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

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Biomarkers of alveolar epithelial injury and endothelial dysfunction are associated with scores of pulmonary edema in invasively ventilated patients. / Atmowihardjo, Leila N.; Heijnen, Nanon F. L.; Smit, Marry R. et al.

In: American journal of physiology. Lung cellular and molecular physiology, Vol. 324, No. 1, 01.01.2023, p. L38-L47.

Research output: Contribution to journal › Article › Academic › peer-review

BibTeX

@article{19d708b8e5ff4eb88a5072bc952cf863,

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

abstract = "Pulmonary 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.",

keywords = "ARDS, endothelial dysfunction, epithelial injury, pulmonary edema, vascular permeability",

author = "Atmowihardjo, {Leila N.} and Heijnen, {Nanon F. L.} and Smit, {Marry R.} and Hagens, {Laura A.} and Filippini, {Daan F. L.} and Claudio Zimatore and Schultz, {Marcus J.} and Schnabel, {Ronny M.} and Bergmans, {Dennis C. J. J.} and {DARTS consortium} and Jurjan Aman and Bos, {Lieuwe D. J.}",

year = "2023",

month = jan,

day = "1",

doi = "10.1152/ajplung.00185.2022",

language = "English",

volume = "324",

pages = "L38--L47",

journal = "American journal of physiology. Lung cellular and molecular physiology",

issn = "1040-0605",

publisher = "American Physiological Society",

number = "1",

}

RIS

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 - DARTS consortium

AU - Aman, Jurjan

AU - Bos, Lieuwe D. J.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - Pulmonary 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.

AB - Pulmonary 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.

KW - ARDS

KW - endothelial dysfunction

KW - epithelial injury

KW - pulmonary edema

KW - vascular permeability

UR - http://www.scopus.com/inward/record.url?scp=85144635826&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00185.2022

DO - 10.1152/ajplung.00185.2022

M3 - Article

C2 - 36348302

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

SN - 1040-0605

IS - 1

ER -

ID: 28029593

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