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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要过去十年，电子烟（e-香烟）的使用量迅速增长。因为电子香烟在市场上相对较新，关于其健康影响的生物学数据很少，特别是如何影响健康这些健康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相关的危害信号，但在很大程度上遗漏了几个重要元素先前的研究，包括（1）临床相关损伤（如急性损伤）后对肺部健康影响的评估病毒或细菌感染； (2) 对细胞培养物、动物、和人体模型； (3) 关注受监管的特定设备和电子烟油特性并可能进行修改以减少对健康的不利影响。 UCSF TCORS 拥有丰富的学习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，以及我们的研究初步数据表明，电子烟特性的变化可能会对肺部健康。该项目提出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装置和液体特性的变化影响其急性肺部影响，无论是在健康条件下还是在急性呼吸道感染的情况下和/或炎。该假设将通过两个具体目标进行测试：（1）测试不同设备的特性如何（施加的功率和金属线圈组件）影响电子烟的急性肺部效应，包括细胞培养物和小鼠对病毒或细菌性肺损伤的易感性，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）； (2) 测试不同烟油的特性（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细胞培养物和小鼠中的细菌性肺损伤，以及人体吸入内毒素（电子烟用户和双用户）。这两个目标都始于对不同电子烟的影响进行系统评估细胞培养和小鼠模型的特征。该评估将在有或没有传染性的情况下进行和炎症刺激，包括病毒（流感）和细菌（肺炎球菌）感染。电子烟然后，这些模型中最重要的特征将在成熟的模型中进行测试人体肺损伤实验模型，其中健康志愿者吸入内毒素，然后支气管镜检查并进行支气管肺泡灌洗。该项目通过以下方式对 UCSF TCORS 的整体主题做出了贡献：重点关注特定电子烟装置和电子烟液特性对肺部健康的急性影响。这些研究将产生关于特定电子烟装置和电子烟液如何无论是在健康状态还是在以下情况下，其特征都会影响其引起急性肺损伤的可能性急性感染或炎症刺激，这将为产品特性的监管提供信息。