Lee Keu Sung, Choi Young Hwa, Kim Young Sun, Baik Seung Hee, Oh Yoon Jung, Sheen Seung Soo, Park Joo Hun, Hwang Sung Chul, Park Kwang Joo
Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
Respir Med. 2008 Mar;102(3):464-9. doi: 10.1016/j.rmed.2007.10.001. Epub 2007 Nov 7.
Apoptosis is thought to play an important role in the development of acute respiratory distress syndrome (ARDS). We evaluated the bronchoalveolar lavage (BAL) fluid from ARDS patients focusing on apoptosis.
The study enrolled 31 ARDS patients and 20 healthy controls. BAL fluid levels of caspase-cleaved cytokeratin-18 (CK-18) and soluble mediators such as interleukin-8 (IL-8), soluble Fas (sFas), soluble Fas ligand (sFasL), growth-related oncogene-alpha (GRO-alpha), granulocyte colony-stimulating factor (G-CSF), and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) were measured using enzyme-linked immunosorbent assay (ELISA).
The BAL fluid caspase-cleaved CK-18 levels in ARDS patients were higher than those in controls, reflecting increased epithelial apoptosis, and were correlated with lung injury scores (rs=0.49). The BAL fluid levels of all mediators were significantly higher in ARDS patients than in controls. In ARDS patients, the BAL fluid IL-8 level was positively correlated with the levels of sFas (rs=0.57), GRO-alpha (rs=0.47), and TRAIL (rs=0.45). The BAL fluid IL-8 (rs=0.61), sFas (rs=0.57), G-CSF (rs=0.44), and TRAIL (rs=0.33) levels were correlated with the BAL fluid neutrophil count. The G-CSF levels were significantly higher in non-surviving than in surviving ARDS patients [median 183.4 pg/mL (interquartile range 76.7-315.9) vs. 63.8 pg/mL (36.2-137.2); p<0.05]. The sFas levels were positively correlated with the PaO2/FiO2 ratio (rs=0.40), and the TRAIL levels were negatively correlated with the multiple organ dysfunction scores (rs=-0.37).
Among the mediators in BAL fluid from ARDS patients, G-CSF had the most significant prognostic implications, and the sFas and TRAIL levels were correlated with clinical severity.
细胞凋亡被认为在急性呼吸窘迫综合征(ARDS)的发展中起重要作用。我们评估了ARDS患者的支气管肺泡灌洗(BAL)液,重点关注细胞凋亡。
该研究纳入了31例ARDS患者和20例健康对照。使用酶联免疫吸附测定(ELISA)测量BAL液中半胱天冬酶切割的细胞角蛋白-18(CK-18)以及白细胞介素-8(IL-8)、可溶性Fas(sFas)、可溶性Fas配体(sFasL)、生长相关癌基因-α(GRO-α)、粒细胞集落刺激因子(G-CSF)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)等可溶性介质的水平。
ARDS患者BAL液中半胱天冬酶切割的CK-18水平高于对照组,反映上皮细胞凋亡增加,且与肺损伤评分相关(rs = 0.49)。ARDS患者所有介质的BAL液水平均显著高于对照组。在ARDS患者中,BAL液IL-8水平与sFas(rs = 0.57)、GRO-α(rs = 0.47)和TRAIL(rs = 0.45)水平呈正相关。BAL液IL-8(rs = 0.61)、sFas(rs = 0.57)、G-CSF(rs = 0.44)和TRAIL(rs = 0.33)水平与BAL液中性粒细胞计数相关。非存活ARDS患者的G-CSF水平显著高于存活患者[中位数183.4 pg/mL(四分位间距76.7 - 315.9)对63.8 pg/mL(36.2 - 137.2);p < 0.05]。sFas水平与PaO2/FiO2比值呈正相关(rs = 0.40),TRAIL水平与多器官功能障碍评分呈负相关(rs = -0.37)。
在ARDS患者的BAL液介质中,G-CSF具有最显著的预后意义,sFas和TRAIL水平与临床严重程度相关。