MRI and Biological Markers of Acute E-Cigarette Exposure in Smokers and Vapers

项目摘要 近年来，电子烟（e-cig）的使用以惊人的速度增长，预计销售额将超过 烟草行业的竞争对手在十年内。这一趋势是由电子烟是一种 更安全的替代烟草为基础的香烟，即使没有短期或长期的健康影响的电子 CIG是目前已知的。人们错误地认为，电子烟，因为没有燃烧涉及， 不含烟草烟雾中的成分，如自由基。然而，有证据表明 从研究人员的实验室和其他地方，一个单一的vaping事件elevated一个不良反应量化， 一些生理指标的术语。具体来说，我们最近在健康的非吸烟者中的工作， 开发的定量MRI方法表明体循环的血管扩张能力受损， 减少充血，在下肢诱导缺血后，在单次vaping后明显 非尼古丁电子烟的商业品牌。我们在到目前为止的初步工作中进一步表明 建议观察到的影响是由炎症和氧化应激，在血清中证明， 来自健康的非吸烟者在相同的综合方案期间在vaping事件之前和之后采取的。这里 我们建议把上述工作扩展至经常吸食香烟及电子烟的人士， 每种暴露类型（t-cig，e-cig ±尼古丁）单次发作的急性反应，通过 一系列的定量磁共振成像测试检查包括测量血管反应性， 顺应性和氧代谢，沿着炎症和氧化应激的生物标志物。我们 假设所有三种范例都将引起短暂的反应， 电子烟拟议研究的预期结果将为电子烟的急性影响提供新的见解 在存在和不存在尼古丁的情况下雾化吸入内皮功能障碍的标志物， 氧化应激，无论是在整体和细胞水平，从而帮助监管机构评估的风险， 香烟使用，符合RFA-OD-19-028：烟草监管科学的目标。具体地说， 我们的目标针对其中明确规定的以下科学兴趣和优先领域：“评估生物标志物， 暴露，以及生物标志物，以评估非卷烟烟草产品的危害或毒性，包括ENDS; 尼古丁的毒理学影响;评估非卷烟烟草短期和长期影响的生物标志物 烟草制品;区分烟草特有的细胞/组织功能/生理学变化的临床评价 暴露（例如，已知表明长期疾病发展和进展 （健康影响）”。

PROJECT SUMMARY Electronic cigarette (e-cig) use has grown at an alarming rate during recent years with sales projected to exceed those of their tobacco counterparts within a decade. This trend has been spurred by the notion that e-cigs are a safer alternative to tobacco-based cigarettes even though neither short nor long-term health implications of e- cig are currently understood. It has falsely been assumed that e-cigs, because no combustion is involved, are free of the constituents found in tobacco smoke such as free radicals. There is, however, emerging evidence from the investigators’ lab and elsewhere that a single vaping episode elicits an adverse reaction quantifiable in terms of a number of physiologic measures. Specifically, our recent work in healthy nonsmokers, using newly developed quantitative MRI methods, indicates impaired vasodilatory capacity of the systemic circulation and reduced hyperemia, following induced ischemia in the lower extremity, evident after a single episode of vaping a commercial brand of non-nicotinized e-cig. We have further shown in preliminary work leading up to the present proposal that the observed effects are paralleled by inflammation and oxidative stress, as evidenced in serum from healthy non-smokers taken before and after a vaping episode during the same integrated protocol. Here we propose to extend the above work to active tobacco cigarette (t-cig) smokers and e-cig vapers to examine the acute response from a single episode of each type of exposure (t-cig, e-cig ± nicotine), by means of an extended battery of quantitative MRI tests. The examination involves measurements of vascular reactivity, compliance and oxygen metabolism, along with biological markers of inflammation and oxidative stress. We hypothesize that all three paradigms will cause a transient response that will be greatest for t-cigs and nicotinized e-cigs. The projected outcome of the proposed research will provide new insight into the acute effects of e-cig aerosol inhalation in the presence and absence of nicotine in terms of markers of endothelial dysfunction and oxidative stress, both at the holistic and cellular level, and thereby aid regulators in assessing the risk of e- cigarette use, in conformance with the objectives of RFA-OD-19-028: Tobacco Regulatory Science. Specifically, our aims address the following scientific interest and priority areas explicitly stated therein: “biomarkers to assess exposure, as well as biomarkers to assess harm or toxicity of non-cigarette tobacco products, including ENDS; toxicological impact of nicotine; biomarkers to assess short- and long-term effects of non-cigarette tobacco products; clinical evaluations to distinguish changes in cell/tissue function/physiology specific to tobacco exposure (e.g., ENDS aerosol exposure) known to indicate longer term disease development and progression (health effects)”.