine the influence of smoking status (using a combination of self-reporting and serum-cotinine data), demographic variables, and diet on biomarker levels. The median 4HBeMA among exclusive smokers (31.5 µg/g creatinine) was higher than in non-users (4.11 µg/g creatinine). Similarly, the median 34HBMA among exclusive smokers (391 µg/g creatinine) was higher than in non-users (296 µg/g creatinine). Furthermore, smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was associated with 475%, 849%, and 1143% higher 4HBeMA (p < 0.0001), respectively. Additionally, smoking 1-10, 11-20, and >20 CPD was associated with 33%, 44%, and 102% higher 34HBMA (p < 0.0001). These results provide significant baseline data for 1,3-butadiene exposure in the U.S. population, and demonstrate that tobacco smoke is a major exposure source.

Acrolein and other toxicant exposures in relation to cardiovascular disease among marijuana and tobacco smokers in a longitudinal cohort of HIV-positive and negative adults.

BACKGROUND: Marijuana smoke contains some of the same toxicants present in tobacco smoke. Marijuana smoking is prevalent among HIV+ individuals, but few studies have characterized smoke-related toxicants or associated health outcomes in exclusive marijuana users. METHODS: This longitudinal study included 245 participants over age 40 (76% HIV+). 33 plasma and 28 urine metabolites of nicotine, ∆-9-trans-tetrahydrocannabinol, polycyclic aromatic hydrocarbons, and volatile organic compounds were assayed by liquid or gas chromatography/mass spectrometry. Exposures and health outcomes were assessed from surveys and medical records. FINDINGS: At baseline, 18% of participants were marijuana-only smokers, 20% tobacco-only smokers, and 24% dual marijuana-tobacco smokers (median (IQR) age 53 (47-60) years, 78% male, 54% white race). Marijuana smoking was independently associated with elevated plasma naphthalenes, 2-hydroxyfluorene sulfate, 4-vinylphenol sulfate, and o-cresol sulfate (p<0·05) and urine acrylonitrile and acrylamide metabolites (p<0·05), but levels were lower than those associated with tobacco smoking. Acrolein metabolite N-Acetyl-S-(3-hydroxypropyl)-l-cysteine (3HPMA) was significantly elevated in plasma and urine in tobacco-only and dual but not marijuana-only smokers, and correlated with nicotine metabolites (p<0·05). The highest tertile of 3HPMA was associated with increased cardiovascular disease diagnoses independent of tobacco smoking, traditional risk factors, and HIV status (odds ratio [95% CI] 3·34 [1·31-8·57]; p = 0·012). INTERPRETATION: Smoke-related toxicants, including acrylonitrile and acrylamide metabolites, are detectable in exclusive marijuana smokers, but exposures are lower compared with tobacco or dual smokers. Acrolein exposure is increased by tobacco smoking but not exclusive marijuana smoking in HIV+ and HIV- adults, and contributes to cardiovascular disease in tobacco smokers. FUNDING: U.S. NIH.

Characterization of acrylonitrile exposure in the United States based on urinary n-acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA): NHANES 2011-2016.

BACKGROUND: Acrylonitrile is a possible human carcinogen that is used in polymers and formed in tobacco smoke. We assessed acrylonitrile exposure in the US population by measuring its urinary metabolites N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (2CYEMA) and N-acetyl-S-(1-cyano-2-hydroxyethyl)-L-cysteine (1CYHEMA) in participants from the 2011-2016 National Health and Nutrition Examination Survey. OBJECTIVE: To assessed acrylonitrile exposure using population-based biomonitoring data of the US civilian, non-institutionalized population. METHODS: Laboratory data for 8057 participants were reported for 2CYEMA and 1CYHEMA using ultrahigh-performance liquid chromatography/tandem mass spectrometry. Exclusive tobacco smokers were distinguished from non-users using a combination of self-reporting and serum cotinine data. We used multiple linear regression models to fit 2CYEMA concentrations with sex, age, race/Hispanic origin, and tobacco user group as predictor variables. RESULTS: The median 2CYEMA level was higher for exclusive cigarette smokers (145 µg/g creatinine) than for non-users (1.38 µg/g creatinine). Compared to unexposed individuals (serum cotinine ≤0.015 ng/ml) and controlling for confounders, presumptive second-hand tobacco smoke exposure (serum cotinine >0.015 to ≤10 ng/ml and 0 cigarettes per day, CPD) was significantly associated with 36% higher 2CYEMA levels (p < 0.0001). Smoking 1-10 CPD was significantly associated with 6720% higher 2CYEMA levels (p < 0.0001). SIGNIFICANCE: We show that tobacco smoke is an important source of acrylonitrile exposure in the US population and provide important biomonitoring data on acrylonitrile exposure.

Characterization of US population levels of urinary methylcarbamoyl mercapturic acid, a metabolite of N,N-dimethylformamide and methyl isocyanate, in the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2011-2016.

Methylcarbamoyl mercapturic acid (MCAMA, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine) is a urinary metabolite of N,N-dimethylformamide and methyl isocyanate, which are volatile organic compounds that are harmful to humans. N,N-dimethylformamide exposure causes liver damage, and methyl isocyanate inhalation damages the lining of the respiratory tract, which can increase risk of chronic obstructive pulmonary disease and asthma. This study characterizes urinary MCAMA levels in the US population and explores associations of MCAMA concentrations with select demographic and environmental factors. We used liquid chromatography tandem mass spectrometry to measure MCAMA in urine collected from study participants ≥ 12 years old (N = 8272) as part of the National Health and Nutrition Examination Survey 2005-2006 and 2011-2016. We produced multiple regression models with MCAMA concentrations as the dependent variable and sex, age, fasting time, race/ethnicity, diet, and cigarette smoking as independent variables. Cigarette smokers and nonsmokers had median urinary MCAMA concentrations of 517 µg/g creatinine and 127 µg/g creatinine, respectively. Sample-weighted multiple regression analysis showed that MCAMA was positively associated with serum cotinine (p < 0.0001). Compared to non-exposed participants (serum cotinine ≤ 0.015 ng/mL), presumptive exposure to second-hand tobacco smoke (serum cotinine > 0.015-≤ 10 ng/mL and 0 cigarettes smoked per day) was associated with 20% higher MCAMA (p < 0.0001). Additionally, smoking 1-10 cigarettes per day was associated with 261% higher MCAMA (p < 0.0001), smoking 11-20 cigarettes per day was associated with 357% higher MCAMA (p < 0.0001), and smoking > 20 cigarettes per day was associated with 416% higher MCAMA (p < 0.0001). These findings underscore the strong association of tobacco smoke exposure with urinary MCAMA biomarker levels.

Large Differences in Urinary Benzene Metabolite S-Phenylmercapturic Acid Quantitation: A Comparison of Five LC-MS-MS Methods.

Benzene is a known genotoxic carcinogen linked to many hematological abnormalities. S-phenylmercapturic acid (PHMA, N-acetyl-S-(phenyl)-L-cysteine, CAS# 4775-80-8) is a urinary metabolite of benzene and is used as a biomarker to assess benzene exposure. Pre-S-phenylmercapturic acid (pre-PHMA) is a PHMA precursor that dehydrates to PHMA at acidic pH. Published analytical methods that measure urinary PHMA adjust urine samples to a wide range of pH values using several types of acid, potentially leading to highly variable results depending on the concentration of pre-PHMA in a sample. Information is lacking on the variation in sample preparation among laboratories regularly measuring PHMA and the effect of those differences on PHMA quantitation in human urine samples. To investigate the differences in PHMA quantitation, we conducted an inter-laboratory comparison that included the analysis of 50 anonymous human urine samples (25 self-identified smokers and 25 self-identified non-smokers), quality control samples and commercially available reference samples in five laboratories using different analytical methods. Observed urinary PHMA concentrations were proportionally higher at lower pH, and results for anonymous urine samples varied widely among the methods. The method with the neutral preparation pH yielded results about 60% lower than the method using the most acidic conditions. Samples spiked with PHMA showed little variation, suggesting that the variability in results in human urine samples across methods is driven by the acid-mediated conversion of pre-PHMA to PHMA.

Examination of xylene exposure in the U.S. Population through biomonitoring: NHANES 2005-2006, 2011-2016.

Aim: Xylenes are aromatic hydrocarbons used for industrial applications such as the production of petrochemicals and plastics. Acute xylene exposures can negatively impact health through neurotoxicity and irritation of respiratory and dermal tissues. We quantified urinary biomarkers of xylene exposure [2-methylhippuric acid (2MHA) and a mixture of 3- and 4-methylhippuric acids (34MH)] in a representative sample of the U.S. population. Methods: Spot urine obtained during the National Health and Nutrition Examination Survey 2005-2006 and 2011-2016 was analysed using ultra-high-performance liquid chromatography/tandem mass spectrometry. Exclusive smokers were distinguished from non-users using a combination of self-report and serum cotinine data. Results: The median 2MHA and 34MH levels were higher for exclusive smokers (100 µg/g and 748 µg/g creatinine, respectively) than for non-users (27.4 µg/g and 168 µg/g creatinine, respectively). Participants who smoked cigarettes had significantly higher 2MHA and 34MH levels (p < 0.0001) than unexposed participants. Smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was significantly associated with 181%, 339% and 393% higher 2MHA levels, respectively. For 34MH, smoking 1-10, 11-20, and >20 CPD was significantly associated with 201%, 398%, and 471% higher 34MH levels, respectively. Conclusion: We confirm that tobacco smoke is a significant source of xylene exposure as measured by urinary 2MHA and 34MH levels.

Quantification of seven microbial volatile organic compounds in human serum by solid-phase microextraction gas chromatography-tandem mass spectrometry.

Microbial volatile organic compounds (MVOCs) are primary and secondary metabolites of fungal and bacterial growth. Changes in environmental conditions (e.g., humidity, light, oxygen, and carbon dioxide) influence microbial growth in indoor environments. Prolonged human exposure to MVOCs has been directly associated with sick building syndrome (SBS), respiratory irritation, and asthma-like symptoms. However, no method exists for assessing MVOC exposure by quantifying them in human serum. We developed a novel, high-throughput automated method for quantifying seven MVOCs (3-methylfuran, 2-hexanone, 2-heptanone, 3-octanone, 1-octen-3-ol, 2-ethyl-1-hexanol, and geosmin) in human serum. The method quantifies the target analytes using solid-phase microextraction gas chromatography-tandem mass spectrometry at low parts-per-billion levels. Limits of detection ranged from 0.076 to 2.77 µg/L. This method provides excellent linearity over the concentration range for the analytes, with coefficients of determination >0.992. Recovery in human serum was between 84.5% and 113%, and analyte precision ranged from 0.38% to 8.78%. The intra-day and inter-day reproducibility showed coefficients of variation ≤11% and ≤8%, respectively. Accurate and precise quantification of MVOCs is necessary for detecting and quantifying harmful human exposures in environments with active microbial growth. The method is well suited for high-throughput analysis to aid investigations of unhealthy exposures to microbial emissions.

Harmonizing Newborn Screening Laboratory Proficiency Test Results Using the CDC NSQAP Reference Materials.

Newborn screening (NBS) laboratories cannot accurately compare mass spectrometry-derived results and cutoff values due to differences in testing methodologies. The objective of this study was to assess harmonization of laboratory proficiency test (PT) results using quality control (QC) data. Newborn Screening Quality Assurance Program (NSQAP) QC and PT data reported from 302 laboratories in 2019 were used to compare results among laboratories. QC materials were provided as dried blood spot cards which included a base pool and the base pool enriched with specific concentrations of metabolites in a linear range. QC data reported by laboratories were regressed on QC data reported by the Centers for Disease Control and Prevention (CDC), and laboratory's regression parameters were used to harmonize their PT result. In general, harmonization tended to reduce overall variation in PT data across laboratories. The metabolites glutarylcarnitine (C5DC), tyrosine, and phenylalanine were displayed to highlight inter- and intra-method variability in NBS results. Several limitations were identified using retrospective data for harmonization, and future studies will address these limitations to further assess feasibility of using NSQAP QC data to harmonize PT data. Harmonizing NBS data using common QC materials appears promising to aid result comparison between laboratories.

Biomarkers of Exposure among USA Adult Hookah Users: Results from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2014).

Hookah smoking has become common in the USA, especially among young adults. This study measured biomarkers of exposure to known tobacco product toxicants in a population-based sample of exclusive, established hookah users. Urinary biomarker data from 1753 adults in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study were used to compare geometric mean concentrations of biomarkers of exposure in exclusive, established past 30-day hookah users to never users of tobacco. Geometric mean ratios were calculated comparing hookah user groups with never users adjusting for age, sex, race/ethnicity, education, past 30-day marijuana use, secondhand smoke exposure and creatinine. Past 30-day hookah users (n = 98) had 10.6 times the urinary cotinine level of never tobacco users. Compared to never tobacco users, past 30-day hookah users had 2.3 times the level of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 1.3 times higher polycyclic aromatic hydrocarbons (PAHs) 3-hydroxyfluorene and 1-hydroxypyrene, 1.8 times higher levels of acrylonitrile, 1.3 times higher levels of acrylamide, and 1.2 times higher levels of acrolein exposure. These data indicate that hookah use is a significant source of exposure to nicotine, carcinogens, and respiratory toxicants.

Quantification of Seven Terpenes in Human Serum by Headspace Solid-Phase Microextraction-Gas Chromatography-Tandem Mass Spectrometry.

Terpenes are a class of volatile organic hydrocarbons commonly produced by vegetation and released into the atmosphere. These compounds are responsible for the scents of pine forests, citrus fruits, and some flowers. Human terpene exposure can come from inhalation, diet, smoking, and more recently, using e-cigarettes. Terpenes are present in tobacco smoke and are used as flavor chemicals in e-liquids. The health effects of terpenes are not widely known, though several studies have suggested that they may prove useful in future medical applications. We have developed a novel, high-throughput method of quantifying seven terpenes (α-pinene, ß-pinene, ß-myrcene, 3-carene, limonene, ß-caryophyllene, and α-humulene) in human serum to aid human-exposure investigations. This method employs headspace sampling using solid-phase microextraction (SPME) coupled to gas chromatography-tandem mass spectrometry to detect and quantify five monoterpenes and two sesquiterpenes in the low parts-per-trillion to low parts-per-billion range. The intraday and interday variability (percent error) of the method are ≤2 and ≤11%, respectively. In addition, this method showed excellent recovery in human serum (between 80 and 120% for all analytes). The assay precision ranges between 4.0 and 11%. Limits of detection ranged between 0.032 and 0.162 µg/L. Using serum cotinine values to classify tobacco use showed that smokers have higher serum concentrations of six terpenes compared to nonusers. Terpene concentrations were 14-78% higher in smokers than nonusers. Our method can provide essential biomonitoring data to establish baseline exposure levels for terpenes in humans.