Alan Shihadeh

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 User Puff Topography, Device Voltage, and Liquid Nicotine Concentration on Electronic Cigarette Nicotine Yield: Measurements and Model Predictions

INTRODUCTION Some electronic cigarette (ECIG) users attain tobacco cigarette-like plasma nicotine concentrations while others do not. Understanding the factors that influence ECIG aerosol nicotine delivery is relevant to regulation, including product labeling and abuse liability. These factors may include user puff topography, ECIG liquid composition, and ECIG design features. This study addresses how these factors can influence ECIG nicotine yield. METHODS Aerosols were machine generated with 1 type of ECIG cartridge (V4L CoolCart) using 5 distinct puff profiles representing a tobacco cigarette smoker (2-s puff duration, 33-ml/s puff velocity), a slow average ECIG user (4 s, 17 ml/s), a fast average user (4 s, 33 ml/s), a slow extreme user (8 s, 17 ml/s), and a fast extreme user (8 s, 33 ml/s). Output voltage (3.3-5.2 V or 3.0-7.5 W) and e-liquid nicotine concentration (18-36 mg/ml labeled concentration) were varied. A theoretical model was also developed to simulate the ECIG aerosol production process and to provide insight into the empirical observations. RESULTS Nicotine yields from 15 puffs varied by more than 50-fold across conditions. Experienced ECIG user profiles (longer puffs) resulted in higher nicotine yields relative to the tobacco smoker (shorter puffs). Puff velocity had no effect on nicotine yield. Higher nicotine concentration and higher voltages resulted in higher nicotine yields. These results were predicted well by the theoretical model (R (2) = 0.99). CONCLUSIONS Depending on puff conditions and product features, 15 puffs from an ECIG can provide far less or far more nicotine than a single tobacco cigarette. ECIG emissions can be predicted using physical principles, with knowledge of puff topography and a few ECIG device design parameters.

Toxicant content, physical properties and biological activity of waterpipe tobacco smoke and its tobacco-free alternatives

Objectives Waterpipe smoking using sweetened, flavoured tobacco products has become a widespread global phenomenon. In this paper, we review chemical, physical and biological properties of waterpipe smoke. Data sources Peer-reviewed publications indexed in major databases between 1991 and 2014. Search keywords included a combination of: waterpipe, narghile, hookah, shisha along with names of chemical compounds and classes of compounds, in addition to terms commonly used in cellular biology and aerosol sizing. Study selection The search was limited to articles published in English which reported novel data on waterpipe tobacco smoke (WTS) toxicant content, biological activity or particle size and which met various criteria for analytical rigour including: method specificity and selectivity, precision, accuracy and recovery, linearity, range, and stability. Data extraction Multiple researchers reviewed the reports and collectively agreed on which data were pertinent for inclusion. Data synthesis Waterpipe smoke contains significant concentrations of toxicants thought to cause dependence, heart disease, lung disease and cancer in cigarette smokers, and includes 27 known or suspected carcinogens. Waterpipe smoke is a respirable aerosol that induces cellular responses associated with pulmonary and arterial diseases. Except nicotine, smoke generated using tobacco-free preparations marketed for ‘health conscious’ users contains the same or greater doses of toxicants, with the same cellular effects as conventional products. Toxicant yield data from the analytical laboratory are consistent with studies of exposure biomarkers in waterpipe users. Conclusions A sufficient evidence base exists to support public health interventions that highlight the fact that WTS presents a serious inhalation hazard.

Electronic cigarette effectiveness and abuse liability: predicting and regulating nicotine flux.

Electronic cigarettes (ECIGs) comprise an aerosolized nicotine delivery product category that provides consumers with probably unprecedented control over extensive features and operating conditions, allowing a wide range of nicotine yields to be obtained. Depending on the combination of such ECIG variables as electrical power input, geometry, liquid composition, and puff behavior, ECIG users can extract in a few puffs far more or far less nicotine than with a conventional combustible cigarette. These features of ECIG design and use present challenges for public health policy, central among which is the question of how to regulate nicotine delivery. In this commentary, we propose a conceptual framework intended to provide a convenient approach for evaluating and regulating the nicotine emitted from ECIGs. This framework employs nicotine flux to account for the total dose and rate at which nicotine reaches the user, 2 key factors in drug abuse liability. The nicotine flux is the nicotine emitted per puff second (e.g., mg/s) by a given ECIG design under given use conditions, and it can be predicted accurately using physical principles. We speculate that if the flux is too low, users likely will abandon the device and maintain conventional tobacco product use. Also, we speculate that if the flux is too high, individuals may suffer toxic side effects and/or the device may have higher-than-necessary abuse liability. By considering ECIG design, operation conditions, liquid composition, and puff behavior variables in combination, we illustrate how ECIG specifications can be realistically mandated to result in a target flux range.

Nicotine and Carbonyl Emissions From Popular Electronic Cigarette Products: Correlation to Liquid Composition and Design Characteristics

Introduction Available in hundreds of device designs and thousands of flavors, electronic cigarette (ECIG) may have differing toxicant emission characteristics. This study assesses nicotine and carbonyl yields in the most popular brands in the U.S. market. These products included disposable, prefilled cartridge, and tank-based ECIGs. Methods Twenty-seven ECIG products of 10 brands were procured and their power outputs were measured. The e-liquids were characterized for pH, nicotine concentration, propylene glycol/vegetable glycerin (PG/VG) ratio, and water content. Aerosols were generated using a puffing machine and nicotine and carbonyls were, respectively, quantified using gas chromatograph and high-performance liquid chromatography. A multiregression model was used to interpret the data. Results Nicotine yields varied from 0.27 to 2.91 mg/15 puffs, a range corresponding to the nicotine yield of less than 1 to more than 3 combustible cigarettes. Nicotine yield was highly correlated with ECIG type and brand, liquid nicotine concentration, and PG/VG ratio, and to a lower significance with electrical power, but not with pH and water content. Carbonyls, including the carcinogen formaldehyde, were detected in all ECIG aerosols, with total carbonyl concentrations ranging from 3.72 to 48.85 µg/15 puffs. Unlike nicotine, carbonyl concentrations were mainly correlated with power. Conclusion In 15 puffs, some ECIG devices emit nicotine quantities that exceed those of tobacco cigarettes. Nicotine emissions vary widely across products but carbonyl emissions showed little variations. In spite of that ECIG users are exposed to toxicologically significant levels of carbonyl compounds, especially formaldehyde. Regression analysis showed the importance of design and e-liquid characteristics as determinants of nicotine and carbonyl emissions. Implications Periodic surveying of characteristics of ECIG products available in the marketplace is valuable for understanding population-wide changes in ECIG use patterns over time.

Acute Exposure to Electronic and Combustible Cigarette Aerosols: Effects in an Animal Model and in Human Alveolar Cells

BACKGROUND Smoking electronic cigarettes (ECIG) is promoted as a safer alternative to smoking combustible cigarettes. This study investigates the effects of ECIG aerosol and cigarette smoke (CS) in an animal model and in human alveolar cell cultures (A549). METHODS Mice were divided into Control, ECIG, and CS. Animals were exposed for 6h/d to either lab air, ECIG or CS, for of 3 days. Total particulate matter exposure for the ECIG was set at higher levels compared to CS. Lung injury was determined by: (1) measurement of wet-to-dry ratio; (2) albumin concentration in the bronchoalveolar lavage fluid; (3) transcriptional expression of inflammatory mediators IL-1β, IL-6, TNF-α; (4) oxidative stress; (5) assessment of cell death; and (6) lung histopathology. Human alveolar cell cultures were treated with various concentrations of ECIG and CS aerosol extracts and the effects on cell proliferation were evaluated. RESULTS Wet-to-dry ratio was higher in CS when compared to ECIG. Albumin leak in bronchoalveolar lavage fluid was evident in CS but not in ECIG. ECIG exposure was only associated with a significant increase in IL-1β. In contrast, CS exposure resulted in significant increases in IL-1β, IL-6, TNF-α expression, and oxidative stress. TUNEL staining demonstrated significant cell death in CS but not in ECIG. At the cellular level, ECIG and CS extracts reduced cell proliferation, however, CS exhibited effects at lower concentrations. CONCLUSION Despite higher exposure conditions, ECIG exhibited less toxic effects on lungs of experimental animals and on A549 cell cultures when compared to CS.

Detection of 5-hydroxymethylfurfural and furfural in the aerosol of electronic cigarettes

Significance The wide availability of sweet flavours has been hypothesised as a factor in the popularity of electronic cigarette (ECIG), especially among youth. Saccharides, which are commonly used to impart a sweet flavour to ECIG liquids, thermally degrade to produce toxic compounds, like aldehydes and furans. This study investigates the formation of furanic compounds in aerosols when ECIG liquid solutions of varying sweetener concentrations are vaped under different power and puff duration. Methods Liquids are prepared by mixing aqueous sucrose, glucose or sorbitol solutions to a 70/30 propylene glycol/glycerin solution. Aerosols are generated and trapped on filter pads using a commercially available ECIG operating at 4.3 and 10.8 W and 4 and 8 s puff duration. Extraction, elimination of matrix interference and quantification are achieved using novel solid phase extraction and gas chromatography tandem mass spectrometry methods (GC-MS). Results Well-resolved GC peaks of 5-hydroxymethylfurfural (HMF) and furfural (FA) are detected. Both HMF and FA are quantified in the aerosols of sweet-flavoured e-liquids under various vaping conditions. Levels of furan emissions are significantly correlated with electric power and sweetener concentration and not with puff duration. Unlike saccharides, the formation of HMF and FA from a sugar alcohol is negligible. Conclusions The addition of sweeteners to ECIG liquids exposes ECIG user to furans, a toxic class of compounds. Under certain conditions, the per-puff yield of HMF and FA in ECIG emissions is comparable to values reported for combustible cigarettes.

Group Waterpipe Tobacco Smoking Increases Smoke Toxicant Concentration

INTRODUCTION Waterpipe tobacco smoking is a global health concern. Laboratory research has focused on individual waterpipe users while group use is common. This study examined user toxicant exposure and smoke toxicant yield associated with individual and group waterpipe smoking. METHODS Twenty-two pairs of waterpipe smokers used a waterpipe individually and as a dyad. Before and after smoking, blood was sampled and expired carbon monoxide (CO) measured; puff topography was recorded throughout. One participant from each pair was selected randomly and their plasma nicotine and expired air CO concentrations were compared when smoking alone to when smoking as part of a dyad. Recorded puff topography was used to machine-produce smoke that was analyzed for toxicant content. RESULTS There was no difference in mean plasma nicotine concentration when an individual smoked as part of a dyad (mean = 14.9 ng/ml; standard error of the mean [SEM] = 3.0) compared to when smoking alone (mean = 10.0 ng/ml; SEM = 1.5). An individual smoking as part of as a dyad had, on average, lower CO (mean = 15.8 ppm; SEM = 2.0) compared to when smoking alone (mean= 21.3 ppm; SEM = 2.7). When two participants smoked as a dyad they took, on average, more puffs (mean = 109.8; SEM = 7.6) than a singleton smoker (mean = 77.7; SEM = 8.1) and a shorter interpuff interval (IPI; dyad mean = 23.8 seconds; SEM = 1.9; singleton mean = 40.8 seconds; SEM = 4.8). Higher concentrations of several toxicants were observed in dyad-produced smoke. DISCUSSION Dyad smoking may increase smoke toxicant content, likely due to the dyads shorter IPIs and greater puff number. More work is needed to understand if group waterpipe smoking alters the health risks of waterpipe tobacco smoking. IMPLICATIONS This study is the first to measure toxicants in smoke generated from a waterpipe when used by a dyad. Relative to smoke generated by a singleton, dyad smoke had higher concentration of some toxicants. These differences may be attributed to differences in puffing behavior, specifically the shorter IPI and greater puff number observed in the dyad condition. Relative to singleton smokers, dyad smokers were exposed to less CO, but nicotine exposure did not differ. More work is needed to assess the health effects of inhalation of more toxicant-laden smoke during group waterpipe use.

Investigating the Effects of Exposure to Waterpipe Smoke on Pregnancy Outcomes Using an Animal Model

INTRODUCTION In recent years, waterpipe tobacco smoking has been increasing in popularity all over the world. In this study, we explored effects of waterpipe smoking on pregnancy outcomes in rats. METHODS Animals were exposed to waterpipe tobacco smoking using a whole body exposure system 2 hours per day during pregnancy. A control group was exposed to fresh air only. RESULTS The results showed significant association between exposure to waterpipe smoke during pregnancy and low birth weight (P < .01) and neonatal death (P < .01). In addition, the rate of growth of offspring of the waterpipe group was significantly lower than that of control group as measured by body weight gain during the first 3 months of life (P < .001). No effect was found for waterpipe smoking on mean number of progeny and male to female ratio among offspring. CONCLUSION Waterpipe smoking is associated with adverse effects on pregnancy outcomes. IMPLICATIONS In this study, we investigated for the first time the effect of waterpipe smoking on pregnancy outcomes using animal model. The results clearly showed that waterpipe smoking is associated with adverse effects on pregnancy outcomes that include low birth weigh, neonatal survival, and growth retardation.

The effect of chronic exposure to waterpipe tobacco smoke on airway inflammation in mice

Purpose: Acute exposure of experimental animals to waterpipe tobacco smoke has been shown to induce lung inflammation and injury. The aim of this study was to investigate the effect of chronic exposure to waterpipe smoke on inflammatory markers and oxidative stress in the mouse lung. Method: Using a whole‐body exposure system, animals were exposed to waterpipe smoke for 6 weeks with a one‐hour daily exposure for 5 days a week. Results: Exposure to waterpipe tobacco smoke induced the recruitment of inflammatory cells to the airway. Significant elevation in macrophages, lymphocytes and neutrophils was detected in the bronchoalveolar lavage fluid of exposed animals (P < 0.01). Furthermore, levels of catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the lung homogenates were elevated (P < 0.05). Finally, waterpipe smoking altered the levels of a panel of inflammatory cytokines including TNF&agr;, IL‐1 &bgr;, IL‐6, IL‐10 and IL‐12 biomarkers in the lung of exposed animals (P < 0.05). Conclusion: These results support the notion that waterpipe tobacco smoking exerts harmful respiratory health effects.