Nasopharyngeal airway dual-transcriptome of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study

Zhaozhong Zhu, Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass. Electronic address: zzhu5@mgh.harvard.edu.
Carlos A. Camargo, Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass.
Yoshihiko Raita, Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass.
Robert J. Freishtat, Center for Genetic Medicine Research, Children's National Hospital, Washington, DC; Division of Emergency Medicine, Children's National Hospital, Washington, DC; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.
Michimasa Fujiogi, Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass.
Andrea Hahn, Center for Genetic Medicine Research, Children's National Hospital, Washington, DC; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC; Division of Infectious Diseases, Children's National Hospital, Washington, DC.
Jonathan M. Mansbach, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Jonathan M. Spergel, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pa.
Marcos Pérez-Losada, Computational Biology Institute, Department of Biostatistics and Bioinformatics, George Washington University School of Medicine and Health Sciences, Washington, DC; CIBIO-InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Vairão, Portugal.
Kohei Hasegawa, Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass.

Document Type

Journal Article

Publication Date

4-26-2022

Journal

The Journal of allergy and clinical immunology

DOI

10.1016/j.jaci.2022.04.017

Keywords

Bronchiolitis; asthma; dual-transcriptome; fatty acids; glycolysis; metabolome; microbiome; transcriptome

Abstract

BACKGROUND: Severe bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. OBJECTIVES: This study sought to examine the integrated role of airway microbiome (both taxonomy and function) and host response in asthma development in this high-risk population. METHODS: This multicenter prospective cohort study of 244 infants with severe bronchiolitis (median age, 3 months) examined the infants' nasopharyngeal metatranscriptomes (microbiomes) and transcriptomes (hosts), as well as metabolomes at hospitalization. The longitudinal relationships investigated include (1) major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), (2) microbial function, and (3) host response with risks of developing asthma by age 6 years. RESULTS: First, the abundance of S pneumoniae was associated with greater risks of asthma (P = .01), particularly in infants with nonrhinovirus infection (P = .04). Second, of 328 microbial functional pathways that are differentially enriched by asthma development, the top pathways (eg, fatty acid and glycolysis pathways; false discovery rate [FDR] < 1 × 10) were driven by these 3 major species (eg, positive association of S pneumoniae with glycolysis; FDR < 0.001). These microbial functional pathways were validated with the parallel metabolome data. Third, 104 transcriptome pathways were differentially enriched (FDR < .05)-for example, downregulated interferon-α and -γ and upregulated T-cell activation pathways. S pneumoniae was associated with most differentially expressed transcripts (eg, DAGLB; FDR < 0.05). CONCLUSIONS: By applying metatranscriptomic, transcriptomic, and metabolomic approaches to a multicenter cohort of infants with bronchiolitis, this study found an interplay between major bacterial species, their function, and host response in the airway, and their longitudinal relationship with asthma development.

Department

Pediatrics

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