Withdrawal from repeated nicotine vapor exposure increases somatic signs of physical dependence, anxiety-like behavior, and brain reward thresholds in adult male rats.

In recent years, there has been a dramatic increase in nicotine vapor consumption via electronic nicotine delivery systems (i.e., e-cigarettes), particularly in adolescents. While recent work has focused on the health effects of nicotine vapor exposure, its effects on the brain and behavior remain unclear. In this study, we assessed the effects that cessation from repeated nicotine vapor exposure had on behavioral and neuronal measures of withdrawal. For Experiment 1, fifty-six adult male rats were tested for plasma cotinine levels, somatic withdrawal signs, and anxiety-like behavior in the elevated plus maze, immediately following precipitated withdrawal from repeated exposure to 12 or 24 mg/mL nicotine vapor. In Experiment 2, twelve adult male rats were tested for intracranial self-stimulation (ICSS) across 14 days of exposure to 24 mg/mL nicotine vapor and across the 14 days immediately following nicotine exposure. Results revealed that plasma cotinine, somatic signs, anxiety-like behavior, and ICSS stimulation thresholds were all observed to be elevated during withdrawal in the 24 mg/mL nicotine group, when compared to vehicle controls (50/50 vegetable glycerin/propylene glycol). The data suggest that cessation from repeated nicotine vapor exposure using our preclinical model leads to nicotine dependence and withdrawal, and demonstrates that the vapor system described in these experiments is a viable pre-clinical model of e-cigarette use in humans. Further characterization of the mechanisms driving nicotine vapor abuse and dependence is needed to improve policies and educational campaigns related to e-cigarette use.

Prenatal exposure to persistent organic pollutants and metals and problematic child behavior at 3–5 years of age: a Greenlandic cohort study

High levels of persistent organic pollutants (POPs) and heavy metals are found in Arctic populations. POP and heavy metals are linked to impaired cognitive development. This study examined associations between prenatal POP and metals exposure and problematic child behavior using the Strength and Difficulties Questionnaire (SDQ). POPs and metals were measured in 102 pregnant Greenlandic women. During follow-up at 3–5 years, parents answered an assisted questionnaire including children’s SDQ scores. Associations were analyzed using linear and logistic regression analyses and adjusted for maternal plasma cotinine, educational level and age at delivery. In the adjusted analyses, the medium tertile of hexachlorobenzene (β = 3.06, p = 0.010), β-hexachlorocyclohexane (β = 3.58, p = 0.004) and trans-nonachlor (β = 2.06, p = 0.082) were positively associated with SDQ scores. The continuous cis-nonachlor (OR = 1.09, p = 0.079), dichloro-diphenyl-dichloroethylene (OR = 1.01, p = 0.077), trans-nonachlor (OR = 1.01, p = 0.091), and sum Organochlorine-Pesticides (OR = 1.00, p = 0.094) were positively associated with abnormal SDQ score and the continuous mirex (OR = 1.28, p = 0.096), oxychlordane (OR = 1.04, p = 0.066), and trans-nonachlor (OR = 1.02, p = 0.071) with abnormal hyperactivity score. We found no consistent evidence of associations between polychlorinated biphenyls, perfluoroalkylated substances and heavy metals and problematic behavior. Prenatal organochlorine pesticide exposure associated significantly with problematic behavior in 3–5 year old children.

Plasma Cotinine Is Positively Associated with Homocysteine in Smokers but Not in Users of Smokeless Tobacco

Plasma total homocysteine (tHcy) is a risk marker, and smoking is an established risk factor for cardiovascular disease. It is unclear if the effect of smoked tobacco on homocysteine is mediated by nicotine or other combustion products in smoked tobacco. Snus (moist smokeless tobacco) is high nicotine-containing tobacco, and little is known about the effect of snus on plasma homocysteine. Therefore, we studied, in a cross-section of subjects (n = 1375) from the Northern Sweden Health and Disease Study, with strictly defined current smokers (n = 194) and snus users (n = 47), the impact of tobacco exposure on tHcy, assessed by self-reported tobacco habits and plasma cotinine concentrations. The snus users had higher cotinine concentrations than the smokers. Cotinine, creatinine, methylmalonic acid, and the methylenetetrahydrofolate reductase genotype (MTHFR) T allele were positively associated with tHcy among the smokers, but not among the snus users. No association was observed between tHcy and the number of cigarettes/day. There was a positive association between cotinine and tHcy in the smokers, but not among the snus users. This indicates that substances other than nicotine in tobacco smoke could be responsible for the differential effects on homocysteine status. Self-reported smoking should be complemented by a cotinine assay whenever possible.

Association between educational level and smoking cessation in an 11-year follow-up study of a national health survey

Aims: There is a lack of longitudinal, population-based studies on the association between education and smoking cessation. A more thorough examination of this association is needed to address inequalities in smoking. Methods: The longitudinal Health 2000 Survey and Health 2011 Survey, representing the Finnish population aged ⩾30 years, were analysed. Of the 1352 baseline daily smokers, 945 (70%) provided a smoking status at the follow-up. The analytic sample size was 884 (excluding the follow-up occasional smokers). Self-reported questionnaire data and measurements (e.g. plasma cotinine) from the baseline were utilised. The outcome variable was smoking cessation at the follow-up, and the main explanatory variable was education. Logistic regression was the main method for statistical analyses. All of the analyses accounted for the sampling design. Results: At the follow-up, 28% of the baseline daily smokers had quit smoking. An adjusted regression model showed that highly educated respondents had a higher likelihood of quitting smoking compared with those with basic education. Controlling for demographic and health-related variables had a modest effect on this association. Higher scores for plasma cotinine, symptoms of depression and heavy alcohol use were associated with a lower likelihood of quitting smoking. The association between education and smoking cessation was weaker for women than it was for men. Conclusions: High education is associated with smoking cessation among the general adult population, especially among men. A higher plasma cotinine level is strongly associated with continued smoking among both sexes. Background variables only modestly affected the association between education and smoking cessation.

Robust Tobacco Smoking Self-Report in two Cohorts of Vulnerable Pregnant Women and Adults

BackgroundStigma associated with tobacco smoking, especially during pregnancy, may lead to underreporting and possible bias in studies relying on self-reported smoking data. Cotinine, a nicotine metabolite with a ∼20h half-life in blood, is often used as a biomarker of smoking. The objective of this study was to examine the concordance between self-reported smoking and plasma cotinine concentration among participants enrolled in two related cohorts of vulnerable individuals: human immunodeficiency virus (HIV)-positive and HIV-negative pregnant women enrolled in the CARMA-PREG cohort and HIV-positive and HIV-negative non-pregnant women and men enrolled in the CARMA-CORE cohort.MethodsFor HIV-positive (n=76) and negative (n=24) pregnant women, plasma cotinine was measured by ELISA in specimens collected during the third trimester, between 28 and 38 weeks of gestation. Plasma cotinine was also measured in HIV-positive (n=43) and negative (n=57) women and men enrolled in the CARMA-CORE cohort.ResultsSelf-reported smokers were more likely to have low income (p<0.001) in both cohorts, and to deliver preterm (p=0.007) in CARMA-PREG. In the CARMA-PREG cohort, concordance between plasma cotinine was 95% for self-reported smoking, and 89% for self-reported non-smoking. In the CARMA-CORE cohort we observed similarly high concordances of 96% and 92% for self-reported smoking and non-smoking, respectively. In this sample, the odds of discordance between self-reported smoking status and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others. Taken together, the overall concordance between plasma cotinine and self-reported data was 94% with a Cohen’s kappa coefficient of 0.860 among all participants.ConclusionsGiven the high proportion of vulnerable people in the CARMA-PREG and CARMA-CORE cohorts, our results may not be fully generalizable to the general population. However, they demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report data.ImplicationsReliable self-reported smoking data is necessary to account for smoking status in subsequent studies. Our results suggest that future studies should ensure that study participants feel sale to speak candidly to non-judgemental research staff to obtain reliable self-report data.

Prenatal tobacco exposure and ADHD symptoms at pre-school age: the Hokkaido Study on Environment and Children’s Health

Background There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated. Methods This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children’s Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n = 3216). Cotinine levels were categorized into 4 groups; ≦ 0.21 ng/ml (non-smoker), 0.22–0.51 ng/ml (low-passive smoker), 0.52–11.48 ng/ml (high-passive smoker), and ≧ 11.49 ng/ml (active smoker). Results Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys. Conclusion Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.

Association between maternal passive smoking and increased risk of delivering small-for-gestational-age infants at full-term using plasma cotinine levels from The Hokkaido Study: a prospective birth cohort

ObjectivesTo investigate the association between plasma cotinine level measured at the 8th gestational month and the delivery of small-for-gestational-age (SGA) infants, using a highly sensitive ELISA method.DesignProspective birth cohort study from The Hokkaido Study on Environment and Children’s Health.SettingHokkaido, Japan.ParticipantsOur sample included 15 198 mother-infant pairs enrolled in 2003–2012.Main outcome measuresSGA, defined as a gestational age-specific weight Z-score below −2.ResultsThe number of SGA infants was 192 (1.3%). The cotinine cut-off level that differentiated SGA infants from other infants was 3.03 ng/mL for both the total population and the full-term births subgroup (sensitivity 0.307; positive predictive value 2.3%). Compared with infants of mothers with a plasma cotinine level of <3.03 ng/mL, infants of mothers with a plasma cotinine level of ≥3.03 ng/mL showed an increased OR for SGA in the total population and the full-term infant group (2.02(95% CI 1.45 to 2.83) and 2.44(95% CI 1.73 to 3.44), respectively).ConclusionA plasma cotinine level of ≥3.03 ng/mL, which included both passive and active smokers, was associated with an increased risk of SGA. This finding is of important relevance when educating pregnant women about avoiding prenatal passive and active smoking due to the adverse effects on their infants, even those born at full-term.