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: 10490338
• 负责人: Felix W Wehrli
• 金额: $ 47.95万
• 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/10490338
• 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; Persons; 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; 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; ultrasound; 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 十年内，他们的烟草对应物。这种趋势已经刺激了电子烟是一个 尽管E-的短期和长期健康影响 目前了解CIG。错误地认为，由于不涉及组合，电子烟是 没有烟草烟雾中发现的成分，例如自由基。但是，有新兴的证据 从调查人员的实验室和其他地方，单个vaping情节引起了广告反应的可量化 多种生理措施的术语。具体来说，我们最近在健康的非吸烟者方面的工作，使用了新的 开发了定量MRI方法，表明全身循环的血管舒张能力受损和 在下肢诱发缺血之后，血症减少了，一次性烟气后的证据 非凝聚电子烟的商业品牌。我们在初步工作中进一步显示了现在 提议观察到的作用与炎症和氧化应激平行，这在串行中证明 从同一集成协议期间进行蒸发事件之前和之后采取的健康的非吸烟者。这里 我们建议将上述工作扩展到活跃的烟草香烟（T-cig）吸烟者和电子烟蒸气以检查 每种类型的暴露（T-cig，e-cig±尼古丁）的急性反应， 扩展的定量MRI测试电池。检查涉及测量血管反应性， 依从性和氧代谢，以及炎症和氧化应激的生物学标志物。我们 假设这三个范式将引起瞬态响应，这对于T-cig和烟素将是最大的 电子烟。拟议研究的预计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，气溶胶吸入在内皮功能障碍和 氧化应激，无论是在整体还是细胞水平上，从而有助于调节器评估E-的风险 使用香烟，符合RFA-OD-19-028的目标：烟草监管科学。具体来说， 我们的目的解决了以下科学兴趣和优先领域，明确说明了：“生物标志物要评估 暴露以及生物标志物评估包括末端在内的非二烟烟草产品的危害或毒性； 尼古丁的毒理学影响；生物标志物评估非烟烟草的短期和长期影响 产品;临床评估以区分细胞/组织功能/生理学的变化特定于烟草 已知的暴露（例如，末端气溶胶暴露）表明长期疾病的发展和进展 （健康影响）”。