After more than a decade of electronic cigarette (E-cig) use in the U.S., uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk. As all E-cigs use propylene glycol and vegetable glycerin (PG:VG) and generate abundant saturated aldehydes, mice were exposed by inhalation to either PG:VG-derived aerosol, formaldehyde (FA), acetaldehyde (AA), or filtered air. Biomarkers of exposure and cardiopulmonary injury were monitored by mass spectrometry (urine metabolites); radiotelemetry (respiratory reflexes); isometric myography (aorta); and, flow cytometry (blood markers). Acute PG:VG exposure significantly affected multiple biomarkers including pulmonary reflex (decreased respiratory rate, -50%); endothelium-dependent relaxation (-61.8±4.2%); decreased WBC (-47±7%); and, increased RBC (+6±1%) and hemoglobin (+4±1%) vs air control group. Notably, FA exposure recapitulated the prominent effects of PG:VG aerosol on pulmonary irritant reflex and endothelial dysfunction, whereas AA exposure did not. To attempt to link PG:VG exposure with FA or AA exposure, urinary formate and acetate levels were measured by GC-MS. Although neither FA nor AA exposure altered excretion of their primary metabolite, formate or acetate, respectively, compared with air-exposed controls, PG:VG aerosol exposure significantly increased post-exposure urinary acetate but not formate. These data suggest that E-cig use may increase cardiopulmonary disease risk independent of the presence of nicotine and/or flavorings. This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA.

中文翻译：

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电子烟溶剂、肺部刺激和内皮功能障碍：乙醛和甲醛的作用


在美国使用电子烟 (E-cig) 十多年后，电子烟的使用和长期心肺疾病风险仍然存在不确定性。由于所有电子烟都使用丙二醇和植物甘油 (PG:VG) 并产生丰富的饱和醛，因此小鼠通过吸入 PG:VG 衍生的气溶胶、甲醛 (FA)、乙醛 (AA) 或过滤空气而暴露。通过质谱法（尿液代谢物）监测暴露和心肺损伤的生物标志物；无线电遥测（呼吸反射）；等长肌造影（主动脉）；以及流式细胞术（血液标记物）。急性 PG:VG 暴露显着影响多种生物标志物，包括肺反射（呼吸频率降低，-50%）；内皮依赖性舒张（-61.8±4.2%）；白细胞减少（-47±7%）；并且，与空气对照组相比，红细胞 (+6±1%) 和血红蛋白 (+4±1%) 增加。值得注意的是，FA 暴露再现了 PG:VG 气雾剂对肺部刺激反射和内皮功能障碍的显着影响，而 AA 暴露则不然。为了尝试将 PG:VG 暴露与 FA 或 AA 暴露联系起来，通过 GC-MS 测量了尿液中甲酸和乙酸盐的水平。尽管与空气暴露对照相比，FA 和 AA 暴露均未分别改变其主要代谢物（甲酸盐或乙酸盐）的排泄，但 PG:VG 气溶胶暴露显着增加暴露后尿乙酸盐，但不增加甲酸盐。这些数据表明，使用电子烟可能会增加心肺疾病的风险，而与尼古丁和/或调味剂的存在无关。这项研究表明，烟草制品气溶胶中的 FA 水平应调节至不会诱发心肺伤害生物标志物的水平。仍然需要吸入 FA 和 AA 暴露的可靠生物标志物。