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香烟烟雾制剂而非电子尼古丁输送系统制剂可在 3D 肺部重复剂量模型中诱导肺部疾病特征。

Cigarette smoke preparations, not electronic nicotine delivery system preparations, induce features of lung disease in a 3D lung repeat-dose model.

机构信息

Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio.

RAI Services Company, Winston-Salem, North Carolina.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2021 Feb 1;320(2):L276-L287. doi: 10.1152/ajplung.00452.2020. Epub 2020 Nov 18.

DOI:10.1152/ajplung.00452.2020
PMID:33207918
Abstract

Cigarette smoking is a risk factor for several lung diseases, including chronic obstructive pulmonary disease, cardiovascular disease, and lung cancer. The potential health effects of chronic use of electronic nicotine delivery systems (ENDS) is unclear. This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in a repeat-dose exposure to evaluate and compare the effect of combustible cigarette and ENDS preparations. We show that 1-h daily exposure of NHBE cultures over a 10-day period to combustible cigarette whole smoke-conditioned media (WS-CM) increased expression of oxidative stress markers, cell proliferation, airway remodeling, and cellular transformation markers and decreased mucociliary function including ion channel function and airway surface liquid. Conversely, aerosol conditioned media (ACM) from ENDS with similar nicotine concentration (equivalent-nicotine units) as WS-CM and nicotine alone had no effect on those parameters. In conclusion, primary NHBE cultures in a repeat-dose exposure system represent a good model to assess the features of lung disease. This study also reveals that cigarette and ENDS preparations differentially elicit several key endpoints, some of which are potential biomarkers for lung cancer or chronic obstructive pulmonary disease (COPD).

摘要

吸烟是多种肺部疾病的危险因素,包括慢性阻塞性肺疾病、心血管疾病和肺癌。长期使用电子尼古丁输送系统(ENDS)的潜在健康影响尚不清楚。本研究利用完全分化的原代正常人类支气管上皮(NHBE)培养物进行重复剂量暴露,以评估和比较可燃香烟和 ENDS 制剂的影响。我们发现,10 天内每天 1 小时暴露于可燃香烟全烟雾调节培养基(WS-CM)中会增加氧化应激标志物、细胞增殖、气道重塑和细胞转化标志物的表达,并降低纤毛功能,包括离子通道功能和气道表面液体。相反,具有与 WS-CM 相似尼古丁浓度(等效尼古丁单位)和尼古丁的 ENDS 气溶胶调节培养基(ACM)对这些参数没有影响。总之,重复剂量暴露系统中的原代 NHBE 培养物是评估肺部疾病特征的良好模型。本研究还揭示了香烟和 ENDS 制剂在多个关键终点上存在差异,其中一些可能是肺癌或慢性阻塞性肺疾病(COPD)的潜在生物标志物。

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