A genome-wide expression analysis in blood identifies pre-elafin as a biomarker in ARDS

Previous microarray-based studies of acute respiratory distress syndrome (ARDS) were performed using various models to mimic disease pathogenesis. The complexity of the pathophysiologic response to direct or indirect lung injury in ARDS is difficult to reconstruct in experimental conditions. Thus, direct analysis of ARDS patient blood may provide valuable information. We investigated genome-wide gene expression profiles in paired whole blood samples from patients with ARDS (n = 8) during the acute stage (within 3 d of diagnosis) and recovery stage of ARDS (around ICU discharge). Among 126 differentially expressed genes, peptidase inhibitor 3 (P13, encoding elafin, a potent neutrophil elastase inhibitor) had the largest fold-change (-3-fold changes, acute stage/recovery stage) in expression, indicating down-regulation during the acute stage of ARDS. We further examined plasma P13 levels in 40 patients with ARDS and 23 at-risk control subjects from the same cohort. There was a coincidence of the microarray findings of lower P13 gene expression with the lower plasma P13 during the acute-stage. The plasma P13 levels were statistically significant different among pre-diagnosis, day of diagnosis, and post-diagnosis groups (ANOVA, P = 0.001), with a trend of decreasing from pre- to post-diagnosis group. The time course of plasma P13 decrease is well correlated with the course of early ARDS development (Pearson correlation coefficient: -0.52, P = 0.0006). Considering that P13 can covalently binding to extracellular matrix in lung, circulating P13 may provide a useful clinical marker for monitoring the early development of ARDS and may have implications for ARDS treatment.