Hyaluronic acid is associated with organ dysfunction in acute respiratory distress syndrome

BACKGROUND Hyaluronic acid (HA), an extracellular matrix component, is degraded in response to local tissue injury or stress. In various animal models of lung injury, HA has been shown to play a mechanistic role in modulating inflammation and injury. While HA is present in the lungs of patients with acute respiratory distress syndrome (ARDS), its relationship to patient outcomes is unknown. METHODS We studied 86 patients with ARDS previously enrolled in the Phase II Randomized Trial of Fish Oil in Patients with Acute Lung Injury (NCT00351533) at five North American medical centers. We examined paired serum and bronchoalveolar lavage fluid (BALF) samples obtained within 48 hours of diagnosis of ARDS. We evaluated the association of HA levels in serum and BALF with local (lung injury score (LIS)) and systemic (sequential organ failure assessment score (SOFA)) measures of organ dysfunction with regression analysis adjusting for age, sex, race, treatment group, and risk factor for ARDS. RESULTS We found that both day-0 circulating and alveolar levels of HA were associated with worsening LIS (p = 0.04 and p = 0.003, respectively), particularly via associations with degree of hypoxemia (p = 0.02 and p < 0.001, respectively) and set positive end-expiratory pressure (p = 0.01 and p = 0.02, respectively). Circulating HA was associated with SOFA score (p < 0.001), driven by associations with the respiratory (p = 0.02), coagulation (p < 0.001), liver (p = 0.006), and renal (p = 0.01) components. Notably, the alveolar HA levels were associated with the respiratory component of the SOFA score (p = 0.003) but not the composite SOFA score (p = 0.27). CONCLUSIONS Elevated alveolar levels of HA are associated with LIS while circulating levels are associated with both lung injury and SOFA scores. These findings suggest that HA has a potential role in both local and systemic organ dysfunction in patients with ARDS.