A103-03 The Impact of One-Lung Ventilation on Development of Postoperative Respiratory Failure During Lung Surgery: A Proteomic Approach for Uncovering Biomarkers

Abstract Rationale Lung surgery is a curative treatment for lung cancer. This surgery is facilitated by deflating the operated lung and delivering all mechanical ventilation to the contralateral lung through one-lung ventilation (OLV). OLV surgery-induced inflammation, along with pre-existing comorbidities, can contribute to lung injury and development of postoperative respiratory failure. We aim to identify protein biomarkers that increase during OLV and identify patients at risk of postoperative respiratory failure. Methods We performed a case-control study of 41 patients nested within a larger prospective cohort study, which recruited 556 eligible consecutive patients undergoing OLV lung surgery. 14 cases (patients with postoperative respiratory failure) were matched with 27 controls based on clinical parameters prognostic for respiratory failure. Bronchoalveolar lavage fluid (BALF) from both lungs, and arterial plasma samples, collected intraoperatively at two time points (pre- and post-OLV), were subjected to data-independent acquisition proteomics using label-free LC-MS/MS. Additionally, neutrophil, and lymphocyte counts were performed on preoperative and postoperative day 1 (POD1) blood samples. Neutrophil-to-lymphocyte ratio (NLR) was calculated and compared between POD1 vs. pre-operative blood samples. Statistical analysis was performed using DEP2, and LIMMA packages for proteomics data and LME4 package with Type III ANOVA for NLR data in R (significant results: FDR ≤ 0.05, fold change ≥ 2 and 1.5 for BALF and plasma, respectively, p-value < 0.05 for NLR). Results Comparing post- vs. pre-OLV ventilated lung BALF proteome revealed significant increase in notable protein groups such as ENPP2, PSME2, and ILF3 proteins in postoperative respiratory failure cases relative to controls. These proteins are involved in lipid conversion, immunoproteasome activity, and inflammation - processes known to be involved in acute respiratory distress syndrome respiratory failure. In plasma proteome, PEPB1 was significantly upregulated in respiratory failure cases relative to matched controls highlighting the role of lipids in post-vs.-pre OLV systemic profile. In both respiratory failure and matched control groups, NLR was increased significantly in POD1 vs. preoperative timepoints but not when accounting for respiratory failure status. Thus, indicating the necessity for sensitive biomarkers of lung injury to identify high risk patients for postoperative respiratory failure. Conclusion BALF and plasma proteomic analysis showed protein biomarkers involved in inflammation and lipid metabolism. By employing a nested case-control design to our proteomic screening approach, we can detect protein biomarkers of postoperative respiratory failure. These can undergo validation and have the potential to identify patients at risk who may benefit from preventive anti-inflammatory therapies. This abstract is funded by: This project was funded by the 2024 Health Sciences Centre Foundation Operating Grant 60756 (Awarded to: Dr. Biniam Kidane) and Research Manitoba Master’s Studentship Award 6301 (Awarded to: Dagem Chernet)