The adverse chronic effects of e-cigarettes: puff profiles, sex, genetics, and flavorings as modifying factors

摘要 电子烟（e-cigs）仅在10年前引入美国市场， 与传统的烟草卷烟不同。传统的香烟是通过 燃烧时，电子烟被“蒸发”（即，加热），由此产生的气溶胶含有数量少得多的 可能有毒的化学物质，如尼古丁和调味剂（例如，肉桂醛和双乙酰），以及 副产物（例如，丙烯醛和甲醛），丙烯 乙二醇和甘油。因此，尽管电子烟被广泛认为是一种更安全的替代品， 虽然吸烟的危害很大，但其使用所造成的实际危险在很大程度上仍未得到探讨。随着电子烟的使用 虽然研究的数量稳步上升，但健康影响研究的数量仍然相对较少，并且集中在短期内， 方面的影响.然而，这些研究表明，在人类中， 受试者和试验动物。到目前为止，一些长期的人类健康影响研究已经调查了e- 香烟作为戒烟工具，但这种流行病学研究被电子烟的“多用途”所混淆。 香烟和以前的（可能同时存在的）传统烟草香烟。因此，研究 在这项资助申请中提出的将避免这种混淆，并利用建立的动物模型，以前 用于长期烟草研究，以调查电子烟对心肺的不良影响， 慢性吸入暴露。特别地，所提出的实验被设计为辨别：1） 在不同电压下产生的具有和不具有添加的调味剂的电子液体气溶胶本身（即， 加热线圈温度）;和2）先天修饰因素的贡献，如性别，谷胱甘肽 生物标志物和途径，以及遗传学，电子烟毒性。我们将检验慢性病的总体假设， 暴露于电子烟气溶胶会产生不利的心肺影响，并且这些影响会被改变 先天因素，如遗传异质性和性别（即，性别）和外部因素，如 香料和电子烟线圈温度。

Abstract Electronic cigarettes (e-cigs), were introduced to the U.S. market only 10 years ago and are markedly different from traditional tobacco-based cigarettes. Whereas traditional cigarettes are smoked through combustion, e-cigarettes are “vaped” (i.e., heated), and the resultant aerosols contain a far smaller number of potentially toxic chemicals, such as nicotine and flavorings (e.g., cinnamaldehyde and diacetyl), as well as byproducts (e.g., acrolein and formaldehyde) caused by the potential overheating of these agents, propylene glycol, and glycerin. Thus, although e-cigarettes are widely believed and marketed as a safer alternative to cigarette smoking, the actual danger posed by its use remains largely unexplored. As the use of e-cigs steadily rises, the number of health effects studies is still relatively small and have focused on short term effects. These studies, however, have demonstrated adverse pulmonary and cardiovascular effects in human subjects and test animals. To date, some long term human health effects studies have investigated e- cigarettes as cessation devices, but such epidemiology studies are confounded by the `poly-use' of e- cigarettes and previous (and possibly concurrent) traditional tobacco cigarettes. Therefore, the studies proposed in this grant application will avoid this confounding and utilize established animal models, previously used in long-term tobacco studies, to investigate the adverse cardiopulmonary effects of e-cigarettes after chronic inhalation exposures. In particular, the proposed experiments are designed to discern: 1) the toxicity of the e-liquid aerosols themselves, with and without added flavorings, generated at different voltages (i.e. heating coil temperatures); and 2) the contribution of innate modifying factors, such as sex, glutathione biomarkers and pathways, and genetics, to e-cigarette toxicity. We will test the overall hypothesis that chronic exposure to e-cigarette aerosols produces adverse cardiopulmonary effects and that these effects are modified by innate factors, such as genetic heterogeneity and sex (i.e., gender), and exogenous factors, such as flavorings and e-cigarette coil temperature.