- Email: [email protected]
Characterization of puff topography of a prototype electronic cigarette in adult exclusive cigarette smokers and adult exclusive electronic cigarette users
Accepted Manuscript Characterization of puff topography of a prototype electronic cigarette in adult exclusive cigarette smokers and adult exclusive electronic cigarette users Andrea Rae Vansickel, Jeffery S. Edmiston, Qiwei Liang, Cheryl Duhon, Chris Connell, David Bennett, Mohamadi Sarkar PII:
S0273-2300(18)30203-4
DOI:
10.1016/j.yrtph.2018.07.019
Reference:
YRTPH 4182
To appear in:
Regulatory Toxicology and Pharmacology
Received Date: 25 October 2017 Revised Date:
21 July 2018
Accepted Date: 23 July 2018
Please cite this article as: Vansickel, A.R., Edmiston, J.S., Liang, Q., Duhon, C., Connell, C., Bennett, D., Sarkar, M., Characterization of puff topography of a prototype electronic cigarette in adult exclusive cigarette smokers and adult exclusive electronic cigarette users, Regulatory Toxicology and Pharmacology (2018), doi: 10.1016/j.yrtph.2018.07.019. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
1
Characterization of puff topography of a prototype electronic cigarette in adult
2
exclusive cigarette smokers and adult exclusive electronic cigarette users
3
Andrea Rae Vansickel1, Jeffery S Edmiston1, Qiwei Liang1, Cheryl Duhon1, Chris
5
Connell1, David Bennett1, Mohamadi Sarkar1,2
RI PT
4
6 7
1
8
Center for Research and Technology
9
601 E. Jackson Street, Richmond, VA, USA
11
M AN U
10
SC
Altria Client Services LLC,
12
2
13
Mohamadi Sarkar,
14
Center for Research and Technology
15
601 E. Jackson Street, Richmond, VA, USA
16
Phone: +1-804-335-2537,
17
Email: [email protected] or [email protected]
TE D
EP
AC C
18
Address for correspondence:
19
Keywords: E-cigarettes, e-vapor products, cartridge-based, topography, puff volume,
20
puff parameters, smokers, e-cigarette users.
1
ACCEPTED MANUSCRIPT
ABSTRACT
22
Puff topography is an important measure of how consumers use e-vapor products. The
23
purpose of this study was to evaluate the feasibility of using SODIM Smoking Puff
24
Analyzer Mobile Device (SPA/M) to measure puff topography during use of a prototype
25
e-cigarette (e-cig) in exclusive cigarette smokers (CS) and e-cig users (EC) under ad lib
26
conditions in a clinic. Adult CS (n=13) and EC (EC; n=10) completed a 7-hr use session
27
with the e-cig (2% tobacco-derived nicotine by weight, cartridge based system
28
approximately the size of a king size cigarette). E-liquid usage was determined from
29
cartridge weight. CS also smoked a single cigarette with the SPA/M. The SPA/M reliably
30
recorded puff parameters throughout the study period, with CS puffs averaging
31
47.9±18.2 ml volume, 2.3±0.8 seconds duration, and 21.5±4.6 ml/second flow rate. EC
32
puffs averaged 53.4±19.2 ml volume, 3.0±1.3 seconds duration, and 19.6±5.0 flow rate.
33
CS average e-liquid use was 292±214 mg and EC averaged 415±305 mg over 7 hours.
34
When compared to a single use of their own brand cigarettes, CS took longer (2.3±0.8
35
vs.1.7±0.4 seconds) puffs with similar puff volume (47.9±18.2 vs. 44.1±10.5 ml) from the
36
e-cig prototype. The puff duration, flow rate and peak flow were significantly lower
37
(p<0.05) with the e-cigs compared to cigarettes. Experienced EC and CS appeared to
38
use the e-cig prototype differently, which is consistent with the literature. The SPA/M
39
could be a useful tool in assessing e-cig use behavior for regulatory purposes.
41
SC
M AN U
TE D
EP
AC C
40
RI PT
21
Word Count: 220 words
42 43 2
ACCEPTED MANUSCRIPT
44
INTRODUCTION
45
Electronic cigarettes (e-cig) or e-vapor products have gained acceptance among
46
tobacco users globally.1-3
47
products is dynamic and must be assessed systematically.
48
organized by the National Institute of Health, understanding puffing topography was
49
identified as one area of research for consideration. The authors reported, “Nicotine
50
yield in the aerosol is influenced by multiple factors, including the way air flow through
51
the device, puff volume, and puff duration (i.e., the “puff topography”).”4
52
In May of 2016, the United States Food and Drug Administration (FDA) asserted
53
jurisdiction over electronic nicotine delivery systems.5
54
Tobacco Products also issued Draft Guidance for Premarket Tobacco Product
55
Applications for Electronic Nicotine Delivery Systems,5 in which user topography is
56
identified as an area for evaluation.
57
topography from e-cigs may not only be of general scientific interest but also serve a
58
regulatory purpose.
59
To date, e-cig puff topography has been evaluated in multiple ways. Hua et al.
60
conducted an analysis of randomly selected YouTube videos in which puff duration and
61
exhalation times were measured.6 In another study, puff durations and exhalation times
62
were determined from video-recordings of in-clinic e-cig use among experienced and
63
inexperienced e-cig users.7 Other studies have used mouthpiece based puff recording
64
devices such as the CreSS pocket device,8-11 or a device developed by American
65
University at Beruit,12-14 or a wireless Personal Use Monitor developed at Rochester
RI PT
User behavior within this evolving category of tobacco
M AN U
SC
In a recent Workshop
At that time, the Center for
AC C
EP
TE D
Therefore, accurate measurements of puffing
3
ACCEPTED MANUSCRIPT
66
Institute of Technology in collaboration with FSI Systems, Inc.15
67
published reports have used the commercially available mouthpiece based SODIM
68
Smoking Puff Analyzer-Mobile (SPA/M) to assess e-cig puff topography.
69
Here we report the results of a small-scale two parallel arm design study that assessed
70
the feasibility of collecting e-cig puff topography in adult cigarette smokers (naïve to e-
71
cig use) and exclusive e-cig users (no cigarette smoking in the past 30 days) with the
72
SPA/M. We validated the SPA/M for use with an e-cig prototype using defined puffing
73
parameters on calibrated smoking machines. We studied the two populations of tobacco
74
consumers to investigate the potential differences in product use between experienced
75
e-cig users compared to cigarette smokers who had not tried e-cigs.
76
METHODS
77
The Chesapeake Institutional Review Board reviewed and approved this study. This
78
study conformed to the principles set forth by the Declaration of Helsinki and general
79
principles of Good Clinical Practice.
80
Participants
81
Forty-eight women and men provided written, informed consent and completed
82
screening procedures. Twenty-three enrolled participants comprised two distinct groups:
83
one group consisted of exclusive cigarette smokers (CS; n = 13, 7 females and 6 males)
84
and the other group consisted of exclusive e-cig users (EC; n = 10, 4 females and 6
85
males). CS had to report smoking 10-20 cigarettes daily for at least one year, and
86
having never used an e-cig. EC had to report using e-vapor products with nicotine, daily
87
for at least 6 months. Participants in both groups were between the ages of 21-65
AC C
EP
TE D
M AN U
SC
RI PT
Currently, no
4
ACCEPTED MANUSCRIPT
years, in good health, not pregnant (women) and reported no other tobacco product use
89
in the 30 days prior to screening. See Table 3 for a demographic summary by study
90
group.
91
Procedures
92
Study conduct occurred at a single research center in Richmond, VA.
93
completed one session that lasted approximately 8 to 8.5 hours.
94
Participants abstained from all tobacco use for at least 8 hours prior to their study day
95
(smoking abstinence verified by exhaled carbon monoxide levels < 10 ppm).
96
Participants arrived at the research center at approximately 9 AM. At approximately
97
9:30 AM, study staff familiarized participants with the SPA/M and the e-cig prototype.
98
Participants took up to five puffs from the e-cig prototypes alone and attached to the
99
SPA/M. Puff topography recording of ad-lib product use commenced at approximately
100
10 AM and lasted for 7 hours. We provided participants with a fresh cartridge halfway
101
through (~1:30 PM) the ad-lib product use period. A research assistant weighed
102
cartridges within 15 minutes before and 15 minutes after each use. Participants ate a
103
standard lunch at approximately 12:15 PM. The 7-hour ad-lib product use period
104
concluded at approximately 5:00 PM. CS smoked one preferred brand cigarette with the
105
SPA/M at approximately 5:30 PM.
106
The participants were not permitted to use any other tobacco or nicotine products, aside
107
from research products, during the study day.
108
recreational activities such as watching television shows, reading, puzzles and games
109
while using the prototype e-cig with the SPA/M.
RI PT
88
AC C
EP
TE D
M AN U
SC
Participants
5
Participants engaged in quiet
ACCEPTED MANUSCRIPT
Materials
111
Puff Topography Device
112
We used the SODIM Smoking Puff Analyzer Mobile (SPA/M; SODIM Instrumentation,
113
Fleury-Les-Aubrais, France) to record puff topography. The SPA/M is a stand-alone
114
recording instrument that allows ambulatory recording of puff topography in clinic or
115
laboratory settings as well as the natural environment. The SPA/M device consists of a
116
sample holder, a data recorder and two pneumatic tubes that connect the holder to the
117
recorder. Although the SPA/M device was originally designed to measure topography
118
from a cigarette, the manufacturer adapted the device to allow measurement of e-cig
119
topography. A cigarette or an e-cig inserts at the smoking end of the sample holder and
120
the participant draws puffs from the opposite end (user end). SPA/M records, in real-
121
time, the pressure drop profiles and the atmospheric pressure during puffing via three
122
pressure transducers. We programmed all the SPA/Ms to sample this information every
123
50 milliseconds. We uploaded all data to a stand-alone, password protected computer
124
for interpretation via the SodAfc data acquisition and interpretation software (SODIM
125
Instrumentation, Fleury-Les-Aubrais, France). The software calculates the flow, peak
126
flow, puff volume, pressure drop, the number of puffs, the puff duration, inter-puff
127
intervals, and the total amount of time spent puffing.
128
Prior to study start, we validated the SPA/M for use with the e-cig prototype. We
129
evaluated the accuracy and precision of the SPA/M topography device for measurement
130
of puff duration, puff volume and puff profile of the e-cig prototype.16 The validation
131
process included verifying calibration, accuracy, precision and robustness of the Sodim
AC C
EP
TE D
M AN U
SC
RI PT
110
6
ACCEPTED MANUSCRIPT
SPA/M device against known instrumentation. First, we verified the SPA/M device flow
133
and pressure differential sensor calibration with a Sodim flow calibrator. Next, we used
134
a 20-port linear (Hawktech) and a single port (Borwaldt KC) smoking machine to create
135
standard puff profiles with the e-cig prototype and 3R4F reference cigarettes.
136
verified the linearity of the SPA/M device with the e-cig prototype and 3R4F research
137
reference cigarettes using a range of puff volumes (35–140 mL), puff durations (2-5
138
sec), and flow rates (7–65 mL/sec) under sine and square wave puff profiles. Due to
139
differences in the 3R4F and e-cig prototype design, a K-coefficient adjustment was
140
calculated to be 1.117 (per manufacturer’s instructions) and used for all e-cig analyses.
141
Accuracy was assessed with a minimum of 3 separate replicates of each puff profile
142
containing 5 machine generated puffs per replicate. Two different smoking machine
143
generated puff profiles, Sine (2 seconds) and Square (5 seconds) Wave puffs, with
144
three different target puff volumes (35, 55, and 100ml) were used to provide a range of
145
potential puff profiles.
146
prototypes and SPA/M devices across the same puff profiles. Intermediate precision
147
was assessed with 5 individually prepared e-cig prototypes and SPA/M devices over 3
148
separate days with the same target smoking machine generated puffs. We primarily
149
assessed puff volume measurements because the reported volume is the combination
150
of the puff duration and flow rate. Therefore, the reported puff volume gives an overall
151
assessment of the measuring capability of the SPA/M.
152
Study Product
153
The e-cig prototype comprised a rechargeable battery (~3.7volt, maximum puff
154
activation time of ~7 seconds) and a cartridge with a quad-hole mouthpiece (4-draw
We
TE D
M AN U
SC
RI PT
132
AC C
EP
Repeatability was assessed with 5 individually prepared e-cig
7
ACCEPTED MANUSCRIPT
technology) containing approximately 400 mg liquid formulation. A filled cartridge
156
weighed approximately 4 g. The cartridge liquid contained 2% tobacco derived nicotine
157
by weight, propylene glycol, glycerin, and water. The fully assembled prototype was
158
approximately the size of a king size conventional cigarette (~85mm long, ~8mm in
159
diameter).
160
battery after each hour of use and cartridges were changed halfway through the 7-hour
161
ad-lib product use period.
162
Own Brand/Preferred Cigarettes: Each CS provided one of their preferred brand
163
cigarettes during screening.
164
Statistical Methods
165
Statistical analysis was conducted using SAS software (version 9.4, Cary, North
166
Carolina).
167
Descriptive statistics (e.g. mean, standard deviation, %CV, frequencies) were
168
performed for all demographic information. The following topography variables were
169
included in the analysis: puff count, inter-puff interval, puff duration, total puff duration,
170
puff volume, total puff volume, puff flow, and puff peak flow.
171
topography data from this study was statistically analyzed and reported with each puff
172
as an observation.17 In the current analysis, the five topography variables of inter-puff
173
interval, puff duration, puff volume, puff flow and puff peak flow were first summarized
174
for each subject. The mean of each subject was used as the observation to get the
175
group descriptive statistics including mean and 95% CI for CS or EC. Students’ T-Test
176
was used to test for the statistical significance between CS and EC. For topography
RI PT
155
Previously, the puff
AC C
EP
TE D
M AN U
SC
Study staff replaced the rechargeable e-cig battery with a fully charged
8
ACCEPTED MANUSCRIPT
variables of puff count, total puff volume and total puff duration, the individual subject
178
values were directly used for descriptive statistics and the Students’ T-Test.
179
Change in cartridge weight was calculated based on the difference before and after use
180
of the cartridges. Students’ T-Test was used for topography variable comparisons
181
between CS and EC, and between CS using a conventional cigarette and during e-cig
182
use.
SC
RI PT
177
AC C
EP
TE D
M AN U
183
9
ACCEPTED MANUSCRIPT
RESULTS
184
Device Validation
186
The SPA/M devices (without an e-cig) demonstrated accuracy and precision within ±
187
2% of the target value. Using the derived K-coefficient, we observed the accuracy of
188
the SPA/M with the e-cig prototype to be within ± 10% of puff volume targets (Table 1).
189
The repeatability and intermediate precision across all puff profiles was within 5%
190
relative standard deviation (Table 2).
191
determined that the SPA/M was suitable for use in the clinical study.
192
Demographic Characteristics
193
The demographic characteristics of the study population are shown in Table 3. Thirteen
194
CS (7 female, 6 male) and 10 EC (4 female, 6 male) participated in the study. EC were
195
generally younger than the CS (average age 34 ± 9.5 [Standard Deviation, SD] vs. 45
196
±11 years). CS smoked an average of 15.4(±4) cigarettes per day and reported
197
smoking an average of 28.5 (±10.7) years. All EC reported smoking cigarettes prior to
198
using e-vapor products and had previously smoked an average of 9.2(±6.3) cigarettes
199
per day for an average of 11.7 (±8.8) years.
200
Number of Puffs
201
Tables 4 and 5 list the puffing topography results. During the seven-hour ad-lib e-cig
202
use period, CS took, on average (±SD), 160 (±92) puffs and EC took a similar amount
203
of puffs and averaged 147 (±93) puffs.
204
Inter-puff Interval
SC
RI PT
185
AC C
EP
TE D
M AN U
Based on the results of the validation, we
10
ACCEPTED MANUSCRIPT
The average SPA/M reported inter-puff intervals for CS were 66.2 (20.2) seconds and
206
for EC, the average inter-puff intervals were 78.6 (27.3) seconds (Table 4). Significant
207
intra-subject variability was observed. The range of average inter-puff intervals for CSs
208
was 23.9 to 118.1 and for ECs, the range was 39.9 to 114 seconds.
209
Puff Duration
210
The average (±SD) e-cig per puff duration was 2.3 (±0.8) seconds for CS. EC average
211
puff duration per puff tended to be longer at 3.0 (±1.3) seconds. High levels of inter and
212
intra-individual variability were observed in the puff duration (Figure 2 (A)).
213
Puff Volume
214
For CS, the average (±SD) puff volume per e-cig puff averaged 47.9 (±18.2) ml. EC
215
tended to take larger puffs averaging 53.4 (±19.2) ml per puff. Total puff volume (i.e.
216
average total volume across the 7-hour ad-lib period) was similar for the CS (8,590 ±
217
7,067 ml) and EC (8,279 ± 6,182 ml). High levels of inter and intra-individual variability
218
was observed in the puff duration (Figure 2 (B)).
219
Flow Rate
220
CS tended to have higher flow rates than EC (not statistically significant). CS had an
221
average (±SD) flow rate of 21.5 (±4.6) ml/sec and EC had an average flow rate of 19.6
222
(±5.0) ml/sec. Average peak flow (maximal flow observed within a puff) was 31.5 (±8.1)
223
ml/sec for CS and 28.0 (±6.8) ml/sec for EC. High levels of inter and intra-individual
224
variability were observed in the puff flow rate (Figure 2 (C+D)).
225
Cartridge Weights
AC C
EP
TE D
M AN U
SC
RI PT
205
11
ACCEPTED MANUSCRIPT
Change in cartridge weights (pre weight – post weight for 2 cartridges) for CS averaged
227
292 (±214) mg for the entire 7-hour period. For EC, the average change in cartridge
228
weights was 415 (±305) mg for the 7-hour period (Table 4).
229
Conventional Cigarettes
230
CS used conventional cigarettes and e-cigs differently. In general, CS using their own
231
brand conventional cigarette had similar puff volumes (44.1 ± 10.5 mL) and lower puff
232
durations (1.7 ±0.4 s) when compared to the e-cig prototype use. CS also had higher
233
flow rates (28.7 ± 6.1 mL/s) and peak flow (44.2 ±11.0 ml/s) during use of cigarettes
234
than during use of the e-cig prototype. The puff duration, average flow rates and peak
235
flow rates were significantly different between conventional cigarettes and e-cigs (Table
236
5).
M AN U
SC
RI PT
226
DISCUSSION
238
In this study, e-cig puff topography measurements were characterized using a validated
239
puff topography-recording instrument under 7-hours of ad-lib use conditions. To our
240
knowledge, this is the first published report to evaluate the SPA/M for e-cig puff
241
topography measurements. E-cig puff topography tended to differ between CS and EC,
242
though these differences were not statistically significant. EC generally took longer
243
puffs (3.0 seconds vs. 2.3 seconds) with lower flow rates (19.6 ml/s vs. 21.5 ml/s)
244
relative to CS. Experienced EC and CS appeared to use the e-cig prototype differently,
245
which is consistent with the literature, and wide inter- and intra-individual variability was
246
observed across both study groups under these study conditions. Within the CS group,
247
our findings indicate that CS puff the e-cig and their own brand cigarette differently. CS
AC C
EP
TE D
237
12
ACCEPTED MANUSCRIPT
took longer, slower puffs on the e-cig prototype than on their usual brand cigarette (puff
249
duration: 2.3 seconds vs. 1.7 seconds; flow rate: 28.6 ml/s vs. 21.5 ml/s). These results
250
suggest that adult CS likely change their puffing behavior, as they become established
251
e-cig users.
252
Our observations are comparable to that reported by Farsalinos et al.7 who also
253
examined e-cig puff differences between experienced e-cig users and e-cig naïve
254
cigarette smokers. Farsalinos et al.7 used video-recordings to determine puff duration,
255
inhalation, and exhalation times over a 20-minute ad-lib use period in experienced e-cig
256
users (n=45) and cigarette smokers (n=35). The authors compared 10 consecutive
257
puffs from a tank-based e-cig or traditional cigarette (smokers only).7 The experienced
258
e-cig users took, on average, 4.2 second puffs whereas the cigarette smokers took 2.1
259
second puffs from the traditional cigarette and 2.4 second puffs from the e-cig.7 These
260
observations were similar to the results of the current study, despite differences in the
261
e-cig use period (20 minutes ad-lib use or 10 puffs versus 7 hours ad-lib use in the
262
current study) and type of
263
versus a cartridge-based closed system in the current study). Hua et al.6 noted similar
264
differences in e-cig puff duration between conventional cigarette smoking (2.4 seconds)
265
and e-cig use (4.3 seconds) when examining YouTube® videos.
266
One limitation of video recordings for puff topography measurements is the inability to
267
record the puff flow rate or volume. Multiple researchers have used mouthpiece-based
268
topography recording devices to capture this additional information. Some studies have
269
used the CreSS device,8-11 while others have used a device developed by American
270
University at Beruit,12-14
TE D
M AN U
SC
RI PT
248
AC C
EP
e-cig studied (eGo-T next-generation tank-like product
and one report used 13
a wireless Personal Use Monitor
ACCEPTED MANUSCRIPT
developed at Rochester Institute of Technology in collaboration with FSI Systems, Inc.15
272
The current study is the first to report use of the SPA/M device that has been previously
273
validated16 to collect this information using e-cigs.
274
Experienced e-cig users have been included in most studies with mouthpiece-based
275
recording devices and a wide range e-cig puffing parameters have been reported. For
276
example, average puff duration values ranged from 1.8 seconds10 to 6.1 seconds14
277
depending on the study and e-cig used. Puff flow rate averages have been reported
278
from 18 ml/s14 to 52 ml/s11 and puff volume averages range from 45 ml8 to 210.8 ml14.
279
The values reported for EC in the current study are within reported ranges (3.0 second
280
puff duration, 19.6 ml/s flow rate, and 53.4 ml puff volume), but the values tended to be
281
towards the lower end of the ranges. This may be due to the e-cigs used and/or the
282
study duration/design. Interestingly, Behar et al.8 reported similar results to the current
283
study, during two 10 min ad libitum use sessions (n=20 participants) with Blu® and V2®
284
e-cigs (e-cigs resembling the size and shape of traditional cigarettes). Average puff
285
durations were 2.75 seconds for Blu® and 2.54 seconds for V2®, average flow rates
286
were 21ml/s for Blu® and 18ml/s for V2® and average puff volume were 56 ml for Blu®
287
and 45 ml for V2®.8
288
users.15 Similar to the results of the current study, the average puff duration was 3.5
289
seconds.
290
higher at 37ml/s and 133 ml respectively. 15
291
A few studies have used mouthpiece-based puff topography devices to investigate e-cig
292
puff topography in cigarette smokers who were “naïve” to e-cig use.
293
evaluated the e-cig puff topography in 16 e-cig naïve cigarette smokers using an eGO
EP
TE D
M AN U
SC
RI PT
271
AC C
Blu® was also used in a 24 hour ad libitum use study of 22 e-cig
However, the average puff flow rate and puff volume were substantially
14
Lopez et al.13
ACCEPTED MANUSCRIPT
294
cartomizer based system.
Participants conducted multiple 10 puff sessions with
295
different nicotine concentrations (range 0-36mg/ml).13
296
concentration and time of the puffing session, average e-cig puff duration ranged from
297
2.27 to 3.21 seconds, puff flow rate ranged from 27.1 ml/s to 33.6 ml/s, and average
298
puff volumes ranged from 63.0 to 97.0 ml.13 These are similar to the values reported in
299
the current study for e-cig naïve cigarette smokers (puff duration 2.3s, puff flow rate
300
21.5 ml/s and puff volume 47.9 ml). The higher puff flow rate and volumes are possibly
301
related to the different types of products used in the two studies and/or study design (10
302
puffs vs. ad libitum use for 7 hours).
303
Lee et al.9 investigated changes in puff topography in 20 e-cig “naïve” cigarette smokers
304
using cartridge-based e-cigs over a two-week period. As participants became more
305
familiar with the e-cig (1 week of use), they took longer (2.2 seconds vs. 3.1 seconds)
306
and slower puffs (30.6 ml/s vs. 25.1 ml/s), with puff volumes remaining similar (64.0 ml
307
vs. 66.5 ml).9 This suggests that cigarette smokers change their puff topography as
308
they become accustomed to using e-cigs. As all of the experienced e-cigarette users in
309
this study had previously smoked cigarettes, the longer and slower puffs in experienced
310
e-cigarette users appears to confirm that cigarette smokers change their puffing
311
topography when using e-cigs compared to conventional cigarettes.
312
The purpose of the current study was to investigate the feasibility of using the SPA/M to
313
measure e-cig puff topography. The relatively small sample size for both groups (N=13
314
CS and N=10 EC), the use of a single prototype e-cig with a single liquid formulation,
315
and in-clinic data limit the generalizability of these findings. The SPA/M served as a
316
reliable means for measuring puff topography under these in-clinic conditions. However,
AC C
EP
TE D
M AN U
SC
RI PT
Depending on nicotine
15
ACCEPTED MANUSCRIPT
there are some shortcomings of this device. First, the SPA/M, in its current form, will
318
stop recording if no puff is detected for a 60-minute period, requiring users to restart the
319
recording each hour or each time a puffing occasion begins, limiting its utility under
320
ambulatory conditions. Second, the main body of the SPA/M is quite large, thereby
321
resulting in a cumbersome and obtrusive device for participants. The study participants
322
expressed that the pneumatic tubing and small sample holder made them feel awkward
323
while puffing. These limitations suggest that while the SPA/M device may be suitable for
324
in-clinic use, further improvements may allow unobtrusive assessments in a “real-world”
325
application. Recent advances in e-cigs have included puff monitoring within the e-cig
326
itself.18 Currently puff topography measurements with these e-cigs are limited to puff
327
number/time and duration, but future models may include puff flow rates and volume.
328
This would arguably be an improvement over all the current mouthpiece based systems
329
for use in assessing real world e-cig puff topography. We included the cigarette as a
330
comparator and assessed the topography at the end of the vaping cessation, subjects
331
smoked only a single own brand cigarettes, which might be considered a limitation.
332
However, cigarette smoking topography is well established and our observations were
333
similar to those reported by other researchers.
334
In conclusion, the results of this initial study demonstrate the feasibility of in-clinic
335
measurement of e-cig puff topography using a commercially available mouthpiece-
336
based puff topography device. The results from this study should be interpreted in the
337
context that the study was designed to evaluate the feasibility of the SPA/M device,
338
future studies may be necessary with a larger sample size to draw definitive statistical
339
inferences regarding differences in topography parameters between e-vapor users and
AC C
EP
TE D
M AN U
SC
RI PT
317
16
ACCEPTED MANUSCRIPT
cigarette smokers. In addition, this study is consistent with previous findings suggesting
341
that cigarette smokers likely change their puffing behavior when transitioning to e-cig
342
use. As e-vapor products evolve, it will be important to understand how new products
343
are used by consumers and the appropriate conditions for generating machine-
344
generated aerosols for comparative purposes.
AC C
EP
TE D
M AN U
SC
345
RI PT
340
17
ACCEPTED MANUSCRIPT
346
Table 1: Accuracy of Sodim SPA/M topography recording device with the prototype e-
347
cig device using different smoking machine generated puff profiles.
348
RI PT
2 Second Smoking Machine Sine Wave Puff Profile Target Puff Volume (ml)
Measured Volume (ml)
Accuracy (% difference from target)
35
34.1
-2.6
55
53.9
100
97.2
SC
-2
-2.8
M AN U
5 Second Smoking Machine Square Wave Puff Profile Target Puff Volume (ml)
Measured Volume (ml)
Accuracy (% difference from target)
35
37.2
6.2
56.2
2.2
103.6
3.6
AC C
349
EP
100
TE D
55
18
ACCEPTED MANUSCRIPT
350
Table 2: Repeatability and intermediate precision of Sodim SPA/M puff topography
351
recording device with the prototype e-cig device using different smoking machine
352
generated puff profiles.
353
M AN U
SC
RI PT
2 Second Smoking Machine Sine Wave Puff Profile Target Puff Volume (ml) Repeatability (%RSD) Intermediate Precision (%RSD) 35 1.57 1.83 55 1.71 2.02 100 2.67 3.15 5 Second Smoking Machine Square Wave Puff Profile Target Puff Volume (ml) Repeatability (%RSD) Intermediate Precision (%RSD) 35 3.13 3.69 55 1.39 1.63 100 1.9 2.25
%RSD = percent relative standard deviation
AC C
EP
TE D
354
19
ACCEPTED MANUSCRIPT
Table 3: Participant Demographic and Tobacco History Information Cigarette Smokers
e-Cig Users
n=13
n=10
7 female
4 female
Gender
RI PT
355
6 male Race
6 male
5 Black
3 Black
5 White
SC
8 White
2 Other
45 (±11, 33 to 65)#
#Cigarettes/day
15.4 (±4; 10 to 20) #
N/A
#Years smoking
28.5 (±10.7; 10 to 47) #
N/A
N/A
Less than 1 to 3†
N/A
10.9 (±5.4; 6 to 24) #
#Refills per day (e-vapor)
#Months since last cigarette #Cigarettes/day before
34 (±9.5; 23-52) #
N/A
13.5 (±6.4; 6 to 24) #
N/A
9.2 (±6.3; 3 to 20) #
N/A
11.7 (±8.8; 1 to 23 years) #
TE D
#Months using e-vapor
M AN U
Age
EP
using e-vapor products #Years smoked before
AC C
using e-vapor products 356
#
Parenthetical information conveys ± one standard deviation; range
357
†
Refill types vary across e-vapor products. Participants self-reported their estimated
358
number of refills per day.
359
20
ACCEPTED MANUSCRIPT
360
Table 4: E-Cig Prototype Puff Topography (7-hours Ad-lib) Cigarette Smokers n=13 Topography variable
Mean (SD)
95%CI
Mean (SD)
Total number of puffs
160 (92)
103.8 - 216.1
147 (93)
80.3 - 213.3
Puff duration (sec)
2.3 (0.8)
1.9 - 2.8
3.0 (1.3)
2.1 - 4.0
Total puff duration (sec)
391 (297)
212 - 571
Puff volume (ml)
47.9 (18.2)
Total puff volume (ml)
RI PT
SC
222 - 753
8590 (7067)
4320 - 12860
8279 (6182)
3857 -12701
Flow rate (ml/sec)
21.5 (4.6)
18.7 - 24.3
19.6 (5.0)
16.1 - 23.2
Peak flow rate (ml/sec)
31.5 (8.1)
26.5 - 36.4
28.0 (6.8)
23.2 - 32.9
Total cartridge weight change (mg)
292 (214)
162 - 421
415 (305)
197 - 632
54.0 - 78.5
78.6 (27.3)
59.0 - 98.1
TE D
39.7 - 67.1
EP
M AN U
498 (371)
53.4 (19.2)
66.2 (20.2)
AC C
363
95%CI
36.9 – 59.0
Inter-puff interval (sec) 361 362
e-Cig Users n=10
no statistical significance was found between the cigarette smokers and e-vapor users in any of the topography variables (p-values > 0.05).
21
ACCEPTED MANUSCRIPT
364
Table 5: Cigarette Smokers Puff Topography during Use of e-Cig Prototype and Their
365
Own Brand Conventional Cigarette e-Cig Use
Cigarette Smoking
n=13
n=13
369 370 371 372 373
Puff duration (sec)
2.3 (0.8)
1.9 - 2.8
1.7 (0.4)
Puff volume (ml)
47.9 (18.2)
36.9 – 59.0
Flow rate (ml/sec)
21.5 (4.6)
Peak flow rate (ml/sec)
31.5 (8.1)
95%CI
SC
Mean (SD)
p-value
0.5591
44.1 (10.5)
36.6 - 51.6
0.0236
18.7 - 24.3
28.6 (6.1)
24.2 -33.0
0.0045
26.5 - 36.4
44.2 (11)
36.3 - 52.0
0.0043
M AN U
1.3 - 2.0
TE D
368
95% CI
EP
367
Mean (SD)
AC C
366
Topography variable
RI PT
Difference
374 375 22
ACCEPTED MANUSCRIPT
377
Figure 1: Example Puff Profiles Cigarette Smokers and e-Cig Users A. Conventional cigarette smoker with e-cig prototype
RI PT
376
SC
378
Time (seconds)
379
381 382
M AN U Time (seconds)
C. e-Cig user with e-cig prototype
AC C
EP
383
B. Conventional cigarette smoker with own brand conventional cigarette
TE D
380
384 385
Time (seconds)
386 23
ACCEPTED MANUSCRIPT
387
A. Individual Puff Durations
M AN U
SC
RI PT
388
Figure 2: Puff Parameter Plots for Individual Subjects Using e-Cig Prototypes
389
B. Individual Average Puff Volumes
392 393 394
AC C
391
EP
TE D
390
395 396 397 24
ACCEPTED MANUSCRIPT
C. Individual Average Puff Flow Rates
SC
RI PT
398
D. Individual Average Peak Puff Flow Rate
402 403 404
AC C
401
EP
TE D
400
M AN U
399
25
ACCEPTED MANUSCRIPT
Figure Captions:
406
Figure 1: Examples of individual puff profiles for conventional cigarette smokers and e-
407
vapor users. The figure shows one conventional and one electronic cigarette puff for
408
one conventional cigarette smoker as well as one electronic cigarette puff for an e-vapor
409
user. Each profile shows puff flow rate over time as well as the calculated puff volume
410
and duration in the upper left hand corner.
411
Figure 2: Puff parameter plots for Individual subjects using e-cigarette prototypes over
412
7-hours ad libitum: average puff duration (A), average puff volume (B), average puff flow
413
rate (C), average peak puff flow rate (D). Conventional cigarette smokers (left panel)
414
and e-Vapor users (right panel). Each plot represents the mean +/- Standard Deviation
415
for all recorded puffs for each individual subject over the 7-hour period.
M AN U
SC
RI PT
405
AC C
EP
TE D
416
26
ACCEPTED MANUSCRIPT
417
References
418
1.
Delnevo CD, Giovenco DP, Steinberg MB, et al. Patterns of Electronic Cigarette Use Among Adults in the United States. Nicotine & tobacco research : official journal of the Society for
420
Research on Nicotine and Tobacco. 2016;18(5):715-719.
421
2.
RI PT
419
Adkison SE, O'Connor RJ, Bansal-Travers M, et al. Electronic nicotine delivery systems:
international tobacco control four-country survey. American journal of preventive medicine.
423
2013;44(3):207-215. 3.
Ayers JW, Ribisl KM, Brownstein JS. Tracking the rise in popularity of electronic nicotine delivery
M AN U
424
SC
422
425
systems (electronic cigarettes) using search query surveillance. American journal of preventive
426
medicine. 2011;40(4):448-453.
427
4.
Walton KM, Abrams DB, Bailey WC, et al. NIH electronic cigarette workshop: developing a research agenda. Nicotine & tobacco research : official journal of the Society for Research on
429
Nicotine and Tobacco. 2015;17(2):259-269.
430
5.
TE D
428
U.S. Department of Health and Human Services (USDHHS), Food and Drug Administration (FDA), Center for Tobacco Products (CTP). Premarket Tobacco Product Applications for Electronic
432
Nicotine Delivery Systems; Draft Guidance for Industry. 2016.
433
http://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM499
434
352.pdf.#sthash.J8E5P1rM.dpuf. Accessed June 10, 2016.
6.
436 437 438
AC C
435
EP
431
Hua M, Yip H, Talbot P. Mining data on usage of electronic nicotine delivery systems (ENDS) from YouTube videos. Tobacco control. 2013;22(2):103-106.
7.
Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V. Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for
27
ACCEPTED MANUSCRIPT
439
research protocol standards definition and for public health authorities' regulation. International
440
journal of environmental research and public health. 2013;10(6):2500-2514. 8.
443
PloS one. 2015;10(2):e0117222. 9.
444 445
RI PT
442
Behar RZ, Hua M, Talbot P. Puffing topography and nicotine intake of electronic cigarette users.
Lee YH, Gawron M, Goniewicz ML. Changes in puffing behavior among smokers who switched from tobacco to electronic cigarettes. Addictive behaviors. 2015;48:1-4.
10.
Goniewicz ML, Kuma T, Gawron M, Knysak J, Kosmider L. Nicotine levels in electronic cigarettes.
SC
441
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and
447
Tobacco. 2013;15(1):158-166.
448
11.
M AN U
446
Norton KJ, June KM, O'Connor RJ. Initial puffing behaviors and subjective responses differ
449
between an electronic nicotine delivery system and traditional cigarettes. Tobacco induced
450
diseases. 2014;12(1):17. 12.
Spindle TR, Breland AB, Karaoghlanian NV, Shihadeh AL, Eissenberg T. Preliminary results of an
TE D
451
examination of electronic cigarette user puff topography: the effect of a mouthpiece-based
453
topography measurement device on plasma nicotine and subjective effects. Nicotine & tobacco
454
research : official journal of the Society for Research on Nicotine and Tobacco. 2015;17(2):142-
455
149. 13.
457
on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.
458
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and
459 460 461
Lopez AA, Hiler MM, Soule EK, et al. Effects of Electronic Cigarette Liquid Nicotine Concentration
AC C
456
EP
452
Tobacco. 2016;18(5):720-723.
14.
Ramoa CP, Hiler MM, Spindle TR, et al. Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report. Tobacco control. 2016;25(e1):e6-9.
28
ACCEPTED MANUSCRIPT
462
15.
463 464
Robinson RJ, Hensel EC, Morabito PN, Roundtree KA. Electronic Cigarette Topography in the Natural Environment. PloS one. 2015;10(6):e0129296.
16.
Connell CT, Bennett DR, Meruva NK, Vansickel AR, Edmiston JS. POS2-93: Validation of a smoking puff analyzer for use with an electronic cigarette prototype. Poster presented at:
466
SRNT's 20th Annual Meeting; February 5-8, 2014; Seattle, WA.
467
17.
RI PT
465
Vansickel AR, Edmiston J, Liang Q, Duhon C, Liu J, Sarkar M. POS3-65: Characterization of
electronic cigarette prototype puff topography in adult exclusive cigarette smokers and adult
469
exclusive electronic cigarette users. Poster presented at: SRNT 20th Annual Meeting; February
470
5-8, 2014, 2014; Seattle, WA. 18.
M AN U
471
SC
468
Dawkins LE, Kimber CF, Doig M, Feyerabend C, Corcoran O. Self-titration by experienced e-
472
cigarette users: blood nicotine delivery and subjective effects. Psychopharmacology.
473
2016;233(15-16):2933-2941.
AC C
EP
TE D
474
29
ACCEPTED MANUSCRIPT
Research Highlights: 1) Validated topography device was used to characterize puffing topography amongst cigarette smokers and e-vapor users.
RI PT
2) Cigarette smokers appear to use e-cigarettes differently than experienced e-cigarette users. 3) Experienced e-cigarette users generally took longer puffs with lower flow rates relative to cigarette smokers
AC C
EP
TE D
M AN U
SC
4) The topography device could be a useful tool for in-clinic measurement of e-cigarette use behavior.
S0273-2300(18)30203-4
DOI:
10.1016/j.yrtph.2018.07.019
Reference:
YRTPH 4182
To appear in:
Regulatory Toxicology and Pharmacology
Received Date: 25 October 2017 Revised Date:
21 July 2018
Accepted Date: 23 July 2018
Please cite this article as: Vansickel, A.R., Edmiston, J.S., Liang, Q., Duhon, C., Connell, C., Bennett, D., Sarkar, M., Characterization of puff topography of a prototype electronic cigarette in adult exclusive cigarette smokers and adult exclusive electronic cigarette users, Regulatory Toxicology and Pharmacology (2018), doi: 10.1016/j.yrtph.2018.07.019. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
1
Characterization of puff topography of a prototype electronic cigarette in adult
2
exclusive cigarette smokers and adult exclusive electronic cigarette users
3
Andrea Rae Vansickel1, Jeffery S Edmiston1, Qiwei Liang1, Cheryl Duhon1, Chris
5
Connell1, David Bennett1, Mohamadi Sarkar1,2
RI PT
4
6 7
1
8
Center for Research and Technology
9
601 E. Jackson Street, Richmond, VA, USA
11
M AN U
10
SC
Altria Client Services LLC,
12
2
13
Mohamadi Sarkar,
14
Center for Research and Technology
15
601 E. Jackson Street, Richmond, VA, USA
16
Phone: +1-804-335-2537,
17
Email: [email protected] or [email protected]
TE D
EP
AC C
18
Address for correspondence:
19
Keywords: E-cigarettes, e-vapor products, cartridge-based, topography, puff volume,
20
puff parameters, smokers, e-cigarette users.
1
ACCEPTED MANUSCRIPT
ABSTRACT
22
Puff topography is an important measure of how consumers use e-vapor products. The
23
purpose of this study was to evaluate the feasibility of using SODIM Smoking Puff
24
Analyzer Mobile Device (SPA/M) to measure puff topography during use of a prototype
25
e-cigarette (e-cig) in exclusive cigarette smokers (CS) and e-cig users (EC) under ad lib
26
conditions in a clinic. Adult CS (n=13) and EC (EC; n=10) completed a 7-hr use session
27
with the e-cig (2% tobacco-derived nicotine by weight, cartridge based system
28
approximately the size of a king size cigarette). E-liquid usage was determined from
29
cartridge weight. CS also smoked a single cigarette with the SPA/M. The SPA/M reliably
30
recorded puff parameters throughout the study period, with CS puffs averaging
31
47.9±18.2 ml volume, 2.3±0.8 seconds duration, and 21.5±4.6 ml/second flow rate. EC
32
puffs averaged 53.4±19.2 ml volume, 3.0±1.3 seconds duration, and 19.6±5.0 flow rate.
33
CS average e-liquid use was 292±214 mg and EC averaged 415±305 mg over 7 hours.
34
When compared to a single use of their own brand cigarettes, CS took longer (2.3±0.8
35
vs.1.7±0.4 seconds) puffs with similar puff volume (47.9±18.2 vs. 44.1±10.5 ml) from the
36
e-cig prototype. The puff duration, flow rate and peak flow were significantly lower
37
(p<0.05) with the e-cigs compared to cigarettes. Experienced EC and CS appeared to
38
use the e-cig prototype differently, which is consistent with the literature. The SPA/M
39
could be a useful tool in assessing e-cig use behavior for regulatory purposes.
41
SC
M AN U
TE D
EP
AC C
40
RI PT
21
Word Count: 220 words
42 43 2
ACCEPTED MANUSCRIPT
44
INTRODUCTION
45
Electronic cigarettes (e-cig) or e-vapor products have gained acceptance among
46
tobacco users globally.1-3
47
products is dynamic and must be assessed systematically.
48
organized by the National Institute of Health, understanding puffing topography was
49
identified as one area of research for consideration. The authors reported, “Nicotine
50
yield in the aerosol is influenced by multiple factors, including the way air flow through
51
the device, puff volume, and puff duration (i.e., the “puff topography”).”4
52
In May of 2016, the United States Food and Drug Administration (FDA) asserted
53
jurisdiction over electronic nicotine delivery systems.5
54
Tobacco Products also issued Draft Guidance for Premarket Tobacco Product
55
Applications for Electronic Nicotine Delivery Systems,5 in which user topography is
56
identified as an area for evaluation.
57
topography from e-cigs may not only be of general scientific interest but also serve a
58
regulatory purpose.
59
To date, e-cig puff topography has been evaluated in multiple ways. Hua et al.
60
conducted an analysis of randomly selected YouTube videos in which puff duration and
61
exhalation times were measured.6 In another study, puff durations and exhalation times
62
were determined from video-recordings of in-clinic e-cig use among experienced and
63
inexperienced e-cig users.7 Other studies have used mouthpiece based puff recording
64
devices such as the CreSS pocket device,8-11 or a device developed by American
65
University at Beruit,12-14 or a wireless Personal Use Monitor developed at Rochester
RI PT
User behavior within this evolving category of tobacco
M AN U
SC
In a recent Workshop
At that time, the Center for
AC C
EP
TE D
Therefore, accurate measurements of puffing
3
ACCEPTED MANUSCRIPT
66
Institute of Technology in collaboration with FSI Systems, Inc.15
67
published reports have used the commercially available mouthpiece based SODIM
68
Smoking Puff Analyzer-Mobile (SPA/M) to assess e-cig puff topography.
69
Here we report the results of a small-scale two parallel arm design study that assessed
70
the feasibility of collecting e-cig puff topography in adult cigarette smokers (naïve to e-
71
cig use) and exclusive e-cig users (no cigarette smoking in the past 30 days) with the
72
SPA/M. We validated the SPA/M for use with an e-cig prototype using defined puffing
73
parameters on calibrated smoking machines. We studied the two populations of tobacco
74
consumers to investigate the potential differences in product use between experienced
75
e-cig users compared to cigarette smokers who had not tried e-cigs.
76
METHODS
77
The Chesapeake Institutional Review Board reviewed and approved this study. This
78
study conformed to the principles set forth by the Declaration of Helsinki and general
79
principles of Good Clinical Practice.
80
Participants
81
Forty-eight women and men provided written, informed consent and completed
82
screening procedures. Twenty-three enrolled participants comprised two distinct groups:
83
one group consisted of exclusive cigarette smokers (CS; n = 13, 7 females and 6 males)
84
and the other group consisted of exclusive e-cig users (EC; n = 10, 4 females and 6
85
males). CS had to report smoking 10-20 cigarettes daily for at least one year, and
86
having never used an e-cig. EC had to report using e-vapor products with nicotine, daily
87
for at least 6 months. Participants in both groups were between the ages of 21-65
AC C
EP
TE D
M AN U
SC
RI PT
Currently, no
4
ACCEPTED MANUSCRIPT
years, in good health, not pregnant (women) and reported no other tobacco product use
89
in the 30 days prior to screening. See Table 3 for a demographic summary by study
90
group.
91
Procedures
92
Study conduct occurred at a single research center in Richmond, VA.
93
completed one session that lasted approximately 8 to 8.5 hours.
94
Participants abstained from all tobacco use for at least 8 hours prior to their study day
95
(smoking abstinence verified by exhaled carbon monoxide levels < 10 ppm).
96
Participants arrived at the research center at approximately 9 AM. At approximately
97
9:30 AM, study staff familiarized participants with the SPA/M and the e-cig prototype.
98
Participants took up to five puffs from the e-cig prototypes alone and attached to the
99
SPA/M. Puff topography recording of ad-lib product use commenced at approximately
100
10 AM and lasted for 7 hours. We provided participants with a fresh cartridge halfway
101
through (~1:30 PM) the ad-lib product use period. A research assistant weighed
102
cartridges within 15 minutes before and 15 minutes after each use. Participants ate a
103
standard lunch at approximately 12:15 PM. The 7-hour ad-lib product use period
104
concluded at approximately 5:00 PM. CS smoked one preferred brand cigarette with the
105
SPA/M at approximately 5:30 PM.
106
The participants were not permitted to use any other tobacco or nicotine products, aside
107
from research products, during the study day.
108
recreational activities such as watching television shows, reading, puzzles and games
109
while using the prototype e-cig with the SPA/M.
RI PT
88
AC C
EP
TE D
M AN U
SC
Participants
5
Participants engaged in quiet
ACCEPTED MANUSCRIPT
Materials
111
Puff Topography Device
112
We used the SODIM Smoking Puff Analyzer Mobile (SPA/M; SODIM Instrumentation,
113
Fleury-Les-Aubrais, France) to record puff topography. The SPA/M is a stand-alone
114
recording instrument that allows ambulatory recording of puff topography in clinic or
115
laboratory settings as well as the natural environment. The SPA/M device consists of a
116
sample holder, a data recorder and two pneumatic tubes that connect the holder to the
117
recorder. Although the SPA/M device was originally designed to measure topography
118
from a cigarette, the manufacturer adapted the device to allow measurement of e-cig
119
topography. A cigarette or an e-cig inserts at the smoking end of the sample holder and
120
the participant draws puffs from the opposite end (user end). SPA/M records, in real-
121
time, the pressure drop profiles and the atmospheric pressure during puffing via three
122
pressure transducers. We programmed all the SPA/Ms to sample this information every
123
50 milliseconds. We uploaded all data to a stand-alone, password protected computer
124
for interpretation via the SodAfc data acquisition and interpretation software (SODIM
125
Instrumentation, Fleury-Les-Aubrais, France). The software calculates the flow, peak
126
flow, puff volume, pressure drop, the number of puffs, the puff duration, inter-puff
127
intervals, and the total amount of time spent puffing.
128
Prior to study start, we validated the SPA/M for use with the e-cig prototype. We
129
evaluated the accuracy and precision of the SPA/M topography device for measurement
130
of puff duration, puff volume and puff profile of the e-cig prototype.16 The validation
131
process included verifying calibration, accuracy, precision and robustness of the Sodim
AC C
EP
TE D
M AN U
SC
RI PT
110
6
ACCEPTED MANUSCRIPT
SPA/M device against known instrumentation. First, we verified the SPA/M device flow
133
and pressure differential sensor calibration with a Sodim flow calibrator. Next, we used
134
a 20-port linear (Hawktech) and a single port (Borwaldt KC) smoking machine to create
135
standard puff profiles with the e-cig prototype and 3R4F reference cigarettes.
136
verified the linearity of the SPA/M device with the e-cig prototype and 3R4F research
137
reference cigarettes using a range of puff volumes (35–140 mL), puff durations (2-5
138
sec), and flow rates (7–65 mL/sec) under sine and square wave puff profiles. Due to
139
differences in the 3R4F and e-cig prototype design, a K-coefficient adjustment was
140
calculated to be 1.117 (per manufacturer’s instructions) and used for all e-cig analyses.
141
Accuracy was assessed with a minimum of 3 separate replicates of each puff profile
142
containing 5 machine generated puffs per replicate. Two different smoking machine
143
generated puff profiles, Sine (2 seconds) and Square (5 seconds) Wave puffs, with
144
three different target puff volumes (35, 55, and 100ml) were used to provide a range of
145
potential puff profiles.
146
prototypes and SPA/M devices across the same puff profiles. Intermediate precision
147
was assessed with 5 individually prepared e-cig prototypes and SPA/M devices over 3
148
separate days with the same target smoking machine generated puffs. We primarily
149
assessed puff volume measurements because the reported volume is the combination
150
of the puff duration and flow rate. Therefore, the reported puff volume gives an overall
151
assessment of the measuring capability of the SPA/M.
152
Study Product
153
The e-cig prototype comprised a rechargeable battery (~3.7volt, maximum puff
154
activation time of ~7 seconds) and a cartridge with a quad-hole mouthpiece (4-draw
We
TE D
M AN U
SC
RI PT
132
AC C
EP
Repeatability was assessed with 5 individually prepared e-cig
7
ACCEPTED MANUSCRIPT
technology) containing approximately 400 mg liquid formulation. A filled cartridge
156
weighed approximately 4 g. The cartridge liquid contained 2% tobacco derived nicotine
157
by weight, propylene glycol, glycerin, and water. The fully assembled prototype was
158
approximately the size of a king size conventional cigarette (~85mm long, ~8mm in
159
diameter).
160
battery after each hour of use and cartridges were changed halfway through the 7-hour
161
ad-lib product use period.
162
Own Brand/Preferred Cigarettes: Each CS provided one of their preferred brand
163
cigarettes during screening.
164
Statistical Methods
165
Statistical analysis was conducted using SAS software (version 9.4, Cary, North
166
Carolina).
167
Descriptive statistics (e.g. mean, standard deviation, %CV, frequencies) were
168
performed for all demographic information. The following topography variables were
169
included in the analysis: puff count, inter-puff interval, puff duration, total puff duration,
170
puff volume, total puff volume, puff flow, and puff peak flow.
171
topography data from this study was statistically analyzed and reported with each puff
172
as an observation.17 In the current analysis, the five topography variables of inter-puff
173
interval, puff duration, puff volume, puff flow and puff peak flow were first summarized
174
for each subject. The mean of each subject was used as the observation to get the
175
group descriptive statistics including mean and 95% CI for CS or EC. Students’ T-Test
176
was used to test for the statistical significance between CS and EC. For topography
RI PT
155
Previously, the puff
AC C
EP
TE D
M AN U
SC
Study staff replaced the rechargeable e-cig battery with a fully charged
8
ACCEPTED MANUSCRIPT
variables of puff count, total puff volume and total puff duration, the individual subject
178
values were directly used for descriptive statistics and the Students’ T-Test.
179
Change in cartridge weight was calculated based on the difference before and after use
180
of the cartridges. Students’ T-Test was used for topography variable comparisons
181
between CS and EC, and between CS using a conventional cigarette and during e-cig
182
use.
SC
RI PT
177
AC C
EP
TE D
M AN U
183
9
ACCEPTED MANUSCRIPT
RESULTS
184
Device Validation
186
The SPA/M devices (without an e-cig) demonstrated accuracy and precision within ±
187
2% of the target value. Using the derived K-coefficient, we observed the accuracy of
188
the SPA/M with the e-cig prototype to be within ± 10% of puff volume targets (Table 1).
189
The repeatability and intermediate precision across all puff profiles was within 5%
190
relative standard deviation (Table 2).
191
determined that the SPA/M was suitable for use in the clinical study.
192
Demographic Characteristics
193
The demographic characteristics of the study population are shown in Table 3. Thirteen
194
CS (7 female, 6 male) and 10 EC (4 female, 6 male) participated in the study. EC were
195
generally younger than the CS (average age 34 ± 9.5 [Standard Deviation, SD] vs. 45
196
±11 years). CS smoked an average of 15.4(±4) cigarettes per day and reported
197
smoking an average of 28.5 (±10.7) years. All EC reported smoking cigarettes prior to
198
using e-vapor products and had previously smoked an average of 9.2(±6.3) cigarettes
199
per day for an average of 11.7 (±8.8) years.
200
Number of Puffs
201
Tables 4 and 5 list the puffing topography results. During the seven-hour ad-lib e-cig
202
use period, CS took, on average (±SD), 160 (±92) puffs and EC took a similar amount
203
of puffs and averaged 147 (±93) puffs.
204
Inter-puff Interval
SC
RI PT
185
AC C
EP
TE D
M AN U
Based on the results of the validation, we
10
ACCEPTED MANUSCRIPT
The average SPA/M reported inter-puff intervals for CS were 66.2 (20.2) seconds and
206
for EC, the average inter-puff intervals were 78.6 (27.3) seconds (Table 4). Significant
207
intra-subject variability was observed. The range of average inter-puff intervals for CSs
208
was 23.9 to 118.1 and for ECs, the range was 39.9 to 114 seconds.
209
Puff Duration
210
The average (±SD) e-cig per puff duration was 2.3 (±0.8) seconds for CS. EC average
211
puff duration per puff tended to be longer at 3.0 (±1.3) seconds. High levels of inter and
212
intra-individual variability were observed in the puff duration (Figure 2 (A)).
213
Puff Volume
214
For CS, the average (±SD) puff volume per e-cig puff averaged 47.9 (±18.2) ml. EC
215
tended to take larger puffs averaging 53.4 (±19.2) ml per puff. Total puff volume (i.e.
216
average total volume across the 7-hour ad-lib period) was similar for the CS (8,590 ±
217
7,067 ml) and EC (8,279 ± 6,182 ml). High levels of inter and intra-individual variability
218
was observed in the puff duration (Figure 2 (B)).
219
Flow Rate
220
CS tended to have higher flow rates than EC (not statistically significant). CS had an
221
average (±SD) flow rate of 21.5 (±4.6) ml/sec and EC had an average flow rate of 19.6
222
(±5.0) ml/sec. Average peak flow (maximal flow observed within a puff) was 31.5 (±8.1)
223
ml/sec for CS and 28.0 (±6.8) ml/sec for EC. High levels of inter and intra-individual
224
variability were observed in the puff flow rate (Figure 2 (C+D)).
225
Cartridge Weights
AC C
EP
TE D
M AN U
SC
RI PT
205
11
ACCEPTED MANUSCRIPT
Change in cartridge weights (pre weight – post weight for 2 cartridges) for CS averaged
227
292 (±214) mg for the entire 7-hour period. For EC, the average change in cartridge
228
weights was 415 (±305) mg for the 7-hour period (Table 4).
229
Conventional Cigarettes
230
CS used conventional cigarettes and e-cigs differently. In general, CS using their own
231
brand conventional cigarette had similar puff volumes (44.1 ± 10.5 mL) and lower puff
232
durations (1.7 ±0.4 s) when compared to the e-cig prototype use. CS also had higher
233
flow rates (28.7 ± 6.1 mL/s) and peak flow (44.2 ±11.0 ml/s) during use of cigarettes
234
than during use of the e-cig prototype. The puff duration, average flow rates and peak
235
flow rates were significantly different between conventional cigarettes and e-cigs (Table
236
5).
M AN U
SC
RI PT
226
DISCUSSION
238
In this study, e-cig puff topography measurements were characterized using a validated
239
puff topography-recording instrument under 7-hours of ad-lib use conditions. To our
240
knowledge, this is the first published report to evaluate the SPA/M for e-cig puff
241
topography measurements. E-cig puff topography tended to differ between CS and EC,
242
though these differences were not statistically significant. EC generally took longer
243
puffs (3.0 seconds vs. 2.3 seconds) with lower flow rates (19.6 ml/s vs. 21.5 ml/s)
244
relative to CS. Experienced EC and CS appeared to use the e-cig prototype differently,
245
which is consistent with the literature, and wide inter- and intra-individual variability was
246
observed across both study groups under these study conditions. Within the CS group,
247
our findings indicate that CS puff the e-cig and their own brand cigarette differently. CS
AC C
EP
TE D
237
12
ACCEPTED MANUSCRIPT
took longer, slower puffs on the e-cig prototype than on their usual brand cigarette (puff
249
duration: 2.3 seconds vs. 1.7 seconds; flow rate: 28.6 ml/s vs. 21.5 ml/s). These results
250
suggest that adult CS likely change their puffing behavior, as they become established
251
e-cig users.
252
Our observations are comparable to that reported by Farsalinos et al.7 who also
253
examined e-cig puff differences between experienced e-cig users and e-cig naïve
254
cigarette smokers. Farsalinos et al.7 used video-recordings to determine puff duration,
255
inhalation, and exhalation times over a 20-minute ad-lib use period in experienced e-cig
256
users (n=45) and cigarette smokers (n=35). The authors compared 10 consecutive
257
puffs from a tank-based e-cig or traditional cigarette (smokers only).7 The experienced
258
e-cig users took, on average, 4.2 second puffs whereas the cigarette smokers took 2.1
259
second puffs from the traditional cigarette and 2.4 second puffs from the e-cig.7 These
260
observations were similar to the results of the current study, despite differences in the
261
e-cig use period (20 minutes ad-lib use or 10 puffs versus 7 hours ad-lib use in the
262
current study) and type of
263
versus a cartridge-based closed system in the current study). Hua et al.6 noted similar
264
differences in e-cig puff duration between conventional cigarette smoking (2.4 seconds)
265
and e-cig use (4.3 seconds) when examining YouTube® videos.
266
One limitation of video recordings for puff topography measurements is the inability to
267
record the puff flow rate or volume. Multiple researchers have used mouthpiece-based
268
topography recording devices to capture this additional information. Some studies have
269
used the CreSS device,8-11 while others have used a device developed by American
270
University at Beruit,12-14
TE D
M AN U
SC
RI PT
248
AC C
EP
e-cig studied (eGo-T next-generation tank-like product
and one report used 13
a wireless Personal Use Monitor
ACCEPTED MANUSCRIPT
developed at Rochester Institute of Technology in collaboration with FSI Systems, Inc.15
272
The current study is the first to report use of the SPA/M device that has been previously
273
validated16 to collect this information using e-cigs.
274
Experienced e-cig users have been included in most studies with mouthpiece-based
275
recording devices and a wide range e-cig puffing parameters have been reported. For
276
example, average puff duration values ranged from 1.8 seconds10 to 6.1 seconds14
277
depending on the study and e-cig used. Puff flow rate averages have been reported
278
from 18 ml/s14 to 52 ml/s11 and puff volume averages range from 45 ml8 to 210.8 ml14.
279
The values reported for EC in the current study are within reported ranges (3.0 second
280
puff duration, 19.6 ml/s flow rate, and 53.4 ml puff volume), but the values tended to be
281
towards the lower end of the ranges. This may be due to the e-cigs used and/or the
282
study duration/design. Interestingly, Behar et al.8 reported similar results to the current
283
study, during two 10 min ad libitum use sessions (n=20 participants) with Blu® and V2®
284
e-cigs (e-cigs resembling the size and shape of traditional cigarettes). Average puff
285
durations were 2.75 seconds for Blu® and 2.54 seconds for V2®, average flow rates
286
were 21ml/s for Blu® and 18ml/s for V2® and average puff volume were 56 ml for Blu®
287
and 45 ml for V2®.8
288
users.15 Similar to the results of the current study, the average puff duration was 3.5
289
seconds.
290
higher at 37ml/s and 133 ml respectively. 15
291
A few studies have used mouthpiece-based puff topography devices to investigate e-cig
292
puff topography in cigarette smokers who were “naïve” to e-cig use.
293
evaluated the e-cig puff topography in 16 e-cig naïve cigarette smokers using an eGO
EP
TE D
M AN U
SC
RI PT
271
AC C
Blu® was also used in a 24 hour ad libitum use study of 22 e-cig
However, the average puff flow rate and puff volume were substantially
14
Lopez et al.13
ACCEPTED MANUSCRIPT
294
cartomizer based system.
Participants conducted multiple 10 puff sessions with
295
different nicotine concentrations (range 0-36mg/ml).13
296
concentration and time of the puffing session, average e-cig puff duration ranged from
297
2.27 to 3.21 seconds, puff flow rate ranged from 27.1 ml/s to 33.6 ml/s, and average
298
puff volumes ranged from 63.0 to 97.0 ml.13 These are similar to the values reported in
299
the current study for e-cig naïve cigarette smokers (puff duration 2.3s, puff flow rate
300
21.5 ml/s and puff volume 47.9 ml). The higher puff flow rate and volumes are possibly
301
related to the different types of products used in the two studies and/or study design (10
302
puffs vs. ad libitum use for 7 hours).
303
Lee et al.9 investigated changes in puff topography in 20 e-cig “naïve” cigarette smokers
304
using cartridge-based e-cigs over a two-week period. As participants became more
305
familiar with the e-cig (1 week of use), they took longer (2.2 seconds vs. 3.1 seconds)
306
and slower puffs (30.6 ml/s vs. 25.1 ml/s), with puff volumes remaining similar (64.0 ml
307
vs. 66.5 ml).9 This suggests that cigarette smokers change their puff topography as
308
they become accustomed to using e-cigs. As all of the experienced e-cigarette users in
309
this study had previously smoked cigarettes, the longer and slower puffs in experienced
310
e-cigarette users appears to confirm that cigarette smokers change their puffing
311
topography when using e-cigs compared to conventional cigarettes.
312
The purpose of the current study was to investigate the feasibility of using the SPA/M to
313
measure e-cig puff topography. The relatively small sample size for both groups (N=13
314
CS and N=10 EC), the use of a single prototype e-cig with a single liquid formulation,
315
and in-clinic data limit the generalizability of these findings. The SPA/M served as a
316
reliable means for measuring puff topography under these in-clinic conditions. However,
AC C
EP
TE D
M AN U
SC
RI PT
Depending on nicotine
15
ACCEPTED MANUSCRIPT
there are some shortcomings of this device. First, the SPA/M, in its current form, will
318
stop recording if no puff is detected for a 60-minute period, requiring users to restart the
319
recording each hour or each time a puffing occasion begins, limiting its utility under
320
ambulatory conditions. Second, the main body of the SPA/M is quite large, thereby
321
resulting in a cumbersome and obtrusive device for participants. The study participants
322
expressed that the pneumatic tubing and small sample holder made them feel awkward
323
while puffing. These limitations suggest that while the SPA/M device may be suitable for
324
in-clinic use, further improvements may allow unobtrusive assessments in a “real-world”
325
application. Recent advances in e-cigs have included puff monitoring within the e-cig
326
itself.18 Currently puff topography measurements with these e-cigs are limited to puff
327
number/time and duration, but future models may include puff flow rates and volume.
328
This would arguably be an improvement over all the current mouthpiece based systems
329
for use in assessing real world e-cig puff topography. We included the cigarette as a
330
comparator and assessed the topography at the end of the vaping cessation, subjects
331
smoked only a single own brand cigarettes, which might be considered a limitation.
332
However, cigarette smoking topography is well established and our observations were
333
similar to those reported by other researchers.
334
In conclusion, the results of this initial study demonstrate the feasibility of in-clinic
335
measurement of e-cig puff topography using a commercially available mouthpiece-
336
based puff topography device. The results from this study should be interpreted in the
337
context that the study was designed to evaluate the feasibility of the SPA/M device,
338
future studies may be necessary with a larger sample size to draw definitive statistical
339
inferences regarding differences in topography parameters between e-vapor users and
AC C
EP
TE D
M AN U
SC
RI PT
317
16
ACCEPTED MANUSCRIPT
cigarette smokers. In addition, this study is consistent with previous findings suggesting
341
that cigarette smokers likely change their puffing behavior when transitioning to e-cig
342
use. As e-vapor products evolve, it will be important to understand how new products
343
are used by consumers and the appropriate conditions for generating machine-
344
generated aerosols for comparative purposes.
AC C
EP
TE D
M AN U
SC
345
RI PT
340
17
ACCEPTED MANUSCRIPT
346
Table 1: Accuracy of Sodim SPA/M topography recording device with the prototype e-
347
cig device using different smoking machine generated puff profiles.
348
RI PT
2 Second Smoking Machine Sine Wave Puff Profile Target Puff Volume (ml)
Measured Volume (ml)
Accuracy (% difference from target)
35
34.1
-2.6
55
53.9
100
97.2
SC
-2
-2.8
M AN U
5 Second Smoking Machine Square Wave Puff Profile Target Puff Volume (ml)
Measured Volume (ml)
Accuracy (% difference from target)
35
37.2
6.2
56.2
2.2
103.6
3.6
AC C
349
EP
100
TE D
55
18
ACCEPTED MANUSCRIPT
350
Table 2: Repeatability and intermediate precision of Sodim SPA/M puff topography
351
recording device with the prototype e-cig device using different smoking machine
352
generated puff profiles.
353
M AN U
SC
RI PT
2 Second Smoking Machine Sine Wave Puff Profile Target Puff Volume (ml) Repeatability (%RSD) Intermediate Precision (%RSD) 35 1.57 1.83 55 1.71 2.02 100 2.67 3.15 5 Second Smoking Machine Square Wave Puff Profile Target Puff Volume (ml) Repeatability (%RSD) Intermediate Precision (%RSD) 35 3.13 3.69 55 1.39 1.63 100 1.9 2.25
%RSD = percent relative standard deviation
AC C
EP
TE D
354
19
ACCEPTED MANUSCRIPT
Table 3: Participant Demographic and Tobacco History Information Cigarette Smokers
e-Cig Users
n=13
n=10
7 female
4 female
Gender
RI PT
355
6 male Race
6 male
5 Black
3 Black
5 White
SC
8 White
2 Other
45 (±11, 33 to 65)#
#Cigarettes/day
15.4 (±4; 10 to 20) #
N/A
#Years smoking
28.5 (±10.7; 10 to 47) #
N/A
N/A
Less than 1 to 3†
N/A
10.9 (±5.4; 6 to 24) #
#Refills per day (e-vapor)
#Months since last cigarette #Cigarettes/day before
34 (±9.5; 23-52) #
N/A
13.5 (±6.4; 6 to 24) #
N/A
9.2 (±6.3; 3 to 20) #
N/A
11.7 (±8.8; 1 to 23 years) #
TE D
#Months using e-vapor
M AN U
Age
EP
using e-vapor products #Years smoked before
AC C
using e-vapor products 356
#
Parenthetical information conveys ± one standard deviation; range
357
†
Refill types vary across e-vapor products. Participants self-reported their estimated
358
number of refills per day.
359
20
ACCEPTED MANUSCRIPT
360
Table 4: E-Cig Prototype Puff Topography (7-hours Ad-lib) Cigarette Smokers n=13 Topography variable
Mean (SD)
95%CI
Mean (SD)
Total number of puffs
160 (92)
103.8 - 216.1
147 (93)
80.3 - 213.3
Puff duration (sec)
2.3 (0.8)
1.9 - 2.8
3.0 (1.3)
2.1 - 4.0
Total puff duration (sec)
391 (297)
212 - 571
Puff volume (ml)
47.9 (18.2)
Total puff volume (ml)
RI PT
SC
222 - 753
8590 (7067)
4320 - 12860
8279 (6182)
3857 -12701
Flow rate (ml/sec)
21.5 (4.6)
18.7 - 24.3
19.6 (5.0)
16.1 - 23.2
Peak flow rate (ml/sec)
31.5 (8.1)
26.5 - 36.4
28.0 (6.8)
23.2 - 32.9
Total cartridge weight change (mg)
292 (214)
162 - 421
415 (305)
197 - 632
54.0 - 78.5
78.6 (27.3)
59.0 - 98.1
TE D
39.7 - 67.1
EP
M AN U
498 (371)
53.4 (19.2)
66.2 (20.2)
AC C
363
95%CI
36.9 – 59.0
Inter-puff interval (sec) 361 362
e-Cig Users n=10
no statistical significance was found between the cigarette smokers and e-vapor users in any of the topography variables (p-values > 0.05).
21
ACCEPTED MANUSCRIPT
364
Table 5: Cigarette Smokers Puff Topography during Use of e-Cig Prototype and Their
365
Own Brand Conventional Cigarette e-Cig Use
Cigarette Smoking
n=13
n=13
369 370 371 372 373
Puff duration (sec)
2.3 (0.8)
1.9 - 2.8
1.7 (0.4)
Puff volume (ml)
47.9 (18.2)
36.9 – 59.0
Flow rate (ml/sec)
21.5 (4.6)
Peak flow rate (ml/sec)
31.5 (8.1)
95%CI
SC
Mean (SD)
p-value
0.5591
44.1 (10.5)
36.6 - 51.6
0.0236
18.7 - 24.3
28.6 (6.1)
24.2 -33.0
0.0045
26.5 - 36.4
44.2 (11)
36.3 - 52.0
0.0043
M AN U
1.3 - 2.0
TE D
368
95% CI
EP
367
Mean (SD)
AC C
366
Topography variable
RI PT
Difference
374 375 22
ACCEPTED MANUSCRIPT
377
Figure 1: Example Puff Profiles Cigarette Smokers and e-Cig Users A. Conventional cigarette smoker with e-cig prototype
RI PT
376
SC
378
Time (seconds)
379
381 382
M AN U Time (seconds)
C. e-Cig user with e-cig prototype
AC C
EP
383
B. Conventional cigarette smoker with own brand conventional cigarette
TE D
380
384 385
Time (seconds)
386 23
ACCEPTED MANUSCRIPT
387
A. Individual Puff Durations
M AN U
SC
RI PT
388
Figure 2: Puff Parameter Plots for Individual Subjects Using e-Cig Prototypes
389
B. Individual Average Puff Volumes
392 393 394
AC C
391
EP
TE D
390
395 396 397 24
ACCEPTED MANUSCRIPT
C. Individual Average Puff Flow Rates
SC
RI PT
398
D. Individual Average Peak Puff Flow Rate
402 403 404
AC C
401
EP
TE D
400
M AN U
399
25
ACCEPTED MANUSCRIPT
Figure Captions:
406
Figure 1: Examples of individual puff profiles for conventional cigarette smokers and e-
407
vapor users. The figure shows one conventional and one electronic cigarette puff for
408
one conventional cigarette smoker as well as one electronic cigarette puff for an e-vapor
409
user. Each profile shows puff flow rate over time as well as the calculated puff volume
410
and duration in the upper left hand corner.
411
Figure 2: Puff parameter plots for Individual subjects using e-cigarette prototypes over
412
7-hours ad libitum: average puff duration (A), average puff volume (B), average puff flow
413
rate (C), average peak puff flow rate (D). Conventional cigarette smokers (left panel)
414
and e-Vapor users (right panel). Each plot represents the mean +/- Standard Deviation
415
for all recorded puffs for each individual subject over the 7-hour period.
M AN U
SC
RI PT
405
AC C
EP
TE D
416
26
ACCEPTED MANUSCRIPT
417
References
418
1.
Delnevo CD, Giovenco DP, Steinberg MB, et al. Patterns of Electronic Cigarette Use Among Adults in the United States. Nicotine & tobacco research : official journal of the Society for
420
Research on Nicotine and Tobacco. 2016;18(5):715-719.
421
2.
RI PT
419
Adkison SE, O'Connor RJ, Bansal-Travers M, et al. Electronic nicotine delivery systems:
international tobacco control four-country survey. American journal of preventive medicine.
423
2013;44(3):207-215. 3.
Ayers JW, Ribisl KM, Brownstein JS. Tracking the rise in popularity of electronic nicotine delivery
M AN U
424
SC
422
425
systems (electronic cigarettes) using search query surveillance. American journal of preventive
426
medicine. 2011;40(4):448-453.
427
4.
Walton KM, Abrams DB, Bailey WC, et al. NIH electronic cigarette workshop: developing a research agenda. Nicotine & tobacco research : official journal of the Society for Research on
429
Nicotine and Tobacco. 2015;17(2):259-269.
430
5.
TE D
428
U.S. Department of Health and Human Services (USDHHS), Food and Drug Administration (FDA), Center for Tobacco Products (CTP). Premarket Tobacco Product Applications for Electronic
432
Nicotine Delivery Systems; Draft Guidance for Industry. 2016.
433
http://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM499
434
352.pdf.#sthash.J8E5P1rM.dpuf. Accessed June 10, 2016.
6.
436 437 438
AC C
435
EP
431
Hua M, Yip H, Talbot P. Mining data on usage of electronic nicotine delivery systems (ENDS) from YouTube videos. Tobacco control. 2013;22(2):103-106.
7.
Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V. Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for
27
ACCEPTED MANUSCRIPT
439
research protocol standards definition and for public health authorities' regulation. International
440
journal of environmental research and public health. 2013;10(6):2500-2514. 8.
443
PloS one. 2015;10(2):e0117222. 9.
444 445
RI PT
442
Behar RZ, Hua M, Talbot P. Puffing topography and nicotine intake of electronic cigarette users.
Lee YH, Gawron M, Goniewicz ML. Changes in puffing behavior among smokers who switched from tobacco to electronic cigarettes. Addictive behaviors. 2015;48:1-4.
10.
Goniewicz ML, Kuma T, Gawron M, Knysak J, Kosmider L. Nicotine levels in electronic cigarettes.
SC
441
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and
447
Tobacco. 2013;15(1):158-166.
448
11.
M AN U
446
Norton KJ, June KM, O'Connor RJ. Initial puffing behaviors and subjective responses differ
449
between an electronic nicotine delivery system and traditional cigarettes. Tobacco induced
450
diseases. 2014;12(1):17. 12.
Spindle TR, Breland AB, Karaoghlanian NV, Shihadeh AL, Eissenberg T. Preliminary results of an
TE D
451
examination of electronic cigarette user puff topography: the effect of a mouthpiece-based
453
topography measurement device on plasma nicotine and subjective effects. Nicotine & tobacco
454
research : official journal of the Society for Research on Nicotine and Tobacco. 2015;17(2):142-
455
149. 13.
457
on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.
458
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and
459 460 461
Lopez AA, Hiler MM, Soule EK, et al. Effects of Electronic Cigarette Liquid Nicotine Concentration
AC C
456
EP
452
Tobacco. 2016;18(5):720-723.
14.
Ramoa CP, Hiler MM, Spindle TR, et al. Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report. Tobacco control. 2016;25(e1):e6-9.
28
ACCEPTED MANUSCRIPT
462
15.
463 464
Robinson RJ, Hensel EC, Morabito PN, Roundtree KA. Electronic Cigarette Topography in the Natural Environment. PloS one. 2015;10(6):e0129296.
16.
Connell CT, Bennett DR, Meruva NK, Vansickel AR, Edmiston JS. POS2-93: Validation of a smoking puff analyzer for use with an electronic cigarette prototype. Poster presented at:
466
SRNT's 20th Annual Meeting; February 5-8, 2014; Seattle, WA.
467
17.
RI PT
465
Vansickel AR, Edmiston J, Liang Q, Duhon C, Liu J, Sarkar M. POS3-65: Characterization of
electronic cigarette prototype puff topography in adult exclusive cigarette smokers and adult
469
exclusive electronic cigarette users. Poster presented at: SRNT 20th Annual Meeting; February
470
5-8, 2014, 2014; Seattle, WA. 18.
M AN U
471
SC
468
Dawkins LE, Kimber CF, Doig M, Feyerabend C, Corcoran O. Self-titration by experienced e-
472
cigarette users: blood nicotine delivery and subjective effects. Psychopharmacology.
473
2016;233(15-16):2933-2941.
AC C
EP
TE D
474
29
ACCEPTED MANUSCRIPT
Research Highlights: 1) Validated topography device was used to characterize puffing topography amongst cigarette smokers and e-vapor users.
RI PT
2) Cigarette smokers appear to use e-cigarettes differently than experienced e-cigarette users. 3) Experienced e-cigarette users generally took longer puffs with lower flow rates relative to cigarette smokers
AC C
EP
TE D
M AN U
SC
4) The topography device could be a useful tool for in-clinic measurement of e-cigarette use behavior.