Introduction: Cluster of differentiation 163 (CD163), a macrophage-expressed scavenger receptor, is a profibrotic biomarker associated with disease progression and poor outcomes in idiopathic pulmonary fibrosis (IPF). Similar genomic and histologic patterns of CD163-mediated fibrosis have been noted in ARDS, but physiological facets remain unclear. This analysis examined associations between CD163, indices of lung overdistension, and outcomes in ARDS patients. Methods: This prospective 2-center cohort study enrolled adults with ARDS within four days of initiating invasive ventilation (March 2017 to November 2022). Measures of lung mechanics and plasma were collected at enrollment and every 12±4 hours for up to 72 hours or until extubation. Static indices of overdistension collected included plateau pressure, positive end-expiratory pressure (PEEP), and end-inspiratory and expiratory transpulmonary pressures. Dynamic indices measured included tidal volume per predicted body weight (VT/PBW), airway driving pressure, and transpulmonary driving pressure. PaO2/FiO2 was recorded at each time point. CD163 was analyzed on the log scale. Survival was assessed at 28 days. Data means and standard deviations are reported with analyses including linear, logistic, and Cox regression models. Results: 72 patients were included (mean age 56±15 years; APACHE II score 35±6.5). At baseline, in unadjusted analyses, higher CD163 was significantly associated with lower PaO2/FiO2 (β=-0.003, 95%CI:-0.0051 to -0.0003, p=0.03) and with dynamic indices of lung mechanics: VT/PBW (β=0.14, 95% CI:0.001 to 0.286, p=0.05), airway driving pressure (β=0.049, 95% CI:0.008 to 0.090, p=0.02), and transpulmonary driving pressure (β=0.05, 95% CI:0.008 to 0.095, p=0.02). These associations remained significant after adjustment for APACHE II. CD163 was not associated with static indices of lung stress. Adjusted for APACHE II score and ARDS severity, elevated CD163 was associated with increased hazard of death (HR=2.32, 95% CI:1.37 to 3.94, p=0.0017) and delayed extubation (HR=0.547, 95% CI:0.380 to 0.788, p=0.0012). Conclusions: CD163 was highly correlated with dynamic measures of overdistension and patient outcomes in adults with ARDS. Further exploration of CD163 is warranted for its prognostic ability and potential as a therapeutic target.
Serra et al. (Sun,) studied this question.