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涉及烟草制品中心（CTP）在健康影响科学研究下的研究重点。 RFA-OD-17-006中定义的领域，以及本TCORS的总体综合科学主题 用于测试烟草制品中香料的效果并表征其呼吸特性的聚结器 毒性许多香料化学品正在使用的新兴烟草产品，包括电子 尼古丁释放系统（ENDS），水烟和小雪茄，通过摄入的安全性进行了评价 只.这些调味品在以雾化形式吸入时的安全性尚未得到充分的测试。在 目前，还没有一个管理程序来评估烟草中的香料对呼吸系统健康的危害 产品.该项目将主要关注呼吸系统健康的影响，包括炎症， 暴露，以及与疾病终点相关的临床标志物，将直接支持毒性 科学领域。在这些健康影响研究中，我们将有必要收集有关产品的数据。 可能影响健康影响的使用模式，包括总消费量、地形和风味 偏好，这将有助于为行为科学领域提供信息。我们建议测试的假设， 吸入调味ENDS气雾剂有可能引起慢性呼吸道炎症， 潜在的炎症作用和观察到的与调味ENDS使用相关的呼吸系统副作用将 取决于产品中使用的特定调味化学品和产品使用的模式。我们的目标是 以更好地表征归因于使用调味烟草产品的呼吸健康影响。我们 建议进行两项人体研究，以评估每日吸入调味产品对呼吸系统健康的影响。 结束用户在各种口味之间切换。这两项研究旨在：AIM 1（研究1）：评估 ENDS使用者在自发“转换”期间呼吸道症状和生物标志物水平的变化 AIM 2（研究2）：评价ENDS使用者从不同口味转换为不同口味时的呼吸道症状。 潜在高毒性的风味剂潜在低毒性的风味剂;和AIM 3（研究1和2）：表征ENDS 用户的偏好、选择、使用模式以及在各种口味之间的切换。在研究1中，我们将 建立ENDS使用者队列，以评估自发“转换”期间呼吸道症状的变化 在一年多的时间里，在研究2中，我们将进行一项随机、平行组开放标签试验， 评估ENDS使用者从高毒性转向低毒性口味的呼吸道症状（如 项目1）。终点包括炎症和氧化应激的临床相关生物标志物， 呼吸功能的变化，主观呼吸症状和副作用，以及免疫表达 以及鼻上皮细胞中的炎症反应基因。监管科学的成果： ENDS使用者的呼吸系统健康影响将提供与加香烟草安全性相关的关键信息 产品，这将通知FDA的监管工作，包括产品标准。