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

项目总结 电子烟(e-cig)的使用在最近几年以惊人的速度增长，预计销量将超过 在十年内，它们的烟草同行的数量也增加了。这一趋势是由电子烟是一种 更安全的烟草香烟替代品，尽管电子烟对健康既不短期也不长期影响- CIG目前是被理解的。人们错误地假设电子烟，因为不涉及燃烧，所以 不含烟草烟雾中的成分，如自由基。然而，有新的证据表明， 来自研究人员的实验室和其他地方，一个单独的蒸发事件引起的不良反应可以在 一系列生理指标的术语。具体地说，我们最近在健康非吸烟者中的工作，使用了新的 开发的定量核磁共振方法，表明体循环血管扩张能力受损， 在诱导的肢体缺血后，充血减少，在单次汽化后明显 非尼古丁电子烟的商业品牌。我们在到目前为止的前期工作中已经进一步表现出 认为观察到的影响与炎症和氧化应激平行，这在血清中得到了证明 来自健康的非吸烟者，在相同的综合方案中在蒸发事件之前和之后服用。这里 我们建议把上述工作扩展至主动吸烟人士及电子烟尿布，以进行检验。 每种类型的暴露(T-CIG、E-CIG±尼古丁)的单个发作的急性反应，通过 延长了定量核磁共振测试的电池。该检查涉及血管反应性的测量， 顺应性和氧代谢，以及炎症和氧化应激的生物标记物。我们 假设所有三种范例都将导致对t-cig和尼古丁烟化最大的瞬时反应 电子烟。拟议研究的预测结果将使人们对电子CIG的严重影响有新的认识。 尼古丁存在和不存在时雾化吸入对内皮细胞功能障碍和 氧化应激，在整体和细胞水平上，从而帮助监管机构评估e- 香烟使用，符合RFA-OD-19-028：烟草管制科学的目标。具体来说， 我们的目标是解决其中明确规定的下列科学兴趣和优先领域： 暴露，以及评估非香烟烟草产品的危害或毒性的生物标记物，包括末端； 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 产品.区分烟草特有的细胞/组织功能/生理变化的临床评价 暴露(例如，结束气雾剂暴露)可指示较长期的疾病发展和进展 (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)”.