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

• Published in: Critical care medicine Vol. 53; no. 7; p. e1457
• Main 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 S D, Sapru, Anil
• Format: Journal Article
• Language: English
• Published: United States 01.07.2025
• Subjects: Adolescent; Biomarkers - blood; Child; Child, Preschool; Female; Humans; Infant; Intensive Care Units, Pediatric; Intercellular Adhesion Molecule-1 - blood; Male; Prospective Studies; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - mortality; Respiratory Insufficiency - blood; Respiratory Insufficiency - mortality; acute respiratory distress syndrome; network analysis; acute respiratory failure; inflammation; pediatric acute respiratory distress syndrome; soluble intercellular adhesion molecule
• DOI: 10.1097/CCM.0000000000006719

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. Secondary analysis of prospective cohort studies. Multicenter PICUs. 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). None. 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. Elevated sICAM-1 levels were associated with poor outcomes in two separate cohorts of ARDS and ARF patients. Network analysis revealed sICAM-1 as a central hub, characterized by high centrality metrics. These findings underscore the multifaceted role of sICAM-1 in leukocyte transmigration, inflammation, and endothelial dysfunction and highlight its critical role in ARDS pathophysiology.