Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease

Rationale: Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression.
Methods: CF patients aged 12-38 months (n=24; 3/24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the PRAGMA-CF method to quantify total lung damage (PRAGMA-Dis) and components such as bronchiectasis. Small molecules in bronchoalveolar lavage fluid (BALF) were measured with high-resolution, accurate-mass metabolomics. Myeloperoxidase was quantified by ELISA and activity assays.
Results: Increased PRAGMA-Dis was driven by bronchiectasis and correlated with airway neutrophils. PRAGMA-Dis correlated with 104 metabolomic features (p<0.05, q<0.25). The most significant annotated feature was methionine sulfoxide, a product of methionine oxidation by myeloperoxidase-derived oxidants. We confirmed the identity of meth...