Skip to main content
Download PDF

Association between use of heated tobacco products and long-term respiratory effects considering smoking history: internet-based cross-sectional study in Japan

BMC Public Health volume 24, Article number: 2785 (2024) Cite this article

Abstract

Background

With the use of heated tobacco products (HTPs) becoming more widespread in Japan, interest in the health effects of HTP has grown. Since the majority of HTP users are former smokers, information about the user’s smoking history and health status before HTP use is needed when assessing the health effects of HTP use. The limited epidemiological studies available did not consistently consider this information adequately, therefore we conducted a cross-sectional study investigating the association between HTP use and respiratory chronic diseases and symptoms.

Methods

The questionnaires were sent to a research panel members in Japan via the Internet, and individuals who met the study criteria and were either current exclusive HTP users, current exclusive cigarette users or those had never used tobacco products were selected. Information about the participants’ smoking history and health status before they used HTPs was obtained. The effects of participant smoking history before HTP use and the impacts on outcomes upon switching to HTP were assessed using a logistic regression model. The odds ratio (OR) for current exclusive HTP users relative to never tobacco users was calculated. The OR was calculated under two scenarios, one in which the smoking history was ignored or one in which the smoking history was considered.

Results

Of the participants from whom responses to the questionnaires were obtained, 17,406 participants were included in the analysis. Almost all participating current exclusive HTP users had a history of long-term smoking (mean: 30.8 years), and the occurrence of outcomes both before and after the start using HTP was reported. The ORs, without adjustment and with adjustment for smoking history before HTP use were, 3.23 (95% CI: 1.37–7.61) and 1.85 (95% CI: 0.70–4.89) respectively in COPD, same as other outcomes.

Conclusions

These results suggest that smoking history before HTP using affects the occurrence of outcomes, and underscore the importance of considering smoking history when assessing the health effect of HTP use. Since the duration of HTP use is considerably shorter than that of cigarette use at present, further research, such as follow-up surveys assessing the long-term respiratory effects of HTP use, will be necessary.

Peer Review reports

Background

Heated tobacco products (HTPs), which are products that generate aerosols by heating tobacco, have been widely used among adult smokers in Japan following their launch in 2015 [1]. With this increasing use, interest in the health effects of HTP use has emerged. Growing scientific evidence on these effects includes many reports on the analysis of the components generated in vapor, in vitro/in vivo toxicity assessments, and changes in short-term biomarkers in humans observed in clinical studies [2, 3]. According to clinical studies on vapor exposure, when a smoker switches completely from combustible cigarettes (CCs) to HTPs, biomarkers related to exposure to harmful substances have been shown to decrease markedly [3, 4]. It has been reported that, in smokers switching from CCs to HTPs, biomarkers associated with biological processes such as oxidative stress, inflammation, lipometabolism and platelet activation/coagulation (biomarkers of potential harm) are similar to biomarkers of potential harm levels in people who have never used tobacco (never tobacco users) or former tobacco users [3, 5]. On the other hand, there is cross-sectional study showing adverse respiratory effects of HTP use [6].

Although the available scientific evidence to date indicates that HTPs have the potential to reduce the risk of smoking, due to the relatively recent availability of HTPs, reports on the long-term (more than several years) health effects associated with HTP use are limited, leaving any long-term health effects unclear. To assess these effects, research with long-term follow-up cohorts will be necessary, and several more years will have to pass before these results can be obtained. Consequently, at present, only a few reports from cross-sectional studies are available. Odani et al. [6] conducted a cross-sectional study among patients with cancer scheduled for surgery and reported that Prevalence Ratio (PR) for the occurrence of airway obstruction in current exclusive HTP users relative to never tobacco users was 2.32 (95% CI: 1.54–3.49), which is comparable to the PR of current exclusive cigarette smokers (2.57). Yoshioka et al. [7] also conducted a cross-sectional study in Japan over the Internet and reported that the PR for occurrence of periodontal disease in current exclusive HTP users relative to never tobacco users was 1.43 (95% CI: 1.08–1.88).

On the other hand, like HTPs, electronic cigarettes (e-cigarettes), have been cited in public health reports [8,9,10,11] for reducing harmful substances in tobacco smoke. Since e-cigarettes have been on the market for a longer period than HTPs, more research reports on the health effects of e-cigarette use than HTPs. A relationship between e-cigarette use and chronic obstructive pulmonary disease (COPD), asthma and symptoms such as wheezing has been shown. Xie et al. [12] conducted a cross-sectional study using data from the Population Assessment of Tobacco and Health (PATH) study and reported that the odds ratio (OR) for the occurrence of COPD in current e-cigarette users relative to never tobacco users was 1.62 (95% CI: 1.28–2.04). Schneller et al. [13] reported, based on a cross-sectional study using the same PATH study data used by Xie et al., that the OR of wheezing was 1.44 (95% CI: 1.01–2.06).

While these cross-sectional studies suggest various respiratory health effects associated with the use of HTPs and e-cigarettes, the number of years since the use of HTPs or e-cigarettes use is less than that since the use of CCs. Given that most users of these products have a history of smoking [14, 15], it is likely that their smoking status and health status before the start of HTP use contribute to the occurrence of chronic diseases such as COPD [16] which took many years to develop.

Almost all studies up to the present often do not obtain sufficient information on the smoking history of HTP and e-cigarette users (such as whether they smoked before the use of HTPs or e-cigarettes, the number of years of smoking, or the number of cigarettes smoked) or on their health status before they started using HTPs or e-cigarettes (such as their history of chronic diseases or other outcomes, or the occurrence of diseases or symptoms related to the occurrence of outcomes).

Because HTPs are becoming more widely used and given that there is insufficient scientific evidence on the long-term health effects associated with their use, accumulating such evidence is important.

Thus, to investigate the effect of exclusive HTP use on chronic respiratory diseases or symptoms incidence, we conducted a survey in Japan, one of the largest markets for HTPs [17], designed to include the following information: (i) individual smoking history and health status before HTP use and (ii) the temporal order of the relationship between the occurrence of chronic respiratory diseases and symptoms, which are the main outcomes, and the start of HTP use.

Methods

Study design

This was an observational, cross-sectional survey using Internet questionnaires, conducted from 2022 to 2023 to survey the long-term health effects of HTP use. The survey design involved the comparison of a group currently exclusively using HTPs (the HTP group) and a group currently exclusively using combustible cigarettes (the CC group) with a group that had never used tobacco products (the never-user group).

The survey was administrated by the healthcare-related survey company Medilead Inc., and participants were recruited from a large-scale survey panel operated by Cross Marketing Inc., a major survey company in Japan, which is affiliated company with Medilead Inc. This survey panel consists of approximately 5 million people and allows the collection of not only basic attribute information such as sex, age and residential area but also, information necessary for surveys, such as tobacco use status, by means of Internet questionnaires.

The duration of the survey was 3 months (from December 2022 to March 2023), and an invitation to participate in this survey was sent to all survey panel members, and those willing to participate applied. The questionnaires relating to the criteria for participation in each group (the HTP group, CC group and never-user group) and including informed consent forms provided along with written information about participation in the survey were sent to the survey panel members who applied (the screening survey). The participants who responded, met the criteria for participation in the groups and provided consent were sent the questionnaire for the main survey.

The questionnaire in this study asked about the following information: whether respiratory system diseases or symptoms were present; their time of onset, current and historical tobacco use status, factors involved in the occurrence of respiratory system diseases and symptoms (information about the attributes of participants, their medical history and their lifestyle habits). This questionnaire was developed for this study in Japanese. The English translated version of this questionnaire is shown in supplementary material 1.

Participants in each group from whom responses to the questionnaires in this survey were obtained were matched by sex and age (5-year age groups) based on the HTP group.

Participants

The general requirements for participants were to have the intention to participate in this study, to understand the content of the written information for consent in this study, to have provided consent, to be men or women aged at least 20 years at the time of obtaining consent, and to meet the following criteria for their relevant group.

  1. (1)

    HTP group

    Participants who habitually used HTPs for a period of at least 6 months before the survey date, and whose tobacco use status after starting habitual use of HTPs was as follows: mean monthly use of combustible cigarettes of no more than 2 cigarettes, mean monthly use of other tobacco products (products containing nicotine including e-cigarettes and smokeless tobacco) of no more than 2 times, mean monthly use of HTPs of at least 3 sticks, mean frequency of use of HTPs of at least 4 days per week, no periods of 1 month or more without using HTPs, and use of at least 100 HTP sticks by the survey date (in the case of the low-temperature type, at least 25 tobacco capsules).

  1. (2)

    CC group

    Participants who habitually used CCs for a period of at least 6 months before the survey date, and whose tobacco use status was as follows after starting habitual use of CCs: mean monthly use of HTPs of no more than 2 sticks, mean monthly use of other tobacco products (products containing nicotine including e-cigarettes and smokeless tobacco) of no more than 2 times, mean monthly use of CCs of at least 3 cigarettes, mean frequency of use of CCs of at least 4 days per week, no periods of 1 month or more without using CCs, and use of at least 100 CCs by the survey date.

  1. (3)

    Never-user group

    Participants who had no experience of habitually using tobacco products and who had used a total of fewer than 100 cigarettes (/sticks) of tobacco products by the survey date.

    In addition, persons working for tobacco companies and persons related to the survey organizers were excluded from all groups.

Measures of outcome

In this study, the primary outcome was whether self-reported respiratory diseases (COPD, asthma) or symptoms (shortness of breath, wheezing, cough, phlegm, lung function abnormality) occurred. Transient symptoms such as those due to the effect of colds were not included, and the symptoms included were those that occurred chronically or repeatedly and frequently. In this study, information on the occurrence of the diseases and symptoms [18] reported to be related to smoking was obtained from the following questions, separated into occurrences before and after the start of use of the tobacco products, to confirm the temporal order of the onset time of outcomes and the start of use in current exclusive HTP users and current exclusive CC users. About diseases: “Please indicate any diseases that have been diagnosed by physician since (before) you started using heated tobacco products (combustible cigarettes),” and about symptoms: “Please indicate any symptoms that have been diagnosed by physician or symptoms that have been noticed by you since (before) you started using heated tobacco products (combustible cigarettes).”

Information about never tobacco users was obtained with the following questions. About diseases: “Please indicate any diseases that have been diagnosed by physician since the age of 20,” and about symptoms: “Please indicate any symptoms that have been diagnosed by physician or symptoms that have been noticed by you since the age of 20.”

Participants were asked to select yes/no for whether they had been diagnosed with or become aware of each disease and symptom, and for those who answered yes, they were asked about the age at which they were diagnosed or became aware of the disease and symptom.

Measures of tobacco product use

In addition to the information necessary for the definitions of the HTP group and CC group in the “Participants” section (whether participants had used the tobacco products for at least 6 months, their current frequency of use, the amount used over their lifetime, and the amount of other tobacco products used), information on their tobacco use status for tobacco products they were currently using (number of years of use and amount used) was obtained with the following questions. “From what age did you start habitually smoking heated tobacco products (combustible cigarettes)?” “Please tell us the mean average daily amount of heated tobacco products (combustible cigarettes) you currently use (the number of cigarettes/sticks). If you use multiple products, please respond by giving the total number.”

The following questions were asked of current exclusive HTP users who had CC use for at least 1 month before the start of HTP use, to obtain information about their CC use before the start of HTP use.

“Please tell us the age at which you started using combustible cigarettes and the age at which you last smoked them (when you switched completely to heated tobacco products).” “Please tell us the mean daily number of cigarettes you smoked when you were smoking combustible cigarettes in the past.”

Confounding factors

The following factors other than tobacco use affect the occurrence of outcomes that were used in past cross-sectional studies investigating the relationship of e-cigarette or HTP use to the occurrence of outcomes (COPD [12, 19,20,21,22,23,24,25], asthma [12, 19, 21, 23, 26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41], wheezing [13, 35, 42,43,44,45,46], shortness of breath/cough/phlegm [35, 36, 44, 45], lung function abnormality [47]) and cohort study [48] investigating the relationship between smoking and COPD were used as adjustment factors in this study: age, sex, BMI, resident area population size, education level, household income, whether employed or unemployed, lifestyle habits (frequency of exercise, frequency of alcohol drinking, level of stress), and whether historical or concurrent diseases were present (diabetes, lipid abnormality, hypertension, stroke, allergic dermatitis/rhinitis, angina pectoris, coronary heart disease (CHD)). Information about passive smoking was not obtained in this study, because no statistical effect from passive smoking was observed [16, 40] in past cross-sectional studies of HTPs or e-cigarettes.

In addition to these known adjustment factors, whether outcomes recurred, whether COVID-19 infection occurred, and the Brinkman index (BI) [49], an index indicating the level of smoking, which is calculated by multiplying the number of years of smoking by the daily number of cigarettes smoked and was used to indicate CC use status before the start of HTP use in current exclusive HTP users, were also used as adjustment factors.

These variables were categorized as follows: sex (male and female), resident area population (< 50,000 people, 50,000–200,000 people, 200,000–500,000, > 500,000 people), education level (junior high school/high school/technical college graduate/professional training college graduate/junior college graduate, university/graduate college graduate), household income (< 5 million yen, 5–10 million yen, 10–16 million yen, > 16 million yen), employment or unemployment (paid employment, other), frequency of exercise (almost none, 1–3 days per month/1–2 days per week, 3–4 days per week/almost every day), frequency of alcohol drinking (does not drink, gave up/almost never drinks, 1–3 days per month/1–4 days per week, at least 5 days per week), and level of stress (low, normal, high).

Statistical analysis

First, we calculated the number and frequency value (mean and standard deviation for age and BMI) of each variable as baseline characteristics. Additionally, the intergroup bias of confounding factors was investigated using Krusal-Wallis test (analysis of variance for age and BMI). Second, we calculated years of participant’s tobacco use (duration of product use, smoking before HTP use).

Third, the total incidences of the most recent outcomes as of the survey date in each participant group were tabulated. In the HTP and CC groups, outcomes were categorized by whether they occurred before or after the start of HTP or CC use, and the incidences of outcomes before and after the start of HTP or CC use (incidence before tobacco use, incidence after tobacco use).

If a response was obtained that stated that the same outcome was diagnosed before the most recent occurrence of the outcome as of the survey date, this was treated as the most recent occurrence of the outcome being a recurrence. In the HTP group and CC group, if an outcome was diagnosed as having occurred both before and after the start of HTP or CC use, this was treated as a recurrence of the outcome after HTP or CC use.

Forth, to analyze the effect of HTP or CC use, we performed an analysis using a logistic regression model with the occurrence of outcomes as the objective variable, smoking group and confounding factors as explanatory variables. The ORs of the HTP group and CC group relative to the never-user group were calculated.

Furthermore, to exploratively analyze the effect of the smoking experience of current exclusive HTP users before the start of HTP use on the occurrence of outcomes, the OR of the HTP group relative to the never-user group was calculated using a logistic regression model with the occurrences of outcomes after the start of HTP use, excluding occurrences of outcomes before the start of HTP use, as an objective variable. This OR was compared with the OR with the occurrences of outcomes, including outcomes before the start of HTP use, (all outcomes that occurred most recently as of the survey date) as an objective variable. In addition, to eliminate the effect from smoking before the start of HTP use, BI was added as an explanatory variable to models with the occurrences of outcomes after the start of HTP use as their objective variable. In terms of respiratory symptoms, to clarify the analysis results, we add the analysis for combined respiratory symptoms that combined the incidence of each symptom (wheezing, shortness of breath, cough, phlegm, and lung function abnormality).　Since the survey uses an intergroup comparison design, with matching performed by sex and age (5-year age groups) based on the HTP group, no adjustment was made to reflect the demographics of Japan has been made.

Sensitivity analysis was performed to verify the effect of BI in the model with BI (the main analysis). The results of the main analysis were compared with the results of analysis of participants in the HTP group with no history of smoking (n = 415). Additionally, to confirm the effect of bias associated with exclusion from randomization due to matching, similar analysis was performed for the participants before matching (n = 18,585) and this was compared to the main analysis.

The data were analyzed using SAS version 9.4 (SAS Institute Japan Ltd.).

Ethical considerations

This study was conducted in accordance with the ethical guidelines for healthcare and health research in humans and was registered in the UMIN Clinical Trials Registry (UMIN000049494, registration date November 14th, 2022). Before the start of the survey, an ethics review of the survey-related documents was performed by the Institutional Review Board of Health Outcome Research Institute, and the study was approved (No. 2022-02). Web-based informed consent for participation in the survey was obtained from all participants.

Results

Number of participants

As shown in Fig. 1, the screening survey questionnaire was sent to 1,400,735 people in the registration panel of the survey company and participants who met the inclusion criteria for each group were selected. The selected participants were sent the questionnaire for this study, and of the participants in each group from whom responses were obtained, participants in the CC group and never-user group were selected to match the sex and age (5-year age groups) in the HTP group. As a result, the incidence rates of outcomes were compared between the groups using the responses of 5,802 participants in each group.

Fig. 1
figure 1

Flow chart for the participants included in the study

Full size image

Demographic information

The baseline characteristics are shown in Table 1. The intergroup bias was found for BMI, education, income, employment, alcohol drinking, exercise and COVID-19 infection.

Table 1 Demographics of the participants
Full size table

HTP use behavior

The duration of tobacco use among the participants is shown in Table 2. The mean duration of HTP use in the HTP group was 3.7 years, while the mean duration of smoking (in years) before switching completely to HTPs was 30.8 years. Of the 5,802 participants in the HTP group, 415 participants responded that they had no smoking history before starting HTP use.

Table 2 Duration of product use among the participants
Full size table

Incidence of outcomes

The tabulated results of incidences of the most recent outcomes as of the survey date in each participant group are shown in Table 3. For each outcome, the incidences after the start of HTP or CC use and recurrences were found. There were 57 events of COPD that occurred most recently before the survey date in the HTP group, and 35 of these, events occurred after the start of HTP use.

Table 3 Number of incidences in the participant groups
Full size table

The ORs for the incidence of outcomes in the HTP group and CC group relative to the never-user group are shown in Table 4.

To assess the effect of HTP use on the occurrence of COPD, occurrence before the start of HTP use should be excluded, therefore the OR for occurrences after the start of HTP use (35 events) relative to occurrences in the never-user group (13 events) was calculated using a logistic regression model, and a result of 1.85 (95% CI: 0.70–4.89) was obtained. The ORs for asthma, shortness of breath, wheezing, cough, phlegm, lung function abnormalities and combined respiratory symptoms were also obtained in the same way. Tabulated results of incidences and calculated OR are shown in supplementary Tables 1,2.

Table 4 Results of logistic regression analysis
Full size table

The results of the sensitivity analysis are shown in Table 5. To verify the effect of BI, the same analysis as for the main analysis, the results of which are shown in Table 4, was performed for HTP users without smoking history (415 participants). These results were similar to the results for the main analysis, which included BI, and the obtained results were consistent with the effect of smoking history before HTP use on the occurrence of outcomes. (In addition, the results relative to CC group were shown in supplementary Table 3.) The results similar to those of the main analysis were also obtained from the analysis of participants before matching (n = 18,585). (supplementary Table 4)

Table 5 Results of logistic regression analysis for HTP users never used CC
Full size table

Discussion

Effect of smoking history before HTP use

Among the participants in this study, the mean duration of HTP use in the HTP group was 3.7 years. In addition, approximately 90% of the HTP group had CC use, and the mean duration of CC use was 30.8 years, therefore, smoking before HTP use likely contributed greatly to the occurrence of diseases and symptoms after HTP use was started. Therefore, in this survey, we obtained 2 pieces of information to adjust for the effect of smoking before HTP use in current exclusive HTP users.

The first piece of information consists of checking the incidence of outcomes that occurred before the start of HTP use (incidence before tobacco use). By differentiating this from the incidence of outcomes after HTP use (incidence after tobacco use), we removed the occurrence of outcomes before the start of HTP use, to which HTP use did not contribute. This is one of the strengths of our study, and unlike existing cross-sectional studies, the temporal relationship between the occurrence of outcomes and the start of HTP use was assessed. As a result, we found that many of the diseases and symptoms that occurred before the start of HTP use.

The second piece of information is that on the daily number of cigarettes smoked and the duration of smoking (in years) before the start of HTP use.

The results of logistic regression analysis using this information showed that, for each outcome, the OR with the incidences after the start of HTP use, excluding the incidences before the start of HTP use (incidence after tobacco use) as the objective variable, was greatly lower than the OR with the total incidence, including incidences of outcomes before the start of HTP use, as the objective variable. This finding suggested that smoking before the start of HTP use had a significant effect.

The OR of the HTP group relative to the never-user group was not statistically significant for the incidences of any outcome except phlegm, suggesting that when the duration of HTP use is short, it is difficult to confirm the effect of HTP use on the incidence of outcomes, and particularly the incidence of chronic diseases.

As another method for assessing the effect of exclusive HTP use on outcomes, we also calculated the OR of the HTP users without smoking history (415 participants) relative to the never-user group using a same model. Since responses were obtained from 5802 participants in the HTP group, the same number as in the CC group and never-user group, it was possible to obtain a subgroup of current exclusive HTP users without smoking history, which is the second strength of this study. The OR of the HTP group relative to the never-user group was similar to main analysis.

Given these our results and smoking is a risk factor for developing COPD and that it takes many years to develop [16, 50], it is considered that smoking before HTP use contributes greatly to the occurrence of COPD after the start of HTP use. Asthma and respiratory symptoms (shortness of breath, wheezing, cough, phlegm, lung function abnormality) are also related to smoking [18]. Asthma in Japanese adults occurred in all age groups [51], and the number of years until onset is vary. However, considering that chronic inflammation is involved [50], it can be considered that it takes times for asthma to develop, our results suggested that smoking before HTP use contributed greatly to the occurrence of asthma after the start of HTP use, same as COPD.

Regarding respiratory symptoms, since these symptoms occur before chronic diseases such as COPD and asthma [50], it can be considered to develop in a shorter period than chronic diseases, and the involvement of smoking before HTP use is thought to be smaller than that of COPD and asthma. In fact, the differences in the OR with the total incidence and the OR with the incidences after the start of HTP use for each respiratory symptom were found, however the differences were not as large as those for COPD and asthma.

Comparison with reports considering the effect of smoking history

The above results suggested that to assess the relationship between HTP use and the occurrence of respiratory diseases and symptoms, considering smoking history before the start of HTP use and associated health status is important. Among the cross-sectional studies on respiratory diseases and symptoms, there are several reports relating to e-cigarettes that take into account the effect of smoking history. The cross-sectional studies of e-cigarette use in adults [20, 46] using the large-scale database BRFSS and PATH study reported a relationship between the occurrence of COPD or wheezing and e-cigarette use in current exclusive e-cigarette users without and with smoking history. In a report by Xie et al., [20] the ORs for the occurrence of COPD in current exclusive e-cigarette users without and with smoking history, were 1.47 (1.01–2.12) and 3.24 (2.78–3.78), respectively, relative to never tobacco users, suggesting that smoking history before e-cigarette use has an effect on the occurrence of COPD.

In a report by Li et al., [46] the ORs for the occurrence of wheezing (ever had wheezing or whistling in chest at any time in past) in current exclusive e-cigarette users without and with smoking history were 1.42 (0.75–2.70) and 2.27 (1.71–3.01) respectively, relative to never tobacco users. The ORs for the occurrence of separately defined wheezing (wheezing or whistling in chest in past 12 months) were 1.49 (0.84–2.67) and 2.21 (1.68–2.91) respectively, suggesting that the effect of smoking history is similar to that reported by Xie et al. [20] Studies into the effect of past smoking on asthma in adults have been reported. In a report by Parekh et al., [21] which involved a cross-sectional study of women of childbearing age (using data from the large-scale database BRFSS), the ORs for the occurrence of asthma in current exclusive e-cigarette users without and with smoking history were 1.74 (1.29–2.35) and 1.33 (0.95–1.86), respectively, relative to never tobacco users, showing that e-cigarette use had less effect on the occurrence of asthma in users with smoking history. This result cannot consistently explain the effect of past smoking on the occurrence of asthma.

Comparison with past results of cross-sectional studies of HTP use

Studies surveying the relationship between HTP use and respiratory diseases and symptoms include a cross-sectional study that surveyed the association between HTP use and airway obstruction after patients were switched from smoking (Odani et al. [6]). The PR for occurrence of airway obstruction in current exclusive HTP users relative to never tobacco users was 2.32 (95% CI: 1.54–3.49). This PR was comparable to the PR of current exclusive cigarette smokers relative to never tobacco users, 2.57 (95% CI: 2.01–3.28).

In this study, considering that 89 of the 92 current exclusive HTP users were smokers before switching to HTP, smoking history may influence the development of airway obstruction in current exclusive HTP users. The PR for the occurrence of airway obstruction of current exclusive HTP users with smoking history relative to never HTP users with smoking history was 1.42 (1.002-2.00). This PR was significantly lower compared to the PR of current exclusive cigarette smokers relative to never tobacco users, 2.57. When the data were adjusted for past smoking history, the effect of HTP use on the occurrence of airway obstruction decreased. This finding is similar to our research results.

Limitation

Our study has several limitations. First, since this was a cross-sectional study, we cannot assess any causal relationship between HTP use and the occurrence of outcomes. However, by confirming that outcomes had occurred after HTP use and adjusting for smoking history before HTP use and whether outcomes recurred, we were able to perform a reasonable assessment of the effect of HTP use alone on the occurrence of outcomes.

Second, the endpoints of this study included retrospective endpoints involving responses about remembered past events, and since participants may not be able to respond accurately about past events, there are some limitations in terms of the accuracy of the data. However, among the incidences of outcomes, the incidences (excluding recurrences) of COPD and asthma in all participants (aged 20 years and over) were 0.54% and 2.16% respectively, and both of these incidences were slightly greater than the proportions of patients aged 20 years and over in Japan in 2020, which were 0.34% and 1.16% [51, 52], but the incidences in this survey relating to whether or not an outcome occurred can likely be guaranteed to have a certain degree of accuracy, given that experiences of occurrence over a lifetime are counted.

Third, this study is based on questionnaires using self-reporting, and information on the diagnosis of outcomes was not from medical records, and some misclassification of all information, including tobacco use status [53, 54], may be unavoidable, which may impede the assessment of causal relatedness. Fourth, since the questionnaire survey in this study was administrated via the Internet, selection bias may exist due to the use of personal computers and smartphones. Additionally, participants were selected in eligible individuals from survey panel members who were willing to apply, therefore bias due to this procedure also may exist.

Fifth, while Internet-based surveys have the advantages of being low cost and can be conducted in a short period, participants may submit only partial data and abandon the questionnaire, and it is also difficult to explain the objective of the survey [55]. Because of this, it is possible that participants may have responded without fully understanding the content of the questions.

Conclusion

Our study assessed any respiratory health effects resulting from HTP use only, excluding factors other than HTP use, for example, by using information about smoking history or occurrences of outcomes before the start of HTP use. The results showed that, when assessing the effect of HTP use on health, it is necessary to take into account information about smoking history and associated health status before the start of HTP use.

Since the duration of HTP use is considerably shorter than that of CC use at present, further research such as follow-up surveys assessing the long-term respiratory effects of HTP use and relative to exclusive continued cigarette smoking will be necessary.

Data availability

The datasets used during the current study are available from the corresponding author upon reasonable request.

Abbreviations

HTP:

Heated Tobacco Products

CC:

Combustible Cigarette

FDA:

Food and Drug Administration

PR:

Prevalence Ratio

CI:

Confidence Interval

OR:

Odds Ratio

e-cigarette:

Electronic cigarette

COPD:

Chronic Obstructive Pulmonary Disease

BMI:

Body Mass Index

CHD:

Coronary Heart Diseases

BI:

Brinkman Index

PATH:

The Population Assessment of Tobacco and Health

BRFFS:

Behavioral Risk Factor Surveillance System

References

  1. Odani S, Tabuchi T. Prevalence of heated tobacco product use in Japan: the 2020 JASTIS study. Tob Control. 2022;31(e1):e64–5. https://doi.org/10.1136/tobaccocontrol-2020-056257.

    Article  PubMed  Google Scholar 

  2. Dempsey R, Rodrigo G, Vonmoos F, Gunduz I, Belushkin M, Esposito M. Preliminary toxicological assessment of heated tobacco products: a review of the literature and proposed strategy. Toxicol Rep. 2023;10:195–205. https://doi.org/10.1016/j.toxrep.2023.01.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Akiyama Y, Sherwood N. Systematic review of biomarker findings from clinical studies of electronic cigarettes and heated tobacco products. Toxicol Rep. 2021;27(8):282–94. https://doi.org/10.1016/j.toxrep.2023.01.008.

    Article  CAS  Google Scholar 

  4. Nishihara D, Yuki D, Suzuki T, Sakaguchi C, Nagata Y, Kakehi A. A randomized control study in healthy adult smokers to assess reduced exposure to selected cigarette smoke constituents in switching to the novel heated tobacco product DT3.0a. Clin Pharmacol Drug Dev. 2023. https://doi.org/10.1002/cpdd.1322.

  5. Sakaguchi C, Nagata Y, Kikuchi A, Takeshige Y, Minami N. Differences in levels of biomarkers of potential harm among users of a heat-not-burn tobacco product, cigarette smokers, and never-smokers in japan: a post-marketing observational study. Nicotine Tob Res. 2021;23(7):1143–52. https://doi.org/10.1002/cpdd.132210.1093/ntr/ntab014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Odani S, Koyama S, Miyashiro I, Tanigami H, Ohashi Y, Tabuchi T. Association between heated tobacco product use and airway obstruction: a single-centre observational study, Japan. BMJ Open Respir Res. 2024;11(1). https://doi.org/10.1136/bmjresp-2023-001793.

  7. Yohshioka T, Tabuchi T. Combustible cigarettes, heated tobacco products, combined product use, and periodontal disease: a cross-sectional JASTIS study. PLoS One. 2021;16(3). https://doi.org/10.1371/journal.pone.0248989

  8. World Health Organization. WHO Report on the Global Tobacco Epidemic 2019. Available from: https://www.who.int/publications/i/item/9789241516204.

  9. Royal College of Physicians. Nicotine without smoke Tobacco harm reduction - a report by the Tobacco advisory group of the royal college of physicians. 2016. Available from: https://www.rcplondon.ac.uk/projects/outputs/nicotine-without-smoke-tobacco-harm-reduction.

  10. Public Health England. Evidence review of e-cigarettes and heated tobacco products 2018 - a report commissioned by public health England. Available from: https://www.gov.uk/government/publications/e-cigarettes-and-heated-tobacco-products-evidence-review/evidence-review-of-e-cigarettes-and-heated-tobacco-products-2018-executive-summary.

  11. National Academies of Sciences, Engineering and Medicine. Public health consequences of E-cigarettes. 2018. Available from: https://nap.nationalacademies.org/catalog/24952/public-health-consequences-of-e-cigarettes.

  12. Xie W, Kathuria H, Galiatsatos P, Blaha MJ, Hamburg NM, Robertson RM, Bhatnagar A, Benjamin EJ, Stokes AC. Association of electronic cigarette use with incident respiratory conditions among US adults from 2013 to 2018. JAMA Netw Open. 2020;3(11):e2020816. https://doi.org/10.1001/jamanetworkopen.2020.20816.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schneller LM, Tavárez ZQ, Goniewicz ML, Xie Z, Mclntosh S, Rahman I, O’Connor J, Ossip DJ, Li D. Cross-sectional association between exclusive and concurrent use of cigarettes, ENDS, and cigars, the three most popular tobacco products, and wheezing symptoms among U.S adults. Nicotine Tob Res. 2020;22(Suppl 1):S76–84. https://doi.org/10.1093/ntr/ntaa199.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V. Characteristics, perceived side effects and benefits of electronic cigarette use: a worldwide survey of more than 19,000 consumers. Int J Environ Res Public Health. 2014;11(4):4356–73. https://doi.org/10.3390/ijerph110404356.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Takino I, Motomiya A, Nakai S. A study on the current status of heated tobacco and electronic cigarette smoking and changes in smoking status. Indoor Environ. 2023;26(3):181–94. https://doi.org/10.7879/siej.26.181.

    Article  Google Scholar 

  16. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2024 GOLD report. https://goldcopd.org/2024-gold-report/.

  17. Sun T, Anandan A, Lim C, East K, Xu S, Quah A, Rutherford B, Johnson B, Qi Y, Stjepanovic D, Leung J, Connor J, Gartner C, Hall W, Vu G, Chan G. Global prevalence of heated tobacco product use, 2015–22: a systematic review and meta-analysis. Addiction. 2023;118(8):1430–44. https://doi.org/10.1111/add.16199.

    Article  PubMed  Google Scholar 

  18. U.S. Department of Health and Human Services (HHS) Offfice of the Surgeon General. A report of the surgeon general 2014: the health consequences of smoking—50 years of progress. Available from: https://www.hhs.gov/surgeongeneral/reports-and-publications/tobacco/index.html.

  19. Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory disorder in an adult sample. Drug Alcohol Depend. 2019;194:363–70. https://doi.org/10.1016/j.drugalcdep.2018.10.004.

    Article  PubMed  Google Scholar 

  20. Xie Z, Ossip DJ, Rahman I, Li D. Use of electronic cigarettes and self-reported chronic obstructive pulmonary disease diagnosis in adults. Nicotine Tob Res. 2020;22(7):1155–61. https://doi.org/10.1093/ntr/ntz234.

    Article  CAS  PubMed  Google Scholar 

  21. Parekh T, Owens C, Fay K, Phillips J, Kitsantas P. Use of e-cigarettes and development of respiratory conditions in women of childbearing age. South Med J. 2020;113(10):488–94. https://doi.org/10.14423/SMJ.0000000000001158.

    Article  PubMed  Google Scholar 

  22. Barrameda R, Nguyen T, Wong V, Castro G, Vega PR, Lozano J, Zevallos J. Use of e-cigarettes and self-reported lung disease among US adults. Public Health Rep. 2020;135(6):785–95. https://doi.org/10.1177/0033354920951140.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bircan E, Bezirhan U, Porter A, Fagan P, Orloff MS. Electronic cigarette use and its association with asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome among never cigarette smokers. Tob Induc Dis. 2021;19:23. https://doi.org/10.18332/tid/132833.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Antwi GO, Rhodes DL. Association between e-cigarette use and chronic obstructive pulmonary disease in non-asthmatic adults in the USA. J Public Health (Oxf). 2022;44(1):158–64. https://doi.org/10.1093/pubmed/fdaa229.

    Article  PubMed  Google Scholar 

  25. Dirisanala S, Laller S, Ganti N, Taj S, Patel N, Singh Arora K, Williams I, Hameed A, Kuditipudi AD, Lei YW, Tirupathi R, Gupta S, Patel U, Venkata VS. E-cigarette use and prevalence of lung diseases among the U.S. population: a NHANES survey. J Investig Med. 2023;71(6):613–22. https://doi.org/10.1177/10815589231167357.

    Article  PubMed  Google Scholar 

  26. Choi K, Bernat D. E-cigarette use among Florida youth with and without asthma. Am J Prev Med. 2016;51(4):446–53. https://doi.org/10.1016/j.amepre.2016.03.010.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Schweitzer RJ, Wills TA, Tam E, Pagano I, Choi K. E-cigarette use and asthma in a multiethnic sample of adolescents. Prev Med. 2017;105:226–31. https://doi.org/10.1016/j.ypmed.2017.09.023.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Perez MF, Atuegwu NC, Oncken C, Mead EL, Mortensen EM. Association between electronic cigarette use and asthma in never-smokers. Ann Am Thorac Soc. 2019;16(11):1453–6. https://doi.org/10.1513/AnnalsATS.201904-338RL.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Dardari ZA, DeFilippis AP, Bhatnagar A, Blaha MJ. The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017. BMC Pulm Med. 2019;19(1):180. https://doi.org/10.1186/s12890-019-0950-3.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Entwistle MR, Valle K, Schweizer D, Cisneros R. Electronic cigarette (e-cigarette) use and frequency of asthma symptoms in adult asthmatics in California. J Asthma. 2021;58(11):1460–6. https://doi.org/10.1080/02770903.2020.1805751.

    Article  CAS  PubMed  Google Scholar 

  31. Kim SY, Sim S, Choi HG. Atopic dermatitis is associated with active and passive cigarette smoking in adolescents. PLoS One. 2017;12(11):e0187453. https://doi.org/10.1371/journal.pone.0187453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Larsen K, Faulkner GEJ, Boak A, Hamilton HA, Mann RE, Irving HM, To T, for the Canadian Respiratory Research Network. Looking beyond cigarettes: are Ontario adolescents with asthma less likely to smoke e-cigarettes, marijuana, waterpipes or tobacco cigarettes? Respir Med. 2016;120:10–5. https://doi.org/10.1016/j.rmed.2016.09.013.

    Article  PubMed  Google Scholar 

  33. Wang Y, Laestadius L, Stimpson JP, Wilson FA. Association between E-C. Use and acculturation among adult immigrants in the United States. Subst Abuse. 2019;13:1178221819855086. https://doi.org/10.1177/1178221819855086.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wills TA, Choi K, Pagano I. E-cigarette use associated with asthma independent of cigarette smoking and marijuana in a 2017 national sample of adolescents. J Adolesc Health. 2020;67(4):524–30. https://doi.org/10.1016/j.jadohealth.2020.03.001.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Cherian C, Buta E, Simon P, Gueorguieva R, Krishnan-Sarin S. Association of vaping and respiratory health among youth in the Population Assessment of Tobacco and Health (PATH) study wave 3. Int J Environ Res Public Health. 2021;18(15):8208. https://doi.org/10.3390/ijerph18158208.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Chaffee BW, Barrington-Trimis J, Liu F, Wu R, McConnell R, Krishnan-Sarin S, Leventhal AM, Kong G. E-Cigarette use and adverse respiratory symptoms among adolescents and young adults in the United States. Prev Med. 2021;153:106766. https://doi.org/10.1016/j.ypmed.2021.106766.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Han YY, Rosser F, Forno E, Celedón JC. Electronic vapor products, marijuana use, smoking and asthma in U.S. adolescents. J Allergy Clin Immunol. 2020;145(3):1025–8. https://doi.org/10.1016/j.jaci.2019.12.001.

    Article  PubMed  Google Scholar 

  38. Walker CJ, Christian WJ. Estimating the population attributable fraction of asthma due to electronic cigarette use and other risk factors using kentucky behavioral risk factor survey data, 2016–2017. Subst Use Misuse. 2021;56(3):353–8. https://doi.org/10.1080/10826084.2020.1868002.

    Article  PubMed  Google Scholar 

  39. Brunette MF, Halenar MJ, Edwards KC, Taylor A, Emond JA, Tanski SE, Woloshin S, Paulin LM, Hyland A, Lauten K, Mahoney M, Blanco C, Borek N, DaSilva LC, Gardner LD, Kimmel HL, Sargent JD. Association between tobacco product use and asthma among US adults from the Population Assessment of Tobacco and Health (PATH) study waves 2–4. BMJ Open Respir Res. 2023;10(1):e001187. https://doi.org/10.1136/bmjresp-2021-001187.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Han CH, Chung JH. Factors associated with electronic cigarette use among adolescents asthma in the Republic of Korea. J Asthma. 2021;58(11):1451–9. https://doi.org/10.1080/02770903.2020.1802745.

    Article  PubMed  Google Scholar 

  41. Roh T, Uyamasi K, Aggarwal A, Obeng A, Carrillo G. Association between e-cigarette use and asthma among US adolescents: youth risk behavior surveillance system 2015–2019. Prev Med. 2023;175:107695. https://doi.org/10.1016/j.ypmed.2023.107695.

    Article  PubMed  Google Scholar 

  42. McConnell R, Barrington-Trimis JL, Wang K, Urman R, Hong H, Unger J, Samet J, Leventhal A, Berhane K. Electronic cigarette use and respiratory symptoms in adolescents. Am J Respir Crit Care Med. 2017;195(8):1043–9. https://doi.org/10.1164/rccm.201604-0804OC.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tackett A, Keller-Hamilton B, Smith CE, Hébert ET, Metcalf JP, Queimado L, Stevens EM, Wallace SW, McQuaid EL, Wagener TL. Evaluation of respiratory symptoms among youth e-cigarette users. JAMA Netw Open. 2020;3(10):e2020671. https://doi.org/10.1001/jamanetworkopen.2020.20671.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lee WK, Smith CL, Gao CX, Borg BM, Nilsen K, Brown D, Makar A, McCrabb T, Thompson BR, Abramson MJ. Are e-cigarette use and vaping associated with increased respiratory symptoms and poorer lung function in a population exposed to smoke from a coal mine fire? Respirology. 2021;26(10):974–81. https://doi.org/10.1111/resp.14113.

    Article  PubMed  Google Scholar 

  45. Yao T, Max W, Sung HY, Glantz SA, Goldberg RL, Wang JB, Wang Y, Lightwood J, Cataldo J. Relationship between spending on electronic cigarettes, 30-day use, and disease symptoms among current adult cigarette smokers in the U.S. PLoS One. 2017;12(11):e0187399. https://doi.org/10.1371/journal.pone.0187399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Li D, Sundar IK, McIntosh S, Ossip DJ, Goniewicz ML, O’Connor RJ, Rahman I. Association of smoking and electronic cigarette use with wheezing and related respiratory symptoms in adults: cross-sectional results from the Population Assessment of Tobacco and Health (PATH) study, wave 2. Tob Control. 2020;29:140–7. https://doi.org/10.1136/tobaccocontrol-2018-054694.

    Article  PubMed  Google Scholar 

  47. Joshi D, Duong M, Kirkland S, Raina P. Impact of electronic cigarette ever use on lung function in adults aged 45–85: a cross-sectional analysis from the Canadian longitudinal study on aging. BMJ Open. 2021;11(10):e051519. https://doi.org/10.1136/bmjopen-2021-051519.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Li Y, Yamagishi K, Yatsuya H, Tamakoshi A, Iso H. Smoking cessation and COPD mortality among Japanese men and women: the JACC study. Prev Med. 2012;55(6):639–43. https://doi.org/10.1016/j.ypmed.2012.09.006.

    Article  CAS  PubMed  Google Scholar 

  49. Brinkman GL, Coates EO Jr. The effect of bronchitis, smoking, and occupation on ventilation. Am Rev Respir Dis. 1963;87:684–93. https://doi.org/10.1164/arrd.1963.87.5.684.

    Article  CAS  PubMed  Google Scholar 

  50. U.S. Department of Health and Human Services (HHS) Offfice of the Surgeon General. A report of the surgeon general 2010: how tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease. Available from: https://www.hhs.gov/surgeongeneral/reports-and-publications/tobacco/index.html.

  51. Ministry of Health, Labour and Welfare Japan. Patient Survey 2020. Available from: https://www.e-stat.go.jp/stat-search/files?page=1&layout=datalist&toukei=00450022&tstat=000001031167&cycle=7&tclass1=000001166809&tclass2=000001166811&tclass3=000001166812&tclass4=000001166813&stat_infid=000032212009&tclass5val=0.

  52. Statistics Bureau of Japan. Population census 2020. Available from: https://www.e-stat.go.jp/dbview?sid=0003448228.

  53. Gorber SC, Schofield-Hurwitz S, Hardt J. The accuracy of self- reported smoking: a systematic review of the relationship between self-reported and Cotinine-assessed smoking status. Nicotine Tob Res. 2009;11:12–24. https://doi.org/10.1093/ntr/ntn010.

    Article  Google Scholar 

  54. Zettergren A, Sompa S, Palmberg L, Ljungman P, Pershagen G, Andersson N, Lindh C, Georgelis A, Kull I, Melen E, Ekström S, Bergstrom A. Assessing tobacco use in Swedish young adults from self-report and urinary cotinine: a validation study using the BAMSE birth cohort. BMJ Open. 2023;13(7):e072582. https://doi.org/10.1136/bmjopen-2023-072582.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Siva M, Nayak DP, Narayan KA. Strengths and weaknesses of online surveys: IOSR-JHSS 2019;24(5) 31–38. https://doi.org/10.9790/0837-2405053138.

Download references

Acknowledgements

We thank Medilead (https://www.medi-l.com/) for operating this survey.

Funding

This work was supported by Japan Tobacco Inc. The views and conclusions contained herein are solely those of the authors and do not necessarily represent the views and conclusions of Japan Tobacco Inc.

Author information

Authors and Affiliations

  1. Scientific and Regulatory Affairs Division, Japan Tobacco Inc., Kamiyacho Trust Tower, 1-1, Toranomon 4-chome, Minato-Ku, Tokyo, Japan

    Yuki Kimura

  2. Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, Japan

    Minoru Sugita

Authors
  1. Yuki Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Minoru Sugita
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YK designed the study, conducted statistical analysis and interpreted the results and wrote the first draft of the manuscript. MS contributed to the technical guidance and results discussion. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yuki Kimura.

Ethics declarations

Ethics approval and consent to participate

We obtained web-based informed consent from all participants. This study was approved by the Institutional Review Board of Health Outcome Research Institute (No. 2022-02). This study was conducted in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects and registered at the UMIN Clinical Trials Registry (UMIN000049494).

The data were anonymized before statistical analyzes.

Consent for publication

Not applicable.

Competing interests

YK is employee of Japan Tobacco, Inc. MS have carried out consultancy work for Japan Tobacco, Inc.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kimura, Y., Sugita, M. Association between use of heated tobacco products and long-term respiratory effects considering smoking history: internet-based cross-sectional study in Japan. BMC Public Health 24, 2785 (2024). https://doi.org/10.1186/s12889-024-20257-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12889-024-20257-7

Keywords

BMC Public Health

ISSN: 1471-2458

Contact us