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

项目摘要 使用电子尼古丁输送系统（ENDS）会增加患多种疾病的风险，包括 口腔的那些。具体而言，关注的是牙龈炎症的诱导和增加 牙周病是指牙周组织对细菌侵袭的易感性，最终导致牙周病（PD）的发展。如何以及 为什么使用ENDS可能造成PD风险尚不清楚，因为缺乏关于使用行为的全面数据， 暴露和疾病结果。此外，缺乏与ENDS使用相关的PD的早期指标， 这阻碍了初步诊断和疾病预防策略的发展。我们很早就假设 ENDS相关的口腔健康不良结果的指标可以通过ENDS的变化来识别和解释 偏好/使用和生物反应。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，利用专门设计的目的来评价ENDS的使用和临床表现 口腔疾病（目标1），常见的ENDS产品和疾病的分子机制（目标2），以及可翻译的 疾病易感性指标（目标3）。这种创新的方法将有助于我们了解 ENDS介导的口腔健康效应的机制和生物标志物，可直接应用于疾病 预防战略。在目标1中，我们将招募从未建立烟草使用者群体和目前的独家烟草使用者。 ENDS使用者评估ENDS使用行为、口腔健康和风险因素。为此，我们将采用 制定了社会媒体招募战略，以招募参与者并评估参与者的特征， ENDS的使用和口腔健康史通过集中的问卷调查。此外，还将检查ENDS的使用情况 通过实时监测ENDS膨化地形。将通过以下方法评估疾病的临床表现： 口腔健康检查和龈下微生物组检查。阐明基于产品的 ENDS暴露我们将利用体外气液界面模型系统暴露原发牙龈 角质形成细胞/巨噬细胞球状体与气溶胶的关系。这些暴露情景将利用既定的 比较毒性评估方案，同时纳入代表ENDS的暴露 使用我们招募的参与者。具体来说，这些体外实验将评估品牌特异性 调节炎症、氧化应激、DNA损伤/修复、上皮-间充质转化，以及 细菌入侵在目标3中，我们将利用分子流行病学方法评估ENDS的影响 通过检查参与者唾液、牙龈细胞和龈下菌斑来使用。这些代表容易 检查口腔疾病和PD开始的早期指标的可用矩阵，包括 炎症、氧化应激、DNA损伤/修复、上皮-间质转化和微生物 改变。具体来说，我们的目标是建立参与者特征，ENDS使用， 有助于PD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.