Project 3 - Lung Health and Inflammation

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ABSTRACT – PROJECT 3: Lung Health and Inflammation Research has shown that adolescent cigarette smoking alters lung development, adversely affects respiratory health, and contributes to chronic low-grade, systemic inflammation linked with the development of vascular disease and cancer. However, the effects of vaping have not been fully evaluated. Rather than waiting decades to fully assess the risk of vaping on the development of disease, we propose to characterize early respiratory, physiological, and molecular effects of vaping during adolescence. Given the increasing number of adolescents who vape frequently (20+ days a month), a better understanding of the health consequences of vaping is critical to inform public health communication efforts. To address the gaps in knowledge of the potential harms of vaping, the Multidisciplinary Assessment of Risks of Vaping in Early Life (MARVEL) Project 3 will test the hypothesis that vaping impairs respiratory health as early as adolescence, and that vaping results in overlapping molecular signatures with cigarette smoke exposure and smoking-related disease pathogenesis. Specifically, we will: 1) Characterize the effects of vaping on respiratory health in adolescence; 2) Identify molecular alterations in airways associated with vaping and respiratory health outcomes; and 3) Characterize oxidative stress and systemic inflammatory alterations associated with vaping. To detect early respiratory, physiological, and molecular effects of vaping during adolescence, we will leverage comprehensive phenotypic characterization including bronchitic symptoms of over 4000 high school students from the Online Survey, and repeated measures of lung function (St. George’s Respiratory Questionnaire and spirometry) and collection of biospecimens (nasal epithelial cells and blood) from 360 high school students, at two lab visits 18 months apart. Nasal epithelial cells are robust surrogates for lower airway bronchial epithelial cells, and will be used to examine the effects of vaping on the epigenome and transcriptome. Peripheral blood will be used to examine the effects of vaping on systemic inflammation. Dose-dependency will be assessed by detailed self- report, biomarkers (saliva cotinine, TNE, CEMA) and product characterization. Knowledge gained from Project 3 will inform the development of health communications in Project 4 relevant to the early respiratory and systemic inflammatory effects of vaping during adolescence.