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

Authors

Michihito Kyo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-1101, USA.
Zhaozhong Zhu, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-1101, USA.
Makiko Nanishi, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-1101, USA.
Ryohei Shibata, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-1101, USA.
Tadao Ooka, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-1101, USA.
Robert J. Freishtat, Department of Genomics and Precision Medicine, George Washington University, Washington, DC 20052, USA.
Jonathan M. Mansbach, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Carlos A. Camargo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-1101, USA.
Kohei Hasegawa, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-1101, USA.

Document Type

Journal Article

Publication Date

7-22-2022

Journal

Metabolites

Volume

12

Issue

8

DOI

10.3390/metabo12080674

Keywords

asthma; bronchiolitis; glutathione; infant; metabolome; oxidative stress; severity

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, = 0.04). In infants hospitalized for bronchiolitis, glutathione-related metabolites were associated with bronchiolitis severity and asthma risk.

APA Citation

Kyo, Michihito; Zhu, Zhaozhong; Nanishi, Makiko; Shibata, Ryohei; Ooka, Tadao; Freishtat, Robert J.; Mansbach, Jonathan M.; Camargo, Carlos A.; and Hasegawa, Kohei, "Association of Nasopharyngeal and Serum Glutathione Metabolism with Bronchiolitis Severity and Asthma Risk: A Prospective Multicenter Cohort Study" (2022). GW Authored Works. Paper 1270.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1270

Department

Pediatrics