Biomarkers of Neutrophil-Mediated Glutathione and Protein Oxidation in Tracheal Aspirates From Preterm Infants: Association With Bacterial Infection

Abstract

Bronchopulmonary dysplasia is associated with neutrophil infiltration into the lungs and oxidative injury. However, the pathological importance of neutrophil oxidants is still not clear. Nosocomial pneumonia is also implicated, but the evidence is limited, in part because of the difficulty of distinguishing genuine infection from bacterial colonization. Good biomarkers of neutrophil oxidant activity and lung infection are needed. We tested whether glutathione sulfonamide, a product of glutathione oxidation by myeloperoxidase-derived hypochlorous acid (HOCl) and a potential new neutrophil oxidant biomarker, is detectable in endotracheal aspirates from ventilated preterm infants. As infectious organisms stimulate neutrophils to generate HOCl, we determined whether levels of HOCl-specific biomarkers were increased in samples that were bacterial culture positive. Glutathione sulfonamide was detected in 66 of 87 endotracheal aspirate samples. Levels correlated with myeloperoxidase activity and another HOCl-specific marker, chlorotyrosine. Median levels of glutathione sulfonamide (4-fold) and other biomarkers (2-fold) were significantly higher in culture positive aspirates. Staphylococcus epidermidis, a frequent colonizer, was associated with glutathione sulfonamide levels no different from those in negative samples. Glutathione sulfonamide showed good sensitivity and specificity for detecting bacterial growth and has promise for detecting lung infection.