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Translational Studies on Electronic Cigarette-derived Oxidants and their Long-term Pulmonary Effects

电子烟衍生氧化剂及其长期肺部影响的转化研究

基本信息

批准号：
9980676
负责人：
JOHN P RICHIE
金额：
$ 47.18万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9980676
关键词：
Acrolein Activated Charcoal Address Aerosols Aldehydes Animal Model Animals Behavior Biological Markers C57BL/6 Mouse Chemicals Chronic Chronic Disease Chronic Obstructive Airway Disease Cigarette Clinical Data Development Devices Disease Disease model Electronic cigarette Estrogen receptor positive Evaluation Exposure to Female Filtration Free Radicals Generations Health Histology Human Inflammation Inflammatory Intervention Studies JUUL Laboratory Animals Laboratory Finding Liquid substance Lung Lung diseases Malignant Neoplasms Measures Monitor Mus Nicotine Nose Outcome Study Oxidants Oxidative Stress Oxides Patients Pattern Play Policies Research Research Priority Resolution Respiratory physiology Role Smoker Source Symptoms Tobacco Toxic effect Toxicology Work air filter analytical method arm base cigarette smoke cigarette smoke-induced COPD cigarette smoking combustible cigarette design disease phenotype e-cigarette aerosols electronic cigarette use electronic liquid exposure to cigarette smoke improved in vivo lung injury male mouse model outcome forecast oxidative damage primary endpoint primary outcome respiratory smoking cessation specific biomarkers tobacco products tobacco regulatory science toxicant translational approach translational study

项目摘要

Abstract Cigarette smoke (CS) is a major source of reactive oxidants. Oxidative stress and damage resulting from exposure to oxidants such as free radicals and aldehydes play critical roles in the development and progression of most tobacco-caused diseases, including cancer and chronic obstructive pulmonary disease (COPD). Using state-of-the-art high resolution analytical methods to detect and measure oxidants, we have demonstrated that electronic cigarettes (EC) aerosols contain highly reactive free radicals and aldehydes; albeit at levels which are typically 10- to 1000-fold lower than in cigarette smoke. We found that free radicals were produced in all generations of EC products currently on the market, but that levels vary significantly by EC product design and usage behaviors. Based on these studies and the known importance of oxidative stress/damage in pulmonary diseases, our proposal focuses on toxicities caused by exposure to EC-derived free radicals and aldehydes and their role in the development of COPD. Specifically, we hypothesize that 1) EC aerosol exposure will be associated with negative long-term pulmonary health effects, albeit to a lesser extent than combustible cigarette smoke exposure, and 2) switching from combustible cigarettes to EC will lead to reductions in oxidant exposures and, thus, improved prognosis in COPD. In this proposal, we will utilize a highly translational approach, conducting long-term in vivo exposure studies in a CS-induced COPD mouse model and a pilot clinical intervention study of switching to EC in mild-moderate COPD smokers. The specific objectives are to quantitate absolute levels of EC or CS oxidants at the point of exposure in the animal model and to determine the relative impact of these oxidants through the examination of lung function (primary endpoint). Pulmonary biomarkers of oxidative stress and inflammation will also be examined. The specific aims have been designed to allow for a thorough evaluation of the long term health consequences of EC use in naïve and CS exposed mice comparing effects of high vs. low oxidant products, and the impact of selective filtration of oxidant-induced lung damage in the mouse (Aim 1); impact of switching from cigarette smoke exposure to EC aerosols to mimic switching in humans (Aim 2); and translatability of laboratory findings in smokers with mild-moderate COPD (Aim 3). Overall, these studies will significantly contribute to the field of tobacco regulatory science by focusing on the toxicological importance of oxidant exposure from specific EC devices. These data will be of particular value to the FDA for the development of regulatory policies aimed at reducing harm imposed by tobacco products.

摘要