Association of Nasopharyngeal and Serum Glutathione Metabolism with Bronchiolitis Severity and Asthma Risk: A Prospective Multicenter Cohort Study

Abstract

Infants hospitalized for bronchiolitis are at high risk for asthma. Glutathione-related metabolites may antagonize oxidative stress, which induces airway injuries in respiratory infection and subsequent airway remodeling. However, little is known about the relationship of glutathione-related metabolites with bronchiolitis severity and the risk of asthma. In a multicenter prospective observational cohort study of infants hospitalized for bronchiolitis, we measured nasopharyngeal and serum glutathione-related metabolites by using liquid chromatography–tandem mass spectrometry. We then examined their association with bronchiolitis severity (defined by positive pressure ventilation (PPV) use). We also identified severity-related glutathione-related metabolite signatures and examined their association with asthma at age 6 years. In 1013 infants, we identified 12 nasopharyngeal and 10 serum glutathione-related metabolites. In the multivariable models, lower relative abundances of seven metabolites, e.g., substrates of glutathione, including cysteine (adjOR 0.21, 95%CI 0.06–0.76), glycine (adjOR 0.25, 95%CI 0.07–0.85), and glutamate (adjOR 0.25, 95%CI 0.07–0.88), were significantly associated with PPV use (all FDR < 0.05). These associations were consistent with serum glutathione-related metabolites. The nasopharyngeal glutathione-related metabolite signature was also associated with a significantly higher risk of asthma (adjOR 0.90, 95%CI 0.82–0.99, p = 0.04). In infants hospitalized for bronchiolitis, glutathione-related metabolites were associated with bronchiolitis severity and asthma risk.

Integrative genetics-metabolomics analysis of infant bronchiolitis-childhood asthma link: A multicenter prospective study

“…the upper airway (21, [34][35][36][37][38], serum (36,38), and urine (39) metabolome signature (e.g., altered sphingolipid, phospholipid, and fatty acid metabolism)-with the subsequent development of asthma. Independent from these metabolomics investigations, GWASs have identified genetic regions associated with respiratory syncytial virus (RSV) infection (41)(42)(43), severe bronchiolitis (41,42,44), and asthma risk (12-17, 43, 45-49).…”

Perturbations of Glutathione and Sphingosine Metabolites in Port Wine Birthmark Patient-Derived Induced Pluripotent Stem Cells

“…Glutathione plays major beneficial roles in maintaining cellular redox homeostasis by acting as a free radical scavenger and a detoxifying agent; it contributes to multiple cellular processes including proliferation, cell division, and differentiation [ 31 , 32 ]. Alternatively, dysregulated glutathione metabolism has been shown to have a pathogenic role in malignancy and many diseases [ 31 , 38 , 39 ]. Glutathione levels are increased in many types of tumor cells [ 40 , 41 , 42 ].…”