What factors reliably predict electronic cigarette nicotine delivery?

BACKGROUND: The ability of an electronic cigarette (e-cigarette) to deliver nicotine effectively may be dependent on features of the device, the liquid and the user. Some of these features have been examined in previous work (eg, liquid nicotine concentration and puff topography), while others have not (eg, nicotine dependence and demographic characteristics). The purpose of this secondary analysis is to examine such features as predictors of e-cigarette nicotine delivery using a relatively large sample. METHODS: Four studies were combined in which e-cigarette-experienced users (n=63; 89% men; 75% white) and e-cigarette-naïve cigarette smokers (n=67; 66% men; 54% white) took 10 puffs from an eGo-style e-cigarette (~7.3 watts) filled with liquid that had a nicotine concentration of 18, 25 or 36 mg/mL. Thus, held constant across all studies were device features of battery/cartomiser style and power level and the topography parameters of puff number and interpuff interval. Blood was sampled before and after use, and puff topography was measured. Three general linear models were conducted to predict plasma nicotine concentrations (pre-post increase) for: (1) e-cigarette users only, (2) smokers only and (3) both groups combined. Predictor variables included puff duration, puff volume, liquid nicotine concentration, presession plasma nicotine concentration, nicotine dependence score (smokers only), gender and race. RESULTS: In all models tested, longer puff durations and higher liquid nicotine concentrations were associated significantly with increased nicotine delivery (ps<0.05). For e-cigarette users only, higher presession nicotine concentration was associated significantly with increased nicotine delivery (p<0.05). CONCLUSIONS: Puff duration and liquid nicotine concentration may be among the more important factors to consider as regulators attempt to balance e-cigarette safety with efficacy. These findings should be interpreted in the context of devices with relatively low power output, a variable not studied here but likely also directly relevant to product regulation.

An Ultra-High-Pressure Liquid Chromatographic Tandem Mass Spectrometry Method for the Analysis of Benzoyl Ester Derivatized Glycols and Glycerol.

Presented is an ultra-high-pressure liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method developed for the detection of propylene glycol, glycerol, ethylene glycol and diethylene glycol using isotopically labeled standards in urine as part of ongoing studies to evaluate whether urinary propylene glycol and/or vegetable glycerin concentration are indicators of recent use. Propylene glycol and vegetable glycerol are found in many products that are consumed and used including electronic cigarettes (e-cigarettes). E-cigarettes are battery-powered devices used as an alternative to traditional cigarettes. The liquid formulations aerosolized in these devices largely consist of propylene glycol and/or vegetable glycerol. Published reports regarding the ratio of propylene glycol to glycerol content in these formulations ranged from 50:50 to 100 percent of either. For the analysis of urine specimens from both users and non-users of e-cigarettes, calibrators, controls and specimens were derivatized using benzoyl chloride prior to analysis. They were analyzed using a Waters AcQuity Xevo TQ-S Micro UPLC-MS/MS. Chromatographic separation was performed on an AcQuity UPLC BEH C18 1.7 um, 2.1 × 50 mm, column using a 20 mM ammonium formate in water and 20 mM ammonium formate in methanol as the mobile phase. The method was validated using SWGTOX guidelines for linearity, precision and accuracy, stability, carryover and limit of detection. The linear range was determined using a seven-point calibration curve ranging between 0.5 and 100 mcg/mL. The bias for all validation controls was determined to be ±20% of the expected concentrations with CVs of <15%. A total of 124 urine specimens analyzed collected with 50 specimens collected from self-reported non-smokers (cigarettes/e-cigarettes) confirmed cotinine free using the DRI® Cotinine Assay (Thermo Scientific, Waltham, MA) and 74 specimens collected before and after 12 hours self-reported e-cigarettes abstinence e-cigarette users. Propylene glycol and glycerol were determined to have concentration ranges of "none detected" to 1470 and "none detected" to 2950 mcg/mL, respectively.

Effects of electronic cigarette liquid solvents propylene glycol and vegetable glycerin on user nicotine delivery, heart rate, subjective effects, and puff topography.

BACKGROUND: Electronic cigarettes (ECIGs) are a class of tobacco products that produce different effects (e.g., nicotine delivery), depending on the device, liquid, and behavioral factors. However, the influence of the two primary ECIG liquid solvents, propylene glycol (PG) and vegetable glycerin (VG), on ECIG acute effects is unknown. METHODS: Thirty ECIG-experienced, ≥12-h nicotine- abstinent participants completed four conditions consisting of two ECIG-use bouts (10 puffs, 30 s interpuff-interval) differing only by liquid PG:VG ratio (2PG:98VG, 20PG:80VG, 55PG:45VG, 100PG). Device power (7.3 W) and liquid nicotine concentration (18 mg/ml) remained constant. Nicotine delivery, subjective effects, heart rate (HR), and puff topography were assessed. RESULTS: In the 100PG condition, participants took shorter and smaller puffs but obtained significantly more nicotine relative to the two VG-based conditions. Total nicotine exposure (i.e., area under the curve) was also significantly higher during use of the two PG-based liquids. However, participants reported that the 100 PG liquid was significantly less "pleasant" and "satisfying" relative to the other liquids (all ps < .05). Increases in HR and decreases in abstinence symptoms (e.g., "craving") did not differ across conditions. CONCLUSIONS: PG:VG ratio influenced nicotine delivery, some subjective effects, and puff topography. Lower overall product satisfaction associated with the 100PG liquid suggests factors other than nicotine delivery (e.g., aerosol visibility) may play a role in maintaining ECIG use. Regulating ECIG acute effects such as nicotine delivery and subjective effects may require simultaneous attention to liquid PG:VG ratio as well as device, liquid, and behavioral factors known to influence these outcomes.

Electronic cigarette use and indoor air quality in a natural setting.

INTRODUCTION: Secondhand smoke (SHS) from combustible cigarettes causes numerous diseases. Policies have been developed to prevent SHS exposure from indoor cigarette use to reduce health risks to non-smokers. However, fewer policies have been implemented to deter electronic cigarette (ECIG) use indoors, and limited research has examined the impact of secondhand exposure to ECIG aerosol. METHODS: Indoor air quality was measured at a 2-day ECIG event held in a large room at a hotel. Fine particulate matter (PM) was measured using 2 devices that measured concentrations of PM 2.5 µm aerodynamic diameter or smaller (PM2.5). Measurements were taken before the event, over 2 days when the event was ongoing, and the day after the event. PM2.5 measurements were also taken from the restaurant at the hotel hosting the event and a restaurant at a nearby hotel. RESULTS: During 6 time points when the event was ongoing, between 59 and 86 active ECIG users were present in the event room (room volume=4023 m3). While the event was ongoing, median PM2.5 concentrations in the event room increased from a baseline of 1.92-3.20 µg/m3 to concentrations that ranged from 311.68 µg/m3 (IQR 253.44-411.84 µg/m3) to 818.88 µg/m3 (IQR 760.64-975.04 µg/m3). CONCLUSIONS: PM2.5 concentrations observed at the ECIG event were higher than concentrations reported previously in hookah cafés and bars that allow cigarette smoking. This study indicates that indoor ECIG use exposes non-users to secondhand ECIG aerosol. Regulatory bodies should consider establishing policies that prohibit ECIG use anywhere combustible cigarette use is prohibited.

The Influence of a Mouthpiece-Based Topography Measurement Device on Electronic Cigarette User's Plasma Nicotine Concentration, Heart Rate, and Subjective Effects Under Directed and Ad Libitum Use Conditions.

INTRODUCTION: Electronic cigarettes e-cigarettes aerosolize a liquid solution often containing nicotine. e-cigarette nicotine delivery may be influenced by user puffing behaviors ("puff topography"). E-cigarette puff topography can be recorded using mouthpiece-based computerized systems. The present study sought to examine the extent to which these systems influence e-cigarette nicotine delivery and other e-cigarette associated acute effects under ad libitum use conditions. METHODS: Plasma nicotine concentration, heart rate, and subjective effects were assessed in 29 experienced e-cigarette users using their preferred e-cigarette battery and liquid (≥12mg/mL nicotine) in two sessions differing only by the presence of a mouthpiece-based device. In both sessions, participants completed a directed e-cigarette use bout (10 puffs, 30-s interpuff interval) and a 90-min ad libitum bout. Puff topography was recorded in the session with the topography mouthpiece. RESULTS: Plasma nicotine, heart rate, and subjective effects, aside from "Did the e-cigarette Taste Good?" were independent of topography measurement (higher mean taste ratings were observed in the no topography condition). Mean (SEM) plasma nicotine concentration following the ad libitum bout was 34.3ng/mL (4.9) in the no topography condition and 35.7ng/mL (4.3) in the topography condition. Longer puff durations, longer interpuff intervals, and larger puff volumes were observed in the ad libitum relative to the directed bout. CONCLUSIONS: 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. Future studies using ad libitum e-cigarette use bouts would facilitate understanding of e-cigarette toxicant yield. IMPLICATIONS: 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.

Electronic cigarette use and uptake of cigarette smoking: A longitudinal examination of U.S. college students.

INTRODUCTION: Electronic cigarette (e-cigarette) use prevalence is increasing among U.S. adolescents and adults but recent longitudinal data for college/university students are scarce. Furthermore, the extent that e-cigarette use is associated with the onset of cigarette smoking and the factors that lead to the uptake of e-cigarettes in college students has not been explored. METHODS: 3757 participants from a Mid-Atlantic university (women: 66%; White: 45%; Black: 21%; Asian: 19%; Hispanic/Latino: 6%) were surveyed in 2014 and again in 2015. RESULTS: Among participants reporting never smoking at time 1, those who had ever tried e-cigarettes or were currently using e-cigarettes (at least one use in past 30days) were more likely to have ever tried cigarettes by time 2 relative to individuals who had not used e-cigarettes. Ever use of e-cigarettes (but not current use) also increased participants' likelihood of being current cigarette smokers at time 2. Among initial never users of e-cigarettes or cigarettes, males and ever marijuana users had an increased probability of trying e-cigarettes by time 2. Furthermore, less perseverance (an index of impulsivity) and ever use of other tobacco products increased initial never users' chances of trying both cigarettes and e-cigarettes by time 2. CONCLUSIONS: Given that never-smoking participants who had tried e-cigarettes were more likely to initiate cigarette use later, limiting young adults' access to these products may be beneficial. As the long-term health implications of e-cigarette use become clearer, predictors of e-cigarette use could help identify future populations likely to use and abuse these products.

Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report.

INTRODUCTION: Electronic cigarettes (ECIGs) aerosolise a liquid that usually contains propylene glycol and/or vegetable glycerine, flavourants and the dependence-producing drug, nicotine, in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration and plasma nicotine concentration and puffing behaviour in experienced ECIG users. METHODS: Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil 'cartomiser' loaded with 1 mL of a flavoured propylene glycol/vegetable glycerine 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 s puff interval) separated by 60 min. 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.

Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.

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 study examined the extent to which ECIG liquid nicotine concentration is related to user plasma nicotine concentration in ECIG-naïve tobacco cigarette smokers. METHODS: Sixteen ECIG-naïve cigarette smokers completed four laboratory sessions that differed by the nicotine concentration of the liquid (0, 8, 18, or 36 mg/ml) that was placed into a 1.5 Ohm, dual coil "cartomizer" powered by a 3.3V battery. In each session, participants completed two, 10-puff ECIG use bouts with a 30-second inter-puff interval; bouts were separated by 60 minutes. Venous blood was sampled before and after bouts for later analysis of plasma nicotine concentration; puff duration, volume, and average flow rate were measured during each bout. RESULTS: In bout 1, relative to the 0mg/ml nicotine condition (mean = 3.8 ng/ml, SD = 3.3), plasma nicotine concentration increased significantly immediately after the bout for the 8 (mean = 8.8 ng/ml, SD = 6.3), 18 (mean = 13.2 ng/ml, SD = 13.2), and 36 mg/ml (mean = 17.0 ng/ml, SD = 17.9) liquid concentration. A similar pattern was observed after bout 2. Average puff duration in the 36 mg/ml condition was significantly shorter compared to the 0mg/ml nicotine condition. Puff volume increased during the second bout for 8 and 18 mg/ml conditions. CONCLUSIONS: For a given ECIG device, nicotine delivery may be directly related to liquid concentration. ECIG-naïve cigarette smokers can, from their first use bout, attain cigarette-like nicotine delivery profiles with some currently available ECIG products. IMPLICATIONS: 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.