PMID: 

Chem Res Toxicol. 2019 Jun 17 ;32(6):1241-1249. Epub 2019 May 23. PMID: 31079450

Abstract Title: 

Sucralose-Enhanced Degradation of Electronic Cigarette Liquids during Vaping.

Abstract: 

Electronic cigarette liquids (e-liquids) with sweetener additives such as sucralose, a synthetic chlorinated disaccharide, are popular among some e-cigarette consumers; sucralose can be added either by the manufacturer or by the consumer. The prevalence of sucralose in commercial e-liquids is not known, nor is the typical concentration of sucralose when present; labels are not required to disclose ingredient information. Here, we report the effects of sucralose on e-liquid degradation upon e-cigarette vaping as studied usingH NMR spectroscopy, ion chromatography, and gas chromatography coupled with detection by mass spectrometry or flame ionization detector. Sucralose was found to be subject to degradation when included in propylene glycol + glycerol based e-liquids and vaped; the presence of sucralose in the e-liquids also resulted in altered and enhanced solvent degradation. In particular, production of aldehydes (carbonyls) and hemiacetals (which have implications for health) was enhanced, as demonstrated byH NMR. The presence of sucralose at 0.03 mol % (0.14 wt %) in an e-liquid also resulted in production of potentially harmful organochlorine compounds and catalyzed the cyclization of aldehydes with solvents to acetals upon vaping; the presence of chloride in e-liquid aerosols was confirmed by ion chromatography. Quantities of sucralose as low as 0.05 mol % (0.24 wt %) in e-liquids lead to significant production of solvent degradation products.

read more

PMID: 

Chem Res Toxicol. 2019 Jun 17 ;32(6):982-985. Epub 2019 May 29. PMID: 31117350

Abstract Title: 

Common E-Cigarette Flavoring Chemicals Impair Neutrophil Phagocytosis and Oxidative Burst.

Abstract: 

E-cigarette flavorings have not been thoroughly evaluated for inhalational toxicity. We have shown that the flavoring chemical cinnamaldehyde impairs human neutrophils, macrophages, and natural killer cells. Here we investigated the effects of other common e-liquid flavoring chemicals on phagocytosis and oxidative burst in neutrophils. We demonstrate that cinnamaldehyde and ethyl vanillin dose-dependently decrease oxidative burst and that benzaldehyde and benzaldehyde propylene glycol acetal dose-dependently impair phagocytosis. Isoamyl acetate did not affect either measure of neutrophil function. These data suggest that inhaling aromatic aldehydic flavoring chemicals, such as cinnamaldehyde, benzaldehyde, benzaldehyde propylene glycol acetal, or ethyl vanillin, could impair neutrophil function.

read more

PMID: 

J Am Heart Assoc. 2019 Jun 18 ;8(12):e012317. Epub 2019 Jun 5. PMID: 31165662

Abstract Title: 

Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health.

Abstract: 

Background E-cigarettes are popular for smoking cessation and as an alternative to combustible cigarettes. We assess the association between e-cigarette use and having had a myocardial infarction ( MI ) and whether reverse causality can explain the observed cross-sectional association between e-cigarette use and MI . Methods and Results Cross-sectional analysis of the Population Assessment of Tobacco and Health Wave 1 for association between e-cigarette use and having had and MI . Longitudinal analysis of Population Assessment of Tobacco and Health Waves 1 and 2 for reverse causality analysis. Logistic regression was performed to determine the associations between e-cigarette initiation and MI , adjusting for cigarette smoking, demographic and clinical variables. Every-day (adjusted odds ratio, 2.25, 95% CI : 1.23-4.11) and some-day (1.99, 95% CI : 1.11-3.58) e-cigarette use were independently associated with increased odds of having had an MI with a significant dose-response ( P0.62), suggesting that reverse causality cannot explain the cross-sectional association between e-cigarette use and MI observed at Wave 1. Conclusions Some-day and every-day e-cigarette use are associated with increased risk of having had a myocardial infarction, adjusted for combustible cigarette smoking. Effect of e-cigarettes are similar as conventional cigarette and dual use of e-cigarettes and conventional cigarettes at the same time is risker than using either product alone.

read more

PMID: 

Ann N Y Acad Sci. 2019 Sep ;1452(1):65-77. Epub 2019 Jul 17. PMID: 31317551

Abstract Title: 

Impact of maternal e-cigarette vapor exposure on renal health in the offspring.

Abstract: 

Maternal smoking during pregnancy is a significant risk factor of renal pathology in the offspring. E-cigarettes are perceived to be a safe option and are increasingly used by pregnant women either continuously during pregnancy or as a replacement for tobacco cigarettes. This study aimed to determine the effects of replacing tobacco cigarettes with e-cigarettes during pregnancy, and continuous e-cigarette use during pregnancy on the offspring's kidneys. Female Balb/c mice were exposed to either air (sham) or tobacco cigarette smoke (SE) for 6 weeks prior to mating, during gestation and lactation. A subset of the"SE group"received e-cigarette vapor (containing nicotine) after mating until pups weaned. Additional female mice were continuously exposed to e-vapor (either with or without nicotine) for 6 weeks prior to mating until pups weaned. Kidneys and urine from the male offspring were assessed at postnatal day 1, day 20 (weaning), and 13 weeks of age (adulthood). E-cigarette replacement was less detrimental to renal development and albuminuria than continuous SE during pregnancy. However, continuous e-vapor exposure during pregnancy increased markers of oxidative stress, inflammation, and fibrosis in the adult offspring, independent of nicotine. E-cigarette use during pregnancy confers future risk to the offspring's kidneys.

read more

PMID: 

Int J Environ Res Public Health. 2019 07 11 ;16(14). Epub 2019 Jul 11. PMID: 31373329

Abstract Title: 

E-cigarette Aerosol Condensate Enhances Metabolism of Benzo(a)pyrene to Genotoxic Products, and Induces CYP1A1 and CYP1B1, Likely by Activation of the Aryl Hydrocarbon Receptor.

Abstract: 

E-cigarette aerosol contains lower levels of most known carcinogens than tobacco smoke, but many users of e-cigarettes are also smokers, and these individuals may be vulnerable to possible promoting and/or cocarcinogenic effects of e-cigarettes. We investigated the possibility that a condensate of e-cigarette aerosol (EAC) enhances the metabolism of the tobacco carcinogen, benzo(a)pyrene (BaP), to genotoxic products in a human oral keratinocyte cell line. Cells were pretreated with EAC from two popular e-cigs and then with BaP. Metabolism to its ultimate carcinogenic metabolite, anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro B[a]P (BPDE), was assayed by measuring isomers of its spontaneous hydrolysis products, BaP tetrols. The pretreatment of cells with EAC enhanced the rate of BaP tetrol formation several fold. Pretreatment with the e-liquid resulted in a smaller enhancement. The treatment of cells with EAC induced CYP1A1/1B1 mRNA and protein. The enhancement of BaP tetrol formation was inhibited by the aryl hydrocarbon receptor (AhR) inhibitor,α-napthoflavone, indicating EAC likely induces CYP1A1/1B1 and enhances BaP metabolism by activating the AhR. To our knowledge, this is first report demonstrating that e-cigarettes can potentiate the genotoxic effects of a tobacco smoke carcinogen.

read more

PMID: 

Am J Respir Crit Care Med. 2019 Aug 7. Epub 2019 Aug 7. PMID: 31390877

Abstract Title: 

Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung.

Abstract: 

RATIONALE: Proteolysis is a key aspect of the lung's innate immune system. Proteases, including neutrophil elastase and matrix metalloproteases (MMPs), modulate cell signaling, inflammation, tissue remodeling and leukocyte recruitment via cleavage of their target proteins. Excessive proteolysis occurs with chronic tobacco use and is causative for bronchiectasis and emphysema. The effect of e-cigarettes (vaping) on proteolysis is unknown.OBJECTIVES: We used protease levels as biomarkers of harm to determine the impact of vaping on the lung.METHODS: We performed research bronchoscopies on healthy non-smokers, cigarette smokers and e-cigarette users (vapers) and determined protease levels in bronchoalveolar lavage (BAL). In parallel, we studied the effects of e-cigarette components on protease secretion in isolated human blood neutrophils and BAL-derived macrophages. We also analyzed the nicotine concentration in induced sputum and BAL.MEASUREMENTS AND MAIN RESULTS: Neutrophil elastase, MMP-2 and MMP-9 activities/protein levels were equally elevated in both vapers' and smokers' BAL relative to non-smokers. In contrast, antiprotease levels were unchanged. We also found that exposure of isolated neutrophils and macrophages to nicotine elicited dose-dependent increases in protease release. After vaping, measurable levels of nicotine were detectable in sputum and BAL, which corresponded to the EC50s for protease release seen in immune cells.CONCLUSIONS: We conclude that vaping induces nicotine-dependent protease release from resident pulmonary immune cells. Thus, chronic vaping disrupts the protease-antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease. These data indicate that vaping may not be safer than tobacco smoking.

read more

PMID: 

Lung. 2019 Aug 28. Epub 2019 Aug 28. PMID: 31463548

Abstract Title: 

Electronic Cigarette Advertising Impacts Adversely on Smoking Behaviour Within a London Student Cohort: A Cross-Sectional Structured Survey.

Abstract: 

INTRODUCTION: In contrast to tobacco smoking, electronic cigarette ("vaping") advertisement had been approved in the United Kingdom (UK) in January 2013. Currently, there are an estimated 3.2 million UK e-cigarette users. The impact of e-cigarette advertisement on tobacco use has not been studied in detail. We hypothesised that e-cigarette advertisement impacts on conventional smoking behaviour.METHODS: A cross-sectional structured survey assessed the impact of e-cigarette advertising on the perceived social acceptability of cigarette and e-cigarette smoking and on using either cigarettes or e-cigarettes (on a scale of 1 to 5/'not at all' to 'a lot'). The survey was administered between January to March 2015 to London university students, before and after viewing 5 UK adverts including a TV commercial.RESULTS: Data were collected from 106 participants (22 ± 2 years, 66% male), comprising cigarette smokers (32%), non-smokers (54%) and ex-smokers (14%). This included vapers (16%), non-vapers (77%) and ex-vapers (7%). After viewing the adverts, smokers (2.6 ± 1.0 vs. 3.8 ± 1.1, p = 0.001) and non-smokers (3.2 ± 0.7 vs. 3.7 ± 0.8, p = 0.007) felt smoking was more socially acceptable, compared to before viewing them. Participants were more likely to try both e-cigarettes (1.90 ± 1.03 to 3.09 ± 1.11, p 

read more

PMID: 

Toxicol Sci. 2019 Aug 28. Epub 2019 Aug 28. PMID: 31505003

Abstract Title: 

Neurological effects in the offspring after switching from tobacco cigarettes to e-cigarettes during pregnancy in a mouse model.

Abstract: 

BACKGROUND: Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a 'safer' alternative to tobacco cigarettes during pregnancy, however, there are a limited number of studies to suggest that it is actually 'safe'.STUDY DESIGN: Balb/C female mice were exposed to ambient air (n = 8; Sham), or tobacco cigarette smoke (n = 8; SE) before gestation, during gestation and lactation. A third group was exposed to cigarette smoke before gestation followed by e-cigarette aerosols during gestation and lactation (n = 8; Switch). Male offspring (12-week old, n = 10-14/group) underwent behavioural assessments to investigate short-term memory, anxiety and activity using the novel object recognition (NOR) and elevated plus maze (EPM) tests. Brains were collected at postnatal day (P)1, P20 and Week13 for global DNA methylation, epigenetic gene expression, and neuronal cell counts.RESULTS: The offspring from mothers switching to e-cigarettes exhibited no change in exploration/activity, but showed a decrease in global DNA methylation, Aurora Kinase (Aurk) A and AurkB gene expression and a reduction in neuronal cell numbers in the cornu ammonis 1 region of the dorsal hippocampus compared to the SE group.CONCLUSIONS: Continuous tobacco cigarette smoke exposure during pregnancy resulted in marked neurological deficits in the offspring. Switching to e-cigarettes during pregnancy reduced these neurological deficits compared to cigarette smoke exposure. However, neurological changes were still observed, so we therefore conclude that e-cigarette use during pregnancy is not advised.

read more

PMID: 

Tob Induc Dis. 2019 ;17:44. Epub 2019 May 21. PMID: 31516487

Abstract Title: 

Use of Electronic Nicotine Delivery Systems (ENDS) by pregnant women I: Risk of small-for-gestational-age birth.

Abstract: 

INTRODUCTION: The 2016 US Surgeon General's Report suggests that the use of electronic nicotine delivery systems (ENDS) is a fetal risk factor. However, no previous study has estimated their effect on adverse pregnancy outcomes. We assessed the prevalence of current ENDS use in pregnant women and explored the effect on birth weight and smallness-for-gestational-age (SGA), correcting for misclassification from nondisclosure of smoking status.METHODS: We conducted a cohort study with 248 pregnant women using questionnaire data and biomarkers (salivary cotinine, exhaled carbon monoxide, and hair nicotine). We evaluated the association between birth weight and the risk of SGA by applying multivariate linear and log-binomial regression to reproductive outcome data for 232 participants. Participants who did not disclose their smoking status were excluded from the referent group. Sensitivity analysis corrected for misclassification of smoking/ENDS use status.RESULTS: The prevalence of current ENDS use among pregnant women was 6.8% (95% CI: 4.4-10.2%); most of these (75%) were concurrent smokers. Using self-reports, the estimated risk ratio of SGA for ENDS users was nearly two times the risk in the unexposed (RR=1.9, 95% CI: 0.6-5.5), and over three times that for ENDS-only users versus the unexposed (RR=3.1, 95% CI: 0.8-11.7). Excluding from the referent group smokers who did not disclose their smoking status, the risk of SGA for ENDS-only use was 5 times the risk in the unexposed (RR=5.1, 95% CI: 1.1- 22.2), and almost four times for all types of ENDS users (RR=3.8, 95% CI: 1.3-11.2). SGA risk ratios for ENDS users, corrected for misclassification due to self-report, were 6.5-8.5 times that of the unexposed.CONCLUSIONS: Our data suggest that ENDS use is associated with an increased risk of SGA.

read more

PMID: 

Atherosclerosis. 2016 12 ;255:179-185. Epub 2016 Sep 22. PMID: 27693003

Abstract Title: 

Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers.

Abstract: 

BACKGROUND AND AIMS: The use of electronic cigarettes is increasing dramatically on a global scale and its effects on human health remain uncertain. In the present study, we measured endothelial progenitor cells (EPCs) and microvesicles (MVs) in healthy young volunteers following short-term exposure to inhalation of e-cigarette vapor (ECV) to determine vascular changes.METHODS: Sixteen healthy seldom smokers were randomized into two groups either exposed or not exposed to 10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were analyzed by flow cytometry. MVs were phenotyped according to origin (platelet (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclearcontent (SYTO 13 dye). In addition, expression of inflammation markers such P-selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was investigated. Fractional exhaled nitric oxide (FeNO) was also measured at baseline and after 24 h.RESULTS: EPC levels in blood were significantly increased 1 h following exposure to ECV and returned to baseline values after 24 h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p 

read more