Early Periodontal Health Impacts of Electronic Nicotine Delivery System (ENDS) Usage

电子尼古丁输送系统 (ENDS) 使用对早期牙周健康的影响

• 批准号: 10691174
• 负责人: Jonathan Henry Shannahan
• 金额: $ 62.4万
• 依托单位: UNDERWRITERS LABORATORIES INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10691174
• 关键词: 3-Dimensional; Address; Aerosols; Air; Antioxidants; Behavior; Biological; Biological Markers; Biological Models; Cells; Characteristics; Clinical; Clinical assessments; Complex; DNA Damage; DNA Repair; Data; Dental; Dental Hygienists; Development; Devices; Diagnosis; Disease; Disease Outcome; Disease Progression; Disease susceptibility; Early identification; Electronic Nicotine Delivery Systems; Environment; Epithelial; Event; Exposure to; Gingiva; Hazardous Chemicals; Health; Health Status; Human; Hygiene; Immune response; In Vitro; Individual; Inflammation; Injury; Intervention; JUUL; Knowledge; Lead; Link; Liquid substance; Mediating; Mesenchymal; Methods; Molecular; Molecular Epidemiology; Monitor; Mouth Diseases; Oral; Oral Manifestations; Oral cavity; Oral health; Outcome; Oxidative Stress; Oxidative Stress Induction; Participant; Pathway interactions; Patient Recruitments; Pattern; Periodontal Diseases; Phenotype; Predisposition; Prevention strategy; Proteomics; Protocols documentation; Public Health; Questionnaires; Recording of previous events; Risk; Risk Factors; Role; Saliva; Smoker; Swab; Testing; Therapeutic Intervention; Time; Tobacco; Toxic effect; Toxicology; Training; Variant; base; cigarette smoking; clinical application; cohort; combustible cigarette; comparative; craniofacial; design; disorder prevention; disorder risk; early onset; experimental study; innovation; keratinocyte; macrophage; metabolomics; microbial; microbiome; novel; novel marker; oral microbiome; oxidative DNA damage; oxidative damage; preference; prevent; real time monitoring; recruit; response; social media; subgingival microbiome; therapeutic development; tobacco products; tobacco user

Project Summary The use of electronic nicotine delivery systems (ENDS) increases the risk of a number of diseases including those of the oral cavity. Specifically, of concern is the induction of gingival inflammation and increased susceptibility to bacterial invasion, ultimately leading to the development of periodontal disease (PD). How and why ENDS use may pose PD risk is unclear as there is a lack of comprehensive data on usage behaviors, exposures, and disease outcomes. Further, there is a lack of early indicators of PD associated with ENDS usage, which impedes initial diagnosis and the development of disease prevention strategies. We hypothesize early indicators of adverse ENDS-related oral health outcomes can be identified and explained by variations in ENDS preference/usage and biological responses. To address this hypothesis, we will establish a behavior-exposure- toxicity-disease paradigm utilizing aims specifically designed to evaluate ENDS usage and clinical manifestations of oral disease (Aim 1), common ENDS products and molecular mechanisms of disease (Aim 2), and translatable indicators of disease susceptibility (Aim 3). This innovative approach will facilitate our knowledge regarding the mechanisms and biomarkers of ENDS-mediated oral health effects that can be directly applied to disease prevention strategies. In Aim 1, we will recruit cohorts of never-established tobacco users and current exclusive ENDS users to evaluate ENDS usage behaviors, oral health, and risk factors. In this aim, we will employ an established social media recruitment strategy to recruit participants and evaluate participant characteristics, ENDS usage, and oral health history via focused questionnaires. Additionally, ENDS usage will be examined through real-time monitoring of ENDS puffing topography. Clinical manifestations of disease will be assessed by an oral health exam and examination of the subgingival microbiome. To elucidate the role of product-based ENDS exposures we will utilize an in vitro air liquid interface model system to expose primary gingival keratinocyte/macrophage spheroids to aerosols in Aim 2. These exposure scenarios will utilize established protocols for comparative toxicity assessments while also incorporating exposures representative of ENDS usage from our recruited participants. Specifically, these in vitro experiments will assess brand-specific modulation of inflammation, oxidative stress, DNA damage/repair, epithelial-mesenchymal transitions, and bacterial invasion. In Aim 3, we will utilize a molecular epidemiology approach to assess the impact of ENDS usage by the examination of participant saliva, gingival cells, and subgingival plaques. These represent readily available matrices to examine early indicators of oral disease and PD initiation including biomarkers of inflammation, oxidative stress, DNA damage/repair, epithelial-mesenchymal transitions, and microbial alterations. Specifically, we aim to establish a pathway between participant characteristics, ENDS usage, and toxicological mechanisms contributing to PD development that can be applied to protect public health.

项目摘要 电子尼古丁传递系统（末端）的使用增加了多种疾病的风险 口腔的那些。具体而言，令人关注的是诱导牙龈炎症和增加 细菌侵袭的敏感性，最终导致牙周疾病的发展（PD）。如何和 为什么目的使用可能会构成PD风险，因为缺乏有关使用行为的全面数据， 暴露和疾病结局。此外，缺乏与目的用法相关的PD的早期指标， 这阻碍了初始诊断和疾病预防策略的发展。我们提早假设 与末端相关的口服健康结果的指标可以通过末端的变化来识别和解释 偏好/用法和生物反应。为了解决这一假设，我们将建立一个行为曝光 使用专门设计的目的用于评估目的用法和临床表现的毒性疾病范式 口腔疾病（AIM 1），疾病的普通末端产物和分子机制（AIM 2）和可翻译 疾病易感性的指标（AIM 3）。这种创新的方法将促进我们关于 末端介导的口腔健康影响的机制和生物标志物可以直接应用于疾病 预防策略。在AIM 1中，我们将招募许多永不建立的烟草用户和当前独家 结束用户以评估最终用法行为，口腔健康和危险因素。在此目标中，我们将采用 建立的社交媒体招聘策略以招募参与者并评估参与者特征， 结束用法和通过重点问卷调查的口腔健康史。此外，将检查结束用法 通过实时监控末端的浮肿地形。疾病的临床表现将由 口腔健康考试和尺寸微生物组的检查。阐明基于产品的作用 结束暴露，我们将利用体外空气液体界面模型系统暴露原发性牙龈 在AIM 2中，角膜细胞/巨噬细胞球体到气溶胶。这些暴露情况将利用已建立的情况 比较毒性评估的方案，同时还合并了代表目的的暴露 我们招募的参与者的使用。具体而言，这些体外实验将评估特定品牌 调节炎症，氧化应激，DNA损伤/修复，上皮 - 间质转变和 细菌入侵。在AIM 3中，我们将利用一种分子流行病学方法来评估目的的影响 通过检查参与者唾液，牙龈细胞和尺寸斑块来使用。这些很容易代表 可用的矩阵检查口腔疾病和PD启动的早期指标，包括生物标志物 炎症，氧化应激，DNA损伤/修复，上皮间质转变和微生物 改变。具体而言，我们旨在在参与者特征，结束用法和 有助于PD开发的毒理学机制可用于保护公共卫生。