Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.
Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.
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DOI：
10.1136/thoraxjnl-2015-207886
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发表时间：
2016-12
期刊：
影响因子：
10
通讯作者：
Calfee CS
中科院分区：
文献类型：
--
作者：
Moazed F;Burnham EL;Vandivier RW;O'Kane CM;Shyamsundar M;Hamid U;Abbott J;Thickett DR;Matthay MA;McAuley DF;Calfee CS
香烟烟雾暴露与急性呼吸窘迫综合征（ARDS）的风险增加有关;然而，这种关系的潜在机制在很大程度上仍然未知。使用已建立的生物标志物评估吸烟者和非吸烟者在吸入和不吸入脂多糖（LPS）的情况下肺损伤和炎症的途径。我们在2个不同的健康志愿者队列中测量了吸烟者和非吸烟者的炎症和肺损伤的血浆和支气管肺泡灌洗（BAL）生物标志物，一个未受刺激（n=20），一个接受50 μg LPS吸入（n=30）。吸入LPS后，吸烟者与非吸烟者相比，通过BAL总蛋白测量的肺泡毛细血管膜通透性增加（中位数：274 vs 208 µg/mL，p = 0.04）。与不吸烟者相比，吸烟者的炎症反应加剧，BAL白细胞介素-1 β（p = 0.002）、中性粒细胞（p = 0.02）、血浆白细胞介素-8（p = 0.003）和血浆基质金属蛋白酶-8（p = 0.006）增加。吸烟者LPS后肺泡上皮损伤比非吸烟者更严重，血浆表面活性蛋白D升高（p = 0.04），BAL表面活性蛋白D降低（p = 0.02）。最后，吸烟者BAL血管内皮生长因子（VEGF）降低（p < 0.0001），可溶性VEGF受体-1升高（p = 0.0001）。香烟烟雾暴露可能通过对“二次打击”的异常反应而易患ARDS，伴随肺泡-毛细血管膜通透性增加、炎症加剧、上皮损伤增加和内皮功能障碍。LPS吸入可作为评价现有和新烟草制品的急性肺效应的有用实验模型。
Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. To assess pathways of lung injury and inflammation in smokers and nonsmokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in 2 distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 µg LPS inhalation (n=30). After LPS inhalation, cigarette smokers had increased alveolar capillary membrane permeability as measured by BAL total protein, compared to nonsmokers (median: 274 vs 208 µg/mL, p = 0.04). Smokers had exaggerated inflammation compared to nonsmokers, with increased BAL interleukin-1β (p = 0.002), neutrophils (p = 0.02), plasma interleukin-8 (p = 0.003), and plasma matrix metalloproteinase-8 (p = 0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p = 0.04) and decreased BAL (p = 0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p < 0.0001) with increased soluble VEGF receptor-1 (p = 0.0001). Cigarette smoke exposure may predispose to ARDS through an abnormal response to a “second hit,” with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products.