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