Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients with acute lung injury.
OBJECTIVE
Deposition of fibrin in the alveolar space is a hallmark of acute lung injury (ALI). Plasminogen activator inhibitor-1 (PAI-1) is an antifibrinolytic agent that is activated during inflammation. Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI. This relationship has not been examined in children. The objective of this study was to test whether increased plasma PAI-1 levels are associated with worse clinical outcomes in pediatric patients with ALI.


METHODS
We measured plasma PAI-1 levels on the first day of ALI among 94 pediatric patients enrolled in two separate prospective, multicenter investigations and followed them for clinical outcomes. All patients met American European Consensus Conference criteria for ALI.


RESULTS
A total of 94 patients were included. The median age was 3.2 years (range 16 days-18 years), the PaO(2)/F(i)O(2) was 141 +/- 72 (mean +/- SD), and overall mortality was 14/94 (15%). PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01). The adjusted odds of mortality doubled for every log increase in the level of plasma PAI-1 after adjustment for age and severity of illness.


CONCLUSIONS
Higher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI. These findings suggest that impaired fibrinolysis may play a role in the pathogenesis of ALI in pediatric patients and suggest that PAI-1 may serve as a useful biomarker of prognosis in patients with ALI.
Sapru
Anil
A
Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, Box 0106, San Francisco, CA 94143, USA. anil.sapru@ucsf.edu
Curley
Martha A Q
MA
Brady
Sandra
S
Matthay
Michael A
MA
Flori
Heidi
H
D055371:Acute Lung Injury / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate; D017211:Treatment Failure
D017395:Plasminogen Activator Inhibitor 1; D005337:Fibrin