A Randomized Multilocation Study of Puffing Topography in Chinese Adult Smokers using Heated Tobacco Products and Conventional Cigarettes

doi:10.21203/rs.3.rs-4626978/v1

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A Randomized Multilocation Study of Puffing Topography in Chinese Adult Smokers using Heated Tobacco Products and Conventional Cigarettes

https://doi.org/10.21203/rs.3.rs-4626978/v1

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Objectives: Heated tobacco products (HTPs) constitute a novel and emerging type of tobacco product. Actual puffing topography and nicotine exposure studies are indispensable in tobacco and nicotine products risk assessment. In this study, we aimed to collect and compare usage behavioural data on HTPs to those of conventional cigarettes (CCs) by recording the puffing topography parameters of users under laboratory conditions. Methods: Two hundred voluntary adult cigarette users (164 male, 36 female) from 4 Chinese cities were recruited and randomly divided into 3 groups: the tobacco flavoured HTP (Original-HTP) group, the menthol-flavoured HTP (Menthol-HTP) group, and the CC group. The volunteers were acclimatized to the 3 tobacco products with a nicotine content of 1.0 mg/stick, for 1 week. Data on the 8 types of puffing parameters were collected for every participant via a commercial calibrated puff behaviour recorder. These data were analysed alongside the levels of 8 urinary nicotine metabolites after product usage. Results: When using the same type of nicotine stick, the volunteers in the two HTP groups had significantly higher puff numbers, puff volumes, flow velocities and peak flow rates than those in the CC group. Conversely, participants in the CC group had longer interpuff intervals and higher urinary nicotine concentrations. Differences in the puffing topography among the four cities were not significant. Conclusion: There were substantial differences in the overall puffing volume and urinary nicotine metabolite levels between Chinese smokers who used HTPs and those who used CCs. These findings indicate that assessments of risk associated with the use of tobacco and nicotine products need to adequately assess the actual use patterns and nicotine exposure levels of users of different types of products.

Biological sciences/Biochemistry

Biological sciences/Physiology

Health sciences/Risk factors

heated tobacco product

conventional cigarette

puffing topography

demographic characteristics

user behavior

The use of tobacco products contributes to the development of numerous preventable diseases; however, there are still many smokers who have not or are unable to quit [1]. Among the harmful components of tobacco, nicotine is the main component that causes addiction. All users of tobacco products have the potential to become addicted to the product. The effects of nicotine intake and exposure to harmful substances from tobacco products on the human body are complex, and assessments of such effects need to be conducted on different aspects of actual product use [2].

The health risks of cigarette smoking are well known. In recent years, many tobacco companies have developed alternative tobacco and nicotine products, such as vape products and heated tobacco products (HTPs), which were created with the aim of reducing the levels of toxins in aerosols by replacing the traditional burning mode of tobacco [3]. Unlike vape products, HTPs and CCs emit aerosols by heating or burning Nicotiana benthamiana leaves. In 2014, HTPs were launched in Japan and then in European markets [4], and with their claimed benefits of harm reduction and aiding smoke cessation, their use has increased in recent years [5]. HTPs are designed to heat tobacco below the ignition temperature and deliver aerosolized nicotine and other tobacco constituents for inhalation [6]. Based on controlled heating technologies, different HTPs are now available for producing aerosols containing nicotine without burning tobacco [7]. Therefore, theoretically, HTPs have the potential to reduce the exposure to harmful substances that occurs through tobacco using behaviour. As a new form of nicotine delivery, HTPs have significantly different smoke generation principles and components from those of CCs [8]. According to data from the tobacco industry, the toxicant content in the aerosols of some commercial HTPs is approximately 90–95% lower than that in CC smoke, and the levels of harmful and potentially harmful components (HPHCs), such as aldehydes and volatile organic compounds, in heated cigarette smoke are also significantly lower [9]. In a review of 25 relevant studies published in English between 2015 and 2021, the exclusive HTP use was suggested to reduce the risk of some chronic diseases, including respiratory disease, cardiovascular diseases and cancer, relative to the risks associated with cigarette smoking. However, HTP use by non-smokers may pose a risk for these diseases; therefore, HTPs have been proposed as an alternative to CCs only for heavy smokers who have failed comprehensive treatment for nicotine addiction [8]. As an additional benefit, HTPs do not emit second-hand smoke and may reduce environmental pollution [3]. Together, these findings provide valuable clues to confirm that HTPs have potential for harm reduction.

Several types of HTPs have been introduced into the market thus far, and they are sold in more than 40 countries [8]. Apart from those countries, recent market research has shown that many Chinese smokers are interested in HTPs [10], either in combination with other tobacco products or as quitting aids. However, some studies have shown that these types of novel tobacco products can also attract users who would otherwise never smoke [11]. Therefore, the impact of HTPs on health still needs to be further explored from different perspectives.

In real world scenarios, emission analysis of the chemical composition of HTP aerosols is an important step in determining whether HTPs have both individual- and population-level harm reduction potential. In fact, some studies have reported that the levels of harmful and potentially harmful constituents (HPHCs) in emissions from HTPs are significantly lower than those in emissions from CCs [1, 12]. Emission data for chemical analysis are typically collected under standard machine-smoking regimens defined by the International Organization for Standardization (ISO) or the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) [13]. However, standardized regimens are intended for product comparison purposes and do not necessarily reflect human puffing behaviour. To estimate the real emissions or the levels of chemicals inhaled by users of HTPs, which are more important for assessing these products’ true harm reduction potential, data pertaining to puffing topography parameters reflecting real-world usage must be gathered.

The puffing topography of a tobacco product is influenced by the design and specifications of the product as well as the smoking habits and preferences of the user. Puffing topography data not only reflect the personal preferences and smoking habits of smokers to a considerable extent but also significantly affect toxicant intake by tobacco users [14, 15]. Harsher puffing conditions, such as more, longer, and larger puffs, yield higher levels of most toxicant emissions [16]. For instance, many studies have reported puffing topographic data among smokers using different generations of vape products [13, 17, 18], most of which have shown that puff duration, interpuff interval and puff volume among vaping users vary from those among CC users. In addition, different flavours of vape products can result in different puff durations and different levels of plasma nicotine, as measured in a previous clinical study [14]. Together, these observations provide evidence that both the levels and forms of nicotine affect the user's puffing topography.

To date, there have been few studies on the puffing topographies of HTPs compared with those of CCs for Chinese smokers [19]. It is important to study the puffing topography of HTPs in smokers with different demographic characteristics. In our study, we aimed to measure the puffing topography behaviour of participants according to HTP flavour (one original-flavoured and one menthol-flavoured) and compare these findings to those of CC smokers under similar standardized conditions to further understand the effects of nicotine exposure and metabolism of heated cigarettes on the human body. This randomized study provides insights into their potential adaptation and the switching of Chinese CC smokers to HTPs. Increasing the understanding of any product characteristics that pertain to HTP use may also facilitate the development of a standard protocol for HTP testing and clinical studies [13]. In addition, this study provides a basis for the experimental design of methods for evaluating exposure to heated cigarette smoke and provides a reference for the design and development of HTPs that are suitable for consumer habits.

2.1 Data collection

Information on participants’ smoking history and demographics was collected before the first round of the study using a self-administered questionnaire designed for the study. Puffman^™ puff behaviour recorders (Puffman Automation and Instruments Company, China) were used to measure the puffing topography parameters of every participant in this study. The technical specifications are shown in Table 1.

Table 1

The technical parameters of the puff behaviour recorder used in this research.
No.	Technical Parameter	Values
1	Puff volume range	0-150 mL
2	Precision of puff volume	± 2%
3	Flow velocity range	10–50 mL/s
4	Precision of flow velocity	± 2%
5	Puff duration range	0–99 s
6	Precision of puff duration	± 100 ms
7	Interpuff interval range	0–10 Min
8	Precision of interpuff interval	± 100 ms
9	Pressure drop	1 kPa
10	Precision of pressure drop	± 1%
11	Data collection frequency	100 Hz

Before using each puff behaviour recorder in this test, trial runs were performed to compare the recorded data and to ensure that they were calibrated and within the specified ranges. During the study, care was taken to remove any aerosol residuals within the product adaptation hole after every half hour of usage.

All of the HTP devices, consumable tobacco sticks, and test cigarettes used in the study were provided by Shanghai New Tobacco Product Research Institute Co., Ltd. As shown in Fig. 1, the HTP device had a maximum heating temperature of 350°C. The nicotine content of the HTP consumable sticks (both the original tobacco and menthol flavours) was 1.0 mg per stick. CCs were commercially available with a nicotine content of 1.0 mg/stick and a tar content of 11 mg/stick.

2.2 Human participants and study groups

Participants were selected from four cities across China, Shanghai and Suzhou in Eastern China, Hefei in Central China, and Guiyang in Western China. The sample size was calculated using the software G*Power 3.1.9.7. We used a random sampling method to assign 50 participants in each city, totalling 200 participants, and then divided them randomly into three groups: group 1 (n = 71), group 2 (n = 68) and group 3 (n = 60). Tests were run from July to August 2022.

The inclusion criteria for the participants were as follows: aged 19–65 years; no self-reported cardiovascular, respiratory or reproductive disease; no psychiatric or other serious psychiatric disorder; and not pregnant or breastfeeding. These reported conditions were supported by their medical records. The volunteers had not taken any medication in the last week that could interfere with the test purpose; had smoked 5–20 cigarettes with ISO tar yields between 10–12 mg and nicotine levels of 1.0 mg daily for at least 2 years (current brand for > 6 months) [20]. The exclusion criteria were current or previous known illicit drug abuse, current or previous mental disorder, diagnosed cardiovascular disease, chronic obstructive pulmonary disease, other respiratory diseases or cancer of any kind, or any other incompatibilities (for example: cognitive impairment) with the purpose of the study.

The investigators of the study also evaluated the participants’ adherence to the experimental protocol. Informed consent was obtained from all the participants after the purpose of the study was explained. The Biomedical Ethics Review Committee of Tongren Traditional Chinese Medicine Hospital approved the study (Approval number: TRSZYY-2022-02).

2.3 Definition of puffing topographic variables

The puff number was defined as the total number of puffing one single cigarette or single HTP stick. Puff volume was continuously recorded in units of mL during a single mouth puffing process. Puff duration referred to the duration of a single mouth puffing process. The interpuff interval was defined as the time interval between two adjacent mouth puffing events. The flow velocity, peak flow rate and peak time were recorded or calculated based on the single CC or HTP that the participants puffed in each round of the experiment. Intention-to-quit smoking was a variable that measured whether a participant had a willingness to quit smoking when receiving the questionnaire survey, and the results were divided into two categories: yes and no.

2.4 Puffing topography assessment

Participants in each group were allowed to familiarize themselves with the use of the study HTP devices and the puff behaviour recorder. Efforts were made to encourage them to puff naturally and to reproduce their usual puff behaviours. The adaptation period lasted six days, during which each participant was provided with an average of 5 cigarettes and HTP sticks. Instructors were available when needed to guide the participants to customize their stable puffing behaviours.

In the first round of the experiment on day one, participants were assigned to puff CCs, Original-HTPs, and Menthol-HTPs based on the assignment plan. On the seventh day, they were required to smoke a single CC or HTP stick within 5 minutes of their group assignment. These assessments were conducted in similar experimental environments, including ambient setting, indoor temperature and ventilation. Throughout the entire process of puffing, we recorded the smoking behavioural parameters, including the puff number, puff volume, puff duration, interpuff interval, flow velocity, peak flow rate, and peak time, using the puff behaviour recorder as well as atmospheric pressure at the same time. The test process was video recorded to verify each participant’s compliance and ensure that all of the data had been correctly obtained.

In the second round, beginning on the eighth day, the participants in group 1, group 2 and group 3 were switched to puffing Original-HTPs, Menthol-HTPs and CCs, respectively. In the last round, beginning on the fifteenth day, participants in group 1, group 2 and group 3 were switched to puffing menthol-HTPs, CCs and Original-HTPs, respectively. Similar to the first round, we set a six-day adaptation period for the second and third rounds and required each participant to smoke a CC or HTP within 5 minutes of their assignment and recorded the above smoking behavioural parameters at the same time (Fig. 2).

We calculated the means or the median (puff number) of the above puffing parameters and atmospheric pressure in three repeats of the experiment to describe the puffing topographies after excluding the influence of puff order.

2.5 Urine collection and nicotine metabolites analysis

On the last day of each round, urine samples were collected in the morning and 8 hours after smoking to assess the individual’s nicotine exposure level from the sample cigarette. During this period, all volunteers freely drank water to facilitate the passage of urine. The levels of the following eight nicotine metabolites in urine were tested: nicotine (NIC), cotinine (COT), cotinine-N-β-D-glucuronide (COTG), (1’S, 2’S)-nicotine-1’-oxide (NNO), (S)-cotinine N-oxide (CNO), trans-3-hydroxycotinine (OHCOT), nornicotine (NNIC), and norcotinine (NCOT). Each urine sample was labelled with the participant's name, group ID, and date, and once collected, it was immediately stored in liquid nitrogen for urinalysis at a later date using a previously reported method [10].

2.6 Statistical analysis

The data were checked for consistency and any abnormalities. Data on the characteristics of the participants are presented as the mean and standard deviation (SD) for continuous variables if normally distributed or as the median and interquartile range (IQR) if nonnormally distributed. Categorical variables are presented as numbers and percentages (%). We compared continuous variables among the three groups according to the type of tobacco stick used, namely, CC, Original - HTP and Menthol - HTP, using one-way analysis of variance (ANOVA) if the data were normally distributed. When a significant difference was found between the groups, Tukey’s post hoc test was applied to determine the source of the difference. For nonnormally distributed data or data with heterogeneity in variance, the Kruskal‒Wallis test was used for multiple-group comparisons of the average values. For categorical variable data, the chi-square test was used for comparisons of proportions. A value of 0.05 was used as the threshold for significance. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 23.0 and G*Power 3.1.9.7.

In the 3-round experiment, 200 participants in 3 groups were assigned to puff CCs, Original-HTPs, and Menthol-HTPs. Throughout the entire experimental phase, none of the participants reported any adverse reactions or physical discomfort during or 1 week after the study. The puffing parameters recorded by the puffing behaviour recorders and the urinary nicotine metabolites were fully documented and analysed.

3.1. Demographic characteristics and smoking history

The average age of the participants was 34.04 ± 10.52 years, ranging from 19 to 65 years. In total, 164 (82.0%) participants were male, and all participants were current smokers; 96 (48.0%) had smoked for more than 10 years, and the average duration of cigarette smoking was 10.65 ± 8.38 years. The average body mass index (BMI) of the participants was 22.95 ± 3.04 kg/m², and among them, 14.0%, 54.5%, 25.0%, and 6.5% were classified as underweight, normal weight, overweight and obese, respectively. The rates of daily cigarette consumption, intention-to-quit smoking, and occupation among the participants are presented in Table 2.

Table 2

Demographic characteristics of the participants
		N	%
Sex	Male	164	82.0
	Female	36	18.0
Duration of cigarette smoking (y)	< 10	104	52.0
	10~	96	48.0
Daily cigarette consumption	≤ 10/d	107	53.5
	11 ~ 20/d	79	39.5
	≥ 21/d	14	7.0
Body weight	Underweight	28	14.0
	Normal weight	109	54.5
	Overweight	50	25.0
	Obesity	13	6.5
Intention-to-quit smoking	Yes	95	47.5
	No	105	52.5
Occupation	Civil servant	1	0.5
	Professional and technical	16	8.0
	Staff member	58	29.0
	Enterprise management	51	25.5
	Worker	22	11.0
	Student	12	6.0
	Self-employed	18	9.0
	Unemployed	3	1.5
	Retired (resigned)	9	4.5
	Others	10	5.0
Total		200	100.0

3.2. Demographic characteristics and smoking history in each city

Although the daily cigarette consumption differed among the participants from the four representative cities, there were no significant differences in the sex, age, weight status or duration of cigarette smoking characteristics(Table 3), indicating that there were few differences in the demographic composition between the participants from the four cities.

Table 3

Demographic characteristics of the participants from the four cities.
	Guiyang	Hefei	Shanghai	Suzhou	χ²/F^/H^*	P
Sex: Male (%)	82.0	86.0	74.0	86.0	3.252	0.354
Age: yrs (mean ± SD)	32.64 ± 10.50	35.66 ± 9.73	33.40 ± 10.61	34.22 ± 10.50	0.781^*	0.506
Weight Status: Underweight (%)	16.0	8.0	16.0	16.0	5.011^**	0.171
Normal (%)	48.0	68.0	38.0	64.0
Overweight (%)	32.0	18.0	34.0	16.0
Obesity (%)	4.0	6.0	12.0	4.0
Duration of cigarette smoking: <10ys (%)	56.0	50.0	50.0	52.0	0.481	0.923
Daily cigarette consumption: ≤10/d (%)	64.0	34.0	82.0	34.0	35.656^**	< 0.001
11 ~ 20/d (%)	32.0	62.0	18.0	46.0
≥ 21/d (%)	4.0	4.0	0.0	20.0
Note: Represents F value in ANOVA, *Represents H value in Kruskal‒Wallis test.

3.3. Differences in puffing topography

Eight puffing parameters were fully recorded. We compared the mean puff number, puff volume, puff duration, interpuff interval, flow velocity, peak flow rate, and peak time among the three groups of participants and found significant differences in all of the above variables (Table 4). Regarding atmospheric conditions during the experiment, there were no significant differences in average atmospheric pressure among the three groups of participants (Table 4). This indicates that the puffing parameters were not affected by atmospheric pressure in this study. In our comparison of the above puffing parameters in each city, we found that except for flow velocity, all of the puffing characteristics showed at least one differences between groups (Fig. 3).The differences in puffing topography among the four cities between the Original-HTPs and Menthol-HTPs were marginally significant. However, the overall trend in variances between HTPs and CCs remained consistent.

Additionally, taking into account of the existence of continuity in the number of puffs taken by participants (e.g., very short interpuff intervals between two adjacent puffs) and also the precision of the puffing behaviour recorder, we also analysed the median puff numbers among CC, Original- HTP, and Menthol-HTPs users, which were 14, 20, and 18, respectively, with significant differences among them (P < 0.01). Among all the participants, a considerable proportion of participants had continuous puffing actions between two adjacent puffs, and the proportions of this behaviour among CC, Original- HTP, and Menthol-HTP users were 45.3%, 36.8%, and 42.3%, respectively.

Table 4

Comparisons of the means of puffing parameters and atmospheric pressure among different types of cigarettes.
Variable	Cigarette type	n	Mean/ Median*	SD	SE	F/H*	P
Puff number (per session)	CC	200	14*	/	/	/	< 0.001
	Original-HTP	200	20*	/	/
	Menthol-HTP	200	18*	/	/
Puff volume (mL)	CCs	200	39.636	14.575	1.031	155.090*	< 0.001
	Original-HTP	200	65.639	21.303	1.506
	Menthol-HTP	200	58.838	22.440	1.587
Puff duration (s)	CC	200	1.877	0.612	0.043	4.366	0.013
	Original-HTP	200	2.048	0.642	0.045
	Menthol-HTP	200	1.889	0.679	0.048
Interpuff interval (s)	CC	200	12.470	3.730	0.264	26.423	< 0.001
	Original-HTP	200	10.283	3.163	0.224
	Menthol-HTP	200	10.300	3.464	0.245
Flow velocity (mL/s)	CC	200	22.106	7.529	0.532	127.849	< 0.001
	Original-HTP	200	33.550	8.094	0.572
	Menthol-HTP	200	31.978	7.642	0.540
Peak flow rate (mL/s)	CC	200	34.321	13.123	0.928	202.548*	< 0.001
	Original-HTP	200	56.036	15.873	1.122
	Menthol-HTP	200	51.112	14.794	1.046
Peak time (s)	CC	200	0.764	0.339	0.024	8.099*	0.017
	Original-HTP	200	0.859	0.436	0.031
	Menthol-HTP	200	0.745	0.371	0.026
Atmospheric pressure (kPa)	CC	200	98.181	6.108	0.432	0	> 0.999
	Original-HTP	200	98.181	6.108	0.432
	Menthol-HTP	200	98.184	6.110	0.432
Note: *Represents H value in the Kruskal‒Wallis test due to heterogeneity in variance.

3.4. Differences in urinary nicotine metabolite levels

The urinary nicotine metabolite level represented the level at which participants were actually exposed to tobacco products. There were significant differences in the average levels of all the urinary nicotine metabolites among the CC, Original-HTP and Menthol-HTP groups of participants, whether the urine sample was collected in the morning or 8 hours after the cigarette was smoked (Table 5). In all the HTP groups, the total urinary nicotine metabolite contents were lower than those in the CC group (Fig. 4). The results suggest that when switching to the same amount of HTP or CC use, smokers who used HTP inhaled less nicotine than that inhaled by CC users.

Table 5

Comparisons of 8 urinary nicotine metabolites among the test products.
Nicotine metabolites (ng/L)	Urine samples	In the morning		8 hours after puffing one stick		P
Nicotine metabolites (ng/L)	Urine samples	Mean	SD	Mean	SD	P
NIC	CCs	30.39	12.26	87.17	14.03	< 0.01
	Original- HTPs	21.76	5.08	49.09	12.31
	Menthol- HTPs	26.68	7.87	67.55	14.39
COT	CCs	4.62	0.87	49.04	5.64	< 0.01
	Original- HTPs	3.45	0.95	41.98	7.97
	Menthol- HTPs	4.25	0.98	26.92	5.04
COTG	CCs	27.01	5.76	289.50	85.49	< 0.01
	Original- HTPs	18.44	5.10	186.60	31.24
	Menthol- HTPs	14.85	3.12	166.60	33.25
NNIC	CCs	0.58	0.15	3.89	1.05	< 0.01
	Original- HTPs	0.55	0.19	1.87	0.47
	Menthol- HTPs	0.41	0.10	1.47	0.58
NCOT	CCs	5.04	1.69	21.81	2.92	< 0.01
	Original- HTPs	2.38	0.62	19.00	3.64
	Menthol- HTPs	3.79	1.71	21.72	4.75
NNO	CCs	4.10	0.66	16.00	2.42	< 0.01
	Original- HTPs	3.58	0.69	15.08	2.49
	Menthol- HTPs	3.53	0.53	10.23	1.83
CNO	CCs	1.86	0.35	4.89	0.90	< 0.01
	Original- HTPs	1.42	0.41	2.51	0.50
	Menthol- HTPs	1.22	0.28	2.65	0.49
OHCOT	CCs	49.45	10.48	165.90	19.26	< 0.01
	Original- HTPs	26.95	5.42	49.68	9.61
	Menthol- HTPs	42.98	9.72	95.87	18.31

There is a growing body of literature demonstrating the importance of tobacco and nicotine product risk assessment. In China, there are 341 million smokers, and their consumption accounts for one-third of the world's cigarette consumption, with an estimated 740 million non-smokers exposed to second-hand smoke [21, 22]. The smoking rates for men and women are 49.7% and 3.54%, respectively [23]. The participants in this study came from four sampling cities in wide geographical regions of China and thus could provide a useful insight into the general smoking population.

The results of this study revealed that the characteristics of HTP users were different from those of CC users in terms of all the measured puffing parameters, which is somewhat similar to the previously reported differences between vape products and CC users [24]. In addition, many of the characteristics of the puffing topographies of HTP users from different regions in this study were also different, with the exception of flow velocity. The difference in flow velocity among the three groups did not show regional differences in this study, which could be related to the differences in the tested HTP products.

The average puff numbers and puff volumes in the Original-HTP group and in the Menthol-HTP group were both significantly higher than those in the CC group. One possible explanation for this may be that HTP users needed to draw larger puffs to obtain similar amounts of the aerosol from HTP consumables due to the lower average aerosol delivery ability of HTPs than of CCs [25]. Although this finding is different from that of Sheng et al.'s study conducted in Henan, China, which showed that the puff volume did not change significantly among cigarette smokers who switched to HTPs [26], the mean puff volumes in the Original-HTP group and in the Menthol-HTP group were both very similar to those in Sheng W et al.'s study and Murphy et al.'s study [27]. The reason for this discrepancy may be related to the number of subjects and the accuracy of the instruments used in the experiments.

Our study also revealed that the average urine nicotine metabolite levels in the urine samples obtained from users of Original-HTPs and Menthol-HTPs were lower than those in the urine samples obtained from users of CCs, whether in the morning or 8 hours after smoking; these findings were consistent with the increase in average puff number and puff volume among the users of Original-HTPs and Menthol-HTPs. This suggests that when smokers switch to smoking HTPs, their puff number and puff volume may be increased due to the decrease in nicotine intake per puff.

We also found that the interpuff intervals in the Original-HTP and Menthol-HTP groups were both significantly shorter than those in the CC group. Jones J et al. reported similar results, namely, that the oral exposure level to nicotine in the smoke of HTPs was lower than that in the smoke of CCs [25]. The shortening of the interpuff interval of HTPs may be related to decreased smoke and nicotine levels with each HTP puff compared to those with CCs. With HTPs, participants must inhale more of the aerosol to meet their own nicotine needs within the same amount of time by shortening the interpuff interval. Similar to that of HTPs, in some studies, the nicotine delivery efficiency of vape products was lower than that of CCs. Norton et al. and Wagener et al. reported that the interpuff interval must also be shortened to improve satisfaction among consumers of vape products [17, 28].

Notably, the average puff numbers and puff volumes in the Original-HTP group and in the Menthol-HTP group were both significantly higher than those in the CC group. One possible explanation for this may be that HTP users need to draw larger puffs to obtain similar amounts of the aerosol from HTP consumables due to the lower average aerosol delivery ability of HTPs than CCs [25]. Although this finding is different from that of Sheng et al.'s study conducted in Henan, China, which showed that the puff volume did not change significantly among cigarette smokers when switching to HTPs [26], the mean puff volumes in the Original-HTP group and in the Menthol-HTP group were both very similar to those in Sheng W et al.'s study and Murphy et al.'s study [27]. The reason for this discrepancy could be related to the number of subjects and the accuracy of the instruments used in the experiments. At the same nicotine concentration, the nicotine transfer efficiency of HTPs may be lower. That is, when an HTP user takes a puff with the same designated nicotine content in the stick, the amount of nicotine inhaled into the body is lower. This finding was confirmed in our previous studies which showed lower levels of nicotine and its metabolic markers in the urine of HTP users than in that of CC users [10, 32].

The main limitations of this study are as follows. Participants from northern China were not included because domestic travel was inconvenient during the research period. In addition, to ensure participants‘ compliance, the time interval between adjacent rounds was relatively compressed. Finally, due to about 40% of the participants having continuous puffing actions between two adjacent puffs, the measured puff numbers might be overestimated to some extent. However, the proportion of participants exhibiting this behaviour was similar among the different HTP product users; therefore, it was unlikely to have a significant impact on the results and conclusions.

In conclusion, our study revealed substantial differences in the puffing topography of the HTP and CC users. When cigarettes with the same nicotine content were used, HTP users had higher puff numbers, puff volumes, flow velocities and peak flow rates. However, the CC users had longer interpuff intervals. A possible explanation is that the volunteers using HTPs needed to obtain satisfactory levels of aerosol and nicotine from HTPs by increasing the puff number and puff volume, as well as shortening the interpuff interval. The evaluation of the urinary cotinine concentrations of the participants showed that conventional cigarette users consumed more nicotine than did HTP users. It is speculated that these differences may be due to the differences in the nicotine content, tar content, and flavour of the tobacco sticks. Within each of the four cities, the general differences in puffing topography remained the same. However, the relationship between the types of tobacco products and the puffing topography of different users requires further exploration. The findings in this research provide evidence that smokers who switch to using HTPs adopt different puffing behaviours, which has implications for risk assessments of different types of tobacco products.

Author Contributions: Methodology, X.L., Y.G. and G.X.; software, P.C. and H.S.; validation, X.L., Y.G. and G.X.; formal analysis, G.L., L.L. and P.C.; investigation, X.L. and L.L.; data curation, Y.G. and P.C.; writing—original draft preparation, X.L.; writing—review and editing, Y.G. and G.X.; visualization, X.L. and G.X.; supervision, Y.G.; project administration, Y.G. and G.X. All authors have read and agreed to the published version of the manuscript.

Funding: This research received no external funding.

Institutional Review Board Statement: The study was approved and conducted by the ethics committee of Tongren Traditional Chinese Medicine Hospital (No. TRSZYY-2022-02) on 30 May 2022. The study was conducted in accordance with the local legislation and institutional requirements.

Informed Consent Statement: Informed consent was obtained from all the subjects involved in the study.

Data Availability Statement: The raw data supporting the conclusion of this article will be made available by the authors without undue reservation.

Acknowledgements: We thank all the volunteers involved in this research. We also thank Prof. Zhenpeng Kai for his guidance and comments on this study.

Conflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The starting point of this study was to examine the effects of different types of tobacco products on smokers' puffing behaviour. This study is useful for further research on risk assessment of tobacco products and accumulates research evidence for the tobacco industry to have a comprehensive understanding of the potential exposure risks of different tobacco products. All findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Shanghai New Tobacco Product Research Institute Co., Ltd.

Competing intersets: The authors declare no competing interests.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). The MDPI and/or the editor(s) claim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

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No competing interests reported.

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You are reading this latest preprint version

A Randomized Multilocation Study of Puffing Topography in Chinese Adult Smokers using Heated Tobacco Products and Conventional Cigarettes

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Version 1

Abstract

Figures

1. Introduction

2. Materials and Methods

2.1 Data collection

2.2 Human participants and study groups

2.3 Definition of puffing topographic variables

2.4 Puffing topography assessment

2.5 Urine collection and nicotine metabolites analysis

2.6 Statistical analysis

3. Results

3.1. Demographic characteristics and smoking history

3.2. Demographic characteristics and smoking history in each city

3.3. Differences in puffing topography

3.4. Differences in urinary nicotine metabolite levels

4. Discussion

5. Conclusion

Declarations

References

Additional Declarations

Status:

Version 1