Effects of Pod E-Cigarettes on Respiratory Mucosal Immune Defenses

荚式电子烟对呼吸道粘膜免疫防御的影响

基本信息

批准号：
10066558
负责人：
Elise Danielle Hickman
金额：
$ 3.43万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
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：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10066558
关键词：
Acute Lung Injury Address Adolescent Adoption Adult Aerosols Affect Air Airway Disease Alveolar Macrophages Benzoic Acids Bioenergetics Biological Assay Biological Markers Biological Models Blood Vessels Bronchoscopy Cell Count Cells Centers for Disease Control and Prevention (U.S.)Chemical Exposure Chemicals Chronic Clinical Clinical Trials Data Devices Disease Outbreaks Electronic cigarette Evolution Exposure to Flavoring Formulation Functional disorder Gene Expression Generations Genus Mentha Glycerol Glycolysis Goals Health Host Defense Human Immune Immune System Diseases Immune response Impairment In Vitro Inflammation Inflammatory Response Innate Immune Response JUUL JUUL vapor Knowledge Laboratories Link Liquid substance Mentors Mitochondria Morphology Mucosal Immune Responses Nicotine Patients Pattern Phagocytes Phagocytosis Pharyngeal structure Predisposition Propylene Glycols Public Health Reporting Research Research Personnel Respiration Respiratory Burst Respiratory Mucosa Respiratory System Salts Sampling Smoker Sputum Stains System Teenagers Testing Tobacco Tobacco use Toxic effect Toxicology Vegetables Vitamin E Acetate Weight Work Youth aerosolized base box mods cell type cohort cytotoxicity defense response e-cigarette aerosols electronic cigarette use electronic cigarette user electronic liquid immune function immune health immunohistochemical markers in vivo in vivo Model individual variation innovation insight lung injury macrophage mouse model neutrophil nicotine use non-smoker novel public health relevance respiratory training opportunity vape pens vaping young adult

项目摘要

PROJECT SUMMARY/ABSTRACT E-cigarettes are a significant public health concern, with over 7 million adults and more than 5 million youth reporting current e-cigarette use. The recent outbreak of e-cigarette and vaping product associated lung injury (EVALI) further highlights the need for research on the effects of e-cigarette use. Pod e-cigarettes, such as JUUL, have rapidly gained popularity since their release in 2016 and now represent over 70% of the e-cigarette market. However, relatively little is known about their effects on the human respiratory system. Specifically, whether and how they affect respiratory mucosal immune defenses, and how these responses compare to those elicited by previous generation e-cigarettes (vape pens, tanks, box mods), represents a critical knowledge gap that will be the focus of this application. We will use tightly linked mechanistic human in vivo and in vitro studies to determine how pod e-cigarettes affect respiratory macrophages, a critical respiratory immune cell type. Preliminary data from our lab and other groups has demonstrated that previous generation e-cigarettes and their components (flavoring chemicals, propylene glycol, vegetable glycerin) have the potential to impair respiratory mucosal immune defenses, including phagocytosis, ciliary beating, oxidative burst, glycolysis, mitochondrial respiration, and immune-related gene expression. Because of JUUL’s unique chemical composition, aerosolization parameters, and puff topography, we anticipate observing additional or differential effects in JUUL users in comparison with previous generation e-cigarette users. We will test this hypothesis in two specific aims: SA1 will determine if users of pod e-cigarette devices have unique innate immune responses in the central airways and SA2 will investigate the effects of aerosolized pod e-liquid and its components on macrophage function ex vivo. To achieve SA1, induced sputum samples from e-cigarette users (both previous generation and pod cohorts), smokers, and nonsmokers will be analyzed for differences in immune cell composition, phagocytic function, mitochondrial energy, morphology, and immunohistochemical staining. Induced sputum will also be analyzed for biomarkers of airway disease, including inflammation, acute lung injury, and vascular damage. To achieve SA2, primary human pulmonary macrophages obtained from bronchoscopies will be adhered to transwells and exposed at air-liquid interface to aerosols from JUUL pods (tobacco & mint flavor), nicotine salts, and benzoic acid alone using a novel in vitro exposure system. The cells will then be assayed for cytotoxicity, inflammatory response, phagocytic function, and bioenergetic capacity to determine the effects of each component of the e- liquid on these endpoints. Data derived from these aims will be integrated to provide highly translational, mechanistic insight into the effects of pod e-cigarette devices on respiratory immune dysfunction, which will address a critical knowledge gap related to the potential health effects of pod e-cigarettes such as JUUL.

项目摘要/摘要电子烟是一个重大的公共卫生问题，有超过700万成年人和超过500万年轻人报告当前的电子烟使用。最近爆发了电子烟和烟与肺损伤（评估）进一步强调了对电子烟的影响的研究。豆荚电子烟，例如Juul，自2016年发行以来，他们迅速越来越受欢迎，现在占电子烟市场的70％以上。但是，关于它们对人类呼吸系统的影响的了解相对较少。具体而言，是否和它们如何影响呼吸粘膜免疫防御措施，以及这些反应如何与由上一代电子烟（Vape Pens，Tanks，Box Mods）代表一个关键的知识差距此应用程序的重点。我们将使用体内和体外研究紧密联系的机械性人体来确定 POD电子烟如何影响呼吸巨噬细胞，一种关键的呼吸免疫细胞类型。初步数据来自我们的实验室和其他小组，证明了上一代电子烟及其组件（调味化学物质，丙二醇，蔬菜甘油）有可能损害呼吸粘膜免疫防御措施，包括吞噬作用，纤毛殴打，氧化物爆发，糖酵解，线粒体呼吸，和免疫相关的基因表达。由于Juul独特的化学成分，气化参数和粉扑地形，我们预计在Juul用户中会观察到其他或差异的影响与上一代电子烟的用户进行比较。我们将以两个具体的目的检验该假设：SA1将确定POD电子烟设备的用户是否在中央航空公司和 SA2将研究雾化的POD电子液体及其成分对巨噬细胞功能的影响。为了实现SA1，来自电子烟使用者（上一代和POD队列）的痰液样品，吸烟者和非吸烟者将分析免疫细胞组成，吞噬功能的差异，线粒体能量，形态和免疫组织化学染色。诱导的痰也将分析气道疾病的生物标志物，包括感染，急性肺损伤和血管损伤。为了实现SA2，从支气管检查获得的原代人肺巨噬细胞将粘附到transwells和在空气界面暴露于Juul Pods（烟草和薄荷风味），尼古丁盐和苯二糖的气溶胶中单独使用新型体外暴露系统酸。然后将分析细胞的细胞毒性，炎症性响应，吞噬功能和生物能的能力，以确定e-的每个成分的影响这些端点上的液体。从这些目标得出的数据将被整合到高度翻译，对POD电子烟设备对呼吸免疫功能障碍的影响的机械洞察力，这将解决与豆荚电子烟（例如Juul）潜在健康影响有关的关键知识差距。