Abstract:
OBJECTIVE: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. DESIGN:Prospective controlled study of ALI/ARDS. SETTING:Intensive care units and laboratory of a university hospital. PATIENTS AND PARTICIPANTS:Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients. INTERVENTIONS: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. RESULTS: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. CONCLUSIONS: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.
journal_name
Intensive Care Medjournal_title
Intensive care medicineauthors
Budinger GR,Chandel NS,Donnelly HK,Eisenbart J,Oberoi M,Jain Mdoi
10.1007/s00134-004-2503-2keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
121-8issue
1eissn
0342-4642issn
1432-1238journal_volume
31pub_type
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pub_type: 杂志文章,meta分析,实务指引,评审
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pub_type: 临床试验,杂志文章
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更新日期:2011-09-01 00:00:00
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journal_title:Intensive care medicine
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更新日期:2003-06-01 00:00:00
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journal_title:Intensive care medicine
pub_type: 临床试验,杂志文章
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更新日期:1998-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:1990-01-01 00:00:00
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