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

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.