Haswell Linsey E, Smart David, Jaunky Tomasz, Baxter Andrew, Santopietro Simone, Meredith Stuart, Camacho Oscar M, Breheny Damien, Thorne David, Gaca Marianna D
British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK.
British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK.
Toxicol Lett. 2021 Sep 1;347:45-57. doi: 10.1016/j.toxlet.2021.04.012. Epub 2021 Apr 21.
Goblet cell hyperplasia and overproduction of airway mucin are characteristic features of the lung epithelium of smokers and COPD patients. Tobacco heating products (THPs) are a potentially less risky alternative to combustible cigarettes, and through continued use solus THPs may reduce smoking-related disease risk. Using the MucilAir™ in vitro lung model, a 6-week feasibility study was conducted investigating the effect of repeated cigarette smoke (1R6F), THP aerosol and air exposure. Tissues were exposed to nicotine-matched whole aerosol doses 3 times/week. Endpoints assessed were dosimetry, tight-junction integrity, cilia beat frequency (CBF) and active area (AA), cytokine secretion and airway mucin MUC5AC expression. Comparison of incubator and air exposed controls indicated exposures did not have a significant effect on the transepithelial electrical resistance (TEER), CBF and AA of the tissues. Cytokine secretion indicated clear differences in secretion patterns in response to 1R6F and THP exposure. 1R6F exposure resulted in a significant decrease in the TEER and AA (p=0.000 and p=0.000, respectively), and an increase in MUC5AC positive cells (p=0.002). Repeated THP exposure did not result in a significant change in MUC5AC positive cells. This study demonstrates repeated cigarette smoke whole aerosol exposure can induce these morphological changes in vitro.
杯状细胞增生和气道黏蛋白过度产生是吸烟者和慢性阻塞性肺疾病（COPD）患者肺上皮的特征性表现。烟草加热产品（THP）是一种潜在风险较低的可燃香烟替代品，持续单独使用THP可能会降低吸烟相关疾病的风险。使用MucilAir™体外肺模型，进行了一项为期6周的可行性研究，调查反复暴露于香烟烟雾（1R6F）、THP气溶胶和空气的影响。组织每周接受3次与尼古丁匹配的全气溶胶剂量暴露。评估的终点包括剂量测定、紧密连接完整性、纤毛摆动频率（CBF）和活性面积（AA）、细胞因子分泌以及气道黏蛋白MUC5AC表达。培养箱暴露组与空气暴露对照组的比较表明，暴露对组织的跨上皮电阻（TEER）、CBF和AA没有显著影响。细胞因子分泌表明，对1R6F和THP暴露的分泌模式存在明显差异。1R6F暴露导致TEER和AA显著降低（分别为p = 0.000和p = 0.000），以及MUC5AC阳性细胞增加（p = 0.002）。反复THP暴露未导致MUC5AC阳性细胞发生显著变化。这项研究表明，反复暴露于香烟烟雾全气溶胶可在体外诱导这些形态学变化。
