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

摘要 电子烟(e-cigs)自引入美国以来，以惊人的速度增长 10年前进入市场，预计10年内销量将超过烟草产品。电子烟通常是按- 被认为是烟草香烟的更安全的替代品，这是令人不安的，因为它的科学有限 关于雾化吸入的长期健康影响的化学和知识匮乏。特别令人震惊的是 市场营销广泛针对青少年，这表明年轻人是主要的目标市场。 电子烟公司的KET。此外，在吸烟者中，没有证据表明使用替代电子烟会导致 为戒烟干杯。事实上，最近的数据显示，从未抽过传统CIGA的电子烟用户-- 戒烟者更有可能在六个月内开始吸烟。电子烟产生主流气雾剂 颗粒浓度与传统香烟中的浓度相似或甚至更高。事实上，电子烟“尿布” 反复吸入高浓度的挥发性有机化合物，更重要的是，超细颗粒和 自由基。后者然后被肺泡吸收，在那里它们转移到通向血管的空间 内皮功能障碍(EDF)是动脉粥样硬化性心血管疾病的主要促进者。 目前可用于检测最早的症状前血管变化的工具， 由EDF，是相对有限的。在研究人员实验室最近的工作基础上，我们量化了 EDF在烟草吸烟者中的多种功能和机械替代措施 用定量磁共振成像(QMRI)检查雾化吸入的效果，并比较由此产生的生物标志物 通过药物治疗。我们假设e-cig气溶胶造成的氧化应激会引起EDF。 与香烟烟雾暴露的结果相当，MRI衍生的生物标志物与炎症指标平行- 血清中测定的CES。我们将通过评估微血管反应来检查急性和长期影响。 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- 波速和神经血管反应性，所有这些都是单一集成MRI方案的一部分。 拟议项目的结果将使人们对电子互联网的急性和慢性影响有新的认识。 从EDF替代标志物的角度研究气雾剂吸入有助于建立未来的公共卫生 建议，特别是在青少年电子烟消费者中。

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.