Biomarkers in Pediatric ARDS: Future Directions

Orwoll, Benjamin E.; Sapru, Anil

Another group of inflammation-related proteins that has been of significant interest is the matrix metalloproteinase (MMP) family. Through their activity in the breakdown and remodeling of tissue matrices (84) , these proteins may have direct functional significance in addition to their utility as biomarkers. MMPs can be produced by multiple cell types, including immune cells, fibroblasts, and epithelial cells, and many different subgroups of MMPs have been identified and classified based on their substrates (85) . Several studies have found associations between levels of MMP-8, MMP-9, MMP-10, and the MMP antagonist tissue inhibitor of metalloproteinases 1 (TIMP-1) and outcomes from sepsis in adults (86) (87) (88) , while one study in a mixed population of ventilated adults found that serum levels of TIMP-1 and MMP-8 were associated with decreased survival and increased severity of hypoxemia (89) . In pediatric patients, there is more substantial evidence base for the role of the MMPs in lung injury and ARDS. In 2001, two different groups demonstrated elevated levels of MMP-8 in the BAL fluid from preterm babies with RDS (62, 63) and found that higher amounts of MMP-8 are associated with progression from RDS to CLD or bronchoalveolar dysplasia (BPD). One group also identified an imbalance between MMP-8 and its inhibitor, TIMP-1, in the BAL fluid, and lower levels of TIMP-1 were associated with hypoxemia and prolonged ventilation (62) . In pARDS patients, two more recent reports have described elevations in BAL fluid MMP-8 and MMP-9 levels in ARDS patients relative to controls as well as associations between these two proteins and the need for prolonged mechanical ventilation (55, 64) . One study also examined the relationship between these MMPs and other neutrophil-derived proteinases, such as human neutrophil elastase (HNE) and myeloperoxidase (MPO), finding positive relationships that may indicate neutrophil activity as a major source for the MMP elevations seen in ARDS (55) .