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

吸烟者和电子烟使用者急性电子烟暴露的 MRI 和生物标志物

• 批准号: 10353104
• 负责人: Felix W Wehrli
• 金额: $ 48.47万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2024-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10353104
• 关键词: Acute; Address; Adolescent; Adverse reactions; Advertising; Aerosols; Air Pollution; Area; Atherosclerosis; Attention; Biological; Biological Availability; Biological Markers; Blood; Blood Circulation; Blood Vessels; C-reactive protein; Caliber; Cells; Cigarette; Cigarette Smoker; Cross-Over Studies; Data; Depressed mood; Development; Disease; Electronic cigarette; Exposure to; Free Radicals; Glycerol; Health; Heart Diseases; Hyperemia; Hypoxia; Imaging Techniques; Immune response; Impairment; Inflammation; Inflammatory; Inhalation; Ischemia; Laboratories; Lead; Long-Term Effects; Lower Extremity; Magnetic Resonance Imaging; Mainstreaming; Measurement; Measures; Mediating; Metabolic; Metabolism; Modality; Mus; Nicotine; Nitric Oxide; Outcome; Oxidative Stress; Oxygen; Participant; Peripheral; Physiologic pulse; Physiological; Physiology; Process; Propylene Glycols; Protocols documentation; Reporting; Reproducibility; Research; Research Personnel; Risk; Sales; Serum; Serum Markers; Smoke; Smoker; Smoking; Surrogate Markers; Techniques; Technology; Teenagers; Testing; Thigh structure; Tissues; Tobacco; Tobacco smoke; Toxic effect; Toxicology; Ultrasonics; Ultrasonography; Ursidae Family; Vascular Endothelium; Venous; Work; arterial stiffness; base; cigarette smoke; cigarette smoking; combustible cigarette; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; endothelial dysfunction; femoral artery; imaging biomarker; imaging modality; inflammatory marker; insight; interest; mRNA Expression; macrophage; nicotine exposure; non-cigarette tobacco product; non-smoker; particle; promoter; protein expression; research clinical testing; response; smoking cessation; tobacco exposure; tobacco regulatory science; trend; ultrafine particle; vaper; vaping

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)”.

项目概要 近年来，电子烟 (e-cig) 的使用量以惊人的速度增长，销售额预计将超过 电子烟是一种电子烟，这一趋势在十年内得到了推动。 尽管电子烟对健康既没有短期也没有长期影响，但它是比烟草香烟更安全的替代品 目前人们对电子烟的理解是错误的，因为电子烟不涉及燃烧。 不含烟草烟雾中的成分，例如自由基。但是，有新的证据显示。 研究人员的实验室和其他地方表明，单次吸电子烟会引起可量化的不良反应 具体来说，我们最近在健康非吸烟者中使用了新的方法。 开发了定量 MRI 方法，表明体循环的血管舒张能力受损， 下肢缺血后充血减少，单次吸电子烟后明显 我们在目前的前期工作中进一步展示了非尼古丁电子烟的商业品牌。 提议观察到的影响与炎症和氧化应激平行，如血清中所证明的 来自健康非吸烟者在同一综合方案中吸电子烟前后采集的数据。 我们建议将上述工作扩展到活跃的烟草卷烟（t-cig）吸烟者和电子烟吸烟者，以进行检查 每种类型的暴露（t-cig、e-cig ± 尼古丁）单次发作的急性反应，通过 扩展的定量 MRI 测试包括测量血管反应性， 顺应性和氧代谢，以及炎症和氧化应激的生物标志物。 认为所有三种范式都会引起短暂的反应，这对于香烟和尼古丁化香烟来说是最大的 拟议研究的预计结果将为电子烟的严重影响提供新的见解。 就内皮功能障碍的标志物而言，在存在或不存在尼古丁的情况下进行气雾吸入 氧化应激，无论是在整体水平还是细胞水平，从而帮助监管机构评估电子风险 卷烟的使用，符合 RFA-OD-19-028 的目标：烟草监管科学。 我们的目标涉及其中明确指出的以下科学兴趣和优先领域：“评估生物标志物 暴露以及评估非卷烟烟草产品（包括电子尼古丁传送系统）危害或毒性的生物标志物； 尼古丁的毒理学影响，以评估非卷烟烟草的短期和长期影响； 产品；临床评估，以区分烟草特有的细胞/组织功能/生理学变化 已知表明长期疾病发生和进展的暴露（例如 ENDS 气溶胶暴露） （健康影响）”。