TY - JOUR
T1 - Biomarkers of alveolar epithelial injury and endothelial dysfunction are associated with scores of pulmonary edema in invasively ventilated patients
AU - Atmowihardjo, Leila N
AU - Heijnen, Nanon F L
AU - Smit, Marry R
AU - Hagens, Laura A
AU - Filippini, Daan F L
AU - Zimatore, Claudio
AU - Schultz, Marcus J
AU - Schnabel, Ronny M
AU - Bergmans, Dennis C J J
AU - Aman, Jurjan
AU - Bos, Lieuwe D J
N1 - Funding Information:
The DARTS project, within which the current study was a predefined analysis, was funded by Health Holland via the Dutch Lung Foundation.
Publisher Copyright:
Copyright © 2023 the American Physiological Society.
PY - 2023/1
Y1 - 2023/1
N2 - BACKGROUND: Pulmonary edema is a central hallmark of Acute Respiratory Distress Syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to permeability but their differential contribution to pulmonary edema development remains understudied.METHODS: 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 hours after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema.RESULTS: 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, non-pulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, while 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), while Ang-2 did not further improve the model.CONCLUSION: 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.
AB - BACKGROUND: Pulmonary edema is a central hallmark of Acute Respiratory Distress Syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to permeability but their differential contribution to pulmonary edema development remains understudied.METHODS: 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 hours after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema.RESULTS: 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, non-pulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, while 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), while Ang-2 did not further improve the model.CONCLUSION: 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.
U2 - 10.1152/ajplung.00185.2022
DO - 10.1152/ajplung.00185.2022
M3 - Article
C2 - 36348302
SN - 1040-0605
VL - 324
SP - L38-L47
JO - American Journal of Physiology-Lung Cellular and Molecular Physiology
JF - American Journal of Physiology-Lung Cellular and Molecular Physiology
IS - 1
ER -