MRI and Serum Markers of Endothelial Stress Resulting from E-Cigarette Aerosol Inhalation

电子烟气溶胶吸入引起的内皮应激的 MRI 和血清标志物

• 批准号: 9751387
• 负责人: Felix W Wehrli
• 金额: $ 46.66万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751387
• 关键词: Acute; Address; Adolescent; Adult; Advertising; Aerosols; Age; Air Pollution; Amines; Atherosclerosis; Biological Markers; Blood Vessels; Blood Viscosity; C-reactive protein; Caliber; Cardiovascular system; Chemistry; Chronic; Cigarette; Cigarette Smoker; Data; Deterioration; Dose; Electronic cigarette; Endothelium; Evaluation; Exposure to; Free Radicals; Future; Glycerol; Health; High School Student; Hyperemia; Impairment; Inflammation; Inflammatory; Inhalation; Knowledge; Laboratories; Lead; Length; Magnetic Resonance Imaging; Mainstreaming; Marketing; Measurable; Measurement; Measures; Mechanics; Mediating; Mus; Nicotine; Outcome; Oxidative Stress; Oxides; Oxygen saturation measurement; Participant; Pharmacology; Physiologic pulse; Physiological; Process; Propylene Glycols; Protocols documentation; Public Health; Recording of previous events; Research; Research Personnel; Risk; Sales; Science; Serum; Serum Markers; Smoke; Smoking; Source; Stress; Surrogate Markers; Systemic disease; Techniques; Teenagers; Tobacco; Transducers; Ultrasonography; Uncertainty; Work; Youth; base; brachial artery; cardiovascular health; carotid intima-media thickness; cigarette smoke; cigarette smoking; electronic cigarette use; electronic cigarette user; endothelial dysfunction; exposure to cigarette smoke; femoral artery; fine particles; indexing; insight; intimal medial thickening; macrophage; neurovascular; non-invasive imaging; non-smoker; particle; pressure; promoter; smoking cessation; tobacco products; tool; trend; ultrafine particle; vaper; volatile organic compound

Summary The popularity of electronic cigarettes (e-cigs) has grown at a startling rate since their introduction to the US market 10 years ago, with sales expected to outpace tobacco products within a decade. E-cigs are often per- ceived as a safer alternative to tobacco-based cigarettes, which is unsettling given the limited science on its chemistry and paucity of knowledge on long-term health effects of aerosol inhalation. Particularly alarming is marketing directed extensively toward adolescents, which indicates that young people are the key target mar- ket of e-cig companies. Further, there is no evidence among cigarette smokers that alternative e-cig use leads to smoking cessation. In fact, recent data suggests e-cig users who have never smoked conventional ciga- rettes are more likely to take up tobacco cigarette smoking within six months. E-cigs yield mainstream aerosols with particle concentrations similar or even higher than those in conventional cigarettes. Indeed, e-cig “vapers” repeatedly inhale high concentrations of volatile organic compounds and, importantly, ultrafine particles and free radicals. The latter are then taken up by the alveoli where they translocate into the vascular space leading to endothelial dysfunction (EDF), the prime promoter of atherosclerotic cardiovascular disease. The current tools available for detecting the earliest presymptomatic vascular changes, brought about by EDF, are relatively limited. Building on recent work in the investigators' laboratory in which we quantified multiple functional and mechanical surrogate measures of EDF in tobacco cigarette smokers we propose to examine the effects of aerosol inhalation by quantitative MRI (qMRI) and compare the resulting biomarkers with pharmacologic measures. We hypothesize that the oxidative stress exerted by e-cig aerosol causes EDF comparable to that from cigarette smoke exposure and that MRI-derived biomarkers parallel inflammatory indi- ces measured in serum. We will examine both acute and longer-term effects by assessing microvascular reac- tivity via dynamic femoral oximetry, arterial hyperemia, femoral artery flow-mediated dilation, central pulse- wave velocity and neurovascular reactivity, all as part of a single integrated MRI protocol. The outcome of the proposed project will provide new insight into the acute and chronic effects of e-cig aerosol inhalation in terms of surrogate markers of EDF and aid toward establishment of future public health advisories, particularly in juvenile e-cig consumers.

总结 自从电子烟被引入美国以来， 10年前，烟草市场的销售预计将在10年内超过烟草产品。电子烟往往是每- 被认为是烟草卷烟的更安全的替代品，考虑到其有限的科学， 化学和缺乏关于雾化吸入对健康的长期影响的知识。让自己担惊受怕 市场营销广泛针对青少年，这表明年轻人是主要目标市场， 电子烟公司的名单。此外，没有证据表明吸烟者使用替代电子烟会导致 到戒烟。事实上，最近的数据表明，从未吸过传统雪茄的电子烟用户- 吸烟者在六个月内开始吸烟的可能性较大。电子烟产生主流气溶胶 颗粒浓度与传统香烟中的颗粒浓度相似或甚至更高。事实上，电子烟“vapers” 反复吸入高浓度的挥发性有机化合物，重要的是，超细颗粒， 自由基后者然后被肺泡吸收，在那里它们移位到血管空间， 内皮功能障碍（EDF），动脉粥样硬化性心血管疾病的主要促进因素。 目前可用于检测最早症状前血管变化的工具， 相对而言，EDF的影响有限。基于最近在研究人员实验室的工作，我们量化了 我们建议， 通过定量MRI（qMRI）检查雾化吸入的效果，并比较所得生物标志物 用药物治疗我们假设电子烟气雾剂产生的氧化应激导致EDF 与香烟烟雾暴露相当，MRI衍生的生物标志物与炎症指标平行， 在血清中测量ces。我们将通过评估微血管反应来检查急性和长期影响， 通过动态股动脉血氧饱和度、动脉充血、股动脉血流介导的扩张、中心脉搏- 波速度和神经血管反应性，所有这些都是单个集成MRI协议的一部分。 建议项目的结果将为电子烟的急性和慢性影响提供新的见解 从EDF的替代标志物的角度来看，雾化吸入有助于建立未来的公共卫生 特别是青少年电子烟消费者。