Abstract
The question addressed by the study Bronchiolitis is not only the leading cause of hospitalisation in U.S. infants but also a major risk factor for asthma development. Growing evidence supports clinical heterogeneity within bronchiolitis. To identify metatranscriptome profiles of infant bronchiolitis, and examine their relationship with host transcriptome and subsequent asthma development.
Materials/patients and methods As part of multicentre prospective cohort study of infants (age <12 months) 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 host transcriptome at hospitalisation and risk for developing asthma.
Results We identified five metatranscriptome profiles of bronchiolitis (n=244):
A) virusRSVmicrobiomecommensals, B) virusRSV/RV-AmicrobiomeH.influenzae,
C) virusRSVmicrobiomeS.pneumoniae, D) virusRSVmicrobiomeM.nonliquefaciens, and
E) virusRSV/RV-CmicrobiomeM.catarrhalis. Compared with profile A, profile B infants were characterised by high proportion of eczema, H. influenzae abundance, and enriched virulence related to antibiotic resistance. These profile B infants also had upregulated TH17 and downregulated type I interferon pathways (FDR<0.005) and significantly higher risk for developing asthma (17.9% versus 38.9%; adjOR, 2.81; 95%CI, 1.11–7.26). Likewise, profile C infants were characterised by high proportion of parental asthma, S. pneumoniae dominance, and enriched glycerolipid and glycerophospholipid metabolism of microbiome. These profile C infants had upregulated receptor for advanced glycation end products signalling pathway (FDR<0.005) and higher risk of asthma (17.9% versus 35.6%; adjOR, 2.49; 95%CI, 1.10–5.87).
Answer to the question Metatranscriptome and clustering analysis identified biologically-distinct metatranscriptome profiles that have differential risks of asthma.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Yoshihiko Raita has nothing to disclose.
Conflict of interest: Marcos Pérez-Losada has nothing to disclose.
Conflict of interest: Robert J. Freishtat has nothing to disclose.
Conflict of interest: Andrea Hahn has nothing to disclose.
Conflict of interest: Eduardo Castro-Nallar has nothing to disclose.
Conflict of interest: Ignacio Ramos-Tapia has nothing to disclose.
Conflict of interest: Nathaniel Stearrett has nothing to disclose.
Conflict of interest: Dr. Yury A. Bochkov has patents on production methods of rhinoviruses.
Conflict of interest: Dr. James E. Gern is a paid consultant to AstraZeneca and Meissa Vaccines Inc., has stock options in Meissa Vaccines Inc., and has patents on production methods of rhinoviruses.
Conflict of interest: Jonathan M. Mansbach has nothing to disclose.
Conflict of interest: Zhaozhong Zhu has nothing to disclose.
Conflict of interest: Carlos A. Camargo Jr. has nothing to disclose.
Conflict of interest: Kohei Hasegawa has nothing to disclose.
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- Received August 20, 2021.
- Accepted November 17, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org