Transpulmonary LOX-1 Levels Are Predictive of Acute Respiratory Distress Syndrome After Cardiac Surgery: A Proof-of-Concept Study

<b>Background/Objectives:</b> Acute respiratory distress syndrome (ARDS) is a life-threatening condition that frequently complicates high-risk cardiac surgery. We evaluated the circulating levels and transpulmonary gradient of intracellular proteins in patients at risk of developing ARDS after cardiac surgery using large scale-proteomics. <b>Methods:</b> We enrolled sixteen patients undergoing high-risk cardiac surgery, followed by planned ICU admission. Circulating levels of intracellular proteins were measured at the onset of the surgical procedure, at ICU admission (H0), and 24 h (H24) after surgery in blood samples simultaneously drawn from both the pulmonary artery and the left atrium. The primary endpoint was the occurrence of ARDS between ICU admission and the subsequent 48 h. <b>Results:</b> Among the studied proteins, the levels of intracellular lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were higher at H24 in the pulmonary artery in patients who developed ARDS (6.96; 95% CI [6.83-7.23]) compared to patients who did not (6.48; 95% CI [6.27-6.66]), <i>p</i>-value = 0.016. The transpulmonary gradient of intracellular LOX-1 levels was not significantly different between ARDS and non-ARDS patients at H0 but it was more negative at H24 in ARDS (-0.23; 95% CI [-0.27, -0.14]) than in non-ARDS patients (0.03; 95% CI [-0.14, 0.32]; <i>p</i>-value= 0.031), with a hazard ratio HR = 0.39 (95% CI [0.18-0.86]); <i>p</i>-value= 0.035. The area under the ROC curve of H24 LOX-1 transpulmonary gradient to predict ARDS occurrence was 0.83 (95% CI [0.62-1.00]). <b>Conclusions:</b> The transpulmonary gradient of intracellular LOX-1 levels was negatively associated with the occurrence of ARDS within the first 48 h after high-risk cardiac surgery, suggesting that lung trapping of LOX-1 may be linked to postoperative ARDS.