Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity risk

Authors

Ryohei Shibata, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: RSHIBATA@mgh.harvard.edu.
Zhaozhong Zhu, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Michihito Kyo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Tadao Ooka, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Health Science, University of Yamanashi, Chuo, Yamanashi, Japan.
Robert J. Freishtat, Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, USA; Division of Emergency Medicine, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Jonathan M. Mansbach, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Marcos Pérez-Losada, Computational Biology Institute, Department of Biostatistics and Bioinformatics, The George Washington University, Washington, DC, USA.
Carlos A. Camargo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Kohei Hasegawa, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Document Type

Journal Article

Publication Date

9-1-2023

Journal

EBioMedicine

Volume

95

DOI

10.1016/j.ebiom.2023.104742

Keywords

Bronchiolitis; Fungi; Metatranscriptome; Mycotype; Severity; Transcriptome

Abstract

BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics. METHODS: In a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity-defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data. RESULTS: In infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungivirus, B) fungivirus, C) fungivirus, D) fungivirus mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02-0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05). INTERPRETATION: In this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics. FUNDING: This study was supported by the National Institutes of Health.

APA Citation

Shibata, Ryohei; Zhu, Zhaozhong; Kyo, Michihito; Ooka, Tadao; Freishtat, Robert J.; Mansbach, Jonathan M.; Pérez-Losada, Marcos; Camargo, Carlos A.; and Hasegawa, Kohei, "Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity risk" (2023). GW Authored Works. Paper 3486.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3486

Department

Biostatistics and Bioinformatics