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

项目摘要/摘要 在过去的十年里，电子烟(电子烟)的使用一直在迅速增长。因为e- 香烟在市场上相对较新，关于它们对健康的影响的生物数据很少，特别是 这些对健康的影响受到特定产品特性的影响。实验证据可以早期识别 与电子烟有关的有害信号，但有几个重要元素在很大程度上没有 先前的研究，包括(1)评估在临床相关的侮辱后对肺健康的影响，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)重点关注受监管的特定设备和电子液体特性 并可能被修改以减少对健康的不利影响。加州大学旧金山分校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产品对急性肺损伤的影响 初步数据显示，电子烟特性的变化可能会对 肺部健康。该项目建议对各种电子烟的影响进行全面评估 急性肺损伤的特征，结合细胞培养、小鼠模型和人类受试者的数据。这个 中心假设是电子烟设备和液体特性的变化会影响它们的急性 在健康状况下和在急性呼吸道感染和/或环境中的肺部影响 发炎。这一假设将通过两个具体目标进行验证：(1)测试不同设备的特性 (外加电源和金属线圈组件)影响电子烟的急性肺部效应，包括 细胞培养和小鼠对病毒或细菌肺损伤的易感性，以及人类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)；和(2)测试不同的电子液体特性(尼古丁 浓度和调味品)影响电子烟的急性肺部效应，包括对病毒的易感性 细胞培养和小鼠的细菌性肺损伤，以及人体吸入内毒素(电子烟) 用户和双重用户)。这两个目标都是从系统地评估各种电子烟的影响开始的。 细胞培养和小鼠模型的特点。这项评估将在感染和不感染的情况下进行 以及炎性刺激，包括病毒(流感)和细菌(肺炎球菌)感染。电子烟 在这些模型中看起来最重要的特性随后将在建立良好的 人体肺损伤实验模型，其中健康志愿者吸入内毒素，随后 支气管镜联合支气管肺泡灌洗。该项目通过以下方式对加州大学旧金山分校的总体TCORS主题做出贡献 重点介绍了特定电子烟装置对急性肺健康的影响和电子烟液体的特点。 这些研究将产生重要的新知识，即具体的电子烟设备和电子液体 无论是在健康状态下还是在环境中，其特征都会影响其引起急性肺损伤的可能性 急性感染性或炎症性刺激，将为产品特性的监管提供信息。

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.