Article Text

Association of heated tobacco product use with smoking cessation in Chinese cigarette smokers in Hong Kong: a prospective study
1. Tzu Tsun Luk1,
2. Xue Weng1,
3. Yongda Socrates Wu1,
4. Hiu Laam Chan1,
5. Ching Yin Lau1,
6. Anthony Cho-shing Kwong2,
7. Vienna Wai-yin Lai2,
8. Tai Hing Lam3,
9. Man Ping Wang1
1. 1 School of Nursing, The University of Hong Kong, Hong Kong, China
2. 2 Hong Kong Council on Smoking and Health, Hong Kong, China
3. 3 School of Public Health, The University of Hong Kong, Hong Kong, China
1. Correspondence to Dr Man Ping Wang, School of Nursing, University of Hong Kong, Hong Kong 999077, China; mpwang{at}hku.hk

## Abstract

Introduction Heated tobacco products (HTPs) are increasingly popular worldwide, but whether they aid or undermine cigarette abstinence remains uncertain. We examined the predictors of HTP initiation and the prospective association of HTP use with cigarette abstinence in community-based smokers in Hong Kong.

Design Secondary analysis of a randomised clinical trial aimed to evaluate the effectiveness of brief advice and referral for smoking cessation. The interventions were not related to HTP use.

Participants and settings 1213 carbon monoxide-verified daily cigarette smokers with intentions to quit or reduce smoking proactively recruited from community sites throughout Hong Kong

Main exposure Current (past 7 day) use of HTP at baseline.

Main outcome Self-reported 7-day point-prevalence cigarette abstinence at 6 months (exclusive use of HTP permitted).

Results At baseline, 201 (16.6%) and 60 (4.9%) were ever and current HTP users, respectively. During the 6-month follow-up period, 110 of 1012 (10.9%) never users at baseline initiated HTPs. Younger age and higher education significantly predicted initiation. After adjusting for sociodemographic, smoking-related and quitting-related factors, current HTP use at baseline was not associated with cigarette abstinence at 6 months (adjusted prevalence ratio (aPR) 1.08, 95% CI 0.63 to 1.85). The results were similar in persistent users from baseline to 1-month/3-month follow-up (vs non-users; aPR 1.14, 95% CI 0.57 to 2.29). Use of smoking cessation service between baseline and 3-month follow-up significantly predicted cigarette abstinence (aPR 1.70, 95% CI 1.26 to 2.30).

Conclusion HTP use was not associated with cigarette abstinence at 6 months in a community-based cohort of smokers with intentions to quit or reduce smoking.

Trial registration details

ClinicalTrials.gov, NCT03565796.

• harm reduction
• cessation
• non-cigarette tobacco products

## Data availability statement

The study protocol and de-identified individual participant data generated during this study are available from the investigators on reasonable request. Requests should be directed to the corresponding author by email.

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## Introduction

Heated tobacco products (HTPs) are being developed and promoted by the tobacco industry under the banner of ‘harm reduction’. First launched in Japan in 2014, HTPs are increasingly popular and appear to surpass electronic cigarettes (e-cigarettes) in some regions in Asia.1–4 Although early reports have suggested relatively lower awareness and use of HTPs in Western countries,5–8 a large survey conducted in the USA, Canada and England reported high interests among youth smokers in trying IQOS,9 an HTP approved for sale by the US Food and Drug Administration since April 2019.10 Examining predictors of HTP use in cigarette smokers and its effect on cigarette abstinence have important public health implications.

The role of HTPs in smoking cessation has remained uncertain, and no jurisdiction has yet approved HTPs as a quit smoking aid. Although emerging studies have suggested that some smokers initiated HTPs to reduce or stop cigarette smoking,11 12 the potential of HTPs in hindering smoking cessation efforts could not be excluded.13 A survey of US young adult current smokers did not find ever use of HTPs associated with recent cigarette quit or reduction attempts and readiness to quit smoking.14 Another survey in Korean adolescent smokers found that ever HTP use was not associated with past-year cigarette quit attempts, compared with those who never used HTPs or e-cigarettes.4 The survey also found ever HTP use was inversely associated with being a former smoker among ever cigarette users, but the time sequence of the variables was unclear.4

HTPs have not been launched in Hong Kong, but the electronic heating devices (chargers and holders), the tobacco sticks and their accessories can be readily obtained through online vendors in social networking sites.15 Two successive population-based surveys showed that the prevalence of ever HTP use doubled from 1.0% in 2017 to 2.1% in 2018.2 Taking advantage of a prospective cohort of cigarette smokers in Hong Kong, we examined the predictors of HTP initiation and the association of HTP use with cigarette abstinence.

## Methods

### Study design

This study was a secondary analysis of a community-based, two-group, pragmatic cluster-randomised clinical trial conducted within the ninth ‘Quit to Win’ Smoke-free Community Campaign, an annual smoking cessation contest organised by the Hong Kong Council on Smoking and Health. Details of the contest have been reported elsewhere.16 17.

### Setting and participants

During June to September 2018, participant recruitment took place in 68 community sites (eg, housing estates, shopping malls, transportation hubs) throughout Hong Kong. Trained university students and volunteers proactively approached smokers in the nearby areas, determined their eligibility and invited them to participate in the smoking cessation contest. Participants were Chinese-speaking Hong Kong residents aged 18 years or older who smoked at least one cigarette daily in the past 3 months, verified by an exhaled carbon monoxide level of ≥4 part per million,18 and were willing to quit or reduce smoking. We excluded smokers who were not able to communicate due to physical or mental problems or those who were engaging in other smoking cessation programmes. All participants were included in the present study regardless of their treatment conditions. After excluding 10 participants with missing data on HTP use at baseline, the analytical sample included 1213 daily smokers.

### Interventions

After providing written consent and completing baseline questionnaires, all participants were cluster-randomised into the intervention group (n=633) or control group (n=580) based on the community sites (clusters) in which they were recruited. All participants received brief advice to quit smoking and a self-help booklet. The intervention group additionally received referrals to a quitline-based or clinic-based smoking cessation service in Hong Kong with a small cash incentive of HK$300 (about US$38.5). These free-of-charge services offer telephone or in-person behavioural support, cessation medications (nicotine replacement therapy, bupropion and varenicline) and acupuncture. The treatment conditions in both groups did not contain any information about HTP use. The results of the trial will be published elsewhere. The moderating role of study group was examined in the present study.

### Measures

The baseline questionnaire was administered in-person during recruitment. The measures included cigarette use and dependence (assessed by the Heaviness of Smoking Index), past cigarette quit attempt (Never/Over 1 year ago/Within 1 year), readiness to quit cigarette smoking and sociodemographic factors (sex, age, education and employment status).

Telephone follow-ups were conducted at 1, 2, 3 and 6 months after baseline to assess the cigarette abstinence status. In the present study, the main outcome was self-reported 7-day point-prevalent cigarette abstinence at 6-month follow-up, which included those who only used HTPs. We also assessed whether they had ever made a serious quit attempt (cigarette abstinence for 24 hours or longer)19 and used a smoking cessation service.

HTP awareness and use at baseline were assessed by the question ‘Have you ever heard of HTPs such as IQOS?’ with responses categorised into ‘no’, ‘yes, just heard of it’ and ‘yes, used it’. Since smokers in Hong Kong tended to confuse HTPs with e-cigarettes, IQOS (the most widely known HTPs at the time of the study) was specified as an example of HTPs to prevent misclassification. Those who reported ever using an HTP were further asked on how many days in the past 7 days did they use HTPs. At 1-month, 3-month and 6-month follow-ups, we also assessed HTP use in the past 30 or 7 days. The question was preceded by a brief description of HTPs: ‘Heated tobacco is a kind of tobacco products that does not need fire for ignition. It consists of a holder for heating a cigarette-like tobacco stick at high temperature to generate aerosols for inhalation. It does not heat e-liquid or other solvents.’ Participants who used an HTP on at least 1 day in the past 7 days at baseline were considered as current users. HTP initiation was defined as having used an HTP in the past 30 or 7 days during follow-up in never users of HTP at baseline.

Reasons for HTP use was assessed at 1-month, 3-month and 6-month follow-ups, with responses categorised into ‘to quit or reduce smoking’, ‘less harmful to self or others’, cleaner than cigarette (less odour)’, ‘curiosity’, and ‘influenced by peers’. The participants could select more than one option.

### Statistical analysis

The characteristics across participants of different HTP use status at baseline were compared using χ2 tests and Kruskal-Wallis tests as appropriate. We used Poisson regression with robust variance20 to estimate the prevalence ratios (PR; interpret as relative risk) of HTP initiation by baseline characteristics in never users of HTP at baseline. The same regression method was used to compare the smoking cessation outcomes between current and non-current users of HTP at baseline, adjusting for sex, age, education attainment, employment status, daily cigarette consumption, time to first cigarette of the day, past cigarette quit attempt and readiness to quit cigarette at baseline.21 To check if the associations varied between the intervention and control groups, we examined the associations stratified by study group and the moderating effect of study group by including a multiplicative interaction term in the regression models.22

By combining data on HTP use at baseline and up to 3-month follow-ups (to ensure HTP use preceded smoking cessation outcomes), we created a composite variable of different patterns of use, in which participants were categorised into ‘Non-users’, ‘HTP users at baseline only’, ‘HTP users at 1-month/3-month follow-up only’ and ‘HTP users at baseline and 1-month/3-month follow-up (persistent users)’. We examined its association with cigarette abstinence at 6 months as a sensitivity analysis. We also modelled any use of HTP from baseline to 3 months (combining current users at baseline and users at 1-month/3-months follow-up into a single category) as the exposure variable. We expect uses of smoking cessation service could increase smoking abstinence.16 17 Therefore, the association of smoking cessation service use between baseline and 3 months with cigarette abstinence at 6 months was examined as a positive exposure control.

In all regression analyses, we used multiple imputation by chained equation to impute missing outcome data due to attrition and missing values in covariates, including age (n=35), education attainment (n=288), employment status (n=196), time to first cigarette of the day (n=8), past cigarette quit attempt (n=31) and readiness to quit (n=12), under the assumption that data were missing at random.23 The imputation models included all variables included in the analytical models, study group and use of smoking cessation service. Since these variables predicted missingness in our study population and included known determinants of smoking cessation outcomes and HTP use,2 17 21 including them in the imputation models makes the missing at random assumption more plausible. Estimates were inferred from 100 sets of imputed data. Fitness of the imputation models was supported by comparable distributions in observed, imputed and completed values.24 Complete case analyses were also conducted.

All analyses were conducted in Stata/MP, V.15.1 (StataCorp, USA). A two-sided p value smaller than 0.05 was considered statistically significant.

## Results

Of the 1213 participants, 789 (65.0%; 95% CI 62.3% to 67.7%;) were aware of HTP at baseline; 201 (95% CI 16.6%; 14.6% to 18.8%) were ever users and 60 (4.9%; 95% CI 3.9% to 6.3%) were current (past 7 day) users. Table 1 shows the baseline characteristics by HTP use status using available case analyses (ie, pairwise deletion). The proportions of ever and current HTP users were significantly higher in participants with younger age and higher education attainment. Daily cigarette consumption and heaviness of smoking index significantly differed across participants of different HTP use status. The prevalence of having a past cigarette quit attempt was similar between never and current users but significantly higher in ever but non-current users of HTP.

Table 1

Characteristics of the participants by use of heated tobacco product at baseline

The retention rates were 79.8% (n=968) at 1 month, 75.6% (n=917) at 2 months, 76.2% (n=924) at 3 months and 72.1% (n=875) at 6 months without significant differences between current and non-current users of HTP (p value ranged from 0.064 to 0.30). Of the 1012 smokers who never used HTPs at baseline, 110 (10.9%; 95% CI 8.5% to 13.4%) initiated HTP use during the 6-month follow-up period (multiply imputed data analyses). Table 2 shows that younger age and higher education attainment were significant predictors of HTP initiation in both bivariate and multivariable analyses. The rate of HTP initiation was lower in participants with greater daily cigarette consumption and shorter time to first cigarette of the day in bivariate analyses, but the associations became insignificant after adjusting for other characteristics. There was no evidence that HTP initiation differed by study group (p>0.91). The results were similar for HTP initiation between baseline and 3-month follow-up and in complete case analyses (online supplementary tables S1 and S2).

### Supplemental material

Table 2

Predictors of HTP initiation between baseline and 6 months in smokers who had never used HTPs at baseline (multiply imputed data analysis)

Table 3 shows no significant association of current HTP use at baseline with self-reported 7-day cigarette abstinence and 24-hour quit attempt at 3-month and 6-month follow-ups in both crude and adjusted models (multiply imputed data analyses). The results based on complete case analyses were similar (online supplementary table S3). The results were also similar when participants with missing outcome were assumed to be non-abstinent (data not shown).There was no evidence that the associations varied between the two study groups (p value for interaction ranged from 0.43 to 0.95; online supplementary table S4).

Table 3

Associations of current (past 7 day) use of HTP at baseline (yes vs no (reference group)) with smoking cessation outcomes (multiply imputed data analysis)

Table 4 shows from the sensitivity analyses that HTP use at baseline only (n=20), HTP use between baseline and 3 months only (n=113) and HTP use at both time points (persistent use; n=40) were not associated with cigarette abstinence at 6 months, compared with non-users (n=1040). The results were similar for any use from baseline to 3 months (n=173). In contrast, use of smoking cessation services between baseline and 3 months (n=200) significantly predicted self-reported cigarette abstinence at 6 months (adjusted PR 1.70; 95% CI 1.26 to 2.30; p<0.001).

Table 4

Associations of different patterns of HTP use and smoking cessation service use with self-reported 7-day PPA at 6 months (multiply imputed data analysis)

Of 119 participants who reported HTP use during follow-up, 99 (83.2%) provided reasons for HTP use (available case analyses). The leading reason was ‘to quit or reduce smoking’ (n=44), followed by ‘cleaner than cigarette (less odour)’ (n=37). Other reasons included ‘less harm to self and others’ (n=17), ‘curiosity’ (n=12) and ‘influenced by peers’ (n=9).

## Discussion

This secondary analysis of a pragmatic randomised clinical trial examined the predictors of HTP initiation and the association of HTP use with cigarette abstinence in a community-based, prospective cohort of daily cigarette smokers who were interested in quitting or reducing smoking. Younger age and higher education attainment were identified as independent predictors of future HTP initiation in smokers who never used HTPs. We found no evidence that current (past 7 day) use of HTP was associated with cigarette abstinence and quit attempt at 3 and 6 months after baseline. The robustness of the finding was corroborated by sensitivity analyses (different patterns of HTP use as exposures) and the positive association of smoking cessation service use with cigarette abstinence (positive exposure control).

To our knowledge, this was the first study examining the prospective association of HTP use with smoking cessation. Previous studies were cross-sectional and used less meaningful exposure (eg, lifetime/ever use) and outcome (eg, quit attempts and intentions) measures.4 14 The observed association between HTP use with cigarette abstinence needs to be interpreted with regards to the patterns of and reasons for use. We found that not all current users of HTPs at baseline were persistent users (40 of 60). Our sensitivity analysis did not find persistent use predicted cigarette cessation, but the results were based on a small number of participants. There are reasons to believe that HTPs, similar to conventional smoking cessation aids like nicotine replacement therapy, may not confer benefits on cessation outcomes if not used regularly. A study in the USA has also found that smokers who used e-cigarette, mostly for quitting cigarettes but used intermittently, were less likely to achieve cigarette abstinence than non-users.22 Besides, although the majority of HTP users who gave reasons for use at follow-ups reported HTPs as aids to quit or reduce cigarette smoking (44 of 99), a substantial proportion used HTPs because they generated less odour than cigarettes (37 of 99). This corroborates our qualitative findings that some smokers used HTPs as a substitute for cigarettes in situations where cigarette smoking is undesirable, such as in smoke-free areas or in the presences of non-smoking family members or colleagues who may be annoyed by the smell of cigarette smoke.15 This may be particularly salient in Hong Kong and elsewhere where the smoking prevalence is low (10.0% in 2017 in Hong Kong)25 and cigarette smoking has been denormalised. For these smokers, HTPs may complement cigarette use and hamper their motivation to quit smoking due to increased convenience to consume tobacco products. Further studies with larger samples of HTP users are needed to identify in what context HTP uses may aid or undermine smoking cessation. Nevertheless, our study has provided initial evidence on how and why cigarette smokers used HTPs and the population-level impact of HTPs on cigarette abstinence in a real-world situation.

We examined the sociodemographic and smoking-related and quitting-related predictors of HTP initiation in cigarette smokers. Previous studies in the general population1–3 5–8 and cigarette smokers26 have found that HTP use was more prevalent in adults of younger age and higher socioeconomic status. Our study adds to the literature by showing that younger age and higher education attainment predicted HTP initiation in cigarette smokers. HTPs may be particularly appealing to these smokers because of the high-tech, stylish design of the products and the alleged harm reduction potential.12 27 28 The high initial cost of purchasing the electronic heating device may also deter smokers with low income from initiating HTP use. The findings suggest policymakers need to be cognizant of the HTPs’ potential in aggravating health disparity in tobacco use if HTPs are promoted as smoking cessation or reduction aids.29

A strength of the study was the use of proactive recruitment strategy to enrol daily cigarette smokers with characteristics that were largely comparable with smokers in the general population (online supplementary table S5), which is difficult to achieve in randomised trials. Of note, the prevalence of awareness (65.2% vs 27.2%) and ever use of HTPs (16.9% vs 8.9%) were found much higher in smokers in the present study at baseline (2018) than in our population-based survey in 2017.2 Although partly attributable to the differences in sampling methods, the sharp increases likely reflect the growing popularity of HTPs in Hong Kong and Asia. Furthermore, a sizeable proportion (10.9%) of smokers who never used HTPs at baseline initiated HTPs during the 6-month follow-up period. The rate is alarming given HTPs have yet been officially marketed in Hong Kong. HTP use needs to be closely monitored to inform timely public health measures.

This study had some limitations. First, causal inference could not be drawn due to the study’s observational design, wherein participants self-selected use of HTPs. Although we adjusted for sociodemographic factors that predicted HTP use and known predictors of cigarette cessation, including cigarette dependence, past quit attempt and readiness to quit,21 unmeasured and residual confounding could not be excluded. Second, despite a satisfactory follow-up rate of 72.1% given the population-based design of the parent trial, we did not have complete data. We used multiple imputation to impute missing values, which reduced selection bias and increased precision of estimates while preserving the uncertainties of missing data. The results based on complete case analyses were similar, and the SEs were mostly smaller for the multiply imputed data analyses, suggesting the efficiency gain of multiple imputation over complete case analyses. Third, all measures were self-reported. Although the parent trial included biochemically validated abstinence as an outcome, validation was only done in participants who reported abstinence from all tobacco products (including HTPs). Evidence on the biochemical method to distinguish cigarette smoking from HTP use has remained scarce.30 Common methods of validation, including exhaled carbon monoxide and cotinine tests, are not useful because smokers who completely switched to HTPs are still exposed to carbon monoxide (although at a lower level) and nicotine present in emissions from HTPs.31 Nevertheless, self-reported abstinence is considered adequate for large, population-based trials with minimal contacts between participants and investigators.30 Fourth, we could not reliably assess the number of cigarette per day in smokers who also used HTPs during follow-up because some dual users mistakenly reported the total number of tobacco sticks and cigarettes when asked about the number of cigarette per day. Future studies with more precise questions on cigarette and HTP consumptions are warranted to examine the association of HTP use with smoking reduction. Finally, the present study analysed data from a randomised trial of brief interventions for smoking cessation. However, the intervention did not contain information about HTP use, and we found no evidence that the uptake of HTPs differed by study group and that study group moderated the association of HTP use with cigarette cessation.

• Heated tobacco products (HTPs) have been touted as less harmful alternatives to cigarette smoking by the tobacco industry, but no study has ever examined the prospective association of HTP use with cigarette smoking cessation.

• Younger age and higher education attainment were independent predictors of future HTPs initiation in adult smokers.

• In a community-based cohort of daily cigarette smokers intended to quit or reduce smoking, HTP use at baseline and up to 3-month follow-up was not associated with cigarette abstinence at 6 months. In contrast, use of established smoking cessation services at 3 months strongly predicted cigarette abstinence at 6 months.

## Data availability statement

The study protocol and de-identified individual participant data generated during this study are available from the investigators on reasonable request. Requests should be directed to the corresponding author by email.

## Ethics statements

### Ethics approval

Ethical approval was granted by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 18-318).

## Acknowledgments

We thank the participants for their participation in the study and members of the Smoking Cessation Research Team, HKU School of Nursing, for coordinating the project.