Harmful Constituents and Respiratory Effects of Waterpipe Smoke

项目摘要： 在我们对水烟的毒性和健康影响的认识方面存在着严重的空白 与其他改性烟草产品相比，它的使用率在近年来急剧上升。的 在咖啡馆和餐馆使用水烟的社会文化以及人们认为使用水烟危害较小的看法 香烟，沿着调味烟草产品的分销，继续推动其在 年轻的成年人。疾病预防控制中心最近的一份报告显示， 2014年，它比香烟更受欢迎。提供直接告知和 有助于水管监管行动，我们已经组建了一个多学科的调查小组， 在烟草制品中有害和潜在有害成分（HPHC）测量方面的专业知识 由FDA鉴定，暴露科学，烟草相关生物标志物，体外和体内呼吸毒理学， “组学”方法和计算机模拟，以及标准化的水管吸入系统。我们将测试我们的 假设各种水管产品和膨化方案将产生有害的独特的配置文件， 这些成分在体内和体外模型中会产生连续的毒性健康效应。最近我们 使用类似于贝鲁特方案的抽吸方案开发了水管烟雾暴露的小鼠模型， 我们的初步证据表明，急性暴露于水管烟雾诱导气道 炎症此外，我们还对46个城市的PM2.5、CO、颗粒结合的多环芳烃、NNK和尼古丁进行了量化。 水管场馆和收集的生物标本，从170名员工在这些场馆，这将使我们能够 对主流和二手接触进行建模，并将我们的模型数据与人体生物样本进行比较。我们 已经建立了一个体外空气-液体界面（ALI）暴露系统，结合人体3D 用于比较呼吸道毒理学产品的器官型模型（MucilAir）。具体目标1：确定 使用不同的膨化方案和产品，对主流和二手水管烟的成分进行分析。 具体目标2：对不同水管产品进行体外和体内暴露比较， 评估肺和体外气道上皮细胞中毒性和遗传毒性的多个效应终点。具体目标 3：从体内和体外研究（SA 1和2）中鉴定生物标志物，并检查人尿样 来自最近接触主流/二手水管烟雾的个人。我们将使用生物信息学 整合目标1-3中人体体内和体外数据的方法，以制定总体危害指数。

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.