Pulmonary complement depositions in autopsy of critically ill patients have no relation with ARDS

Abstract

Background: The complement system has frequently been suggested to play a role in the pathophysiology of acute respiratory distress syndrome (ARDS). The current study explored the association between pulmonary depositions of a complement activation product and the clinical diagnosis of ARDS. Methods: Lung tissue material from autopsied critically ill patients who died whilst on invasively mechanical ventilation was collected and stained for complement C3d. The diagnosis of ARDS was by the Berlin Definition. Lung injury scores (LIS) and driving pressures were calculated, 48 and 24 h prior to death. A pathologist who remained blinded for the clinical data scored the extent of C3d depositions, using a C3d deposition score (a minimum and maximum score of 0 and 24), and of diffuse alveolar damage (DAD). The primary analysis focused on the association between the C3d deposition score and the clinical diagnosis of ARDS. Secondary analyses focused on associations between the C3d deposition score and the presence of diffuse alveolar damage (DAD) in histopathology, and LIS and driving pressures in the last 2 days before death. Results: Of 36 patients of whom autopsy material was available, 12 were diagnosed as having had ARDS. In all patients, C3d depositions were found in various parts of the lungs, and to a different extent. Notably, C3d deposition scores were similar for patients with ARDS and those without ARDS (4.5 [3.3–6.8] vs. 5.0 [4.0–6.0]; not significant). C3d deposition scores were also independent from the presence or absence of DAD, and correlations between C3d scores and LIS and driving pressures prior to death were poor. Conclusion: Pulmonary C3d depositions are found in the lungs of all deceased ICU patients, independent of the diagnosis of ARDS. The presence of complement C3d was not associated with the presence of DAD on histopathology and had a poor correlation with ventilation characteristics prior to death.