Abstract
BackgroundIn cystic fibrosis (CF) there is an urgent need for earlier diagnosis of pulmonary infections and inflammation using blood- and urine-based biomarkers. MethodsUsing mass spectrometry, oxidation products of glutathione and uric acid were measured in matched samples of bronchoalveolar lavage (BAL), serum and urine from 36 infants and children with CF, and related to markers of neutrophilic inflammation and infection in BAL. ResultsOxidation products of glutathione (glutathione sulfonamide, GSA) and uric acid (allantoin), were elevated in BAL of children with pulmonary infections with Pseudomonas aeruginosa (PsA) compared to those without (p<0.05) and correlated with other markers of neutrophilic inflammation. Serum GSA was significantly elevated in children with PsA infections (p<0.01). Urinary GSA correlated with pulmonary GSA (r=0.42, p<0.05) and markers of neutrophilic inflammation. ConclusionsThis proof-of-concept study demonstrates that urinary GSA but not allantoin shows promise as a non-invasive marker of neutrophilic inflammation in early CF lung disease.
Highlights
Lung disease in cystic fibrosis (CF) begins in early life, is progressive and characterized by neutrophil-dominated inflammation [1,2,3]
Children infected with any organisms other than Pseudomonas aeruginosa (PsA) had higher levels of oxidative biomarkers, IL-8 and neutrophil elastase compared to uninfected children (Fig. 2, Supplementary Fig. 2), but this difference did not reach statistical significance, possibly due to the smaller sample size
The data from the present study show that levels of Glutathione sulfonamide (GSA) and allantoin in the bronchoalveolar lavage (BAL) correlate with neutrophil-derived oxidation activity in the lungs of infants and young children with early CF lung disease
Summary
Lung disease in cystic fibrosis (CF) begins in early life, is progressive and characterized by neutrophil-dominated inflammation [1,2,3]. Major risk factors for progressive lung disease include inflammation and infection, severe CF genotype and free NE activity in the BAL [1,5]. All of these can be present in the complete absence of clinically-apparent lung disease [1,2]. Results: Oxidation products of glutathione (glutathione sulfonamide, GSA) and uric acid (allantoin), were elevated in BAL of children with pulmonary infections with Pseudomonas aeruginosa (PsA) compared to those without (p b 0.05) and correlated with other markers of neutrophilic inflammation.
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