Biomarkers in acute respiratory distress syndrome: from pathobiology to improving patient care

Abstract

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by alveolar flooding with protein-rich pulmonary edema fluid. Despite an improved understanding of ARDS pathogenesis, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help identify patients at highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. This review begins with a general description of biomarker use in clinical medicine. We then review evidence that supports the value of various ARDS biomarkers organized by the cellular injury processes central to ARDS development: endothelial injury, epithelial injury, disordered inflammation and coagulation, fibrosis, and apoptosis. Finally, we summarize the growing contributions of genomic and proteomic research and suggest ways in which the field may evolve in the coming years.

Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy

“…We also hypothesized that these two subphenotypes would respond differently to randomly assigned fluid therapy. In our previous analysis, subphenotype 2 was characterized by higher levels of inflammatory cytokines and higher levels of both intercellular adhesion molecule-1 and von Willebrand factor, markers of endothelial cell injury (5,6). Therefore, given that subphenotype 2 had evidence of more baseline inflammation and endothelial cell injury, features that would favor more extravascular fluid accumulation, we hypothesized a priori that subphenotype 2 would have higher mortality and fewer ventilator-free days in response to a liberal fluid strategy.…”

Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome

“…Its diagnostic and prognostic values have been reported, and its correlation with severity is established in ARDS (10)(11)(12). The availability of the measurement of plasma biomarker sRAGE could be of particular interest to assess response to therapy during ARDS, in preclinical studies (39) and ultimately in patients (40). The impact of mechanical ventilation (MV) settings on sRAGE levels has been reported in ARDS patients, with prognostic values in those receiving higher tidal volumes (11), and the effects of various strategies, including alveolar recruitment strategy and lung imaging-based MV settings are under investigation by our team.…”

ARDS Subphenotypes: Understanding a Heterogeneous Syndrome

“…Numerous genomic, transcriptomic, proteomic, and metabolomic factors have been studied for this purpose, with the greatest depth of research focused on plasma protein biomarkers of ARDS. These include markers of systemic inflammation (interleukin [IL]-6, IL-8, soluble tumor necrosis factor [TNF] receptor-1, IL-18), epithelial injury (angiopoietin-2, intercellular adhesion molecule-1), endothelial injury (soluble receptor for advanced glycation end products [sRAGE], surfactant protein-D), and disordered coagulation (plasminogen activator inhibitor-1, protein C), all of which have been shown to hold prognostic value [24]. Baseline levels of sRAGE, for example, independently predicted 90-day mortality in one meta-analysis [25].…”