Proteomics endotyping of infants with severe bronchiolitis and risk of childhood asthma

Authors

Tadao Ooka, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Yoshihiko Raita, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Michimasa Fujiogi, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Robert J. Freishtat, Center for Genetic Medicine Research and Division of Emergency Medicine Children's National Hospital, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Robert E. Gerszten, Division of Cardiovascular Medicine and Cardiovascular Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Jonathan M. Mansbach, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Zhaozhong Zhu, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Carlos A. Camargo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kohei Hasegawa, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Document Type

Journal Article

Publication Date

5-27-2022

Journal

Allergy

DOI

10.1111/all.15390

Keywords

asthma; bronchiolitis; endotyping; infants; proteome

Abstract

BACKGROUND: Bronchiolitis is the leading cause of hospitalization in U.S. infants and a major risk factor for childhood asthma. Growing evidence supports clinical heterogeneity within bronchiolitis. We aimed to identify endotypes of infant bronchiolitis by integrating clinical, virus, and serum proteome data, and examine their relationships with asthma development. METHODS: This is a multicenter prospective cohort study of infants hospitalized for physician-diagnosis of bronchiolitis. We identified bronchiolitis endotypes by applying unsupervised machine learning (clustering) approaches to integrated clinical, virus (respiratory syncytial virus [RSV], rhinovirus [RV]), and serum proteome data measured at hospitalization. We then examined their longitudinal association with the risk for developing asthma by age 6 years. RESULTS: In 140 infants hospitalized with bronchiolitis, we identified three endotypes: (1) clinical virus proteome , (2) clinical virus proteome , and (3) clinical virus proteome endotypes. Endotype 1 infants were characterized by high proportion of IgE sensitization and RV infection. These endotype 1 infants also had dysregulated NFκB pathways (FDR < 0.001) and significantly higher risks for developing asthma (53% vs. 22%; adjOR 4.04; 95% CI, 1.49-11.0; p = 0.006), compared with endotype 3 (clinically resembling "classic" bronchiolitis). Likewise, endotype 2 infants were characterized by low proportion of IgE sensitization and high proportion of RSV or RV infection. These endotype 2 infants had dysregulated tumor necrosis factor (TNF)-mediated signaling pathway (FDR <0.001) and significantly higher risks for developing asthma (44% vs. 22%; adjOR 2.71; 95% CI, 1.03-7.11, p = 0.04). CONCLUSION: In this multicenter cohort, integrated clustering of clinical, virus, and proteome data identified biologically distinct endotypes of bronchiolitis that have differential risks of asthma development.

APA Citation

Ooka, Tadao; Raita, Yoshihiko; Fujiogi, Michimasa; Freishtat, Robert J.; Gerszten, Robert E.; Mansbach, Jonathan M.; Zhu, Zhaozhong; Camargo, Carlos A.; and Hasegawa, Kohei, "Proteomics endotyping of infants with severe bronchiolitis and risk of childhood asthma" (2022). GW Authored Works. Paper 907.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/907

Department

Pediatrics