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Public health advocates and regulatory agencies must act now to restrict youth access to e-cigarettes before decades of progress in tobacco control is undone. Additionally, raising the legal age to 21 years (‘Tobacco 21’) to purchase tobacco products has gained traction as an evidenced-based measure to prevent teen access to all tobacco products, including e-cigarettes. Funding This study was funded by an Intramural Research Grant Award to RB from Department of Pediatrics, Stony Brook University School of Medicine and Stony Brook Children’s Hospital, New York. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2016. (accessed 25 May 2018).

In a randomized trial involving 886 smokers, e-cigarettes were more effective than nicotine-replacement therapy with respect to the 1-year abstinence rate (18% vs. 10%). Throat or mouth irritation was more common in the e-cigarette group, and nausea was more common in the nicotine-replacement group.

RNA-seq is a high-throughput sequencing technology widely used for gene transcript discovery and quantification under different biological or biomedical conditions. A fundamental research question in most RNA-seq experiments is the identification of differentially expressed genes among experimental conditions or sample groups. Numerous statistical methods for RNA-seq differential analysis have been proposed since the emergence of the RNA-seq assay. To evaluate popular differential analysis methods used in the open source R and Bioconductor packages, we conducted multiple simulation studies to compare the performance of eight RNA-seq differential analysis methods used in RNA-seq data analysis (edgeR, DESeq, DESeq2, baySeq, EBSeq, NOISeq, SAMSeq, Voom). The comparisons were across different scenarios with either equal or unequal library sizes, different distribution assumptions and sample sizes. We measured performance using false discovery rate (FDR) control, power, and stability. No significant differences were observed for FDR control, power, or stability across methods, whether with equal or unequal library sizes. For RNA-seq count data with negative binomial distribution, when sample size is 3 in each group, EBSeq performed better than the other methods as indicated by FDR control, power, and stability. When sample sizes increase to 6 or 12 in each group, DESeq2 performed slightly better than other methods. All methods have improved performance when sample size increases to 12 in each group except DESeq. For RNA-seq count data with log-normal distribution, both DESeq and DESeq2 methods performed better than other methods in terms of FDR control, power, and stability across all sample sizes. Real RNA-seq experimental data were also used to compare the total number of discoveries and stability of discoveries for each method. For RNA-seq data analysis, the EBSeq method is recommended for studies with sample size as small as 3 in each group, and the DESeq2 method is recommended for sample size of 6 or higher in each group when the data follow the negative binomial distribution. Both DESeq and DESeq2 methods are recommended when the data follow the log-normal distribution.

Many non-cigarette tobacco products, including e-cigarettes, contain various flavourings, such as fruit flavours. Although many flavourings used in e-cigarettes are generally recognised as safe when used in food products, concerns have been raised about the potential inhalation toxicity of these chemicals. Benzaldehyde, which is a key ingredient in natural fruit flavours, has been shown to cause irritation of respiratory airways in animal and occupational exposure studies. Given the potential inhalation toxicity of this compound, we measured benzaldehyde in aerosol generated in a laboratory setting from flavoured e-cigarettes purchased online and detected benzaldehyde in 108 out of 145 products. The highest levels of benzaldehyde were detected in cherry-flavoured products. The benzaldehyde doses inhaled with 30 puffs from flavoured e-cigarettes were often higher than doses inhaled from a conventional cigarette. Levels in cherry-flavoured products were >1000 times lower than doses inhaled in the workplace. While e-cigarettes seem to be a promising harm reduction tool for smokers, findings indicate that using these products could result in repeated inhalation of benzaldehyde, with long-term users risking regular exposure to the substance. Given the uncertainty surrounding adverse health effects stemming from long-term inhalation of flavouring ingredients such as benzaldehyde, clinicians need to be aware of this emerging risk and ask their patients about use of flavoured e-cigarettes.

Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device.

Flavored e-cigarettes are enticing to new users and established cigarette smokers using e-cigarettes to quit smoking due to the wide variety of flavor options. However, specific flavor combinations that are popular among e-cigarette users are understudied. Recently, the Deeming rule extended the US Food and Drug Administration's authority over all tobacco products, including e-cigarettes. The Population Assessment of Tobacco and Health Study Wave 2 data were analyzed to assess the prevalence of self-reported flavor categories that are used individually and in combination with other flavor categories among past 30-day youth and adult e-cigarette users in the US. Most youth and adult participants reported using a flavored e-cigarette. Reporting an individual flavor category was more common than reporting a combination of flavor categories. Fruit flavor was the most common flavor category reported among youth, and 'menthol/mint' was most common among adults. Fruit and candy/other sweets were the most common flavor categories reported together among both youth and adult past 30-day e-cigarette users. The use of flavored e-cigarettes is very popular among youth and adults. Most consumers reported using a single flavor category, although some consumers did use a combination of flavor categories. Preference for menthol/mint among adults may represent a carryover from associations with tobacco cigarettes. Typically, sweeter flavors, such as fruit, were among the most popular flavor categories reported, both individually and in combination with other flavors, while more bitter flavors (i.e.: clove/spice) were less common. This study identified predominant flavor categories among past 30-day youth and adult e-cigarette users. Findings indicate that the wide variety of flavors available and the freedom to \"mix-and-match\" flavors may maintain use of e-cigarettes among youth and adults, and future research should focus on the composition of the ENDS liquid/vapor to disentangle the contributions of sweeteners and flavorants.

The electronic cigarette (EC) is a plastic device that imitates conventional cigarettes and was developed to deliver nicotine in a toxin-free vapor. Nicotine in a solution is heated and vaporized when a person puffs through the device and is inhaled as a vapor into the mouth. The EC is a new product on the market and little is known about its safety and nicotine delivery efficacy. The aim of the study was to analyze nicotine levels in vapor generated from various EC brands and models. The study was designed to assess efficacy and consistency of various ECs in converting nicotine to vapor and to analyze dynamics of nicotine vaporization. Sixteen ECs were selected based on their popularity in the Polish, U.K. and U.S. markets. Vapors were generated using an automatic smoking machine modified to simulate puffing conditions of real EC users. Nicotine was absorbed in a set of washing bottles with methanol and analyzed with gas chromatography. The total level of nicotine in vapor generated by 20 series of 15 puffs varied from 0.5 to 15.4 mg. Most of the analyzed ECs effectively delivered nicotine during the first 150-180 puffs. On an average, 50%-60% of nicotine from a cartridge was vaporized. ECs generate vapor that contains nicotine, but EC brands and models differ in their efficacy and consistency of nicotine vaporization. In ECs, which vaporize nicotine effectively, the amount inhaled from 15 puffs is lower compared with smoking a conventional cigarette.

BackgroundWheezing is a symptom of potential respiratory disease and known to be associated with smoking. Electronic cigarette use (‘vaping’) has increased exponentially in recent years. This study examined the cross-sectional association of vaping with wheezing and related respiratory symptoms and compare this association with smokers and dual users.MethodsThe Population Assessment of Tobacco and Health study wave 2 data collected from October 2014 to October 2015 with 28 171 adults were used. The cross-sectional association of vaping with self-reported wheezing and related respiratory symptoms relative to smokers and dual users of tobacco and electronic cigarettes were studied using multivariable logistic and cumulative logistic regression models with consideration of complex sampling design.ResultsAmong the 28 171 adult participants, 641 (1.2%) were current vapers who used e-cigarettes exclusively, 8525 (16.6%) were current exclusive smokers, 1106 (2.0%) were dual users and 17 899 (80.2%) were non-users. Compared with non-users, risks of wheezing and related respiratory symptoms were significantly increased in current vapers (adjusted OR (aOR)=1.67, 95% CI: 1.23 to 2.15). Current vapers had significantly lower risk in wheezing and related respiratory symptoms compared with current smokers (aOR=0.68, 95% CI: 0.53 to 0.87). No significant differences were found between dual users and current smokers in risk of wheezing and related respiratory symptoms (aOR=1.06, 95% CI: 0.91 to 1.24).ConclusionsVaping was associated with increased risk of wheezing and related respiratory symptoms. Current vapers had lower risk in wheezing and related respiratory symptoms than current smokers or dual users but higher than non-users. Both dual use and smoking significantly increased the risk of wheezing and related respiratory symptoms.

BackgroundE-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavoured ENDS aerosol when inhaled.MethodsAerosol from ENDS was generated using a smoking machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavours, nicotine carrier, variable nicotine concentrations and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavour names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavouring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly generated ENDS aerosol, tobacco smoke or air (controls) using an air–liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: (1) cell viability, (2) metabolic activity and (3) release of inflammatory mediators (cytokines).ResultsExposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of interleukin (IL)-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage and flavours significantly affected toxicity of ENDS aerosol, with a strawberry-flavoured product being the most cytotoxic.ConclusionsOur data suggest that characteristics of ENDS products, including flavours, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed.

AbstractObjectiveTo examine differences in vaping and smoking prevalence among adolescents in Canada, England, and the United States.DesignRepeat cross sectional surveys.SettingOnline surveys in Canada, England, and the US.ParticipantsNational samples of 16 to 19 year olds in 2017 and 2018, recruited from commercial panels in Canada (n=7891), England (n=7897), and the US (n=8140).Main outcome measuresPrevalence of vaping and smoking was assessed for use ever, in the past 30 days, in the past week, and on 15 days or more in the past month. Use of JUUL (a nicotine salt based electronic cigarette with high nicotine concentration) and usual vaping brands were also assessed. Logistic regression models examined differences in vaping and smoking between countries and over time.ResultsThe prevalence of vaping in the past 30 days, in the past week, and on 15 days or more in the past month increased in Canada and the US between 2017 and 2018 (P<0.001 for all), including among non-smokers and experimental smokers, with no changes in England. Smoking prevalence increased in Canada (P<0.001 for all measures), with modest increases in England, and no changes in the US. The percentage of ever vapers who reported more frequent vaping increased in Canada and the US (P<0.01 for all), but not in England. The use of JUUL increased in all countries, particularly the US and Canada—for example, the proportion of current vapers in the US citing JUUL as their usual brand increased threefold between 2017 and 2018.ConclusionsBetween 2017 and 2018, among 16 to 19 year olds the prevalence of vaping increased in Canada and the US, as did smoking in Canada, with little change in England. The rapidly evolving vaping market and emergence of nicotine salt based products warrant close monitoring.