吸烟是吸烟者严重疾病的原因,包括慢性呼吸道疾病。本研究旨在评估电子蒸汽产品(EVP,myblu™)与肯塔基州参考香烟(3R4F)相比,并评估与慢性呼吸系统疾病相关的终点。终点包括:细胞毒性,屏障完整性(TEER),纤毛功能,免疫组织化学,和促炎标志物。为了更紧密地代表用户暴露场景,我们采用了人气道上皮的体外3D器官型模型(MucilAir™,Epithelix)用于呼吸评估。该模型反复暴露于EVP的整个气溶胶中,或整个3R4F烟雾,在气液界面(ALI),持续4周至30、60或90次,每周3次暴露。3R4F烟雾产生使用ISO20778:2018制度和EVP气溶胶使用ISO20768:2018vaping制度。暴露于未稀释的整个EVP气雾剂并没有触发促炎介质水平的任何显著变化,纤毛跳动功能,与空气对照相比,屏障完整性和细胞毒性。相比之下,暴露于稀释(1:17)的整个香烟烟雾会导致上述所有终点发生重大变化。据我们所知,这是第一项在ALI中评估重复的整个香烟烟雾和整个EVP气溶胶暴露于3D肺部模型的影响的研究。我们的结果增加了越来越多的科学文献,支持EVP相对于可燃香烟的THR潜力以及3D肺模型在人类相关产品风险评估中的适用性。
Smoking is a cause of serious diseases in smokers including chronic respiratory diseases. This study aimed to evaluate the tobacco harm reduction (THR) potential of an electronic vapor product (EVP, myblu™) compared to a Kentucky Reference Cigarette (3R4F), and assessed endpoints related to chronic respiratory diseases. Endpoints included: cytotoxicity, barrier integrity (TEER), cilia function, immunohistochemistry, and pro-inflammatory markers. In order to more closely represent the user exposure scenario, we have employed the in vitro 3D organotypic model of human airway epithelium (MucilAir™, Epithelix) for respiratory assessment. The model was repeatedly exposed to either whole aerosol of the EVP, or whole 3R4F smoke, at the air liquid interface (ALI), for 4 weeks to either 30, 60 or 90 puffs on 3-exposure-per-week basis. 3R4F smoke generation used the ISO 20778:2018 regime and EVP aerosol used the ISO 20768:2018 vaping regime. Exposure to undiluted whole EVP aerosol did not trigger any significant changes in the level of pro-inflammatory mediators, cilia beating function, barrier integrity and cytotoxicity when compared with air controls. In contrast, exposure to diluted (1:17) whole cigarette smoke caused significant changes to all the endpoints mentioned above. To our knowledge, this is the first study evaluating the effects of repeated whole cigarette smoke and whole EVP aerosol exposure to a 3D lung model at the ALI. Our results add to the growing body of scientific literature supporting the THR potential of EVPs relative to combustible cigarettes and the applicability of the 3D lung models in human-relevant product risk assessments.