Investigating The Cardiovascular Toxicity Of Exposure To Electronic Hookah Smoking

摘要 水烟在全世界迅速流行起来。促成这种流行的是 一种未经证实的信念，认为传统的水烟通过水管时可以解毒。更 最近，电子水烟碗含有电子液体，其被电加热，但通过传统的吸入方式吸入， 水管-越来越受欢迎，在美国的年轻女性成年人，谁赞同 市场上声称这些产品甚至比传统的水烟更安全。用传统的水烟， 除了尼古丁和焦油，吸烟者还暴露在富含碳的细颗粒和大量的尼古丁中。 一氧化碳（CO），后者已被证明构成内皮依赖性血管扩张剂。 虽然有毒物质的暴露比传统水烟低得多，而且没有任何CO暴露， 碗递送尼古丁和构成假定的血管毒素的细颗粒。的主要目标 一个项目是调查传统水烟和电子水烟的比较效果 吸入对内皮和血管功能的影响及其在心血管疾病发生中的作用机制 疾病具体来说，我们将研究氧化应激和炎症作为潜在机制的作用， 水烟引起的心血管疾病的作用。我们将检验以下假设：1）在没有 木炭煤球和几乎任何CO暴露，电子水烟碗吸入急性损害内皮细胞 功能，并引起急性中央僵硬，相反的内皮功能增强后观察到的 传统的水烟，这可能是由燃烧木炭排放的大量CO引起的 用于加热香料烟草的煤砖; 2）氧化应激和炎症过程在烟草中起着重要作用。 这些血管变化的关键机制作用。在一项交叉研究中， 从吸烟到吸电子水烟，我们将通过肱动脉血流来评估内皮功能， 脉搏波传导速度和增强指数对18例健康青年主动脉弹性和舒张功能的影响 21-39岁的水烟吸烟者，在即兴吸烟/吸入30分钟之前和之后。以测试 氧化应激介导，我们将确定电子水烟后内皮功能的任何急性损伤是否可以 通过静脉注射维生素C（一种有效的抗氧化剂）可以预防。抗氧化防御缓冲剂，例如 保护性HDL或对氧磷酶-1活性，或氧化脂蛋白的增加。以测试 炎症介导，生物标志物包括抗炎细胞因子IL-10和促炎细胞因子 在治疗前后收集hsCRP、TNF-α、IL-6、IL-8以及吸烟暴露 生物标志物（血浆尼古丁和呼出的CO）。这一建议的结果将填补我们在这方面的空白。 对传统与电子水烟筒对血管和 内皮功能，并在这样做，告知FDA关于水烟产品监管的政策决定。

Abstract Hookah (water-pipe) smoking is rapidly increasing in popularity worldwide. Contributing to this popularity is the unsubstantiated belief that traditional hookah smoke is detoxified as it passes through the water-pipe. More recently, electronic hookah bowls—containing e-liquid that is heated electrically but inhaled through traditional water-pipes—are increasing in popularity in the United States among young female adults, who endorse marketing claims that these products are even safer than traditional hookah. With traditional hookah, in addition to nicotine and tar, smokers are exposed to carbon-enriched fine particles and significant amounts of carbon monoxide (CO), the latter of which has been shown to constitute an endothelial-dependent vasodilator. Though toxicant exposure is much lower than traditional hookah and without any CO exposure, e-hookah bowls deliver nicotine and fine particles that constitute putative vascular toxins. The main objective of this project is to investigate the comparative effects of traditional hookah smoking versus electronic hookah bowl inhalation on endothelial and vascular function and their mechanistic role in the development of cardiovascular disease. Specifically, we will examine the role of oxidative stress and inflammation as potential mechanisms of action in hookah-induced cardiovascular disease. We will test the hypothesis that; 1) in the absence of charcoal briquettes and virtually any CO exposure, e-hookah bowl inhalation acutely impairs endothelial function and evokes acute central stiffness, opposite from the endothelial function augmentation observed after traditional hookah smoking, which is likely mediated by the large CO boost emitted from burning charcoal briquettes used to heat the flavored tobacco; and 2) the processes of oxidative stress and inflammation play a pivotal mechanistic role underlying these vascular changes. In a cross-over study comparing traditional hookah smoking to e-hookah bowl inhalation, we will assess endothelial function measured by brachial artery flow- mediated dilation and aortic stiffness by pulse wave velocity and augmentation index in 18 young healthy hookah smokers 21-39 years old, before and after ad lib 30-minute smoking/ inhalation session. To test for oxidative stress mediation, we will determine if any acute impairment in endothelial function after e-hookah can be prevented by intravenous Vitamin C infusion, a potent anti-oxidant. Antioxidant defensive buffers, such as protective HDL or paraoxonase-1 activity, or an increase in oxidized lipoproteins will be collected. To test for inflammatory mediation, biomarkers including anti-inflammatory cytokine IL-10 and pro-inflammatory cytokines hsCRP, TNF-α, IL-6, IL-8 will be collected before and after the sessions as well as smoking exposure biomarkers (plasma nicotine and expired CO). The results of this proposal stand to fill in gaps in our mechanistic understanding of the comparative effect of traditional vs. e-hookah bowl on vascular and endothelial function and in so doing, inform policy decisions by the FDA about regulation of hookah products.