PT  - JOURNAL ARTICLE
AU  - Joshua D. Chandler
AU  - Camilla Margaroli
AU  - Hamed Horati
AU  - Matthew B. Kilgore
AU  - Mieke Veltman
AU  - H. Ken Liu
AU  - Alexander J. Taurone
AU  - Limin Peng
AU  - Lokesh Guglani
AU  - Karan Uppal
AU  - Young-Mi Go
AU  - Harm A.W.M. Tiddens
AU  - Bob J. Scholte
AU  - Rabindra Tirouvanziam
AU  - Dean P. Jones
AU  - Hettie M. Janssens
TI  - Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease
AID  - 10.1183/13993003.01118-2018
DP  - 2018 Oct 01
TA  - European Respiratory Journal
PG  - 1801118
VI  - 52
IP  - 4
4099  - http://erj.ersjournals.com/content/52/4/1801118.short
4100  - http://erj.ersjournals.com/content/52/4/1801118.full
SO  - Eur Respir J2018 Oct 01; 52
AB  - 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.CF patients aged 12–38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the Perth–Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis (PRAGMA-%Bx). Small molecules in bronchoalveolar lavage fluid (BALF) were measured with high-resolution accurate-mass metabolomics. Myeloperoxidase (MPO) was quantified by ELISA and activity assays.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 (MetO), a product of methionine oxidation by MPO-derived oxidants. We confirmed the identity of MetO in BALF and used reference calibration to confirm correlation with PRAGMA-%Dis (Spearman's ρ=0.582, p=0.0029), extending to bronchiectasis (PRAGMA-%Bx; ρ=0.698, p=1.5×10−4), airway neutrophils (ρ=0.569, p=0.0046) and BALF MPO (ρ=0.803, p=3.9×10−6).BALF MetO associates with structural lung damage, airway neutrophils and MPO in early CF. Further studies are needed to establish whether methionine oxidation directly contributes to early CF lung disease and explore potential therapeutic targets indicated by these findings.Identifying molecules associated with early CF lung disease may lead to new means of limiting progression. We found that airway fluid methionine sulfoxide produced by myeloperoxidase associates with lung disease in CF patients aged 1–3 years. http://ow.ly/m0u630lnSx3