Electronic cigarettes (ECIGs) use electricity to power a heating element that aerosolizes a liquid that often contains solvents, flavorants, and the dependence-producing drug nicotine for user inhalation. ECIGs have evolved rapidly in the past 8 years, and the changes in product design and liquid constituents affect the resulting toxicant yield in the aerosol and delivery to the user. This rapid evolution has been accompanied by dramatic increases in ECIG use prevalence in many countries, including among adults and especially adolescents in the United States. This increased prevalence of a novel product that has the potential to deliver nicotine and other toxicants to users’ lungs drives a rapidly growing research effort. This review highlights the most recent information regarding the design of ECIGs and liquid and aerosol constituents, the epidemiology of ECIG use among adolescents and adults (including correlates of ECIG use), and preclinical and clinical research regarding ECIG effects. The current literature suggests a strong rationale for an empirical regulatory approach toward ECIGs that balances any potential ECIG-mediated decreases in health risks for smokers who use them as substitutes for tobacco cigarettes and against any increased risks for nonsmokers who may be attracted to them.

Electronic cigarette (ECIG) nicotine delivery and other effects may depend on liquid nicotine concentration and user experience. This study is the first to examine systematically the influence of ECIG liquid nicotine concentration and user experience on nicotine delivery, heart rate, puff topography, and subjective effects. Thirty-three ECIG-experienced individuals and 31 ECIG-aïve cigarette smokers completed four laboratory conditions that consisted of two, 10-puff bouts (30-second IPI) with a 3.3 volt ECIG battery attached to a 1.5 Ohm “cartomizer” (7.3 watts) filled with 1 ml ECIG liquid. Conditions differed by liquid nicotine concentration: 0, 8, 18, or 36 mg/ml. Participants’ plasma nicotine concentration was related directly to liquid nicotine concentration and dependent on user experience with significantly higher mean plasma nicotine increases observed in ECIG-experienced individuals relative to ECIG-naïve smokers in each active nicotine condition. When using 36 mg/ml, mean plasma nicotine increase for ECIG-experienced individuals was 17.9 ng/ml (SD = 17.2) and 6.9 (SD = 7.1; p < .05) for ECIG-naive. Between-group differences were likely due to longer puffs taken by experienced ECIG users: collapsed across condition, mean puff duration was 5.6 seconds (SD = 3.0) for ECIG-experienced and 2.9 (SD = 1.5) for ECIG-naive. ECIG-use also suppressed nicotine/tobacco abstinence symptoms in both groups; the magnitude of abstinence symptom suppression depended upon liquid nicotine concentration and user experience. These and other recent results suggest that effective policies intended to limit ECIG nicotine delivery will need to account for factors in addition to liquid nicotine concentration (e.g., device power and user behavior).

In experienced ECIG users, measuring ECIG topography did not influence ECIG-associated nicotine delivery or most measures of withdrawal suppression. Topography measurement systems will need to account for the low flow rates observed for ECIG users.

Smoking-related cancer and other disease account for more than 400,000 U.S. deaths annually. Smoking cessation reduces smoking-related disease rates, but relapse rates are high. Thus, interest in reducing the harm of continued smoking is growing. Potential reduced exposure products (PREPs) are marketed to reduce smokers' exposure to smoke toxicants such as carbon monoxide (CO) and carcinogens and may be harm reduction tools. New PREPs are proliferating, but past experience with "low-yield" cigarettes that failed to reduce smokers' toxicant exposure suggests that comprehensive evaluation is necessary to predict if these new products are likely to alter the harm caused by smoking. The purpose of the study was to develop clinical laboratory methods for PREP evaluation. Smokers (N = 35) completed four, 5-day conditions that differed by product used: Advance, Eclipse, own brand cigarettes, or no cigarettes. Carcinogen (as assessed by one nitrosamine and one polycyclic aromatic hydrocarbon biomarker) and nicotine exposure were assessed via thrice-weekly urine sampling. Withdrawal symptoms were measured daily, and smoking behavior was assessed on the first and last day of each condition. Relative to own brand, Advance reduced exposure to the nitrosamine NNK and CO, and Eclipse reduced exposure to nicotine and the nitrosamine NNK, increased exposure to CO, and resulted in larger, longer, and more frequent puffs. No smoking reduced exposure to the nitrosamine NNK, CO, and nicotine, whereas withdrawal was elevated (all p values <.05). Clinical laboratory evaluation of PREPs for smokers is valuable for measuring users' smoke toxicant exposure, withdrawal, and smoking behavior and should be incorporated into a comprehensive PREP evaluation strategy.

Introduction Electronic cigarettes (ECIGs) aerosolize a liquid that usually contains propylene glycol and/or vegetable glycerin, flavorants, and the dependence-producing drug nicotine in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration on plasma nicotine concentration and puffing behavior in experienced ECIG users. Methods Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil “cartomizer” loaded with 1 ml of a flavored propylene glycol/vegetable glycerin liquid to complete four sessions, at least 2 days apart, that differed by nicotine concentration (0, 8, 18, or 36 mg/ml). In each session, participants completed two 10-puff ECIG use bouts (30-sec puff interval) separated by 60 minutes. Venous blood was sampled to determine plasma nicotine concentration. Puff duration, volume, and average flow rate were measured. Results Immediately after bout 1, mean plasma nicotine concentration was 5.5 ng/ml (SD=7.7) for 0 mg/ml liquid, with significantly (p<0.05) higher mean concentrations observed for the 8 (mean=17.8 ng/ml, SD=14.6), 18 (mean=25.9 ng/ml, SD=17.5), and 36 mg/ml (mean=30.2 ng/ml; SD=20.0) concentrations; a similar pattern was observed for bout 2. For bout 1, at 36 mg/ml, the mean post- minus pre-bout difference was 24.1 ng/ml (SD=18.3). Puff topography data were consistent with previous results and revealed few reliable differences across conditions. Discussion This study demonstrates a relationship between ECIG liquid nicotine concentration and user plasma nicotine concentration in experienced ECIG users. Nicotine delivery from some ECIGs may exceed that of a combustible cigarette. The rationale for this higher level of nicotine delivery is uncertain.

Liquid nicotine concentration can influence plasma nicotine concentration in ECIG-naïve cigarette smokers, and, at some concentrations, the nicotine delivery profile of a 3.3V ECIG with a dual coil, 1.5-Ohm cartomizer approaches that of a combustible tobacco cigarette in this population. Finding a product that delivers nicotine as effectively as a tobacco cigarette, as we report here, may be essential for smokers who want to replace completely their combustible tobacco cigarettes with ECIGs.

These results indicate that, while some tobacco abstinence symptoms may be suppressed with nicotine, suppressing others may also require strategies that address the absence of smoking-related stimuli.

No prior study has examined whether mouthpiece-based topography recording devices influence e-cigarette associated nicotine delivery, heart rate, or subjective effects under ad libitum conditions or assessed ad libitum puff topography in experienced individuals using their preferred e-cigarette battery and liquid with a mouthpiece-based computerized device. E-cigarette use significantly increased plasma nicotine concentration and heart rate while suppressing abstinence symptoms. These effects did not differ when a topography mouthpiece was present. Ad libitum puff topography differed from puff topography recorded during directed puffing. These findings suggest that future studies using ad libitum use bouts would facilitate better understanding of e-cigarette toxicant yield.