UC Davis

With tobacco smoking as a leading cause of preventable morbidity and mortality worldwide, e-cigarette use has gained popularity as a “reduced-risk” nicotine delivery alternative. However, the pulmonary health impacts of switching from combustible tobacco cigarette use to e-cigarette vaping remain poorly understood. This dissertation investigates the impact of switching on the respiratory system using complementary in vivo and in vitro models, including novel methodologies, to elucidate the cellular and molecular mechanisms underlying pulmonary responses in the transition from tobacco cigarette to e-cigarette exposure. In a murine model of tobacco cigarette smoke followed by vape aerosol exposure, we found that dual exposure resulted in enhanced neutrophil recruitment to both airways and lung tissue. We report altered gene expression of several neutrophil recruitment chemokines, leukocyte adhesion molecules, oxidative stress markers, and metabolizing enzymes as a result of dual exposure. To build upon our findings in vivo, we utilized two primary cell culture models derived from the highly translational Rhesus macaque model. In proximal airway epithelial cultures, dual exposure resulted in CYP1A1 gene induction and trending decreases in acute inflammatory cytokines IL-6 and IL-8. We describe detailed methods for the novel generation of distal lung organoid cultures from both fresh and frozen Rhesus macaque lung tissue in the form of alveolospheres, primarily composed of alveolar epithelial type II cells. In this model, dual exposure did not elicit changes in cell viability, acute inflammatory responses, or oxidative stress genes. Our findings emphasize the need for continued research into the potential adverse pulmonary health impacts associated with switching from tobacco cigarette smoking to e-cigarette vaping.