Alveolar epithelial glycocalyx degradation is associated with impaired lung mechanics, lung injury severity, and clinical outcomes in ARDS.

Background: The alveolar epithelial glycocalyx is a layer of glycosaminoglycans (GAGs) and proteoglycans (e.g., syndecan-1) that is located between the apical alveolar epithelium and the surfactant layer. It is degraded in murine models of lung injury and in patients with ARDS. Targeted degradation of the epithelial glycocalyx impairs surfactant function in mice. We sought to determine the relationship between epithelial glycocalyx degradation, pulmonary physiology, and clinical outcomes in patients with ARDS. Methods: We first analyzed the relationship between the concentration of syndecan-1 (a marker of glycocalyx shedding) in directly aspirated pulmonary edema fluid and both lung injury severity and patient outcomes in a retrospective cohort of patients with ARDS or hydrostatic pulmonary edema. Subsequently, we prospectively collected heat-moisture-exchange (HME) filter fluid, a noninvasive approach to distal airspace sampling, at two additional centers and determined the relationships between syndecan-1, respiratory mechanics, patient outcomes, and other established ARDS biomarkers. Results: Airspace fluid syndecan-1 was associated with impaired lung mechanics (static respiratory system compliance and driving pressure), more severe hypoxemia, prolonged mechanical ventilation, and increased mortality. Other airspace biomarkers of lung injury were not associated with lung mechanics. These findings were observed similarly across multiple cohorts, using either directly aspirated pulmonary edema fluid or noninvasively collected HME fluid. Conclusions: Airspace fluid syndecan-1 is associated with the severity of hypoxemia, impaired lung mechanics, and worse clinical outcomes in ARDS patients. These results support further research into therapeutics to restore the integrity of the epithelial glycocalyx in ARDS.