Garcia-Arcos Itsaso, Geraghty Patrick, Baumlin Nathalie, Campos Michael, Dabo Abdoulaye Jules, Jundi Bakr, Cummins Neville, Eden Edward, Grosche Astrid, Salathe Matthias, Foronjy Robert
Division of Pulmonary and Critical Care Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA.
Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
Thorax. 2016 Dec;71(12):1119-1129. doi: 10.1136/thoraxjnl-2015-208039. Epub 2016 Aug 24.
The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells.
Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot.
Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion.
Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use.
电子烟的使用正在迅速增加,但其对肺部健康的影响尚未明确。研究电子烟使用对肺部健康潜在长期影响的临床研究需要数十年时间。为填补这一知识空白,本研究调查了暴露于雾化的不含尼古丁和含尼古丁的电子烟液对小鼠肺部和正常人呼吸道上皮细胞的影响。
小鼠每天暴露于雾化的磷酸盐缓冲盐水、不含尼古丁或含尼古丁的电子烟溶液1小时,持续4个月。使用Vitrocell烟雾暴露机器人将在气液界面培养的正常人支气管上皮(NHBE)细胞暴露于电子烟蒸气或尼古丁溶液中。
吸入含尼古丁的电子烟会增加气道高反应性、远端气腔扩大、粘蛋白产生、细胞因子和蛋白酶表达。暴露于不含尼古丁的电子烟对这些肺部参数没有影响。暴露于含尼古丁的电子烟蒸气的NHBE细胞显示纤毛摆动频率受损、气道表面液体积、囊性纤维化跨膜调节因子和ATP刺激的钾离子电导降低,以及FOXJ1和KCNMA1表达减少。NHBE细胞暴露于尼古丁5天会增加白细胞介素(IL)-6和IL-8的分泌。
暴露于吸入的含尼古丁的电子烟液会引发通常与慢性阻塞性肺疾病(COPD)发展相关的效应,包括细胞因子表达、气道高反应性和肺组织破坏。这些效应在小鼠肺部和人类气道细胞中均依赖于尼古丁,表明吸入的尼古丁除了具有成瘾性外,还会导致气道和肺部疾病。因此,这些发现突出了电子烟使用过程中吸入尼古丁的潜在危险。