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: virusRSVmicrobiomecommensals; profile B: virusRSV/RV-AmicrobiomeH.influenzae; profile C: virusRSVmicrobiomeS.pneumoniae; profile D: virusRSVmicrobiomeM.nonliquefaciens; and profile E: virusRSV/RV-CmicrobiomeM.catarrhalis. Compared with profile A, profile B infants were characterised by a high proportion of eczema, Haemophilus influenzae 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% versus 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, Streptococcus pneumoniae 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% versus 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.
Abstract
This study suggests a complex interplay between respiratory virus, airway microbiome and host immune response in infants with severe bronchiolitis, and their integrated contributions to the subsequent development of childhood asthma https://bit.ly/3xcM4ry
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.00378-2022This article has supplementary material available from erj.ersjournals.com
Conflict of interest: Y. Raita has nothing to disclose.
Conflict of interest: M. Pérez-Losada has nothing to disclose.
Conflict of interest: R.J. Freishtat has nothing to disclose.
Conflict of interest: A. Hahn has nothing to disclose.
Conflict of interest: E. Castro-Nallar has nothing to disclose.
Conflict of interest: I. Ramos-Tapia has nothing to disclose.
Conflict of interest: N.l Stearrett has nothing to disclose.
Conflict of interest: Y.A. Bochkov has patents on production methods of rhinoviruses.
Conflict of interest: J.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: J.M. Mansbach has nothing to disclose.
Conflict of interest: Z. Zhu has nothing to disclose.
Conflict of interest: C.A. Camargo has nothing to disclose.
Conflict of interest: K. Hasegawa has nothing to disclose.
Support statement: This study was supported by grants from the National Institutes of Health (NIH): U01 AI-087881, R01 AI-114552, R01 AI-108588, R01 AI-134940 and UG3/UH3 OD-023253. M. Pérez-Losada was partially supported by the Margaret Q. Landenberger Research Foundation, the NIH National Center for Advancing Translational Sciences (UL1 TR-001876) and the Fundação para a Ciência e a Tegnologia (T495756868-00032862). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funding organisations were not involved in the collection, management or analysis of the data; preparation or approval of the manuscript; or decision to submit the manuscript for publication. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received August 20, 2021.
- Accepted November 17, 2021.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org