Biomarkers in Pediatric ARDS: Future Directions

Orwoll, Benjamin E.; Sapru, Anil

Clara (also known as club) cell secretory protein (CC16) is a protein that is produced and secreted by the Clara cells of the tracheobronchial tree and has been identified as a marker of respiratory epithelial injury (117) . Elevations in plasma levels of CC16 in adult patients have been associated with both the development of ARDS (118) as well as with increased mortality and organ failure scores when compared with controls (119, 120). However, when Ware et al. compared CC16 levels between patients with ALI and those with cardiogenic pulmonary edema they found that the ALI patients had comparatively lower BAL fluid and plasma CC16 levels, suggesting that CC16 elevations may not be specific to ARDS (121) . In children, CC16 has been studied primarily as a biomarker in neonatal RDS and for the development of BPD. However, the results are conflicting. Reports from cord blood and postnatal serum found lower levels of CC16 in patients who went on to develop BPD (19, 29) , while one study demonstrated elevated postnatal serum levels in mechanically ventilated infants and correlations with progression to BPD (30) . Yet, another study of tracheal aspirates in preterm infants showed instead a correlation with gestational age as well as elevations in the setting of acute infection (66) . Though there is significant interest in CC16 as both a biomarker and as a potential therapy (122) , the evidence continues to be inconsistent and more study in larger populations is needed.