ENDS aerosol particle deposition, in utero exposures and children's respiratory health effects (ENDURE) - Summary This project leverages the unique resources of three different institutions to assess offspring respiratory health impacts caused by in utero exposures to Electronic Nicotine Delivery Systems (ENDS) products. ENDS are a diverse class of products such as electronic cigarettes (e-cigs), vaporizers, vape pens, and pods. In this study, we focus on e-cigs as they are the most adopted ENDS devices in recent years. Over 9 million American adults, including women of childbearing age, are current e-cig users. Little, however, is known about the effects of fetal exposures to e- cig aerosols on lung development in the offspring. We propose the “ENDS aerosol particle deposition, in utero exposures and children’s respiratory health effects (ENDURE)” consortium to investigate ENDS aerosol particle deposition in the lungs of mothers who used ENDS products (vaping) or were exposed to household ENDS aerosols and examine the resulting effects on the offspring’s respiratory health. The ViCTER mechanism provides an exceptional opportunity to enhance cross-disciplinary and translational research to study in utero exposure to tobacco products from maternal or environmental sources and its effects on the trajectory of lung health. We hypothesize that constituents of ENDS aerosols with the highest maternal lung deposition will result in the dysregulation of lung inflammatory genes in the offspring, particularly IL-10, leading to asthma susceptibility. To test our hypothesis, we will investigate the deposited dose of harmful substances from ENDS aerosols in human airways and estimate associated health risks (Aim 1). This aim will provide critical information on the deposited dose of ENDS-related harmful substances in the alveolar region through active and passive vaping and associated health risks. Informed by preliminary studies, we will use ENDS products whose aerosols significantly deposit in the lower airways (Vuse and NJOY) and assess the role of Il-10 gene regulation on pulmonary function, inflammation, and lung epigenome in utero ENDS-exposed mouse offspring (Aim 2). For this aim, we will use wild-type (WT) and Il-10 knockout (KO) mouse models with and without house-dust mite (HDM) treatment, to investigate the role of Il-10 in adversely altering airway resistance, inflammation, and the lung epigenome of in utero ENDS exposed offspring in early life. Finally, we will determine the impact of parental ENDS use on infant recurrent wheeze and asthma-like symptoms, and buccal DNA methylation in a cohort of children from Indiana (Aim 3). This project will help bridge the knowledge gap of which ENDS aerosols enter the fetal-maternal circulation and trigger dysregulation of genes associated with the offspring’s lung function and lung development.
