Immunoglobulin E-virus phenotypes of infant bronchiolitis and risk of childhood asthma

Ryohei Shibata; Zhaozhong Zhu; Tadao Ooka; Robert J Freishtat; Jonathan M Mansbach; Marcos Pérez-Losada; Ignacio Ramos-Tapia; Stephen Teach; Carlos A Camargo Jr; Kohei Hasegawa

doi:10.3389/fimmu.2023.1187065

Immunoglobulin E-virus phenotypes of infant bronchiolitis and risk of childhood asthma

Front Immunol. 2023 May 10:14:1187065. doi: 10.3389/fimmu.2023.1187065. eCollection 2023.

Authors

Ryohei Shibata¹, Zhaozhong Zhu¹, Tadao Ooka^{1

2}, Robert J Freishtat^{3

4

5}, Jonathan M Mansbach⁶, Marcos Pérez-Losada⁷, Ignacio Ramos-Tapia⁸, Stephen Teach^{4

5

9}, Carlos A Camargo Jr¹, Kohei Hasegawa¹

Affiliations

¹ Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
² Department of Health Science, University of Yamanashi, Yamanashi, Japan.
³ Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, United States.
⁴ Division of Emergency Medicine, Children's National Hospital, Washington, DC, United States.
⁵ Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
⁶ Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
⁷ Department of Biostatistics and Bioinformatics, Computational Biology Institute, The George Washington University, Washington, DC, United States.
⁸ Microbial Data Science Laboratory, Center for Bioinformatics and Integrative Biology, Universidad Andres Bello, Santiago, Chile.
⁹ Center for Translational Research, Children's National Research Institute, Washington, DC, United States.

Abstract

Background: Bronchiolitis is the leading cause of infant hospitalization in U.S. and is associated with increased risk for childhood asthma. Immunoglobulin E (IgE) not only plays major roles in antiviral immune responses and atopic predisposition, but also offers a potential therapeutic target.

Objective: We aimed to identify phenotypes of infant bronchiolitis by using total IgE (tIgE) and virus data, to determine their association with asthma development, and examine their biological characteristics.

Methods: In a multicenter prospective cohort study of 1,016 infants (age <1 year) hospitalized for bronchiolitis, we applied clustering approaches to identify phenotypes by integrating tIgE and virus (respiratory syncytial virus [RSV], rhinovirus [RV]) data at hospitalization. We examined their longitudinal association with the risk of developing asthma by age 6 years and investigated their biological characteristics by integrating the upper airway mRNA and microRNA data in a subset (n=182).

Results: In infants hospitalized for bronchiolitis, we identified 4 phenotypes: 1) tIgE^lowvirus^RSV-high, 2) tIgE^lowvirus^RSV-low/RV, 3) tIgE^highvirus^RSV-high, and 4) tIgE^highvirus^RSV-low/RV phenotypes. Compared to phenotype 1 infants (resembling "classic" bronchiolitis), phenotype 4 infants (tIgE^highvirus^RSV-low/RV) had a significantly higher risk for developing asthma (19% vs. 43%; adjOR, 2.93; 95% CI, 1.02-8.43; P=.046). Phenotypes 3 and 4 (tIgE^high) had depleted type I interferon and enriched antigen presentation pathways; phenotype 4 also had depleted airway epithelium structure pathways.

Conclusions: In this multicenter cohort, tIgE-virus clustering identified distinct phenotypes of infant bronchiolitis with differential risks of asthma development and unique biological characteristics.

Keywords: RSV (respiratory syncytial virus); asthma; bronchiolitis; immunoglobulin E; mRNA; microRNA; phenotyping; rhinovirus (RV).

Publication types

Multicenter Study
Research Support, N.I.H., Extramural

MeSH terms

Asthma*
Bronchiolitis*
Humans
Immunoglobulin E / genetics
Phenotype
Prospective Studies
Respiratory Syncytial Virus Infections*
Respiratory Syncytial Virus, Human*
Rhinovirus
Viruses*

Substances

Immunoglobulin E

Abstract

Publication types

MeSH terms

Substances

Grants and funding