Discussion
non-ARDS, lung injury, illness, ARDS
REGRESSION, CRITICAL ILLNESS, ARDS, PATHOGENESIS
In this first analysis of the biomarker of MMP-3 from a randomized controlled trial of ARDS, MMP-3 performed well as a prognostic biomarker in ARDS, appropriately classifying patients with a higher risk of mortality and morbidity as measured by AUROC. Plasma MMP-3 levels as both static and dynamic measures showed marked elevations in non-survivors versus survivors, and multivariate regression identified a positive association with MMP-3 day concentrations and 90-day mortality when controlling for severity of illness. Moreover, MMP-3 was elevated in ARDS vs. non-ARDS patients.The prognostic performance of MMP-3 was similar to a previous latent class analysis (LCA) of two randomized controlled ARDS trials (AUROCs ~ 0.75) [Beyond diagnosis, phenotyping using a biomarker, transcriptomic, and clinical data has shown promise to improve prognostication efforts [Differences in treatment response based on phenotype may explain the litany of negative results characteristic of ARDS treatment studies. Famous et al. showed the benefit of the fluid restriction intervention in ARDS occurs only in the hyperinflammatory phenotype and potentially worse outcomes in the non-inflammatory phenotype [Multiple mechanisms linking MMP-3 to lung injury have been identified. Multiple MMPs contribute to ARDS pathogenesis, and MMP-3 has been shown as the primary driver of inflammatory MMP profiles [While many biomarkers have been associated with ARDS, few ARDS biomarkers have been suggested as therapeutic targets, including the receptor for advanced glycation end products (RAGE) [Finally, most investigations have evaluated variables at a single time point, assuming that early presentation is a reasonable predictor of overall outcome and treatment response. Yet, critical illness is known to be a highly dynamic state [Strengths of this study included the use of clinical ARDS samples from a large randomized controlled trial, the evaluation of MMP-3 at multiple time points, and the novelty of using MMP-3 to predict ARDS mortality. The utility of MMP-3, particularly in a biomarker panel, may best be seen in its ability to guide clinically complex decisions: e.g., if patients with high MMP-3 who were treated with 