Nasopharyngeal airway long non-coding RNAs of infants with bronchiolitis and subsequent risk of developing childhood asthma

Authors

Hideaki Miyachi, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tadao Ooka, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Health Sciences, University of Yamanashi, Chuo, Yamanashi, Japan.
Marcos Pérez-Losada, Computational Biology Institute, Department of Biostatistics and Bioinformatics, The George Washington University, Washington, DC, 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.
Zhaozhong Zhu, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: zzhu5@mgh.harvard.edu.

Document Type

Journal Article

Publication Date

1-23-2024

Journal

The Journal of allergy and clinical immunology

DOI

10.1016/j.jaci.2024.01.010

Keywords

asthma; bronchiolitis; childhood asthma; infant; lncRNA; long non-coding RNA; multicenter; omics; prospective studies; transcriptomics

Abstract

BACKGROUND: Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a major risk factor for developing childhood asthma. However, the biological mechanisms linking these two conditions remain unclear. OBJECTIVE: We investigated the longitudinal relationship between nasopharyngeal airway long non-coding RNA (lncRNA) in infants with severe bronchiolitis and subsequent asthma development. METHODS: In this multicenter prospective cohort study of infants with severe bronchiolitis, we performed RNA-sequencing of nasopharyngeal airway lncRNAs at index hospitalization. First, we identified differentially expressed-lncRNAs (DE-lncRNAs) associated with asthma development by age 6 years. Second, we investigated the associations of DE-lncRNAs with asthma-related clinical characteristics. Third, to characterize the function of DE-lncRNAs, we performed pathway analysis for mRNA targeted by DE-lncRNAs. Finally, we also examined associations of DE-lncRNAs with nasal cytokines at index hospitalization. RESULTS: Among 343 infants with severe bronchiolitis (median age, 3 months), we identified 190 DE-lncRNAs (FDR<0.05) associated with asthma development (e.g., LINC02145, RAMP2-AS1, PVT1). These DE-lncRNAs were associated with asthma-related clinical characteristics (FDR<0.05)-e.g., respiratory syncytial virus or rhinovirus infection, infant eczema, and IgE sensitization. Furthermore, DE-lncRNAs were characterized by asthma-related pathways, including MAPK, FcɛR, and PI3K-Akt signaling pathways (FDR<0.05). These DE-lncRNAs were also associated with nasal cytokines (e.g., IL-1β, IL-4, IL-13; FDR<0.05). CONCLUSION: In a multicenter cohort study of infants with severe bronchiolitis, we identified nasopharyngeal airway lncRNAs associated with childhood asthma development, characterized by asthma-related clinical characteristics, asthma-related pathways, and nasal cytokines. Our approach identifies lncRNAs underlying the bronchiolitis-asthma link and facilitates the early identification of infants at high-risk of subsequent asthma development.

APA Citation

Miyachi, Hideaki; Ooka, Tadao; Pérez-Losada, Marcos; Camargo, Carlos A.; Hasegawa, Kohei; and Zhu, Zhaozhong, "Nasopharyngeal airway long non-coding RNAs of infants with bronchiolitis and subsequent risk of developing childhood asthma" (2024). GW Authored Works. Paper 4131.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4131

Department

Biostatistics and Bioinformatics