Research Project 3: Respiratory health effects of flavors

研究项目3：香料对呼吸系统健康的影响

• 批准号: 10248509
• 负责人: Maciej Lukasz Goniewicz
• 金额: $ 35.2万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-14 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10248509
• 关键词: Abstinence; Acute; Address; Aerosols; Behavior; Biological Markers; Chemicals; Chronic; Cigarette; Cigarette Smoker; Clinical Markers; Complex Mixtures; Consumption; Data; Disease; Electronic Nicotine Delivery Systems; Emerging Tobacco Products; Epithelial Cells; Evaluation; Flavoring; Genes; Goals; Health; Health Hazards; Human; Immune response; Inflammation; Inflammatory; Inflammatory Response; Ingestion; Inhalation; Long-Term Effects; Manufacturer Name; Menthol; Nasal Epithelium; New York; Observational Study; Outcome; Oxidative Stress; Pattern; Perception; Predisposition; Randomized; Regulation; Research; Research Priority; Research Project Grants; Respiratory Signs and Symptoms; Respiratory System; Respiratory Tract Infections; Respiratory physiology; Risk; Safety; Science; Systemic disease; Testing; Tobacco; Toxic effect; Uncertainty; United States Food and Drug Administration; aerosolized; base; cigarillos; circulating biomarkers; clinically relevant; cohort; hookah; human subject; inclusion criteria; inflammatory marker; interest; irritation; new product development; novel strategies; open label; preference; programs; recruit; respiratory; respiratory health; response; side effect; tobacco flavor; tobacco products; vaping

Project 3 addresses the Center for Tobacco Products (CTP) research priorities under Health Effects scientific domain as defined in RFA-OD-17-006, and the overarching integrative scientific theme of this TCORS coalesce for testing the effects of flavorings in tobacco products and characterize their respiratory toxicity. Many of the flavorings chemicals being used in emerging tobacco products, including electronic nicotine delivery system (ENDS), waterpipe tobacco and cigarillos, were evaluated for safety through ingestion only. These flavorings have not been tested adequately for safety when inhaled in aerosolized form. At present, no regulatory program exists to assess the respiratory health hazards of the flavorings in tobacco products. This project will focus primarily on respiratory health effects, including inflammation, biomarkers of exposure, and clinical markers with relevance to disease endpoints that will directly supports the Toxicity scientific domain. Embedded within these health effects studies, we will of necessity gather data on product usage patterns that may influence health effects, including total consumption, topography, and flavor preference, which will help inform the Behavior scientific domain. We propose to test the hypotheses that inhalation of flavored ENDS aerosol has the potential to cause chronic respiratory tract inflammation, and that potential inflammatory effects and observed respiratory side-effects associated with flavored ENDS use will depend on the specific flavoring chemicals used in the products and the patterns of products use. Our goal is to better characterize the respiratory health effects attributable to the use of flavored tobacco products. We propose two human studies to evaluate respiratory health effects from inhaling flavored products among daily ENDS users as they switch among various flavors. These two studies aim to: AIM 1 (Study 1): Assess changes in respiratory symptoms and biomarker levels among ENDS users during spontaneous `switching' between flavors; AIM 2 (Study 2): Evaluate respiratory symptoms in ENDS users switching from flavors of potentially high-toxicity to flavors of potentially low-toxicity; and AIM 3 (Studies 1&2): Characterize ENDS users' preferences, selection, patterns of use and switching between various flavors. In Study 1, we will establish a cohort of ENDS users to assess changes in respiratory symptoms during spontaneous `switching' among flavors over one year. In Study 2, we will conduct a randomized, parallel-group open-label trial to evaluate respiratory symptoms in ENDS users switching from higher-toxicity to lower-toxicity flavors (as identified by Project 1). Endpoints include clinically relevant biomarkers of inflammation and oxidative stress, changes in respiratory function, subjective respiratory symptoms and side-effects, and expression of immune and inflammatory response genes in nasal epithelial cells. Outcomes for Regulatory Science: Assessment of respiratory health effects in ENDS users will provide crucial information related to safety of flavored tobacco products, which would inform the FDA's regulatory efforts, including product standards.

项目3介绍了烟草产品中心（CTP）研究重点，健康效应科学效果 RFA-OD-17-006中定义的域以及该TCOR的总体综合科学主题 合并以测试烟草产品中调味剂的影响并表征其呼吸道 毒性。许多在新兴烟草产品中使用的香料化学品，包括电子 尼古丁输送系统（末端），水管烟草和雪茄通过摄入评估安全性 仅有的。当以雾化形式吸入时，这些调味剂尚未进行充分的测试。在 目前，没有监管计划来评估烟草调味剂的呼吸健康危害 产品。该项目将主要关注呼吸健康影响，包括炎症，生物标志物 暴露和与疾病终点相关的临床标记，将直接支持毒性 科学领域。嵌入在这些健康效应研究中，我们将需要收集有关产品的数据 可能影响健康影响的使用模式，包括总消费，地形和风味 偏爱，这将有助于告知行为科学领域。我们建议测试假设 吸入调味末端气溶胶有可能引起慢性呼吸道炎症，并且 潜在的炎症作用和观察到的与风味末端使用相关的呼吸副作用将 取决于产品中使用的特定调味化学物质以及产品的使用方式。我们的目标是 更好地表征归因于使用调味烟草产品的呼吸健康效应。我们 提出了两项​​人类研究，以评估每日吸入调味产品的呼吸健康影响 用户在各种口味之间切换时结束。这两项研究旨在：目标1（研究1）：评估 在自发的“切换”期间，用户的呼吸道症状和生物标志物水平的变化 在口味之间； AIM 2（研究2）：评估用户从口味转换的目的中的呼吸症状 潜在的高毒性可能高毒性；和目标3（研究1和2）：末端的特征 用户的喜好，选择，使用模式和在各种口味之间进行切换。在研究1中，我们将 建立一系列用户，以评估自发“切换”期间呼吸道症状的变化 在一年多的口味中。在研究2中，我们将进行一项随机的平行组开放标签试验 评估用户在末端的呼吸道症状，从较高毒性转变为较低毒性的口味（如 由项目1标识）。终点包括炎症和氧化应激的临床相关生物标志物， 呼吸功能，主观呼吸道症状和副作用的变化以及免疫的表达 和鼻皮细胞中的炎症基因。监管科学的结果：评估 目的的呼吸健康效应用户将提供与风味烟草安全有关的关键信息 产品将为FDA的监管工作提供信息，包括产品标准。