Harmful Constituents and Respiratory Effects of Waterpipe Smoke

项目总结： 关于水烟烟雾的毒性和对健康的影响，我们的认识存在严重差距。 相对于其他改性烟草产品，尽管其流行率近年来急剧上升。这个 S咖啡馆和餐馆水烟的社会文化以及水烟危害较小的观念 比起香烟，加味烟草产品的销售继续推动其在 更年轻的成年人。美国疾病控制与预防中心最近的一份报告显示，高中生的水管使用量有所上升 在2014年大幅增长，甚至比香烟更受欢迎。提供直接通知和 有助于水管监管行动，我们已经组建了一个多学科的调查团队， 烟草产品中有害和潜在有害成分(HPHCs)测量方面的专业知识 FDA鉴定，接触科学，烟草相关生物标记物，体外和体内呼吸毒理学， “组学”方法和硅胶建模，以及标准化的水管吸入系统。我们将测试我们的 假设不同的水管产品和吞吐方法会产生独特的有害物质 在体内和体外模型中将产生一系列有毒健康影响的成分。最近，我们 开发了一种小鼠水烟暴露模型，使用了类似于贝鲁特方案的吹气方案， 我们的初步证据表明，急性暴露在水管烟雾中会诱导呼吸道 发炎。此外，我们还量化了PM2.5、CO、颗粒结合的多环芳烃、NNK和尼古丁 并从这些场馆的170名员工那里收集了生物标本，这将使我们能够 对主流和二手暴露进行建模，并将我们的模型数据与人类生物标本进行比较。我们 已经建立了一种体外气液界面(ALI)暴露系统，结合人类3D 呼吸系统毒理学产品比较的有机类型模型(MucilAir)。具体目标1：定义 主流和二手水烟道烟雾的成分使用不同的抽吸方案和产品。 具体目标2：进行不同水管产品的体外和体内暴露比较 评估肺部和体外呼吸道上皮细胞毒性和遗传毒性的多效应终点。特定目标 3：从体内和体外研究(SA1和SA2)中确定生物标志物，并检测人类尿样 来自最近接触过主流/二手烟的个人。我们将使用生物信息学 整合来自AIMS 1-3的人体体内和体外数据的方法，以开发总体风险指数。

Project Summary: There is a critical gap in our knowledge about the toxicity and health effects of waterpipe tobacco smoke relative to other modified tobacco products, even though its prevalence has sharply risen in recent years. The social culture of waterpipes in cafés and restaurants and the perception that waterpipe smoking is less harmful than cigarettes, along with the distribution of flavored tobacco products, continues to drive its popularity among younger adults. A recent report from the CDC showed that waterpipe use among high school students rose sharply in 2014 and was even more popular than cigarettes. To provide data that directly informs and contributes to waterpipe regulatory action, we have assembled a multidisciplinary team of investigators with expertise in the measurement of harmful and potentially harmful constituents (HPHCs) in tobacco products identified by the FDA, exposure science, tobacco related biomarkers, in vitro and in vivo respiratory toxicology, “omics” approaches and in silico modeling, and standardized water-pipe inhalation system. We will test our hypothesis that various waterpipe products and puffing regimens will generate unique profiles of harmful constituents that will yield a continuum of toxic health effects in in vivo and in vitro models. Recently, we developed a mouse model of waterpipe smoke exposure using a puffing regimen similar to the Beirut protocol, and our preliminary evidence demonstrates that acute exposure to waterpipe smoke induces airway inflammation. Furthermore, we have quantified PM2.5, CO, particle-bound PAHs, NNK, and nicotine in 46 waterpipe venues and collected biospecimens from 170 employees in those venues, which will enable us to model mainstream and secondhand exposures and compare our model data to human biospecimens. We have established an in vitro air-liquid interface (ALI) exposure system in combination with a human 3D organotypic model for comparing products for respiratory toxicology (MucilAir). Specific aim 1: To define the constituents of mainstream and secondhand waterpipe smoke using different puffing regimens and products. Specific aim 2: To conduct comparative in vitro and in vivo exposures to different waterpipe products and assess multiple effect endpoints of toxicity and genotoxicity in lungs and in vitro airway epithelia. Specific aim 3: To identify biomarkers from the in vivo and in vitro studies (SA1 and 2) and examine human urine samples from individuals with recent mainstream/secondhand exposure to waterpipe smoke. We will use bioinformatics approaches to integrate human in vivo and in vitro data from Aims 1-3 to develop an overall hazard index.