Nasopharyngeal airway long noncoding RNAs of infants with bronchiolitis and subsequent risk of developing childhood asthma

Hideaki Miyachi; Tadao Ooka; Marcos Pérez-Losada; Carlos A Camargo Jr; Kohei Hasegawa; Zhaozhong Zhu

doi:10.1016/j.jaci.2024.01.010

Nasopharyngeal airway long noncoding RNAs of infants with bronchiolitis and subsequent risk of developing childhood asthma

J Allergy Clin Immunol. 2024 Jan 23:S0091-6749(24)00077-0. doi: 10.1016/j.jaci.2024.01.010. Online ahead of print.

Authors

Hideaki Miyachi¹, Tadao Ooka², Marcos Pérez-Losada³, Carlos A Camargo Jr¹, Kohei Hasegawa¹, Zhaozhong Zhu⁴

Affiliations

¹ Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
² Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass; Department of Health Sciences, University of Yamanashi, Chuo, Yamanashi, Japan.
³ Department of Biostatistics and Bioinformatics, Computational Biology Institute, The George Washington University, Washington, DC.
⁴ Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. Electronic address: zzhu5@mgh.harvard.edu.

PMID: 38272372
DOI: 10.1016/j.jaci.2024.01.010

Abstract

Background: Severe bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for developing childhood asthma. However, the biological mechanisms linking these 2 conditions remain unclear.

Objective: We sought to investigate the longitudinal relationship between nasopharyngeal airway long noncoding 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 examined the 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 (false-discovery rate [FDR] < 0.05) associated with asthma development (eg, LINC02145, RAMP2-AS1, and PVT1). These DE-lncRNAs were associated with asthma-related clinical characteristics (FDR < 0.05), for example, respiratory syncytial virus or rhinovirus infection, infant eczema, and IgE sensitization. Furthermore, DE-lncRNAs were characterized by asthma-related pathways, including mitogen-activated protein kinase, FcɛR, and phosphatidylinositol 3-kinase (PI3K)-protein kinase B signaling pathways (FDR < 0.05). These DE-lncRNAs were also associated with nasal cytokines (eg, IL-1β, IL-4, and IL-13; FDR < 0.05).

Conclusions: 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.

Keywords: Asthma; bronchiolitis; childhood asthma; infant; lncRNA; long noncoding RNA; multicenter; omics; prospective studies; transcriptomics.