Abstract Rationale 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 over time 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. Measures of lung mechanics and plasma were collected at enrollment and every 12±4 hours for up to 72 hours. Static indices of overdistension collected included plateau pressure, positive end-expiratory pressure (PEEP), and end-inspiratory and expiratory transpulmonary pressures. Dynamic indices included tidal volume per predicted body weight (VT/PBW), airway driving pressure, and transpulmonary driving pressure. The relationship of plasma CD163 with indices of lung overdistension and PaO2/FiO2 was analyzed using linear regression for baseline values, and linear mixed models with random intercept for longitudinal changes over time. For all analyses, CD163 was log-transformed to approximate a Gaussian distribution. The association of baseline CD163 with 28-day survival was assessed with Cox regression. Results 72 patients were included (mean age 56±15 years; APACHE II score 35±6). At baseline, in unadjusted analyses with separate models, 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 : VT/PBW (β = 0.14, 95% CI:0.001 to 0.286, p = 0.048), 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. Baseline CD163 was not associated with static indices of lung stress. Longitudinal analyses indicated that changes in CD163 over time also correlated with indices of tidal overdistension: VT/PBW (β = 0.01, p = 0.005), airway driving pressure (β = 0.005, p = 0.05), and transpulmonary driving pressure (β = 0.003, p = 0.03). Change in CD163 over time was also correlated with PEEP (β= -0.004, p = 0.002), but no other static indices of overdistension.CD163 was correlated with 28-day mortality and delayed extubation. Adjusted for APACHE II score and ARDS severity, higher CD163 over the first 72 hours was associated with increased hazard of death (HR = 2.32, 95% CI:1.37 to 3.94, p 0.01) and delayed extubation (HR = 0.547, 95% CI:0.380 to 0.788, p 0.01). Conclusion In ARDS, within-patient changes in CD163 over time were highly correlated with dynamic measures of overdistension over 72 hours and with subsequent risk of untoward outcomes. This abstract is funded by: NIH NHLBI
Serra et al. (Fri,) studied this question.