Chromatographic analysis of VOC patterns in exhaled breath from smokers and nonsmokers.

Cigarette smoking harms nearly every organ of the body and causes many diseases. The analysis of exhaled breath for exogenous and endogenous volatile organic compounds (VOCs) can provide fundamental information on active smoking and insight into the health damage that smoke is creating. Various exhaled VOCs have been reported as typical of smoking habit and recent tobacco consumption, but to date, no eligible biomarkers have been identified. Aiming to identify such potential biomarkers, in this pilot study we analyzed the chemical patterns of exhaled breath from 26 volunteers divided into groups of nonsmokers and subgroups of smokers sampled at different periods of withdrawal from smoking. Solid-phase microextraction technique and gas chromatography/mass spectrometry methods were applied. Many breath VOCs were identified and quantified in very low concentrations (ppbv range), but only a few (toluene, pyridine, pyrrole, benzene, 2-butanone, 2-pentanone and 1-methyldecyclamine) were found to be statistically significant variables by Mann-Whitney test. In our analysis, we did not consider the predictive power of individual VOCs, as well as the criterion of uniqueness for biomarkers suggests, but we used the patterns of the only statistically significant compounds. Probit prediction model based on statistical relevant VOCs-patterns showed that assessment of smoking status is heavily time dependent. In a two-class classifier model, it is possible to predict with high specificity and sensitivity if a subject is a smoker who respected 1 hour of abstinence from smoking (short-term exposure to tobacco) or a smoker (labelled "blank smoker") after a night out of smoking (long-term exposure to tobacco). On the other side, in our study "blank smokers" are more like non-smokers so that the two classes cannot be well distinguished and the corresponding prediction results showed a good sensitivity but low selectivity.

A prospective birth cohort study of maternal prenatal cigarette smoking assessed by self-report and biomarkers on childhood risk of overweight or obesity.

Background: Most studies on the association of in utero exposure to cigarette smoking and childhood overweight or obesity (OWO) were based on maternal self-reported smoking status, and few were based on objective biomarkers. The concordance of self-report smoking, and maternal and cord blood biomarkers of cigarette smoking as well as their effects on children's long-term risk of overweight and obesity are unclear. Methods: In this study, we analyzed data from 2351 mother-child pairs in the Boston Birth Cohort, a sample of US predominantly Black, indigenous, and people of color (BIPOC) that enrolled children at birth and followed prospectively up to age 18 years. In utero smoking exposure was measured by maternal self-report and by maternal and cord plasma biomarkers of smoking: cotinine and hydroxycotinine. We assessed the individual and joint associations of each smoking exposure measure and maternal OWO with childhood OWO using multinomial logistic regressions. We used nested logistic regressions to investigate the childhood OWO prediction performance when adding maternal and cord plasma biomarkers as input covariates on top of self-reported data. Results: Our results demonstrated that in utero cigarette smoking exposure defined by self-report and by maternal or cord metabolites was consistently associated with increased risk of long-term child OWO. Children with cord hydroxycotinine in the fourth quartile (vs. first quartile) had 1.66 (95% confidence interval [CI] 1.03-2.66) times the odds for overweight and 1.57 (95% CI 1.05-2.36) times the odds for obesity. The combined effect of maternal OWO and smoking on offspring risk of obesity is 3.66 (95% CI 2.37-5.67) if using self-reported smoking. Adding maternal and cord plasma biomarker information to self-reported data improved the prediction accuracy of long-term child OWO risk. Conclusions: This longitudinal birth cohort study of US BIPOC underscored the role of maternal smoking as an obesogen for offspring OWO risk. Our findings call for public health intervention strategies to focus on maternal smoking - as a highly modifiable target, including smoking cessation and countermeasures (such as optimal nutrition) that may alleviate the increasing obesity burden in the United States and globally.

Development of a Droplet Digital™ PCR DNA methylation detection and quantification assay of prenatal tobacco exposure.

DNA methylation is a labile modification associated with gene expression control and environmental adaptations. High throughput, scalable and quantitative assessments of specific DNA methylation modifications in complex genomic regions for use in large population studies are needed. The performance of Droplet Digital™ PCR (ddPCR™) was investigated for DNA methylation detection against next-generation bisulfite sequencing (NGS) to demonstrate the ability of ddPCR to detect and validate DNA methylation levels and complex patterns among neighboring CpGs in regions associated with prenatal tobacco exposure. While both techniques are reproducible, ddPCR demonstrates a unique advantage for high-throughput DNA methylation analysis in large-scale population studies and provides the specificity to accurately measure DNA methylation of target CpGs in complex regions.

Serum cotinine and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol levels among non-Hispanic Asian American smokers and nonsmokers as compared to other race/ethnicities: data from NHANES 2011-2012.

The objective of this study was to evaluate serum cotinine and total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol (NNAL) levels from a nationally representative sample of non-Hispanic Asian Americans as compared with other racial/ethnic groups. Data from the latest National Health and Nutrition Examination Survey for the years 2011-2012 were used for this purpose. The total sample size used was 4580. Regression models were fitted to estimate serum cotinine and urinary NNAL levels for smokers and nonsmokers aged 20 years and older adjusted for other factors that affect these levels. For nonsmokers, exposure to second hand smoke at home was associated with about 30 times higher serum cotinine levels when compared to those without such exposure (0.717 ng mL(-1) vs. 0.024 ng mL(-1), p<0.01). NNAL levels among nonsmokers with second hand smoke exposure at home were about twenty times what they were in those without such exposure (9 pg mL(-1) vs. 109 pg mL(-1), p<0.01). As compared to other racial/ethnic groups, the lowest adjusted serum cotinine levels occurred in non-Hispanic Asian smokers (92.6 ng mL(-1)) and Hispanics (84.5 ng mL(-1)) as compared to non-Hispanic whites (143.8 ng mL(-1)) and non-Hispanic blacks (158.4 ng mL(-1)). Urinary NNAL levels for smokers were in the order: non-Hispanic Asian (0.121 ng mL(-1))