Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease
| Autor: | Bob J. Scholte, Mieke Veltman, Camilla Margaroli, Harm A.W.M. Tiddens, Karan Uppal, Joshua D. Chandler, Lokesh Guglani, Rabindra Tirouvanziam, Dean P. Jones, Limin Peng, H. Ken Liu, Alexander J. Taurone, Young-Mi Go, Matthew B. Kilgore, Hettie M. Janssens, Hamed Horati |
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| Přispěvatelé: | Pediatrics |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Male Pathology medicine.medical_specialty Cystic Fibrosis Neutrophils Cystic fibrosis Article 03 medical and health sciences chemistry.chemical_compound Methionine Bronchoscopy medicine Humans Prospective Studies Lung Peroxidase Bronchiectasis biology medicine.diagnostic_test business.industry Infant respiratory system medicine.disease Oxidants respiratory tract diseases 030104 developmental biology medicine.anatomical_structure Bronchoalveolar lavage chemistry Lung disease Myeloperoxidase Child Preschool biology.protein Disease Progression Female Airway business Tomography X-Ray Computed Bronchoalveolar Lavage Fluid Oxidation-Reduction |
| Zdroj: | European Respiratory Journal, 52(4):1801118. European Respiratory Society |
| ISSN: | 1399-3003 0903-1936 |
| Popis: | 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−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. |
| Databáze: | OpenAIRE |
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