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

项目摘要 使用电子尼古丁递送系统增加了一些疾病的风险，包括 口腔中的那些。具体地说，令人担忧的是诱发牙周炎和增加 易受细菌侵袭，最终导致牙周病(PD)的发生。方式和方式 由于缺乏关于使用行为的全面数据，最终使用可能会造成帕金森病风险的原因尚不清楚， 暴露和疾病后果。此外，缺乏与END使用相关联的PD的早期指标， 这阻碍了初步诊断和疾病预防战略的制定。我们很早就做出了假设 不良末端相关口腔健康结果的指标可以通过末端的变化来识别和解释 偏好/使用和生物学反应。为了解决这个假设，我们将建立一个行为暴露- 毒性-疾病范例利用AIMS专门设计来评估终端的使用和临床表现 口腔疾病(目标1)、常见的最终产物和疾病的分子机制(目标2)和可翻译 疾病易感性指标(目标3)。这一创新的方法将有助于我们了解 可直接应用于疾病的END介导的口腔健康效应的机制和生物标志物 预防策略。在目标1中，我们将招募从未确定的烟草使用者和目前独家的 终端用户评估终端使用行为、口腔健康和风险因素。为了实现这一目标，我们将采用 制定了社交媒体招聘战略，以招募参与者并评估参与者的特征， 通过有针对性的问卷调查结束使用情况和口腔健康史。此外，还将检查终端的使用情况 通过对端部膨化形貌的实时监测。疾病的临床表现将通过以下方式进行评估 口腔健康检查和龈下微生物群检查。阐明以产品为基础的 结束暴露我们将使用体外气液界面模型系统来暴露原发牙龈 在AIM 2中，角质形成细胞/巨噬细胞球体到气雾剂。这些暴露情景将利用已建立的 比较毒性评估的协议，同时也纳入代表END的暴露 来自我们招募的参与者的使用情况。具体地说，这些体外实验将评估特定品牌 炎症、氧化应激、DNA损伤/修复、上皮-间充质转化和 细菌入侵。在目标3中，我们将利用分子流行病学方法来评估END的影响。 通过检查参与者的唾液、牙龈细胞和龈下菌斑来使用。这些都是显而易见的 可用于检查口腔疾病和帕金森病启动的早期指标的基质，包括 炎症、氧化应激、DNA损伤/修复、上皮-间充质转化和微生物 改装。具体地说，我们的目标是在参与者特征、终端使用和 有助于帕金森病发展的毒理学机制，可用于保护公众健康。

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.