Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 320, Issue 6, Pages L1147-L1157Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00440.2020
Keywords
immune system; precision medicine; respiratory syncytial virus; transcriptomics; viral bronchiolitis
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Funding
- Helen DeVos Children's Hospital, National Institutes of Health [K01ES025435]
- Michigan State University
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Viral infections affecting the lower respiratory tract impose significant burdens on hospitals, with no vaccines or antiviral agents available for many viruses. Analyzing risk factors and outcomes in patients using minimally invasive blood analysis can improve healthcare delivery. Transcriptomic analysis of infants with bronchiolitis and respiratory syncytial virus revealed immune system, interferon signaling, and cytokine signaling signatures in severe cases, with notable sex differences. Understanding patient-specific transcriptomic signatures is crucial for identifying unique infections, immune responses, and pathways in viral bronchiolitis.
Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDMSD, and L1NC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.
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