Research Project 3: Respiratory health effects of flavors

项目3涉及烟草制品中心(CTP)在健康影响科学项下的研究优先事项 RFA-OD-17-006中定义的领域以及本TCORS的总体综合科学主题 用于测试烟草产品中调味料的效果并表征其呼吸道特性的聚合 毒性。新兴烟草产品中使用的许多调味品化学物质，包括电子产品 尼古丁输送系统(END)、水烟和雪茄的安全性通过摄入进行了评估 只有这样。这些调味品没有经过充分的安全测试，当以雾化形式吸入时。在… 目前，还没有管理程序来评估烟草调味品对呼吸道健康的危害。 产品。这个项目将主要关注对呼吸健康的影响，包括炎症，生物标志物 暴露，以及与疾病终点相关的临床标志物，直接支持毒性 科学领域。在这些健康影响研究中，我们必须收集有关产品的数据 可能影响健康影响的使用模式，包括总消耗量、地形和味道 偏好，这将有助于了解行为科学领域。我们建议检验以下假设 吸入有味道的气雾剂有可能导致慢性呼吸道炎症， 与香料末端使用相关的潜在炎症效应和观察到的呼吸道副作用 取决于产品中使用的特定调味剂和产品使用的模式。我们的目标是 为了更好地说明使用加香烟草产品对呼吸健康的影响。我们 建议进行两项人体研究，以评估每天吸入调味产品对呼吸健康的影响 终端用户在各种口味之间切换。这两项研究旨在：目标1(研究1)：评估 自发性“转换”过程中终端使用者呼吸道症状和生物标志物水平的变化 口味之间；目的2(研究2)：评估终端用户从口味转换为 对潜在低毒口味的潜在高毒性；以及目标3(研究1和2)：表征目的 用户的喜好、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 建立一个终端用户队列，以评估在自发“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、平行分组的开放标签试验 评估从高毒口味转向低毒口味(AS)的最终用户的呼吸道症状 由项目1确定)。终点包括临床上相关的炎症和氧化应激生物标记物， 呼吸功能、主观呼吸道症状和副作用的变化以及免疫功能的表达 鼻腔上皮细胞中的炎症反应基因。监管科学的成果：评估 对最终用户的呼吸健康影响将提供与加香烟草安全性相关的关键信息 产品，这将为FDA的监管努力提供信息，包括产品标准。

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.