Budinger G R Scott, Chandel Navdeep S, Donnelly Helen K, Eisenbart James, Oberoi Monica, Jain Manu
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, 240 East Huron, Chicago, IL 60611, USA.
Intensive Care Med. 2005 Jan;31(1):121-8. doi: 10.1007/s00134-004-2503-2. Epub 2004 Nov 24.
Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes.
Prospective controlled study of ALI/ARDS.
Intensive care units and laboratory of a university hospital.
Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients.
Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-beta1 levels were measured by ELISA.
Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-beta1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-beta1 levels in the ARDS group compared to negative controls (-1.056 log(10)+/-0.1415 vs -1.505 log(10)+/-0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-beta1 levels were associated with more ventilator-free and ICU-free days.
Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-beta1. Activated TGF-beta1 may impact ARDS outcome independent of its effect on procollagen I activation.
诸如I型前胶原等纤维增殖标志物可预测急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）患者的死亡率。我们试图确定肺损伤患者的支气管肺泡灌洗液（BALF）中是否含有能激活I型前胶原启动子的介质，以及这种激活是否能预测重要的临床结局。
对ALI/ARDS进行前瞻性对照研究。
大学医院的重症监护病房和实验室。
急性肺损伤/ARDS、心源性水肿（阴性对照）和肺纤维化（阳性对照）患者。
在ALI/ARDS患者插管后48小时内收集支气管肺泡灌洗液。还从肺纤维化和心源性肺水肿患者中收集BALF。用人肺成纤维细胞转染I型前胶原启动子-荧光素酶构建体，并与BALF一起孵育；然后测量I型前胶原启动子活性。通过酶联免疫吸附测定法测量BALF中活性转化生长因子β1（TGF-β1）水平。
纳入29例ARDS患者、9例阴性对照和6例阳性对照。ARDS患者的BALF诱导I型前胶原启动子激活比阴性对照高41%（p<0.05），并且一种TGF-β1阻断抗体可显著降低ARDS患者的这种激活。与阴性对照相比，ARDS组中TGF-β1水平有升高趋势（-1.056 log(10)+/-0.1415对-1.505 log(10)+/-0.1425）（p<0.09）。I型前胶原启动子激活与死亡率无关；然而，较低的TGF-β1水平与更多的无呼吸机天数和无ICU天数相关。
ALI/ARDS患者的支气管肺泡灌洗液可激活I型前胶原启动子，这部分归因于TGF-β1。激活的TGF-β1可能独立于其对I型前胶原激活的作用而影响ARDS的结局。
