Biomarkers of alveolar epithelial injury and endothelial dysfunction are associated with scores of pulmonary edema in invasively ventilated patients

Atmowihardjo L.N.Heijnen N.F.L.Smit M.R.Hagens L.A.Filippini D.F.L.Zimatore C.Schultz M.J.Schnabel R.M.Bergmans D.C.J.J.Aman J.Bos L.D.J.Mahidol University2023-05-192023-05-192023-01-01American journal of physiology. Lung cellular and molecular physiology Vol.324 No.1 (2023) , L38-L47https://repository.li.mahidol.ac.th/handle/20.500.14594/82337Pulmonary edema is a central hallmark of acute respiratory distress syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to alveolar-capillary permeability but their differential contribution to pulmonary edema development remains understudied. Plasma levels of surfactant protein-D (SP-D), soluble receptor for advanced glycation end products (sRAGE), and angiopoietin-2 (Ang-2) were measured in a prospective, multicenter cohort of invasively ventilated patients. Pulmonary edema was quantified using the radiographic assessment of lung edema (RALE) and global lung ultrasound (LUS) score. Variables were collected within 48 h after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema. In 362 patients, higher SP-D, sRAGE, and Ang-2 concentrations were significantly associated with higher RALE and global LUS scores. After stratification by ARDS subgroups (pulmonary, nonpulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, whereas sRAGE and Ang-2 showed less consistent associations throughout the subgroups. In a multivariable analysis, SP-D levels were most strongly associated with pulmonary edema when combined with sRAGE (RALE score: βSP-D = 6.79 units/log10 pg/mL, βsRAGE = 3.84 units/log10 pg/mL, R2 = 0.23; global LUS score: βSP-D = 3.28 units/log10 pg/mL, βsRAGE = 2.06 units/log10 pg/mL, R2 = 0.086), whereas Ang-2 did not further improve the model. Biomarkers of epithelial injury and endothelial dysfunction were associated with pulmonary edema in invasively ventilated patients. SP-D and sRAGE showed the strongest association, suggesting that epithelial injury may form a final common pathway in the alveolar-capillary barrier dysfunction underlying pulmonary edema.Biochemistry, Genetics and Molecular BiologyBiomarkers of alveolar epithelial injury and endothelial dysfunction are associated with scores of pulmonary edema in invasively ventilated patientsArticleSCOPUS10.1152/ajplung.00185.20222-s2.0-851446358261522150436348302