ObjectiveThe primary objective of this study was to test the hypothesis that in patients intubated for acute lung injury, lower concentrations of surfactant proteins A and D in the pulmonary edema fluid and higher concentrations in the plasma are associated with more severe lung injury and worse clinical outcomes.DesignObservational study.SettingIntensive care unit patients in a tertiary university hospital and a university-affiliated city hospital.PatientsThirty-eight intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference.InterventionsUndiluted pulmonary edema fluid and plasma samples were collected within 24 hrs of endotracheal intubation in all patients.Measurements and Main ResultsThe concentrations of surfactant proteins A and D were measured in pulmonary edema fluid and in plasma. Plasma surfactant protein A, but not surfactant protein D, was higher in patients with fewer days of unassisted ventilation (p= .03) and in patients with an absence of intact alveolar fluid clearance (p= .03). In contrast, pulmonary edema fluid surfactant protein D, but not surfactant protein A, was lower in patients with worse oxygenation, as measured by the alveolar-arterial oxygen difference (p= .01) and was lower in the patients who died (2646 ng/mL) compared with those who survived (5503 ng/mL;p= .02).ConclusionsThese results demonstrate that reduced pulmonary edema fluid surfactant protein D and elevated plasma surfactant protein A concentrations at the onset of acute lung injury may be associated with more severe disease and worse clinical outcome and may serve as valuable biochemical markers of prognosis.