Complement activation in patients at risk of developing the adult respiratory distress syndrome

In this prospective study of 50 patients, 36 of whom developed the adult respiratory distress syndrome (ARDS), early and intense complement activation was demonstrated. These patients were at risk of the ARDS because of multiple injuries, major abdominal surgery, acute pancreatitis, severe burns, or disseminated intravascular coagulation. Abnormal C3 consumption (as measured by the C3d/C3 ratio) and elevated plasma C5a-like activity (as measured by a leukocyte aggregation assay) were associated with, respectively, 84 and 86% of cases of ARDS. Both tests were more sensitive indicators of complement consumption than were assays of total hemolytic complement activity (CH50) or total C3. The C3d/C3 ratio showed a close, inverse correlation with CH50 in 47 healthy subjects, and was increased in 12 control patients after minor surgery. The C5a-like activity was found only in patients at risk of ARDS; it was highly associated with clinical conditions that predispose to the ARDS, but it cannot be considered as a real predictor of ARDS occurrence in these patients. Sequential samples from both sides of the pulmonary circulation showed initial pulmonary clearance followed by the release of C5a-like activity. No simultaneous changes in C3 levels were found, suggesting the possible presence of modulating factors. These observations suggest that other factors (e.g., hypoxia and metabolic cascades) may influence the development of ARDS.