Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study

Authors

Michihito Kyo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA mkyo@hiroshima-u.ac.jp.
Zhaozhong Zhu, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ryohei Shibata, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tadao Ooka, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jonathan M. Mansbach, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Brennan Harmon, Centre for Genetic Medicine Research, Children's National Hospital, Washington, District of Columbia, USA.
Andrea Hahn, Centre for Genetic Medicine Research, Children's National Hospital, Washington, District of Columbia, USA.
Marcos Pérez-Losada, Computational Biology Institute, Department of Biostatistics and Bioinformatics, The George Washington University, Washington, District of Columbia, USA.
Carlos A. Camargo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kohei Hasegawa, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Document Type

Journal Article

Publication Date

7-31-2024

Journal

BMJ open respiratory research

Volume

11

Issue

1

DOI

10.1136/bmjresp-2023-002288

Keywords

critical care; non invasive ventilation; respiratory infection; viral infection

Abstract

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear. METHODS: In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA). RESULTS: In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example, for the microtubule anchoring module, for the cell-substrate junction module. CONCLUSIONS: In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.

APA Citation

Kyo, Michihito; Zhu, Zhaozhong; Shibata, Ryohei; Ooka, Tadao; Mansbach, Jonathan M.; Harmon, Brennan; Hahn, Andrea; Pérez-Losada, Marcos; Camargo, Carlos A.; and Hasegawa, Kohei, "Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study" (2024). GW Authored Works. Paper 5212.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5212

Department

Pediatrics