Puffing topography and mouth level exposure of two closed-system Vype e-cigarettes

INTRODUCTION

Cigarette smoking is one of the leading avoidable causes of disease, including cancer, cardiovascular disease and respiratory diseases linked to the inhalation of cigarette smoke containing multiple chemicals and known toxicants.^1-3 Risk of smoking-related disease is associated with daily consumption and number of years of smoking, therefore quitting is undoubtedly the best way to both increase life expectancy and decrease the health burden of cigarettes.^4-7 Notably however, only 3%-5% of smokers who try to quit without assistance are successful, and fewer than 10% of all smokers achieve long-term abstinence; therefore, other approaches are needed.^8,9

The idea of tobacco harm reduction by ‘decreasing total morbidity and mortality, without completely eliminating tobacco and nicotine use’ was conceived by the US Institute of Medicine in 2001.^10,11 Since then, public health bodies have established tobacco harm reduction policies to encourage smokers to switch to using non-combustible tobacco and nicotine products, such as nicotine replacement therapy (NRT) and electronic cigarettes (e-cigarettes), in place of conventional smoking.^7,12,13

By producing an inhalable aerosol containing much fewer and lower concentrations of toxicants relative to cigarette smoke, e-cigarettes have strong potential to meet the criteria for tobacco harm reduction.¹⁴ In the United Kingdom there were an estimated 2.5 million users in 2018.⁷

In order to be useful in a tobacco harm reduction approach, however, e-cigarettes must be able to deliver nicotine efficiently and meet adult consumer’s preferences, in addition to reduced toxicant emissions.¹⁴ It is therefore important to carry out ‘actual use’ studies that evaluate a consumer’s use behaviour, including consumption, puffing topography (i.e., puff volume, duration and interval) and mouth level exposure (MLE) to nicotine and aerosol. These parameters affect a user’s actual exposure to harmful constituents and play an important role in determining the overall reduced risk potential of alternative nicotine products.^15,16

Importantly, both user behaviour and the sensory effects of e-cigarettes vary considerably depending on the device (e.g., power setting, resistance, open pressure drop) and composition of the e-liquid (e.g., nicotine content, flavours, etc.).^17,18 It is important to obtain data covering a range of different devices and e-liquids to understand the potential contribution that a product might have in reducing tobacco-related harm. This actual use study was undertaken with the aim of understanding user puffing topography and MLE to aerosol relating to two commercially available closed-system e-cigarettes: a pen-type device with 18 mg/ml nicotine e-liquid (Vype ePen3); and a pod-type e-cigarette with 18 mg/ml nicotine and nicotine-free e-liquid (Vype ePod).

Murphy et al 2017, proposed a multi-disciplinary risk assessment framework comprising pre-clinical, clinical, and population studies to assess the risk profile of novel tobacco products.¹⁶ This assessment framework comprises a series of verifiable studies, in 9 different stages, for comprehensive next generation product (NGP) evaluation and the substantiation of health-related claims. This study contributes to the data collected for stage 4 of the framework. Stage 4 studies include quantifying exposure beginning with puffing behaviour and mouth level exposure studies giving insight into how consumers use new products and quantifying the maximum yield possible. Furthermore, puffing behaviour studies are important for assessing if the machine puffing regimes used in laboratory-based pre-clinical measurements are reflective of consumer's actual behaviour.

METHODS

Study design

Two separate studies were conducted in Gosport, UK, in 2019, with two cohorts of e-cigarette users who had been vaping daily for more than 6 months were recruited. Their puffing topography, MLE and sensory perception was measured when using two different types of e-cigarette: a wick and coil device (Vype ePen3) with nicotine e-liquid (part one), and a ceramic block and plate pod device (Vype ePod). The first study evaluated ePen3 device with an 18 mg/ml nicotine cartridge, while the second study evaluated ePod with 0 mg/ml and 18 mg/ml nicotine e-liquids. The study protocol and Informed Consent Form were approved in accordance with the ethical principles outlined.

Study products

The two study products were Vype ePen3 (BAT) and Vype ePod (BAT), which were both commercially available in the United Kingdom at the time of the study. The description of the study products and the composition of the e-liquids used are shown in Table 1, Figure 1 and 2. The ePen3 device was used with Wild Berries e-liquid (18 mg/ml nicotine); the ePod with Mango e-liquids (0 and 18 mg/ml nicotine). The aerosol collected mass (ACM) generated using the CORESTA recommended method No. 81 (CRM81) machine puffing regime for ePen3 and ePod was 8 and 6.5 mg/puff, respectively. The CRM81 puffing regime recommends a 55 ml puff volume, 3 s puff duration and 30 s puff interval.¹⁹ The open pressure drop was 23 and 70 mmWG, respectively, measured at a flow rate of 17.5 ml/s.

Note: a-Data provided by BAT - derived from 5 replicates (50 puffs per replicate), using machine puffing regime 55 ml/3.0s/30 square profile, with 1s pre-puff activation for Vype ePen3; b-Propylene glycol; c-vegetable glycerol; and d-undisclosed amount of flavourings contained in the PG.

Study participants

Two groups of approximately 60 adult participants, including solus users of e-cigarettes and dual users of e-cigarettes and tobacco cigarettes were recruited by an independent market research agency (Survey Marketing Services, Newcastle, UK) in May and October 2019 in accordance with the International Code on Market Opinion and Social Research and Data Analytics.²⁰ The inclusion criteria were age 21-64 years, daily use of e-cigarettes, vaping for at least 6 months, and vaping e-liquid containing 12 mg/ml or higher nicotine. The exclusion criteria were women who were pregnant or breastfeeding, and persons fitted with pacemakers. All participants read and signed an informed consent form before the study and were each given a unique volunteer ID code by the agency, which was used to identify individuals throughout the study. Participants were free to withdraw from the study for any reason at any stage and were reimbursed for participation after completion of the study. They were asked to abstain from using any nicotine product for an hour prior to the study visit.

Study protocol

The same protocol was used for both studies. Participants attended the study centre for approximately 45 minutes per visit (using only one product per visit), during which time they used the study product in two separate product use sessions separated by a 20-min interval. In each session, participants were asked to take 10 puffs on the study product, vaping as they would normally, through a special holder that was attached to a Puffing Analyser (SA7) for measuring puffing topography parameters.²¹ In the 20-min interval, participants completed a short sensory questionnaire. The purpose of the sensory questionnaire was to supplement the puffing topography and help explain any differences seen in the topography and MLE data.

Puffing topography

For the two types of e-cigarette devices, puff volume, puff duration, puff interval and pressure drop were recorded by a desktop puffing analyser (SA7) (Figure 3), originally developed to measure smoking topography.²¹ The SA7 comprises a product holder attached to a data acquisition transmission unit (DAT unit). Two tubes on either side of a 2 mm diameter orifice within the product holder detect the change in pressure during a puff, which is proportional to the flow rate squared.²¹ The product holder was previously modified for use with e-cigarettes.^{22, 23} In each session, participants were asked to take 10 puffs on the study product, vaping as they would normally. The study products were weighed before and after each use to determine the device mass loss (DML), which in turn was used to estimate the mouth level exposure (MLE) to aerosol and nicotine (see below). A clean disposable plastic mouthpiece was attached to the product holder at the beginning of each session (to avoid cross-contamination between participants).

MLE

Participant’s MLE to aerosol collected mass (ACM) and nicotine was estimated from DML by using calibration graphs generated under different machine-puffing regimes.²³ In brief, 10 puffs of each study product were taken under eight different machine puffing regimes using a PM1 vaping machine (Borgwaldt KC, Hamburg, Germany), with puff volumes ranging 40-120 ml and puff durations ranging 1.5-6.0 s, using a bell shaped profile and puff frequency of 30s.

For Vype ePen3, a 1-second pre-puff button activation was applied at the start of each puff. The aerosol for each puffing regime was collected onto a clean 44mmm Cambridge Filter Pad (CFP). Both the CFP and device were weighed before and after puffing to determine ACM and DML, respectively. Nicotine content in the ACM was determined by gas chromatography as described previously.²³

For each product, DML was plotted against the corresponding ACM and nicotine yields to produce calibration graphs with the line of best fit forced through the origin. R² values for the calibration were 0.9820-0.9996. Participants’ MLE was then estimated from the DML using the regression equations as follows:

MLE to ACM = DML × slope_ACM

MLE to nicotine = DML × slope_nicotine

Sensory questionnaire

After the first product use session, participants were asked to complete a sensory questionnaire comprising questions on product likeability, immediate aerosol delivery, draw effort, amount of aerosol filling the mouth, irritation, hit/kick intensity and taste. They were asked to score these sensory attributes on both a magnitude scale, ranging from 1 (low) to 5 (high), and a ‘just-right’ scale with options of too low, slightly too low, just right, slightly too high and too high.

Data analysis

Statistical analysis was carried out using Minitab 19 and SAS v9.4 statistical software. Puffing topography records and sensory data were compiled in a Minitab spreadsheet and mean±standard deviation (SD) values were determined. Puffing topography and MLE data were analysed for significant differences between ePen3 and ePod (18 mg/ml nicotine) using a linear mixed effects model with Product as a fixed effect and Subject as a random effect, to account for N=27 subjects being in both studies. ePod variants (0 and 18 mg/ml nicotine) were compared using a paired t-test at 5% significance level (α). Similarly, Magnitude sensory perception responses were analysed for significant differences between ePen3 and ePod (18 mg/ml nicotine) using similar linear mixed effects model and between ePod variants (0 and 18 mg/ml nicotine) using a paired t-test at the 5% significance level (α). ‘Just right’ sensory perception responses were analysed for significant differences from the ideal value of 3 using a one-sample t-test, where 3- ‘just right’.

RESULTS

Study participants

In the first study, 60 adult vapers (30 males, 30 females; 30 solus users, 30 dual users) were recruited to use the ePen3; in the second, 58 (29 males/29 females; 30 solus users, 28 dual users) were recruited to use the ePod.

In study 1 (ePen3), 52 participants completed all topography measurements, 51 completed all sensory perception questionnaires, and 44 completed both. In Study 2 (ePod), 52 completed all topography measurements, 58 completed all sensory perception questionnaires, and 52 participants completed both (Table 2).

Puffing topography

The mean puff volume, puff duration, puff interval and pressure drop for all participants in each study are summarised in Table 3 and 4.

The pressure drop during puffing was significantly higher (p≤0.0001) for ePod compared with ePen3 (162.1 vs 97.6 mmWG) resulting in significantly lower puff volumes (p≤0.0001) for ePod than ePen3 (49.4 vs 79.8 ml). A much higher pressure drop experienced by users vaping the ePod as compared with the ePen3 may be attributed to the relatively higher open pressure drop of ePod (70 mmWG) compared with ePen3 (23 mmWG) measured at a flow rate of 17.5 ml/s.

Participants took significantly longer puff durations (p≤0.0001) for the 0 mg/ml nicotine ePod than for the 18 mg/ml nicotine ePod (2.68 s vs 2.29 s), and took significantly larger puff volumes (p≤0.0001) for the 0 mg/ml nicotine ePod compared to the 18 mg/ml nicotine ePod (58.4 ml vs 49.4 ml). Longer puff durations and larger puff volumes taken for the nicotine-free e-liquid may be attributed to participants puffing harder in order to achieve the desired satisfaction from the product due to the lack of nicotine.

Mouth level exposure

The data for MLE are summarised in Table 5 and 6.

MLE to aerosol (ACM) was similar (p=0.1637) for both ePen3 and ePod (3.39 mg/puff vs 4.80 mg/puff).

MLE to nicotine was also similar (p=0.3802) for both ePen3 and ePod (0.06 mg/puff vs 0.07 mg/puff).

As expected, the MLE to ACM was significantly higher (p≤.0001) for the 0 mg/ml nicotine ePod compared with the 18 mg/ml nicotine ePod (6.02 mg/puff vs 4.80 mg/puff), whilst the MLE to nicotine was significantly lower (p≤0.0001) for the 0 mg/ml nicotine ePod compared to the 18 mg/ml nicotine ePod (0.00 mg/puff vs 0.07 mg/puff).

Sensory questionnaire

Results from the sensory questionnaire, reported as a mean score from 1 to 5, are summarised in Table 7 and 8. The 18 mg/ml nicotine ePen3 and ePod were perceived to be similar in all of the sensory attributes evaluated (Table 7). However, the 0 mg/ml nicotine ePod was perceived to be significantly lower in aerosol delivery (p=0.0230), mouthful (p=0.0231), irritation (p=0.0002) and Hit/Kick intensity (p≤0.0001) compared with 18 mg/mL nicotine ePod (Table 8).

On the ‘just right’ scale (Table 9), the 0 mg/ml nicotine ePod was perceived to be ‘slightly too hard’ to draw and ‘slightly too low’ for all other attributes. The 18 mg/ml nicotine ePod was perceived to be ‘slightly too hard’ to draw and ‘slightly too low’ for mouthful and taste amount. The 18 mg/ml nicotine ePen3 by contrast was perceived to be ‘just right’ for most attributes and slightly higher than ideal for aerosol delivery, irritation and hit/kick intensity.

Note:* within the ICF boundaries of over 21 years old bracket.

Note: a-Results obtained using a mixed effects model with fixed effect of product and a random effect of subject, p values come from the comparison of the Least squares means, the threshold of statistical significance is 0.05; b- N=52 participants. 2 measures per participant (averaged); c- N=52 participants. 2 measures per participant (averaged).

Note: a-Determined using paired t-test at 5% significance level (α); b- N=52 participants. 2 measures per participant (averaged)

c- N=52 participants. 2 measures per participant (averaged).

Note: a-Results obtained using a mixed effects model with fixed effect of product and a random effect of subject, p values come from the comparison of the least squares means, the threshold of statistical significance is 0.05; b N= =52 participants. 2 measures per participant (averaged); and c- N=52 participants. 2 measures per participant (averaged).

Note: a- Determined using paired t-test at 5% significance level (α); b N=52 participants. 2 measures per participant (averaged); and c N=52 participants. 2 measures per participant (averaged).

Note: a- Results obtained using a mixed effects model with fixed effect of product and a random effect of subject, p values come from the comparison of the least squares means, the threshold of statistical significance is 0.05.

Note: a- Determined using paired t-test at 5% significance level (α).

Note: Determined using a one-sample t-test at the 5% significance level (α) where the hypothesised value 3=‘just right.

DISCUSSION

E-cigarettes have been shown to have lower toxicant emissions in comparison to conventional cigarette smoke and thus have the potential to reduce the health risks associated with cigarette smoking.^14,24 However, exposure to both nicotine and other constituents from these devices is also affected by how the consumer uses them; therefore, it is essential to characterize consumer use behaviour such as puffing topography alongside emissions to obtain an overall estimate of the relative harm from these products.²⁵ Such ‘real-world’ e-cigarette topography data also help to inform laboratory-based emissions testing by identifying the most appropriate puffing parameters for instrumental analyses.²⁶ While a number of previous studies have documented the user puffing topography of e-cigarettes, devices and e-liquids are continually evolving, and the new products should be assessed to gather as much data as possible.^23,27-29 Here we have evaluated user puffing topography and sensory effects for a pen-type (Vype ePen3) and pod-type e-cigarette device (Vype ePod) with 18 mg/ml nicotine e-liquid. The ePod device was also evaluated with 0 mg/ml nicotine e-liquid. Study participants exerted lower pressure drop (PD) and generated higher puff volumes from ePen3 than ePod (97.6 vs 162.1 mmWG and 79.8 vs 49.4 ml, respectively). This may be attributed to the lower open PD of ePen3 compared with ePod (23 vs 70 mmWG at 17.5 ml/s). Despite of the difference in the puffing topography attributes between the two devices, user MLE to ACM and nicotine were observed to be similar. This was reflected in the similar overall likeability and scores for the sensory attributes evaluated. The nicotine delivery for these products were considerably lower than that delivered by a typical 6 mg ‘tar’ cigarette (1.3±0.5 mg/stick).³⁰

Previous studies of various e-cigarettes ranging from early ‘cig-a-likes’ to new prototypes have reported mean puff volumes ranging from 41.2 ml for a recent prototype device with distiller plate technology and 51.0 ml for two cartomizer devices, to 101.4 ml for early tank devices.^23,27,28 The current values (ePen3, 79.8 ml; ePod, 49.4 ml) fall within this reported range. Similarly, previously reported puff durations range from 1.4 s and 2.65 s to 4.16 s, with current values (ePen3, 2.13 s; ePod, 2.29 s) falling within this range.^23,27,28

Many factors have been reported to affect puffing topography including e-liquid flavour, which may affect mean puff duration and mean number of puffs, and nicotine content, where higher nicotine leads to shorter puff durations.^17,31-34 Similarly, in the second study, participants vaping ePod with 0 mg/ml nicotine e-liquid were observed to take longer puff duration compared to those using 18 mg/ml nicotine e-liquid (2.68 s vs 2.29 s). Consequently, generating higher puff volumes in the process. This may be explained by the participants engaged in compensatory puffing, owing to the lack of nicotine in the e-liquid.³²

Other factors that may influence puffing topography include PG:VG ratio, where high PG content leads to shorter and smaller puffs, and device settings such as power, with higher power settings leading to shorter puff duration.^18,35 In the present study, however, PG:VG ratios of the two 18 mg/ml e-liquids were similar (ePen3 54.00:33.50 vs ePod 50.00:47.69) and the two devices had fixed power settings of 7.8W (ePen3) and 6.5W (ePod). Puffing topography also differs by level of established experience in the product user with longer puffs taken by experienced users relative to naïve product users.^33,36 A recent study showed that inexperienced e-cigarette users increased their inter-puff interval and puff duration over a 2-week trial period.³⁷ In the present study, these potential differences were avoided by recruiting only experienced vapers. Because sensory perception of a nicotine product and its use are key aspects in trying to encourage a smoker to switch to reduced risk products, we also assessed the participants’ subjective responses (via a questionnaire) after using the products. Overall, the participants reported similar likeability and other sensory scores for the two devices with 18 mg/ml nicotine e-liquid; similar characteristics of the aerosol generated. However, the ePod device with 0 mg/ml nicotine e-liquid was perceived to be lower in aerosol delivery, mouthful, irritation, hit/kick intensity and less liked overall compared with the 18 mg/ml nicotine e-liquid, presumably due to the lack of nicotine in the ePod device.

Limitations

The study had some limitations. In the topography sessions, participants were asked to take 10 puffs from the study products and it is possible that longer puff durations and larger puff volumes may be observed during ad libitum as compared with fixed puffing sessions.³⁸ In addition, while two puffing sessions were recorded for each participant, it is possible that an e-cigarette user may show variability in puffing topography recorded at different times and in different situations.^39,40 Furthermore, the present study recorded a snapshot of use behaviour for participants trying an unfamiliar device, and puff duration and volume has been shown to increase with product use over time.⁴¹

CONCLUSION

Alongside aerosol emissions testing, actual use studies provide key information on the manner in which consumers use nicotine and tobacco products and thus help to estimate the overall exposure to harm from these products, as well as providing parameters to inform laboratory-based testing. Hypothetically, the effect of increasing puffing volume on aerosol delivery would be less for e-cigarettes than for cigarettes, as it is independent of the heating of the tobacco and is principally used to condense the vapour into an aerosol. The average puff volumes observed with ePen3 and ePod (18 mg/ml nicotine) were 79.8 ml and 49.4 ml, respectively. Even though the puff volume for ePen3 was higher than the 55 ml machine puff volume recommended by CORESTA (2015), this volume is still relevant to consumers. In the two studies the mean puff duration for ePen3 and ePod (18 mg/ml nicotine) was 2.13 and 2.29 s respectively. Usually, consumers depress the activation button before puffing (for approximately 1 s), meaning that the heating coil is activated for a 1 s longer than the measured puff duration. As a result, the e-cigarette aerosolisation duration (or time when the heating coil was activated) for ePen3 was probably closer to the 3 s puff duration recommended by CORESTA (2015). The fixed puff protocol along with the confined study where users vaped through a special holder tethered to a puffing analyser may have resulted in the short puff interval compared to the 30 s puff interval recommended by CORESTA (2015). In summary, the puffing topography attributes like puff volume, puff duration and puff interval broadly support the CRM 81 machine puffing regimes (CORESTA 2015) used for in vitro and chemical analysis. Notably, MLE to aerosol and nicotine from ePen3 and ePod were similar (3.89 vs 4.80 and 0.06 vs 0.07 mg respectively) despite the very different designs of the devices. The nicotine delivery for these products were considerably lower than that delivered by a typical 6 mg ‘tar’ cigarette (1.3±0.5 mg/stick).

ACKNOWLEDGEMENTS

We would like to thank Vicky McKeown for providing the samples and logistic support; Jesse Thissen and Filimon Meichanetzidis for their assistance with the statistical analysis.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. US Department of Health and Human Services. The Health Consequences of Smoking 50 Years of Progress: a Report of the Surgeon General, 2014. Available at: https://www.hhs.gov/surgeongeneral/reportpublications/tobacco/index.html. Accessed on 28 February 2020.
2. 2. Rodgman A, Perfetti TA. The Chemical Components of Tobacco and Tobacco Smoke. 2nd ed. USA: CRC Press; 2013.
3. 3. Fowles J, Dybing E. Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke. Tob Control. 2003;12(4):424-30.
4. 4. Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years' observations on male British doctors. BMJ. 1994;309(6959):901-11.
5. 5. Royal College of Physicians. Harm reduction in nicotine addiction: helping people who can’t quit. A report by the tobacco advisory group of the Royal College of Physicians. London: RCP; 2007.
6. 6. Wipfli H. The Tobacco Atlas. American J Epidemiol. 2012;176(12):1193.
7. 7. Public Health England. Health matters: stopping smoking - what works?, 2019. Available at: https://www.gov.uk/government/publications/healthmatters-stopping-smoking-what-works. Accessed on 28 February 2020.
8. 8. Babb S, Malarcher A, Schauer G, Asman K, Jamal A. Quitting Smoking Among Adults - United States, 2000-2015. MMWR Morb Mortal Wkly Rep. 2017;65(52):1457-64.
9. 9. Chaiton M, Diemert L, Cohen JE, Bondy SJ, Selby P, Philipneri A, et al. Estimating the number of quit attempts it takes to quit smoking successfully in a longitudinal cohort of smokers. BMJ Open. 2016;6(6):e011045.
10. 10. Stratton K, Shetty P, Wallace R, Bondurant S. Clearing the smoke: the science base for tobacco harm reduction--executive summary. Tob Control. 2001;10(2):189-95.
11. 11. Institute of Medicine (IOM). Clearing the Smoke—Assessing the Science Base for Tobacco Harm Reduction. Washington, DC: The National Academies Press; 2001.
12. 12. Royal College of Physicians. Nicotine with smoke: Tobacco harm reduction, 2016. Available at: https://www.rcplondon.ac.uk/projects/outputs/nicotine-without-smoke. Accessed on 28 February 2020.
13. 13. Royal College of General Practitioners. RCGP Position Statement on the use of electronic nicotine vapour products (e-cigarettes), 2017. Available at: https://www.rcgp.org.uk//media/Files/Policy/2017/R CGP-E-cig-position-statement-sept-2017. Accessed on 03 July 2020.
14. 14. Margham J, McAdam K, Forster M, Liu C, Wright C, Mariner D, Proctor C. Chemical Composition of Aerosol from an E-Cigarette: A Quantitative Comparison with Cigarette Smoke. Chem Res Toxicol. 2016;29(10):1662-78.
15. 15. FDA. Guidance for Industry- Modified Risk Tobacco Product Applications – Draft Guidance, 2012. Available at: https://www.fda.gov/media/83300. Accessed on 04 October 2021.
16. 16. Murphy J, Gaca M, Lowe F, Minet E, Breheny D, Prasad K, et al. Assessing modified risk tobacco and nicotine products: Description of the scientific framework and assessment of a closed modular electronic cigarette. Regul Toxicol Pharmacol. 2017;90:342-57.
17. 17. Voos N, Smith D, Kaiser L, Mahoney MC, Bradizza CM, Kozlowski LT, et al. Effect of e-cigarette flavors on nicotine delivery and puffing topography: results from a randomized clinical trial of daily smokers. Psychopharmacology (Berl). 2020;237(2):491-502.
18. 18. Farsalinos K, Poulas K, Voudris V. Changes in Puffing Topography and Nicotine Consumption Depending on the Power Setting of Electronic Cigarettes. Nicotine Tob Res. 2018;20(8):993-7.
19. 19. CRM (CORESTA RECOMMENDED METHOD). No. 81 Routine Analytical Machine for E-Cigarette Aerosol Generation and Collection – Definitions and Standard Conditions, 2015. Available at: https://www.coresta.org/routine-analyticae-cigarettedefinitions-and-standard. Accessed on 04 October 2021.
20. 20. International Chamber of Commerce (ICC)/ESOMAR. International code on market, opinion and social research and data analytics, 2016. Available at: https://www.esomar.org/uploads/pdf/prof. Accessed on 04 October 2021.
21. 21. Slayford S, Frost B. A device to measure a smokers’ puffing topography and real-time puff by puff “tar” delivery. Beitr Tab Int. 2014;26(18):74-84.
22. 22. Cunningham A, Slayford S, Vas C, Gee J, Costigan S, Prasad K. Development, validation and application of a device to measure e-cigarette users' puffing topography. Sci Rep. 2016;6:35071.
23. 23. Jones J, Slayford S, Gray A, Brick K, Prasad K, Proctor C. A cross-category puffing topography, mouth level exposure and consumption study among Italian users of tobacco and nicotine products. Sci Rep. 2020;10(1):12.
24. 24. Heide J, Adam TW, Jacobs E, Wolter JM, Ehlert S, Walte A, et al. Puff-Resolved Analysis and Selected Quantification of Chemicals in the Gas Phase of E-Cigarettes, Heat-Not-Burn Devices, and Conventional Cigarettes Using Single-Photon Ionization Time-of-Flight Mass Spectrometry (SPI-TOFMS): A Comparative Study. Nicotine Tob Res. 2021;23(12):2135-44.
25. 25. Hensel EC, Eddingsaas NC, DiFrancesco AG, Jayasekera S, O'Dea S, Robinson RJ. Framework to Estimate Total Particulate Mass and Nicotine Delivered to E-cig Users from Natural Environment Monitoring Data. Sci Rep. 2019;9(1):8752.
26. 26. McAdam K, Davis P, Ashmore L, Eaton D, Jakaj B, Eldridge A, et al. Influence of machine-based puffing parameters on aerosol and smoke emissions from next generation nicotine inhalation products. Regul Toxicol Pharmacol. 2019;101:156-65.
27. 27. Behar RZ, Hua M, Talbot P. Puffing topography and nicotine intake of electronic cigarette users. PLoS One. 2015;10(2):e0117222.
28. 28. Spindle TR, Breland AB, Karaoghlanian NV, Shihadeh AL, Eissenberg T. Preliminary results of an examination of electronic cigarette user puff topography: the effect of a mouthpiece-based topography measurement device on plasma nicotine and subjective effects. Nicotine Tob Res. 2015;17(2):142-9.
29. 29. Kosmider L, Jackson A, Leigh N, O'Connor R, Goniewicz ML. Circadian puffing behavior and topography among e-cigarette users. Tob Regul Sci. 2018;4(5):41-9.
30. 30. Gee J, Prasad K, Slayford S, Gray A, Nother K, Cunningham A, et al C. Assessment of tobacco heating product THP1.0. Part 8: Study to determine puffing topography, mouth level exposure and consumption among Japanese users. Regul Toxicol Pharmacol. 2018;93:84-91.
31. 31. Helen G, Shahid M, Chu S, Benowitz NL. Impact of e-liquid flavors on e-cigarette vaping behavior. Drug Alcohol Depend. 2018;189:42-8.
32. 32. Dawkins LE, Kimber CF, Doig M, Feyerabend C, Corcoran O. Self-titration by experienced e-cigarette users: blood nicotine delivery and subjective effects. Psychopharmacology (Berl). 2016;233(15-16):2933-41.
33. 33. Hiler M, Breland A, Spindle T, Maloney S, Lipato T, Karaoghlanian N, et al. Electronic cigarette user plasma nicotine concentration, puff topography, heart rate, and subjective effects: Influence of liquid nicotine concentration and user experience. Exp Clin Psychopharmacol. 2017;25(5):380-92.
34. 34. Hiler M, Karaoghlanian N, Talih S, Maloney S, Breland A, Shihadeh A, et al. Effects of electronic cigarette heating coil resistance and liquid nicotine concentration on user nicotine delivery, heart rate, subjective effects, puff topography, and liquid consumption. Exp Clin Psychopharmacol. 2020;28(5):527-39.
35. 35. Spindle TR, Talih S, Hiler MM, Karaoghlanian N, Halquist MS, Breland AB, et al. Effects of electronic cigarette liquid solvents propylene glycol and vegetable glycerin on user nicotine delivery, heart rate, subjective effects, and puff topography. Drug Alcohol Depend. 2018;188:193-9.
36. 36. Lee YO, Nonnemaker JM, Bradfield B, Hensel EC, Robinson RJ. Examining Daily Electronic Cigarette Puff Topography Among Established and Nonestablished Cigarette Smokers in their Natural Environment. Nicotine Tob Res. 2018;20(10):1283-8.
37. 37. Kimber CF, Soar K, Dawkins LE. Changes in puffing topography and subjective effects over a 2-week period in e-cigarette naive smokers: Effects of device type and nicotine concentrations. Addict Behav. 2021;118:106909.
38. 38. Spindle TR, Hiler MM, Breland AB, Karaoghlanian NV, Shihadeh AL, Eissenberg T. 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. Nicotine Tob Res. 2017;19(4):469-76.
39. 39. Robinson RJ, Hensel EC, Roundtree KA, Difrancesco AG, Nonnemaker JM, Lee YO. Week long topography study of young adults using electronic cigarettes in their natural environment. PLoS One. 2016;11(10):e0164038.
40. 40. Lee YO, Morgan-Lopez AA, Nonnemaker JM, Pepper JK, Hensel EC, Robinson RJ. Latent Class Analysis of E-cigarette Use Sessions in Their Natural Environments. Nicotine Tob Res. 2019;21(10):1408-13.
41. 41. Wagener TL, Avery JA, Leavens ELS, Simmons WK. Associated changes in e-cigarette puff duration and cigarettes smoked per day. Nicotine Tob Res. 2021;23(4):760-4.