Project Summary/Abstract Respiratory disease carries a significant worldwide burden of morbidity and mortality. Currently it is well understood that tobacco smoking is a major cause of pulmonary/lung inflammation, which can progress onto pulmonary disease. However, significantly less is known about the effects of e-cigarettes (E-cigs) on the lung. Our study will assess whether vaped e-liquid (the actual product consumed/”vaped” by the E-cig user) exposure renders the lung more susceptible to pulmonary distress/disease using an ex vivo human bronchial epithelial cells (HBEC) model followed by our developed in vivo (C57BL/6J) lung injury model. We will also investigate the immune cell populations involved in any resultant lung injury. Hence, the goals of the current proposal are to model lung cell immune dysfunction using HBEC (Aim 1). To assess immune cell involvement/recruitment and lung pathology post-vape exposure using our in vivo model (Aim 2). We will then determine whether pre-exposure to e-liquid aerosol renders C57BL/6J mice more susceptible to pulmonary distress/disease using Klebsiella pneumoniae as a pathogen challenge model (Aim 3). Completion of the proposed Aims will ultimately shed light on the possible health implications of new and emerging tobacco products (such as E-cigs) and provide mechanistic detail on the possible initiation and progression of lung disease in E-cig users.