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

项目 1：不同电子烟特性对急性肺损伤的影响

• 批准号: 10468882
• 负责人: Carolyn Calfee
• 金额: $ 58.34万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468882
• 关键词: Acute; Acute Lung Injury; Acute respiratory infection; Address; Adolescent; Adolescent and Young Adult; Adult; Advocate; Affect; Animal Model; Animals; Bacteria; Bacterial Infections; Biological; Biology; Bronchitis; Bronchoscopy with Bronchoalveolar Lavage; Cell Culture Techniques; Characteristics; Cigarette; Data; Devices; Electronic cigarette; Elements; Emerging Tobacco Products; Endothelium; Endotoxins; England; Epithelial; Evaluation; Experimental Models; Flavoring; Harm Reduction; Health; Host Defense; Human; Immune Response Genes; Immunosuppression; Impact evaluation; Inflammation; Inflammatory; Influenza; Inhalation; Knowledge; Laboratories; Liquid substance; Lung; Metals; Modeling; Mus; Nasal Epithelium; Nicotine; Physiology; Pneumococcal Infections; Policies; Predisposition; Prevalence; Public Health; Pulmonary Inflammation; Regulation; Research; Signal Transduction; Stimulus; Surveys; Symptoms; Testing; United States Food and Drug Administration; Variant; Viral; Virus; Virus Diseases; Wheezing; behavioral economics; cigarette smoking; clinically relevant; combustible cigarette; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; electronic liquid; experience; healthy volunteer; human data; human model; human subject; lung health; lung injury; mouse model; tobacco products

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.

项目摘要/摘要 在过去的十年中，使用电子烟（电子烟）一直在迅速增长。因为e- 香烟在市场上是相对较新的，几乎没有关于其健康影响的生物学数据，尤其是如何 这些健康影响受特定产品特征的影响。实验证据可以早日识别 与电子烟有关的危害信号，但是几个重要的要素在很大程度上缺少 先前的研究，包括（1）在临床相关侮辱之后对肺部健康影响的评估，例如急性 病毒或细菌感染； （2）对细胞培养的急性肺作用的综合评估，动物， 和人类模型； （3）侧重于受调节的特定设备和电子液体特征 并可能被修改以减少不良健康影响。 UCSF TCOR具有丰富的研究经验 使用实验室和人类实验模型以及我们的 初步数据表明，电子烟特征的变化可能对 肺部健康。该项目提出了对不同电子烟的影响的全面评估 急性肺损伤的特征，结合了细胞培养，小鼠模型和人类受试者的数据。这 中心假设是电子烟设备的变化和液体特征会影响其急性 在健康条件下和急性呼吸道感染的情况下和/或 炎。该假设将通过两个特定目的进行检验：（1）测试不同的设备特性 （应用功率和金属线圈组件）影响电子烟的急性肺作用，包括 细胞培养和小鼠病毒或细菌肺损伤的敏感性，以及人类吸入内毒素 受试者（电子烟的用户和双用户）； （2）测试如何不同的电子液体特征（尼古丁 浓度和调味料）影响电子烟的急性肺作用，包括对病毒的敏感性 细胞培养和小鼠中的细菌肺损伤，以及人类受试者吸入内毒素（电子烟） 用户和双用户）。这两个目标始于对不同电子烟的影响的系统评估 细胞培养和小鼠模型中的特征。该评估将在有传染性的情况下进行 和炎性刺激，包括病毒（流感）和细菌（肺炎球菌）感染。电子烟 在这些模型中似乎最重要的特征将在建立良好的 人类的肺损伤实验模型，其中健康的志愿者吸入内毒素，其次是 支气管镜和支气管肺泡灌洗。该项目为整个UCSF TCORS主题做出了贡献 专注于特定电子烟设备和电子液体特征的急性肺部健康作用。 这些研究将产生有关特定电子烟设备和电子液体如何的重要新知识 特征会影响其在健康状态下以及在 急性感染或炎症刺激，这将为产品特征的调节提供信息。