| Title: |
Plasma Soluble Intercellular Adhesion Molecule-1 Has a Central Role in Biomarker Network Analysis and Is Associated With Poor Outcomes in Two Distinct Pediatric Cohorts of Acute Respiratory Distress Syndrome and Acute Respiratory Failure |
| Authors: |
Lim, Michelle J; Whitney, Jane E; Sallee, Colin J; Markovic, Daniela; Bera, Arunima; Sinha, Pratik; Zeigler, Angela; Chen, Lucia; Zinter, Matt S; Ali, Arham; Matthay, Michael A; Schwingshackl, Andreas; Agus, Michael SD; Sapru, Anil; Investigators, on behalf of the Pediatric Acute Lung Injury and Coagulation and Fibrinolysis in Pediatric Insulin Titration Trial Study |
| Source: |
Critical Care Medicine, vol 53, iss 7 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2025 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); Clinical Research (rcdc); Orphan Drug (rcdc); Prevention (rcdc); Pediatric (rcdc); Lung (rcdc); Rare Diseases (rcdc); Acute Respiratory Distress Syndrome (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); 4.2 Evaluation of markers and technologies (hrcs-rac); Respiratory (hrcs-hc); 3 Good Health and Well Being (sdg); Humans (mesh); Intercellular Adhesion Molecule-1 (mesh); Respiratory Distress Syndrome (mesh); Biomarkers (mesh); Male (mesh); Female (mesh); Child (mesh); Prospective Studies (mesh); Child; Preschool (mesh); Infant (mesh); Respiratory Insufficiency (mesh); Intensive Care Units; Pediatric (mesh); Adolescent (mesh); acute respiratory distress syndrome; acute respiratory failure |
| Subject Geographic: |
e1457 - e1469 |
| Description: |
OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on immune, endothelial, and epithelial cells. In the setting of inflammation, it becomes upregulated and spliced into a soluble form (soluble ICAM-1 [sICAM-1]). This study examined the association of sICAM-1 with clinical outcomes in two large pediatric cohorts with acute respiratory distress syndrome (ARDS) and acute respiratory failure (ARF) and examined the relationships between sICAM-1 and other protein biomarkers utilizing network analysis to contextualize its role in ARDS pathophysiology. DESIGN: Secondary analysis of prospective cohort studies. SETTING: Multicenter PICUs. PATIENTS OR SUBJECTS: Critically ill children with ARDS (Pediatric Acute Lung Injury [PALI], 2008-2014) and ARF (Coagulation and Fibrinolysis in Pediatric Insulin Titration Trial [CAF-PINT], 2012-2016). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: sICAM-1 levels were measured from plasma collected within 72 hours of diagnosis. The primary outcome was in-hospital mortality, and secondary outcomes included multiple organ dysfunction and ventilator-free days. We constructed a biomarker correlation-based network that included sICAM-1 and 32 plasma biomarkers reflective of inflammation, endothelial and epithelial injury, and extracellular matrix degradation. Key biomarkers with centrality metrics in the top 10% (≥ 90th percentile) were defined as critical hubs within the network. The study included 214 children from PALI and 251 from CAF-PINT. In-hospital mortality was 18% and 14%, respectively. Baseline median oxygenation index ratios were 10 (interquartile range [IQR], 5.6-19.7) and 8.5 (IQR, 3.5-17.7). Higher plasma sICAM-1 was associated with in-hospital mortality, multiple organ dysfunction, and fewer ventilator-free days in each of the two cohorts (all p < 0.05). Tissue inhibitor of metalloproteinase-1 (composite centrality, 0.99), tumor necrosis factor receptor-1 (0.83), sICAM-1 (0.74), and interleukin-8 (0.74) were identified as network hubs. ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt5hw0b6js; https://escholarship.org/uc/item/5hw0b6js; https://escholarship.org/content/qt5hw0b6js/qt5hw0b6js.pdf |
| DOI: |
10.1097/ccm.0000000000006719 |
| Availability: |
https://escholarship.org/uc/item/5hw0b6js; https://escholarship.org/content/qt5hw0b6js/qt5hw0b6js.pdf; https://doi.org/10.1097/ccm.0000000000006719 |
| Rights: |
public |
| Accession Number: |
edsbas.753B986 |
| Database: |
BASE |