Introduction: Acute lung injury (ALI) and the more severe, acute respiratory distress syndrome (ARDS), are respiratory conditions associated with significant ICU mortality. Current published statistics for the U.S. report 74,000 deaths in 190,000 cases of ALI/ARDS and it is anticipated that as the U.S. faces the inevitability of an aging population, the annual incidence will rise. The underlying pathology of ALI/ARDS is differentiated into direct and indirect, based on precipitating factors. Direct (pneumonia, aspiration and lung trauma) accounts for 57% of total cases, while indirect lung injury, including extrapulmonary sepsis and multisystem trauma, represents 43%. However, compared with direct ALI/ARDS, the pathophysiology of indirect is much less well understood, possibly due to the involvement of multiple systemic factors. Endothelial cell (EC) dysfunction/loss of barrier function is a major component in the pathogenesis of ALI/ARDS based on the increased lung mircovascular hyperpermeability, pulmonary edema and impaired lung function observed in patients that develop ALI/ARDS. Angiopoietin-2 (Ang-2) is an EC specific growth factor believed to play a role in angiogenesis by promoting vessel destabilization, inflammation and pulmonary leakage through its interaction with the EC specific receptor tyrosine kinase, Tie2. While we have recently shown in our shock/trauma mouse model that Ang-2 may play a role in the development of extrapulmonary ALI (Ang-2 levels increase) via its mediation of neutrophil/EC interactions, it is not known to what extent trauma patients with ALI/ARDS show such a change in Ang-2 expression. To begin to address this question, plasma Ang-2 was measured in a random sampling of surgical and trauma ICU patients (n=16) and healthy human volunteers (n=3). We hypothesized that Ang-2 would be significantly elevated in patients with ALI/ARDS.

Methods: Ang-2 was measured in plasma from de-identified trauma and surgical ICU patients using a commercially available human Ang-2 ELISA kit in an IRB approved study. Corresponding de-identified patient data for ALI/ARDS (PaO2:FIO2), extra vs. intrapulmonary infection source, sepsis/SIRS and mortality was collected and compared with patient’s plasma Ang-2 level.

Results: Our findings support the hypothesis that plasma Ang-2 is elevated in trauma patients with ALI/ARDS in a fashion similar to that seen in rodents. Additionally, those patients with extrapulmonary associated SIRS/sepsis appear to have higher levels of plasma Ang-2 when compared to those with intrapulmonary/pneumonia (5887?571pg/ml vs. 3931?691pg/ml, p<0.05). In our small sample group, however, elevated plasma Ang-2 could not be correlated with mortality. These findings support not only the further investigation into the dynamics of plasma Ang-2 levels in the traumatized patient, but also the value of the mechanistic studies of Ang-2 we are carrying out in a relevant model of shock/sepsis induced ALI in mice.