Biomarkers in Pediatric ARDS: Future Directions

Orwoll, Benjamin E.; Sapru, Anil

The surfactant proteins are a group of proteins produced by the alveolar type II cells within the lung and secreted as part of a complex substance called pulmonary surfactant that serves primarily to reduce surface tension in the lung. Alterations or damage to the pulmonary surfactant system have been proposed as a mechanism for some of the changes in pulmonary physiology seen in ARDS (7, 159) . Several studies have examined surfactant protein levels in pediatric patients with lung injury. One large study examining 120 children with respiratory failure requiring intubation found lower levels of tracheal aspirate surfactant protein A (SP-A) and surfactant protein B (SP-B) relative to total aspirate fluid protein in pneumonia and ARDS patients compared with controls. SP-A levels were also correlated with pulmonary compliance (68) . Another, smaller study also found decreased normalized levels of SP-A and SP-B in BAL fluid from children with ARDS, while surfactant protein D (SP-D) was found in elevated amounts with increased breakdown products (21) . The same study also evaluated plasma SP levels, finding that all three SPs (A, B, and D) were elevated in plasma at the time of ARDS diagnosis and that plasma SP-B was independently associated with LOS and duration of mechanical ventilation. Elevations in BAL fluid SP-D levels have also been found in children with VAP compared to ventilated controls (72) , and plasma SP-D levels are also higher in children with bronchopneumonia and associated with increased need for supplemental oxygen (49) . Similar findings of decreased levels of SP-A and SP-B in the BAL fluid were reported in studies of infants with severe bronchiolitis (69, 70) but, in contrast to other reports, SP-D was also reduced. However, SP-D in the serum was elevated in two studies of viral bronchiolitis (50, 51) . In aggregate, these results seem to suggest a relative depletion of pulmonary surfactant proteins and a concomitant increase in plasma concentrations, which may relate to increased permeability at the alveolar-capillary barrier. Thus, plasma and BAL fluid surfactant concentrations have significant potential as biomarkers specific to intrapulmonary processes.