Longitudinal Electronic Cigarette Exposures Impair Respiratory Function and Structure in the Female Apoe/- Mouse.

Abstract

Introduction: Electronic cigarette (EC) usage amongst naïve users in the U.S. has been rising for the last decade. The effects of inhaling e-cig aerosols on respiratory health are not fully understood. The goal of this study was to longitudinally track changes in inflammation alongside abnormalities in lung structure and function following 8, 16, and 24 weeks of EC exposure.

Methods: Female Apoe-/- mice were nose-only exposed to either EC aerosols (JUULTM, 3% nicotine, tobacco flavored, 2 puffs/min, particle concentration of 300 mg/m3) or room air for 95 mins, 5 days/week, for 8, 16, or 24 weeks.

Results: Cytokines, measured from bronchioalveolar lavage fluid supernatant, were elevated at either 16 weeks of exposure (IL-4, IL-10, INF-α) or at the 16- and 24- week time point (IL-6, IL-17). Newtonian resistance, coefficient of respiratory elastance and resistances were larger in EC exposed, compared to air control mice, only at the 16-week time point. Mice at the 8-week and 16-week time point positively responded to methacholine, indicating hyper-reactive airways. Linear mean intercept (LM) was smaller in EC exposed mice, compared to controls, at the 8-week time point and larger at the 24-week time point. No change in LM was observed at the 16-week time point.

Conclusion: It is evident that EC aerosol inhalation caused pathological changes in the function respiratory system after 16 weeks of exposure. Evolution of structural changes including larger LM and increases in tissue thickness compensated each other, resulting in a return to functional normality at the 24-week time point.

Implications: Electronic cigarette use is on the rise, making it necessary to understand the long-term health implications of their use. This study provides the first assessment of structural and functional changes in the lung following prolonged exposure to electronic cigarettes. We find that 16 weeks, but not 8 weeks, of exposure leads to increases in resistances and tissue stiffness, due to an increase in cytoplasm and thickened alveolar septa. At 24 weeks, functional changes appear to reverse while structural abnormalities worsened. This study suggests that electronic cigarettes pose a significant health risk and regulation of them should be considered.