Nasopharyngeal metatranscriptome profiles of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study

Yoshihiko Raita, Dept of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA yraita1@alumni.jh.edu.
Marcos Pérez-Losada, Dept of Biostatistics and Bioinformatics and Computational Biology Institute, The George Washington University, Washington, DC, USA.
Robert J. Freishtat, Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, USA.
Andrea Hahn, Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, USA.
Eduardo Castro-Nallar, Centro de Bioinformática y Biología Integrativa, Universidad Andres Bello, Santiago, Chile.
Ignacio Ramos-Tapia, Centro de Bioinformática y Biología Integrativa, Universidad Andres Bello, Santiago, Chile.
Nathaniel Stearrett, Computational Biology Institute, The George Washington University, Washington, DC, USA.
Yury A. Bochkov, Dept of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
James E. Gern, Dept of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Jonathan M. Mansbach, Dept of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Zhaozhong Zhu, Dept of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Carlos A. Camargo, Dept of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Kohei Hasegawa, Dept of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Document Type

Journal Article

Publication Date

7-1-2022

Journal

The European respiratory journal

Volume

60

Issue

1

DOI

10.1183/13993003.02293-2021

Abstract

BACKGROUND: Bronchiolitis is not only the leading cause of hospitalisation in US infants but also a major risk factor for asthma development. Growing evidence supports clinical heterogeneity within bronchiolitis. Our objectives were to identify metatranscriptome profiles of infant bronchiolitis, and to examine their relationship with the host transcriptome and subsequent asthma development. METHODS: As part of a multicentre prospective cohort study of infants (age <1 year) hospitalised for bronchiolitis, we integrated virus and nasopharyngeal metatranscriptome (species-level taxonomy and function) data measured at hospitalisation. We applied network-based clustering approaches to identify metatranscriptome profiles. We then examined their association with the host transcriptome at hospitalisation and risk for developing asthma. RESULTS: We identified five metatranscriptome profiles of bronchiolitis (n=244): profile A: virusmicrobiome; profile B: virusmicrobiome ; profile C: virusmicrobiome ; profile D: virusmicrobiome ; and profile E: virusmicrobiome . Compared with profile A, profile B infants were characterised by a high proportion of eczema, abundance and enriched virulence related to antibiotic resistance. These profile B infants also had upregulated T-helper 17 and downregulated type I interferon pathways (false discovery rate (FDR) <0.005), and significantly higher risk for developing asthma (17.9% 38.9%; adjusted OR 2.81, 95% CI 1.11-7.26). Likewise, profile C infants were characterised by a high proportion of parental asthma, dominance, and enriched glycerolipid and glycerophospholipid metabolism of the microbiome. These profile C infants had an upregulated RAGE signalling pathway (FDR <0.005) and higher risk of asthma (17.9% 35.6%; adjusted OR 2.49, 95% CI 1.10-5.87). CONCLUSIONS: Metatranscriptome and clustering analysis identified biologically distinct metatranscriptome profiles that have differential risks of asthma.

Department

Pediatrics

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