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Translational Studies on Electronic Cigarette-Derived Oxidants and Their Long-term Pulmonary Effects

Principal Investigator: John P. Richie

Funding Mechanism: National Institutes of Health - Grant

ID number: 1R01HL152436-01

Award Date: 6/12/2020

Institution: Pennsylvania State University

Oxidative stress and damage resulting from exposure to oxidants such as free radicals and aldehydes play critical roles in the development and progression of most tobacco-caused diseases, including chronic obstructive pulmonary disease (COPD). The goal of this project is to evaluate toxicities caused by exposure to e-cigarette-derived free radicals and aldehydes and their role in the development of COPD. Study aims are: (1) to investigate the long-term pulmonary effects of e-cigarette exposure from products delivering high vs. low oxidant levels in a COPD mouse model; (2) to determine the impact of switching from cigarettes to e-cigarettes; and (3) to conduct a pilot single arm trial to determine the impact of switching from cigarettes to e-cigarettes on disease-related clinical symptoms and biomarkers of harm in smokers with preexisting COPD. To address Aim 1, researchers will conduct 3-month exposure studies to compare high vs. low oxidant e-cigarette products (Mod vs. Juul, respectively). To address Aim 2, researchers will pre-expose mice for 1.5 months to cigarette smoke prior to switching them to filtered air, e-cigarette aerosol, or 50/50 e-cigarette aerosol/cigarette smoke for the remaining 1.5 months to mimic the harm from “real world” e-cigarette use patterns in smokers (smoking cessation, switching to e-cigarettes, and dual use). The primary outcomes of Aims 1 and 2 will be development of a COPD phenotype (including changes in lung function and histology) and assessment of systemic and lung-specific biomarkers of oxidative stress/damage and inflammation. To address Aim 3, researchers will provide e-cigarettes to 30 smokers (ages 18-65) with mild/moderate COPD and ask them to use these products exclusively for a year; e-cigarette and cigarette usage will be monitored along with assessments of COPD-related clinical symptoms, spirometric lung function, and biomarkers of oxidative stress and inflammation. These studies will provide new information about the toxicological impact of oxidant exposure from specific e-cigarette devices. 

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