Alveolar plasminogen activator inhibitor-1 predicts ARDS in aspiration pneumonitis

Objective: To test the hypothesis that alveolar plasminogen activator inhibitor-1 (PAI-1) can identify patients with witnessed aspiration at risk for progression to acute respiratory distress syndrome (ARDS). Design: Prospective observational study. Settings: Medical intensive care unit in a tertiary care center. Patients: Fifty-one patients with witnessed aspiration who had a PaO2/FIO2 < 300 for a period no less than 4 h from admission. Interventions: Alveolar fluid sampling was performed within 8 h of intubation via luminal suction of the distal airways using a 13-Fr catheter. Plasma levels were collected simultaneously by venipuncture. Measurements and results: Alveolar PAI-1 antigen levels were more than five times higher in those who progressed to ARDS than in those with uncomplicated aspiration pneumonitis (2687 +/- 1498 ng/ml vs. 587 +/- 535 ng/ml, respectively; p < 0.001), while plasma levels of PAI-1 antigen were not significantly different between the two groups. The measured activity of PAI-1 antigen paralleled the levels observed in both media. A cut-off level of alveolar PAI-1 > 1518 ng/ml was found to be 82.4% (56.6%-96.0%) sensitive and 97.1% (84.6%-99.5%) specific in predicting progression to ARDS. There was also a significant inverse relationship between elevation of PAI-1 antigen levels and the degree of lung injury as assessed by the days of unassisted ventilation (r(2) =0.37; p < 0.001). Conclusions: Elevation of alveolar PAI-1 antigen levels postaspiration is the consequence of local rather than systemic activation of the fibrinolytic system. Measurement of alveolar PAI-1 antigen levels can be a useful clinical marker in predicting progression to ARDS after gastric aspiration.