Commentary on Hartmann‐Boyce et al.: Understanding the harms of dual use of cigarettes and e‐cigarettes requires more precise data Article Swipe

As dual use of e-cigarettes and combustible cigarettes remains a common pattern, more experimental data are needed to determine both the extent of cigarette replacement necessary to achieve clinically meaningful outcomes, and the potential for e-cigarettes to expose users to non-tobacco-related vectors of harm. As dual use of e-cigarettes and cigarettes continues to be observed among both adults and youth [1], more data are needed on both the absolute and relative harms of this use pattern. Hartmann-Boyce et al.’s article reviews the evidence on biomarkers of harm associated with switching to e-cigarette use from smoking, and includes studies comparing exclusive e-cigarette use to exclusive cigarette use, exclusive e-cigarette use to dual use and dual use to exclusive cigarette use. The results show that in addition to exclusive e-cigarette use, dual use also reduces biomarkers of harm relative to exclusive cigarette use; however, the study also highlights the dearth of studies comparing dual users with those who smoke only cigarettes or abstain from all tobacco products [2]. A fuller understanding of the relative harm of dual use compared to persistent exclusive cigarette smoking is important for determining the potential therapeutic uses of e-cigarettes as a reduced-harm product, as well as the risks to specific populations. Specifically, work needs to be conducted to understand: (1) how much switching is necessary to achieve clinically meaningful effects, (2) whether we are missing important vectors of e-cigarette-specific harm by failing to capture non-traditional biomarkers of harm and (3) whether increased overall nicotine exposure from dual use patterns occurs, and the extent to which that may be particularly harmful for youth. One important area that lacks sufficient evidence is how the effects of stable patterns of dual use over the longer-term may differ from short-term effects dual use during a brief transition from cigarette smoking to exclusive e-cigarette use. Data on transitions between dual use states show that while many people go on to exclusive use of one or the other product [3], persistent dual use at different levels is also common [4], particularly in youth [5], and important differences in motivation to quit smoking and other characteristics may exist between stable and transitory dual users [6]. While we can be reasonably certain that individuals who use both cigarettes and e-cigarettes and then transition quickly to exclusive e-cigarette use are improving their health [7], it is not clear whether people who persist in some reduced level of cigarette smoking while struggling to switch fully are improving their health during this period. In other words, how much switching is necessary for meaningful reduction in cigarette-related harms? Experimental data that provide information on precise levels of cigarette versus e-cigarette use among dual users and associated biomarkers of harm are needed to determine both the magnitude and time course of changes in exposure to harmful toxicants. Furthermore, most studies of reduction in health risk associated with switching from cigarettes to e-cigarettes have relied upon biomarkers associated with traditional cigarette smoking, which supports an evidence base focused upon e-cigarettes as a potential reduced-harm product for smokers who cannot otherwise quit [8]. However, we may be missing important vectors of harm unique to e-cigarettes due to a relative lack of biomarker data on other toxicants not traditionally associated with cigarettes: in other words, we cannot find what we are not looking for. Biomarkers such as measures of exposure to volatile organic compounds (VOCs), metals and the polyaromatic hydrocarbons (PAHs) noted in the Hartmann-Boyce article should be routinely included in experimental studies of e-cigarette use [9]. The US-based Population Assessment of Tobacco and Health (PATH) study includes such recommended biomarkers; a recent analysis from PATH concluded that while full switching to e-cigarette use reduced exposure to traditional tobacco markers of harm, switchers also experienced decreases in VOCs and PAHs; dual use was associated with decreases in some tobacco-specific biomarkers of harm, but not in VOCs, metals or most PAHs [10]. However, as such data are observational, more experimental work is needed to determine how various dual use patterns may or may not translate to reduced health risk. Finally, the authors note that they did not assess nicotine exposure as a biomarker as it is not necessarily related to harm. While this is generally true [11], nicotine exposure has important implications for dual use patterns in young smokers. Given the relationship between nicotine dependence in adolescence and continued tobacco use in adulthood [12, 13], and that dual use may be associated with greater rates of dependence than using either product alone [14-16], dual use in this developmental period specifically could contribute to the development of riskier tobacco use trajectories in those youth [17]. As such, comparisons to both exclusive-smoking and non-tobacco-using youth are necessary for assessing the overall burden of harm from dual use in this particularly vulnerable population. RNC would like to acknowledge Dr. Suzanne Colby for her comments on an earlier draft of this work. None.