B75-18 High Bronchoalveolar Club Cell Secretory Protein Levels Are Associated With Acute Respiratory Distress Syndrome Resolution

Rationale Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury, pathologic inflammation, and pulmonary edema. ARDS is the leading cause of respiratory failure, affecting 10% of patients admitted to ICUs worldwide and frequently leading to death or long-term dependence on mechanical ventilation. Elucidating key biological mechanisms that restore lung homeostasis after injury is critical to identify effective therapeutic targets. Club cell secretory protein 16 (CC16) is an endogenous regulator of lung inflammation whose roles in acute lung injury resolution have not been characterized. Methods We collected bronchoalveolar lavage (BAL) samples from patients undergoing clinically indicated bronchoscopies in the Brigham and Women’s Hospital ICUs. BAL fluid CC16 levels were measured by ELISA, normalized to total protein as assessed by bicinchoninic acid assay, and log normalized. CC16 levels were evaluated for correlation with clinical variables including SOFA score, APACHE II score, PaO2:FiO2 ratio, ventilator-free days alive at day 28, and time to resolution of hypoxemia. BAL fluid IL-6 and IL-8 levels were also measured by ELISA. To screen for direct anti-inflammatory actions, A549 cells, a human cell line with features of distal lung epithelium, were exposed to vehicle or CC16 at physiologic and supraphysiologic concentrations for 30 minutes followed by IL-1β for 24 hours. IL-6 and IL-8 levels in cell supernatants were detected by ELISA. Results BAL samples were collected from 21 patients with acute lung injury, 9 of whom met diagnostic criteria for ARDS. BAL fluid CC16 levels ranged from 15 ng/ml to 6351 ng/ml with a median of 869 ng/ml. In patients with ARDS, significant associations were detected between high BAL fluid CC16 levels and faster resolution of hypoxemia (R=-0.90, p = 0.005) as well as higher ventilator-free days alive at day 28 (R = 0.83, p = 0.006). BAL fluid CC16 levels correlated with IL-6 (R = 0.44) and IL-8 levels (R = 0.45) but did not reach statistical significance. No associations were identified with outcomes in patients at risk of ARDS. In A549 cells, exposure to 10,000 ng/mL of CC16 significantly inhibited IL-6 and IL-8 release (p = 0.0004 and 0.0084, respectively). Conclusions Here, in work in progress, we present evidence of a novel association between BAL fluid CC16 levels and ARDS resolution. Additionally, our data suggests that CC16 regulation of pro-inflammatory cytokines may be relevant in ARDS. This abstract is funded by: 5T32HL007633-40