Biomarkers in Pediatric ARDS: Future Directions

Orwoll, Benjamin E.; Sapru, Anil

Several protein biomarkers have been studied as surrogate markers for endothelial injury or increased permeability. Von Willebrand factor (vWF), a protein involved in platelet function produced by ECs and released into the blood upon their activation or damage, was elevated in the plasma of children with ARDS, and early elevation was correlated with mortality and decreased VFDs (48) . These results were consistent with previous findings in infants with RDS (136) as well as with multiple adult studies (137) (138) (139) . Soluble E-selectin is an endothelial leukocyte adhesion protein that is upregulated under conditions of inflammation (140) . E-selectin levels have been associated with ARDS in adults (130, 141, 142) , and a recent study reported elevated plasma E-selectin levels in children with ARDS compared with controls as well as an association with mortality (41) . Among infants with RDS, plasma E-selectin levels have been associated with the development of BPD and were found to decrease with dexamethasone therapy (23, 42, 43) . L-selectin is another member of the selectin family of leukocyte adhesion molecules and is expressed primarily on leukocytes (140) . Consistent with studies in adults (102, 143, 144) , L-selectin levels in the plasma of infants with RDS are decreased among those patients who develop BPD (23) while levels in the BAL fluid are increased, suggesting possible transmigration of leukocytes into the alveolar space (61) . Vascular endothelial growth factor (VEGF), which promotes endothelial and vascular growth, has also been evaluated in neonates with RDS and was found in decreased concentrations in patients with severe RDS, while its soluble receptor (sVEGF-R) was increased (46) . No correlations between BAL fluid VEGF levels and disease incidence or severity have been identified in studies of infants with RDS or BPD (46, 145) .