This study assessed the BOEs and BOPHs among dual users of cigarettes and e-cigarettes by segmenting the dual users into subgroups based on self-reported product use frequency to better assess relative exposure to toxicants and carcinogens within dual user subgroups. Vapers who smoke and infrequent dual users, overall, had lower levels of biomarkers compared to exclusive smokers. On the other hand, smokers who vape, on average, had similar levels of most biomarkers compared to exclusive smokers. The overall levels of exposure were found to be associated with cigarette consumption (i.e., number of days used in the past 30 days) and not associated with e-cigarette use. We analyzed data from the PATH study as it provides the most comprehensive set of biomarkers collected from a large, real-world population-based sample representative of tobacco users in the non-institutionalized U.S. adult population.
The current study provides insights by disentangling dual users into various subgroups rather than the more commonly published reports that consider dual users as a single homogenous group. Notable differences in demographic composition and tobacco use behaviors among the dual user subgroups highlight the heterogeneity in the dual tobacco use category. Every dual user is uniquely defined by the product use behavior, therefore, assessing dual users as a single group does not provide an accurate representation of the exposure levels within the category. For example, a recent study found higher levels of TNE-2, NNAL, 1-HOP, HPMA, and MHB3 among dual users of cigarettes and e-cigarettes compared to exclusive cigarette users.8 That study only provided an assessment of dual users who were every day smokers in the PATH Wave 1 Study, excluding “some days” cigarette smokers who make up a significant number of all dual users. Some of these “some days” dual users report frequent use of cigarette smoking (≥ 20 days) and have high mean levels of biomarkers of exposure even though they consider themselves as “some days” users. Goniewicz et al. reported that dual users of cigarettes and e-cigarettes were also exposed to higher levels of nicotine, two heavy metals (lead and cadmium), five PAHs and thirteen VOCs, than current exclusive cigarette smokers. However, the analysis of dual users segmented by daily and non-daily use of both products provided a more refined assessment of BOEs – daily smokers had higher levels of toxicants than non-daily smokers.12 Recently, Stokes et al. reported no difference in the biomarker concentration of inflammatory (hSCRP, IL-6, fibrinogen, S-ICAM) or oxidative stress (urinary 8-isoprostane) between exclusive smokers and dual users of cigarettes and e-cigarettes.25 The dual user group was defined as a single group without differentiating the frequency of use of both products. Majeed et al. reported clusters of tobacco user population based on the exposure levels; however, our approach provides a unique understanding of exposure among different dual user subgroups based on their product use behavior.26
Our study corroborates the findings regarding BOEs reported by Smith et al.27, indicating that a clear pattern is emerging. As suggested by Borland et al.28 product use frequency is an important indicator for identifying subsets of dual users. We demonstrate that among the four subgroups, those dual users that vape frequently and infrequent dual users, smoked fewer cigarettes and therefore, are lower on the continuum of exposure relative to frequent smokers that vape infrequently and frequent dual users.
Our analysis complements these findings by gaining additional insights from the BOPH levels. The differences in BOPHs within the dual subgroups aligns with the differences in BOEs. All the BOPHs investigated in the infrequent dual user subgroup were comparable to the exclusive e-vapor user and the never tobacco user groups. These observations suggest that dual users exhibiting lower exposure may start moving down the path to lowering the adverse health effects from cigarette smoke. A dose-response relationship exists between cigarette smoking and the mortality from many of the smoking diseases,29 and such a relationship is even acknowledged by the U.S. Surgeon General in the 2004 report on the Health Consequences of Smoking.30 Moreover, in a meta-analysis of published literature, Chang et al.31 report that substantial reduction in cigarette consumption may lower some smoking-related disease risks. While quitting all tobacco products is the most desirable outcome for harm reduction, for those adult smokers unable or unwilling to quit, increased use of e-vapor and ultimately switching to exclusive e-vapor use may provide some benefits. Sustained and large reductions in exposure, like that observed among exclusive e-vapor users compared to exclusive smokers, should reduce the risks of many of the smoking related diseases.
Our analyses should be considered in the context of some potential limitations. Given the cross-sectional nature of our analysis, conclusions cannot be made regarding transitions between the groups; however, the insights about relative exposure are noteworthy. Self-reported product usage can be viewed as yet another limitation as this is subject to various sources of error (e.g., recall bias, social desirability). Nevertheless, self-reported characterization of tobacco product use is widely used by most researchers and is reportedly considered a reasonable approach.32–34 Furthermore, the BOE levels provide confirmation of their classification into various subgroups. The relatively small size (n = 45), among some dual user subgroups and for some biomarkers, may limit generalizability to the population. Moreover, the e-vapor usage behavior during the period of data collection (2013–2014) may not reflect the current use behavior as the e-vapor products have evolved over time from the earlier generation products to the currently popular pod-based products. This limitation can be offset in the future by updating these analyses as more recent biomarker data become available. Lastly, the PATH study only measured cigarette smoke-related BOEs and did not include biomarkers related to e-vapor constituents primarily due to the ubiquitous nature of the major constituents, propylene glycol and glycerin, and unknown long-term effects and associated biomarkers.35
In conclusion, we have demonstrated that dual users of e-vapor products and cigarettes are not a single homogenous group. At least four distinct subgroups were identified based on the frequency of tobacco product use and a continuum of exposure exists within the dual user subgroups. Overall, the levels of BOE and BOPHs in dual users are associated with frequency of cigarette smoking. In order to experience potential harm reduction, dual users must switch completely.