Characterization of mass distribution in a biomimetic aerosol exposure system.

OBJECTIVE: Lack of biomimicry in geometry and flow conditions of emissions systems for analytical testing and biological exposure has led to fundamental limitations, including a poor understanding of dose delivered to specific airway locations. This work characterizes mass distribution of a JUUL® brand e-cigarette in a Biomimetic Aerosol Exposure System (BAES). MATERIALS AND METHODS: A combination of mass balance, direct measurements, and inferences based on direct measurements were used to characterize regional and local dose as a function of system flow path configuration and emissions topography profile. RESULTS: Doses produced by the emissions topography profile with only puffing were significantly different from profiles with clean air inhalation following puffs. Mass characterization results support that dose can be manipulated using flow path geometry. Local and regional deposition was mapped throughout the system. DISCUSSION AND CONCLUSIONS: We estimate the fraction of yield to the mouth deposited at several locations throughout the system for a variety of puffing and respiration topographies and show that emissions topography profile and system flow path geometry affect dose. This work provides proof-of-concept for assessing mass distribution as a function of aerosol generator (e-cigarette product), user airway geometry, and inhalation and puffing topography.

Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?"

Cigarette smoking is positively and robustly associated with cardiovascular disease (CVD), including hypertension, atherosclerosis, cardiac arrhythmias, stroke, thromboembolism, myocardial infarctions, and heart failure. However, after more than a decade of ENDS presence in the U.S. marketplace, uncertainty persists regarding the long-term health consequences of ENDS use for CVD. New approach methods (NAMs) in the field of toxicology are being developed to enhance rapid prediction of human health hazards. Recent technical advances can now consider impact of biological factors such as sex and race/ethnicity, permitting application of NAMs findings to health equity and environmental justice issues. This has been the case for hazard assessments of drugs and environmental chemicals in areas such as cardiovascular, respiratory, and developmental toxicity. Despite these advances, a shortage of widely accepted methodologies to predict the impact of ENDS use on human health slows the application of regulatory oversight and the protection of public health. Minimizing the time between the emergence of risk (e.g., ENDS use) and the administration of well-founded regulatory policy requires thoughtful consideration of the currently available sources of data, their applicability to the prediction of health outcomes, and whether these available data streams are enough to support an actionable decision. This challenge forms the basis of this white paper on how best to reveal potential toxicities of ENDS use in the human cardiovascular system-a primary target of conventional tobacco smoking. We identify current approaches used to evaluate the impacts of tobacco on cardiovascular health, in particular emerging techniques that replace, reduce, and refine slower and more costly animal models with NAMs platforms that can be applied to tobacco regulatory science. The limitations of these emerging platforms are addressed, and systems biology approaches to close the knowledge gap between traditional models and NAMs are proposed. It is hoped that these suggestions and their adoption within the greater scientific community will result in fresh data streams that will support and enhance the scientific evaluation and subsequent decision-making of tobacco regulatory agencies worldwide.

Flow Rate and Wall Shear Stress Characterization of a Biomimetic Aerosol Exposure System.

Current in vitro emissions and exposure systems lack biomimicry, use unrealistic flow conditions, produce unrealistic dose, and provide inaccurate biomechanical cues to cell cultures, limiting ability to correlate in vitro outcomes with in vivo health effects. A biomimetic in vitro system capable of puffing aerosol and clean air inhalation may empower researchers to investigate complex questions related to lung injury and disease. A biomimetic aerosol exposure system (BAES), including an electronic cigarette adapter, oral cavity module (OCM), and bifurcated exposure chamber (BEC) was designed and manufactured. The fraction of aerosol deposited in transit to a filter pad or lost as volatiles was 0.116±0.021 in a traditional emissions setup versus 0.098 ± 0.015 with the adapter. The observed flowrate was within 5% of programed flowrate for puffing (25 mL/s), puff-associated respiration (450 mL/s), and tidal inhalation (350 mL/s). The maximum flowrate observed in the fabricated BAES was 450 mL/s, exceeding the lower target nominal wall shear stress of 0.025 Pa upstream of the bifurcation and fell below the target of 0.02 Pa downstream. This in vitro system addresses several gaps observed in commercially available systems and may be used to study many inhaled aerosols. The current work illustrates how in silico models may be used to correlate results of an in vitro study to in vivo conditions, rather than attempting to design an in vitro system that performs exactly as the human respiratory tract.

Effect of third-party components on emissions from a pod style electronic cigarette.

Electronic nicotine delivery systems (ENDS) have been associated with a dramatic increase in youth becoming addicted to nicotine following decades-long decline in cigarette smoking uptake. The United States Food and Drug Administration, Center for Tobacco Products (FDA/CTP) is responsible for regulating devices and consumable materials associated with ENDS. State and federal regulations regarding flavoring compounds in ENDS liquids (e-liquids) may be circumvented when vendors market refillable reservoirs side-by-side with noncompliant e-liquids. This study investigated the effect of third-party refillable versus manufacturer-supplied single-use reservoirs on total particulate matter (TPM) and nicotine emissions. The maximum TPM yield per puff was 5.6 times higher for the third-party (Blankz) reservoir (12.4 mg/puff) in comparison with the manufacturer's (JUUL) reservoir (2.2 mg/puff), whereas the maximum TPM concentration was over 7 times higher for third party (0.200 mg/ml) versus manufacturer (0.028 mg/ml) pod. The third-party pod was tested with nicotine concentrations ranging from 0% to 4%. The mass ratio of nicotine present in the aerosol (mg Nic/mg TPM) was found to be approximately the same as the mass ratio of the e-liquid (mg Nic/mg e-liquid) for both pods and all 3 nicotine laden e-liquids tested. Toxicant exposure may increase when consumers use third-party pods with ENDS devices. Refillable reservoirs are a significant barrier to regulatory restrictions on potentially toxic additives to e-liquids. It is recommended FDA/CTP require emissions characterization of third-party reservoirs used with each ENDS they are compatible with and should be required to demonstrate no increased potential toxicant exposure in comparison with manufacturer-provided reservoirs.

A proposed cigarette emissions topography protocol reflecting smokers' natural environment use behavior.

BACKGROUND: The FTC, in 2008, rescinded its 1966 guidance regarding use of the Cambridge Filter Method, noting the yields from the method are relatively poor indicators of tar, nicotine, and carbon monoxide exposure. This article proposes a set of puffing conditions for cigarette emissions testing, with the goal of developing product-specific emissions characterizations which can subsequently be used to realistically model the yield of particulate matter and constituents to the mouth of a smoker, while accounting for the actual puffing behavior of the smoker. METHODS: Synthesis of data was conducted on data collected from a prior one-week observation of 26 adult cigarette smokers, using their usual brand cigarette in each smokers' natural environment including the puff flow rate, duration, volume and time of day of each puff taken were recorded with a cigarette topography monitor. Data was analyzed to determine the empirical joint probability function and cumulative distribution function of mean puff flow rate and puff duration. The joint CDF was used to define an emissions topography protocol using concepts common to computational grid generation. RESULTS: Analysis of 8,250 cigarette puffs indicated the middle 95% of mean puff flow rates varied between 15 and 121 [mL/s] while the middle 95% of puff duration varied from 0.55 to 3.42 [s]. CONCLUSIONS: Thirteen conditions of varying mean puff flow rate and puff duration are proposed for a comprehensive cigarette emissions topography protocol. The proposed protocol addresses inadequacies associated with common machine-puffing profiles used for generating cigarette emissions.

Proposed Standard Test Protocols and Outcome Measures for Quantitative Comparison of Emissions from Electronic Nicotine Delivery Systems.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of electronic nicotine delivery systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between inhaled nicotine products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, e-liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration, and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of: (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

Nominal Operating Envelope of Pod and Pen Style Electronic Cigarettes.

Many Electronic Nicotine Delivery Systems (ENDS) employ integrated sensors to detect user puffing behavior and activate the heating coil to initiate aerosol generation. The minimum puff flow rate and duration at which the ENDS device begins to generate aerosol are important parameters in quantifying the viable operating envelope of the device and are essential to formulating a design of experiments for comprehensive emissions characterization. An accurate and unbiased method for quantifying the flow condition operating envelope of ENDS is needed to quantify product characteristics across research laboratories. This study reports an accurate, unbiased method for measuring the minimum and maximum aerosolization puff flow rate and duration of seven pod-style, four pen-style and two disposable ENDS. The minimum aerosolization flow rate ranged from 2.5 to 23 (mL/s) and the minimum aerosolization duration ranged from 0.5 to 1.0 (s) across the ENDS studied. The maximum aerosolization flow rate was defined to be when the onset of liquid aspiration was evident, at flow rates ranging from 50 to 88 (mL/s). Results are presented which provide preliminary estimates for the effective maximum aerosolization flow rate and duration envelope of each ENDS. The variation in operating envelope observed between ENDS products of differing design by various manufacturers has implications for development of standardized emissions testing protocols and data reporting required for regulatory approval of new products.

Feasibility of Using the Hexoskin Smart Garment for Natural Environment Observation of Respiration Topography.

Background: Limited research has been done to measure ambulatory respiratory behavior, in particular those associated with tobacco use, in the natural environment due to a lack of monitoring techniques. Respiratory topography parameters provide useful information for modeling particle deposition in the lung and assessing exposure risk and health effects associated with tobacco use. Commercially available Wearable Respiratory Monitors (WRM), such as the Hexoskin Smart Garment, have embedded sensors that measure chest motion and may be adapted for measuring ambulatory lung volume. Methods: Self-reported "everyday" and "some days" Hookah and Cigarette smokers were recruited for a 3-day natural environment observation study. Participants wore the Hexoskin shirt while using their preferred tobacco product. The shirt was calibrated on them prior to, during, and after the observation period. A novel method for calculating the calibration parameters is presented. Results: NH = 5 Hookah and NC = 3 Cigarette participants were enrolled. Calibration parameters were obtained and applied to the observed chest motion waveform from each participant to obtain their lung volume waveform. Respiratory topography parameters were derived from the lung volume waveform. Conclusion: The feasibility of using the Hexoskin for measuring ambulatory respiratory topography parameters in the natural environment is demonstrated.

Effects of Manufacturing Variation in Electronic Cigarette Coil Resistance and Initial Pod Mass on Coil Lifetime and Aerosol Generation.

This work investigated the effects of manufacturing variations, including coil resistance and initial pod mass, on coil lifetime and aerosol generation of Vuse ALTO pods. Random samples of pods were used until failure (where e-liquid was consumed, and coil resistance increased to high value indicating a coil break). Initial coil resistance, initial pod mass, and e-liquid net mass ranged between 0.89 to 1.14 [Ω], 6.48 to 6.61 [g], and 1.88 to 2.00 [g] respectively. Coil lifetime was µ (mean) = 158, σ (standard deviation) = 21.5 puffs. Total mass of e-liquid consumed until coil failure was µ = 1.93, σ = 0.035 [g]. TPM yield per puff of all test pods for the first session (brand new pods) was µ = 0.0123, σ = 0.0003 [g]. Coil lifetime and TPM yield per puff were not correlated with either variation in initial coil resistance or variation in initial pod mass. The absence of e-liquid in the pod is an important factor in causing coil failure. Small bits of the degraded coil could be potentially introduced to the aerosol. This work suggests that further work is required to investigate the effect of e-liquid composition on coil lifetime and TPM yield per puff.

Surveillance of U.S. Corporate Filings Provides a Proactive Approach to Inform Tobacco Regulatory Research Strategy.

The popularity of electronic cigarettes in the United States and around the world has led to a startling rise in youth nicotine use. The Juul® e-cigarette was introduced in the U.S. market in 2015 and had captured approximately 13% of the U.S. market by 2017. Unlike many other contemporary electronic cigarette companies, the founders behind the Juul® e-cigarette approached their product launch like a traditional high-tech start-up company, not like a tobacco company. This article presents a case study of Juul's corporate and product development history in the context of US regulatory actions. The objective of this article is to demonstrate the value of government-curated archives as leading indicators which can (a) provide insight into emergent technologies and (b) inform emergent regulatory science research questions. A variety of sources were used to gather data about the Juul® e-cigarette and the corporations that surround it. Sources included government agencies, published academic literature, non-profit organizations, corporate and retail websites, and the popular press. Data were disambiguated, authenticated, and categorized prior to being placed on a timeline of events. A timeline of four significant milestones, nineteen corporate filings and events, twelve US regulatory actions, sixty-four patent applications, eighty-seven trademark applications, twenty-three design patents and thirty-two utility patents related to Juul Labs and its associates is presented, spanning the years 2004 through 2020. This work demonstrates the probative value of findings from patent, trademark, and SEC filing literature in establishing a premise for emergent regulatory science research questions which may not yet be supported by traditional archival research literature. The methods presented here can be used to identify key aspects of emerging technologies before products actually enter the market; this shifting policy formulation and problem identification from a paradigm of being reactive in favor of becoming proactive. Such a proactive approach may permit anticipatory regulatory science research and ultimately shorten the elapsed time between market technology innovation and regulatory response.

Feasibility Assessment of Wearable Respiratory Monitors for Ambulatory Inhalation Topography.

Background: Natural environment inhalation topography provides useful information for toxicant exposure, risk assessment and cardiopulmonary performance. Commercially available wearable respiratory monitors (WRMs), which are currently used to measure a variety of physiological parameters such as heart rate and breathing frequency, can be leveraged to obtain inhalation topography, yet little work has been done. This paper assesses the feasibility of adapting these WRMs for measuring inhalation topography. Methods: Commercially available WRMs were compiled and assessed for the ability to report chest motion, data analysis software features, ambulatory observation capabilities, participant acceptability, purchasing constraints and affordability. Results: The following WRMs were found: LifeShirt, Equivital EQ02 LifeMonitor, Smartex WWS, Hexoskin Smart Garment, Zephyr BioHarness, Nox T3&A1, BioRadio, SleepSense Inductance Band, and ezRIP & zRIP Durabelt. None of the WRMs satisfied all six assessment criteria in a manner enabling them to be used for inhalation topography without modification and development. Conclusions: The results indicate that there are WRMs with core technologies and characteristics that can be built upon for ambulatory inhalation topography measurement in the NE.

Characterization and Validation of the Second-generation wPUM Topography Monitors.

INTRODUCTION: Little is known about the natural use behavior of new and emerging tobacco products due to the limited availability of reliable puff topography monitors suitable for ambulatory deployment. An understanding of use behavior is needed to assess the health impact of emerging tobacco products and inform realistic standardized topography profiles for emissions studies. The purpose of this study is to validate four monitors: the wPUM cigalike, vapepen, hookah, and cigarette monitors. AIMS AND METHODS: Each wPUM monitor was characterized and validated for range, accuracy, and resolution for puff flow rate, duration, volume, and interpuff gap in a controlled laboratory environment. Monitor repeatability was assessed for each wPUM monitor using four separate week-long natural environment monitoring studies including cigalike, vapepen, hookah, and cigarette users. RESULTS: The valid flow rate range was 10 to 100 mL/s for cigalike and cigarette monitors, 10 to 95 mL/s for vapepen monitors, and 50 to 400 mL/s hookah monitors. Flow rate accuracy was within ±2 mL/s for cigalike, vapepen, and cigarette monitors and ±6 mL/s for the hookah monitor. Durations and interpuff gaps as small as 0.2 s were measured to within ±0.07 s. Monitor calibrations changed by 4.7% (vapepen), 1.5% (cigarette), 0.5% (cigalike), and 0.1% (hookah) after 1 week of natural environment use. CONCLUSIONS: The wPUM topography monitors were demonstrated to be reliable when deployed in the natural environment for a range of emerging tobacco products. IMPLICATIONS: The current study addresses the lack of available techniques to reliably monitor topography in the natural environment, across multiple emerging tobacco products. Natural environment topography data will inform standardized puffing protocols for premarket tobacco product applications. The ability to quantify topography over extended periods of time will lead to a better understanding of use behavior and better-informed regulations to protect public health.

Method for Quantifying Variation in the Resistance of Electronic Cigarette Coils.

In electronic nicotine delivery systems (ENDS), coil resistance is an important factor in the generation of heat energy used to change e-liquid into vapor. An accurate and unbiased method for testing coil resistance is vital for understanding its effect on emissions and reporting results that are comparable across different types and brands of ENDS and measured in different laboratories. This study proposes a robust, accurate and unbiased method for measuring coil resistance. An apparatus is used which mimics the geometric configuration and assembly of ENDS reservoirs, coils and power control units. The method is demonstrated on two commonly used ENDS devices-the ALTO by Vuse and JUUL. Analysis shows that the proposed method is stable and reliable. The two-wire configuration introduced a positive measurement bias of 0.086 (Ω), which is a significant error for sub-ohm coil designs. The four-wire configuration is far less prone to bias error and is recommended for universal adoption. We observed a significant difference in the coil resistance of 0.593 (Ω) (p < 0.001) between the two products tested. The mean resistance and standard deviation of the reservoir/coil assemblies was shown to be 1.031 (0.067) (Ω) for ALTO and 1.624 (0.033) (Ω) for JUUL. The variation in coil resistance between products and within products can have significant impacts on aerosol emissions.

A Comparison between Cigarette Topography from a One-Week Natural Environment Study to FTC/ISO, Health Canada, and Massachusetts Department of Public Health Puff Profile Standards.

Standardized topography protocols for testing cigarette emissions include the Federal Trade Commission/International Standard Organization (FTC/ISO), the Massachusetts Department of Health (MDPH), and Health Canada (HC). Data are lacking for how well these protocols represent actual use behavior. This study aims to compare puff protocol standards to actual use topography measured in natural environments across a range of cigarette brands. Current smokers between 18 and 65 years of age were recruited. Each participant was provided with a wPUM™ cigarette topography monitor and instructed to use the monitor with their usual brand cigarette ad libitum in their natural environment for one week. Monitors were tested for repeatability, and data were checked for quality and analyzed with the TAP™ topography analysis program. Data from n = 26 participants were analyzed. Puff flow rates ranged from 17.2 to 110.6 mL/s, with a mean (STD) of 40.4 (21.7) mL/s; durations from 0.7 to 3.1 s, with a mean (STD) of 1.5 ± 0.5 s; and volumes from 21.4 to 159.2 mL, with a mean (STD) of 54.9 (29.8) mL. Current topography standards were found to be insufficient to represent smoking across the wide range of real behaviors. These data suggest updated standards are needed such that emissions tests will provide meaningful risk assessments.

Effect of user puffing topography on total particulate matter, nicotine and volatile carbonyl emissions from narghile waterpipes.

OBJECTIVES: Puffing topographies of waterpipe users vary widely as does the puff-to-puff topography of an individual user. The aim of this study was to determine if puff duration and flow rate have an effect on the characteristics of the mainstream emission from waterpipes, including total particulate matter (TPM), mass ratio of nicotine and mass concentration of volatile carbonyls. METHODS: Puffing parameters were chosen to encompass a significant portion of the perimeter space observed from a natural environment study. Tested conditions were 150, 200 and 250 mL sec-1; each run at 2, 3.5 and 5 s durations; 25 s interpuff duration and ~100 puffs per session. Each session was run in quadruplicate using the Programmable Emissions System-2 (PES-2) emissions capture system under identical conditions. Particulate matter, for quantification of TPM and nicotine, was collected on filter pads every ~5 L of aerosol resulting in 6 to 25 samples per session. Volatile carbonyls were sampled using 2,4-Dinitrophenylhydrazine (DNPH)-coated silica. RESULTS: Mass concentration of TPM linearly decreased with increased flow rate, with no dependency on puff duration. Nicotine mass ratio was independent of topography, with average mass ratio of nicotine to TPM of 0.0027±0.0002 (mg/mg). The main carbonyls observed were acetaldehyde and formaldehyde. Puff duration increased emissions of some carbonyls (eg, formaldehyde) but not others (eg, acetaldehyde). CONCLUSIONS: The results presented here highlight that topographies influence the emissions generated from waterpipes including TPM, total nicotine and volatile carbonyls. For laboratory studies to be representative of user exposure, a range of topographies must be studied. Using a range of topographies within a controlled laboratory environment will better inform regulatory policy.

A Proposed Waterpipe Emissions Topography Protocol Reflecting Natural Environment User Behaviour.

Usage of waterpipes is growing in popularity around the world. Limited waterpipe natural environment topography data reduces the ability of the research community to accurately assess emissions and user exposure to toxicants. A portable ergonomic waterpipe monitor was provided to study participants to use every time they smoked their own waterpipe during a one-week monitoring period in conjunction with their own choice shisha tobacco. Users provided demographic information and logged their product use to supplement electronic monitor data. A total of 44 prospective study participants were invited to an intake appointment following an on-line pre-screening survey. Of these, 34 individuals were invited to participate in the study and data for 24 individuals who completed all aspects of the 1-week monitoring protocol is presented. 7493 puffs were observed during 74 waterpipe sessions accumulating over 48 h of waterpipe usage. The 95% CI on mean puff flow rate, duration, volume and interval are presented, yielding grand means of 243 [mL/s], 3.5 [s], 850 [mL], and 28 [s] respectively. The middle 95% of puff flow rates ranged between 62 to 408 [mL/s], durations from 0.8 to 6.8 [s], and puff volumes from 87 to 1762 [mL]. A waterpipe emissions topography protocol consisting of 13 flow conditions is proposed to reflect 93% of the observed range of puff flow rate, puff duration and puff volume with representative inter-puff interval, cumulative session time and aerosol volumes.

Framework to Estimate Total Particulate Mass and Nicotine Delivered to E-cig Users from Natural Environment Monitoring Data.

A framework describing the joint effect of user topography behavior and product characteristics of one exemplar device on the total particulate mass (TPM) and aerosol constituent yield delivered to a user is presented and validated against seven user-specific 'playback' emissions observations. A pen-style e-cig was used to collect emissions across puff flow rates and durations spanning the range observed in the natural environment. Emissions were analyzed with GC-MS and used to construct empirical correlations for TPM concentration and nicotine mass ratio. TPM concentration was demonstrated to depend upon both puff flow rate and duration, while nicotine mass ratio was not observed to be flow-dependent under the conditions presented. The empirical model for TPM and nicotine yield demonstrated agreement with experimental observations, with Pearson correlation coefficients of r = 0.79 and r = 0.86 respectively. The mass of TPM and nicotine delivered to the mouth of an e-cig user are dependent upon the puffing behavior of the user. Product-specific empirical models of emissions may be used in conjunction with participant-specific topography observations to accurately quantify the mass of TPM and nicotine delivered to a user.

Latent Class Analysis of E-cigarette Use Sessions in Their Natural Environments.

BACKGROUND: Delivery of nicotine and substances from electronic nicotine delivery systems, or e-cigarettes, depends in part on how users puff on the devices. Little is known about variation in puffing behavior to inform testing protocols or understand whether puffing behaviors result in increased exposure to emissions. METHODS: We analyzed puff topography data collected using a wireless portable use monitor (wPUM) continuously over 2 weeks among 34 current second-generation e-cigarette users in their everyday lives. For each puff, the wPUM recorded date, time, duration, volume, flow rate, and inter-puff interval. RESULTS: We defined use session and classes at the session level using multilevel latent profile analysis, resulting in two session classes and three person types. Session class 1 ("light") was characterized by 14.7 puffs per session (PPS), low puff volume (59.9 ml), flow rate (28.7 ml/s), and puff duration (202.7 s × 100). Session class 2 ("heavy") was characterized by 16.7 PPS with a high puff volume (290.9 ml), flow rate (71.5 ml/s), and puff duration (441.1 s × 100). Person class 1 had almost exclusively "light" sessions (98.0%), whereas person class 2 had a majority of "heavy" sessions (60.7%) and person class 3 had a majority of "light" sessions (75.3%) but some "heavy" sessions (24.7%). CONCLUSION: Results suggest there are different session topography patterns among e-cigarette users. Further assessment is needed to determine whether some users have increased exposure to constituents and/or health risks because of e-cigarettes. IMPLICATIONS: Our study examines topography characteristics in a users' natural setting to identify two classes of e-cigarette session behavior and three classes of users. These results suggest that it is important for studies on the health effects of e-cigarettes to take variation in user topography into account. It is crucial to accurately understand the topography profiles of session and user types to determine whether some users are at greater exposure to harmful or potentially harmful constituents and risks from e-cigarettes as they are used by consumers.

Behavior-based yield for electronic cigarette users of different strength eliquids based on natural environment topography.

Introduction: The extent to which electronic cigarette users will compensate for lower nicotine eliquids has implications on the risk associated with regulating eliquid composition. This article elucidates topography as a compensatory mechanism by investigating the impact of nicotine strength on total particulate matter (TPM) and nicotine consumed per puff.Methods: Thirty-three experienced vape pen users were assigned an NJOY™ VapePen and AVAIL™ brand Tobacco Row eliquid with their usual nicotine strength (L = 6 mg/mL, M = 12 mg/mL, H = 18 mg/mL) and vaped through RIT's wPUMTM vape pen monitor to record every puff during 1 week. Nicotine and TPM yield per puff was determined accounting for the impact of topography characteristics on emissions and used to compute participant-specific mean yield per puff.Results: Nicotine yields ranged from 0.01 to 0.05 mg/puff and varied widely within each group (L, M, and H nicotine strength). Group-wise mean flow rate was lower for L compared to M (p = 0.2) and duration was higher compared to M (p = 0.09). Larger TPM was consumed per puff for L compared to M (p = 0.07), yet nicotine per puff for L was less than M (p = 0.3). H users took smaller volumes than L (p = 0.1) or M (p = 0.17), and there was little difference between L and M (p = 0.47).Conclusions: Evidence was provided for topography as a compensatory mechanism. Use of low nicotine strength eliquids can increase TPM, which can lead to increase in HPHC. Regulatory review of new products should consider natural use topography and realistic use exposures to nicotine, TPM and HPHCs.

A framework to investigate the impact of topography and product characteristics on electronic cigarette emissions.

SIGNIFICANCE: Protocols for testing and reporting emissions of Harmful and Potentially Harmful Constituents (HPHCs) from electronic cigarettes (e-cigs) are lacking. The premise of this study is that multi-path relationships may be developed to describe interactions between product characteristics, use behavior and emissions to develop appropriate protocols for tobacco product regulatory compliance testing. METHODS: This study proposes a framework consisting of three component terms: HPHC mass concentration, HPHC mass ratio and total particulate mass (TPM) concentration. The framework informs experiments to investigate dependence of aerosol emissions from five electronic cigarettes spanning several design generations and three e-liquids for six repeated trials at each of ten flow conditions. RESULTS: Results are reported for TPM concentration as a function of flow conditions spanning the range of natural environment topography observed in prior studies. An empirical correlation describing TPM concentration as a function of flow conditions and coil power setting (6, 7.5 and 10 watts) for the Innokin iTaste MVP 2.0 vaporizer with Innokin iClear 30 dual coil tank is presented. Additional results document the impact of flow conditions and wick and coil design on TPM concentration through comparison of the Innokin iClear 30 (upper coil, capillary action wick) and the Innokin iClear X.I (lower coil, gravity fed wick) operated at 7.5 watts. The impact of e-liquid on TPM concentration is illustrated by comparing emissions from an NJOY Vape Pen filled with AVAIL Arctic Blast, Tobacco Row, and Mardi Gras e-liquids. TPM concentration is shown to depend upon flow conditions across a range of e-cigarette product designs including cig-a-like, pen-style, box-mod and emergent disposable-cartridge style devices. CONCLUSIONS: A framework provides a foundation for reporting emissions across a variety of e-cigs, e-liquids and research laboratories. The study demonstrates TPM concentration is a function of topography behavior (i.e. puff flow rate and puff duration) for varying device operating power and product characteristics.