PROJECT 1: IMPACT OF DIFFERENT E-CIGARETTE CHARACTERISTICS ON ACUTE LUNG INJURY

项目总结/摘要 在过去的十年中，电子烟（e-cigarettes）的使用一直在迅速增长。因为- 香烟是相对较新的市场，几乎没有生物数据对他们的健康影响，特别是如何 这些健康影响受特定产品特性的影响。实验证据可以早期识别 与电子烟相关的危害信号，但几个重要因素在很大程度上被遗漏了， 先前的研究，包括（1）评估临床相关损伤后的肺部健康影响，如急性 病毒或细菌感染;（2）对细胞培养，动物， 和人体模型;以及（3）关注受监管的特定设备和电子液体特性 并且可以被修改以减少不利的健康影响。UCSF TCORS拥有丰富的研究经验 使用实验室和人体实验模型研究烟草制品对急性肺损伤的影响， 初步数据表明，电子烟特性的变化可能对 肺健康该项目建议对不同电子烟的影响进行全面评估。 急性肺损伤的特征，结合来自细胞培养、小鼠模型和人类受试者的数据。的 中心假设是，电子烟装置和液体特性的变化影响其急性 在健康条件下和急性呼吸道感染情况下的肺部影响，和/或 炎症该假设将通过两个特定目标进行测试：（1）测试不同器械特性 （施加的功率和金属线圈组件）影响电子烟的急性肺部效应，包括 在细胞培养物和小鼠中对病毒或细菌肺损伤的易感性，以及在人体中对吸入内毒素的易感性 受试者（电子烟使用者和双重使用者）;以及（2）测试不同的电子液体特性（尼古丁） 浓度和调味剂）影响电子烟的急性肺部效应，包括对病毒的易感性 以及在细胞培养物和小鼠中的细菌性肺损伤，以及在人类受试者（电子烟）中的吸入内毒素 用户和双重用户）。这两个目标开始与不同的电子烟的影响进行系统的评估 细胞培养和小鼠模型中的特征。本评价将在存在和不存在感染性 和炎症刺激，包括病毒（流感）和细菌（肺炎球菌）感染。电子烟 在这些模型中似乎最重要的特征将在一个完善的 肺损伤的人类实验模型，其中健康志愿者吸入内毒素，然后 支气管镜检查和支气管肺泡灌洗。该项目有助于整体UCSF TCORS主题， 专注于特定电子烟装置和电子液体特性的急性肺部健康影响。 这些研究将产生重要的新知识，关于特定的电子烟设备和电子液体如何在电子烟中产生作用。 这些特征影响其在健康状态和环境中引起急性肺损伤的可能性。 急性感染或炎症刺激，这将告知产品特性的监管。

PROJECT SUMMARY/ABSTRACT Over the past decade, use of electronic cigarettes (e-cigarettes) has been rapidly growing. Because e- cigarettes are relatively new to the market, there is little biologic data on their health effects, particularly how these health effects are affected by specific product characteristics. Experimental evidence can identify early signals of harm associated with e-cigarettes, but several important elements have been largely missing from prior studies, including (1) an assessment of pulmonary health effects after clinically relevant insults, like acute viral or bacterial infection; (2) an integrated assessment of acute pulmonary effects across cell culture, animal, and human models; and (3) a focus on specific device and e-liquid characteristics that are subject to regulation and might be modified to reduce adverse health effects. The UCSF TCORS has extensive experience studying the impact of tobacco products on acute lung injury using laboratory and human experimental models, and our preliminary data indicate that variation in e-cigarette characteristics may have a significant impact on pulmonary health. This project proposes a comprehensive assessment of the impact of varying e-cigarette characteristics on acute lung injury, combining data from cell culture, mouse models, and human subjects. The central hypothesis is that changes in e-cigarette device and liquid characteristics influence their acute pulmonary effects, both under healthy conditions and in the setting of acute respiratory infection and/or inflammation. This hypothesis will be tested via two specific aims: (1) Test how different device characteristics (applied power and metal coil components) impact the acute pulmonary effects of e-cigarettes, including susceptibility to viral or bacterial lung injury in cell culture and in mice, and to inhaled endotoxin in human subjects (e-cigarette users and dual users); and (2) Test how different e-liquid characteristics (nicotine concentration and flavorings) impact the acute pulmonary effects of e-cigarettes, including susceptibility to viral and bacterial lung injury in cell culture and in mice, and to inhaled endotoxin in human subjects (e-cigarette users and dual users). Both aims begin with a systematic evaluation of the impact of varying e-cigarette characteristics in cell culture and mouse models. This evaluation will be conducted with and without infectious and inflammatory stimuli, including viral (influenza) and bacterial (pneumococcal) infection. The e-cigarette characteristics that appear to be most important in these models will then be tested in a well-established human experimental model of lung injury, in which healthy volunteers inhale endotoxin, followed by bronchoscopy with bronchoalveolar lavage. This project contributes to the overall UCSF TCORS theme by focusing on the acute pulmonary health effects of specific e-cigarette device and e-liquid characteristics. These studies will yield important new knowledge regarding how specific e-cigarette device and e-liquid characteristics impact their potential to cause acute lung injury, both in a state of health and in the setting of acute infectious or inflammatory stimuli, which will inform regulation of product characteristics.