Protease-antiprotease imbalance in airway secretions in subjects with acute respiratory failure

Studies have shown that in the acute respiratory distress syndrome (ARDS) there is protease-antiprotease imbalance, reflected as an increase in the ratio of Human Neutrophil Elastase (HNE) to several protease inhibitors in BAL and plasma. This imbalance can be related to the pathophysiology of ARDS and may correlate with clinical outcomes. The purpose of the study was to determine if similar protease-antiprotease imbalance could be detected in airway secretions in subjects at risk of developing ARDS. Free HNE activity (HNEA) and levels of the protease inhibitors alpha-1 antitrypsin (AAT) and secretory leukocyte protease inhibitor (SLPI) were measured in samples of endotracheal aspirates samples collected serially in subjects intubated because of acute respiratory failure in a medical ICU (n=42 subjects, 10 eventually developed ARDS). Contrary to reports studying BAL, we observed that free elastase activity is reduced in airway secretions of subjects that develop ARDS compared to subjects that did not. No differences were noted in AAT and SLPI concentrations in airway secretions among these groups. HNEA/AAT and HNEA/SLPI ratios were reduced in 19 subjects. In ARDS subjects, levels of HNEA returned to normal the first day after the onset of ARDS. There were no differences in survival between subjects who had detectable free HNEA compared with those that did not. Analysis of protease-antiprotease balance in airway secretions of subjects with acute respiratory failure is not useful to discriminate subjects who develop ARDS and does not correlate with survival.