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Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients with acute lung injury.

Sapru A, Curley MA, Brady S, Matthay MA, Flori H - Intensive Care Med (2009)

Bottom Line: Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI.PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01).Higher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI.

View Article: PubMed Central - PubMed

Affiliation: Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, Box 0106, San Francisco, CA 94143, USA. anil.sapru@ucsf.edu

ABSTRACT

Purpose: 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.

Design/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.

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Related in: MedlinePlus

Boxplots of log-transformed day 1 plasma levels of plasminogen activator inhibitor-1 (PAI-1) stratified by 28-day mortality among 94 pediatric patients with acute lung injury (ALI). There was a statistically significant difference in the levels between survivors and nonsurvivors (P < 0.01)
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Fig1: Boxplots of log-transformed day 1 plasma levels of plasminogen activator inhibitor-1 (PAI-1) stratified by 28-day mortality among 94 pediatric patients with acute lung injury (ALI). There was a statistically significant difference in the levels between survivors and nonsurvivors (P < 0.01)

Mentions: A total of 14/94 (15%) patients died prior to hospital discharge. The primary diagnosis, associated multiorgan failure and attributable causes of death are listed in Table 2. PAI-1 levels were higher among nonsurvivors than among survivors. Among nonsurvivors, the median PAI-1 level was 350 ng/mL with an interquartile range from 232 to 1,083 ng/mL, whereas among the survivors the median PAI-1 level was 239 ng/mL with the interquartile range from 90 to 393 ng/mL. Due to their non-normal distribution, PAI-1 levels were log-transformed before applying parametric tests to compare the levels between survivors and nonsurvivors (Fig. 1). There was a statistically significant difference between PAI-1 levels among survivors and nonsurvivors (P < 0.01). Using multivariate logistic regression to adjust for age and the severity of illness, the odds of mortality increased by 2.0 for every log increase in the level of plasma PAI-1 (Table 3). There was no statistically significant difference in PAI-1 levels based on the primary diagnoses.Fig. 1


Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients with acute lung injury.

Sapru A, Curley MA, Brady S, Matthay MA, Flori H - Intensive Care Med (2009)

Boxplots of log-transformed day 1 plasma levels of plasminogen activator inhibitor-1 (PAI-1) stratified by 28-day mortality among 94 pediatric patients with acute lung injury (ALI). There was a statistically significant difference in the levels between survivors and nonsurvivors (P < 0.01)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2807603&req=5

Fig1: Boxplots of log-transformed day 1 plasma levels of plasminogen activator inhibitor-1 (PAI-1) stratified by 28-day mortality among 94 pediatric patients with acute lung injury (ALI). There was a statistically significant difference in the levels between survivors and nonsurvivors (P < 0.01)
Mentions: A total of 14/94 (15%) patients died prior to hospital discharge. The primary diagnosis, associated multiorgan failure and attributable causes of death are listed in Table 2. PAI-1 levels were higher among nonsurvivors than among survivors. Among nonsurvivors, the median PAI-1 level was 350 ng/mL with an interquartile range from 232 to 1,083 ng/mL, whereas among the survivors the median PAI-1 level was 239 ng/mL with the interquartile range from 90 to 393 ng/mL. Due to their non-normal distribution, PAI-1 levels were log-transformed before applying parametric tests to compare the levels between survivors and nonsurvivors (Fig. 1). There was a statistically significant difference between PAI-1 levels among survivors and nonsurvivors (P < 0.01). Using multivariate logistic regression to adjust for age and the severity of illness, the odds of mortality increased by 2.0 for every log increase in the level of plasma PAI-1 (Table 3). There was no statistically significant difference in PAI-1 levels based on the primary diagnoses.Fig. 1

Bottom Line: Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI.PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01).Higher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI.

View Article: PubMed Central - PubMed

Affiliation: Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, Box 0106, San Francisco, CA 94143, USA. anil.sapru@ucsf.edu

ABSTRACT

Purpose: 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.

Design/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.

Show MeSH
Related in: MedlinePlus