Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Appl Toxicol. 2023 May;43(5):680-693. doi: 10.1002/jat.4415. Epub 2022 Nov 30.
E-cigarette, or vaping product use-associated lung injury (EVALI), is a severe respiratory disorder that caused a sudden outbreak of hospitalized young people in 2019. Using cannabis oil containing vaping products, including vitamin E acetate contaminants, was found to be strongly associated with EVALI. However, the underlying tissue impacts of the condition are still largely unknown. Here, we focused on the vehicle cannabinoid oil (CBD oil) and contaminant vitamin E acetate (VEA) effects on airway epithelial cells. Primary human bronchial epithelial (HBE) cultures were exposed to e-liquid aerosols that contained CBD oil and VEA in combination or the common e-liquid components PG/VG with and without nicotine. Cell viability analysis indicated dramatically increased cell death counts after 3 days of CBD exposure, and this effect was even higher after CBD + VEA exposure. Microscopic examination of the cultures revealed cannabinoid and VEA depositions on the epithelial surfaces and cannabinoid accumulation in exposed cells, followed by cell death. These observations were supported by proteomic analysis of the cell secretions that exhibited increases in known markers of airway epithelial toxicity, such as xenobiotic enzymes, factors related to oxidative stress response, and cell death indicators. Overall, our study provides insights into the association between cannabinoid oil and vitamin E acetate vaping and lung injury. Collectively, our results suggest that the adherent accumulation of CBD oil on airway surfaces and the cellular uptake of both CBD oil- and VEA-containing condensates cause elevated metabolic stress, leading to increased cell death rates in human airway epithelial cultures.
电子烟或蒸气产品相关肺损伤（EVALI）是一种严重的呼吸系统疾病，导致 2019 年年轻人住院的突然爆发。使用含有蒸气产品的大麻油，包括维生素 E 醋酸盐污染物，与 EVALI 强烈相关。然而，这种疾病的潜在组织影响在很大程度上仍不清楚。在这里，我们专注于车辆大麻素油（CBD 油）和污染物维生素 E 醋酸盐（VEA）对气道上皮细胞的影响。原代人支气管上皮（HBE）培养物暴露于含有 CBD 油和 VEA 的电子烟液气溶胶中，或含有尼古丁的常见电子烟液成分 PG/VG。细胞活力分析表明，CBD 暴露 3 天后细胞死亡计数明显增加，而 CBD+VEA 暴露后这种效果更高。培养物的显微镜检查显示，大麻素和 VEA 沉积在上皮表面，大麻素在暴露的细胞中积累，随后发生细胞死亡。这些观察结果得到了细胞分泌物的蛋白质组学分析的支持，该分析显示了已知的气道上皮毒性标志物的增加，如异生物质酶、与氧化应激反应相关的因子和细胞死亡指标。总的来说，我们的研究提供了对大麻素油和维生素 E 醋酸盐蒸气与肺损伤之间关联的深入了解。总的来说，我们的结果表明 CBD 油在气道表面的附着积累以及含有 CBD 油和 VEA 的冷凝物的细胞摄取会导致代谢应激增加，从而导致人气道上皮培养物中的细胞死亡率增加。
