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

摘要 电子烟(e-cigs)，10年前才被引入美国市场，并显著地 与传统的烟草卷烟不同。而传统香烟是用烟熏透的 在燃烧过程中，电子烟被“蒸发”(即加热)，由此产生的气雾剂含有数量少得多的 潜在有毒化学品，如尼古丁和调味品(如肉桂醛和双乙酰)，以及 由丙烯潜在过热引起的副产物(如丙烯醛和甲醛) 乙二醇甘油。因此，尽管人们普遍认为电子烟是一种更安全的替代产品，并将其推向市场 吸烟，使用香烟造成的实际危险在很大程度上仍未得到探索。电子烟的使用 稳步上升，健康影响研究的数量仍然相对较少，并侧重于短期 效果。然而，这些研究表明，对人类的肺脏和心血管有不良影响。 受试者和实验动物。到目前为止，一些长期的人类健康影响研究已经调查了电子邮件。 香烟是戒烟的工具，但这种流行病学研究因电子烟的“多次使用”而混乱。 香烟和以前(可能同时存在)的传统烟草香烟。因此，这些研究 在这项拨款申请中提出的建议将避免这种混淆，并利用先前建立的动物模型 用于长期的烟草研究，以调查电子烟对心肺的不良影响 慢性吸入暴露。特别是，拟议的实验旨在辨别：1) 电子液体气雾剂本身，有没有添加调味品，在不同的电压(即 加热盘管温度)；以及2)先天修饰因素的贡献，例如性别、谷胱甘肽 电子烟毒性的生物标记物和途径以及遗传学。我们将测试慢性病的总体假设 暴露在电子烟烟雾中会产生不利的心肺影响，这些影响会得到改善 先天因素，如遗传异质性和性别(即性别)，以及外生因素，如 调味品和电子烟卷曲的温度。

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.