1. Reduced nasal viral load and IFN responses in infants with RSV bronchiolitis and respiratory failure
- Author
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Thwaites, RS, Coates, M, Ito, K, Ghazaly, M, Feather, C, Abdulla, F, Tunstall, T, Jain, P, Cass, L, Rapeport, G, Hansel, TT, Nadel, S, Openshaw, PJ, Imperial College Healthcare NHS Trust- BRC Funding, and National Institute for Health Research
- Subjects
Male ,YOUNG-CHILDREN ,respiratory syncytial virus ,Respiratory System ,Respiratory Syncytial Virus Infections ,INTERFERONS ,Critical Care Medicine ,viral bronchiolitis ,General & Internal Medicine ,INFECTION ,Bronchiolitis, Viral ,Humans ,nasosorption ,innate immunity ,NEUTROPHILS ,11 Medical and Health Sciences ,Science & Technology ,T-CELL EXHAUSTION ,Infant, Newborn ,Infant ,interferon ,ASSOCIATION ,respiratory system ,Viral Load ,CYTOKINE ,Nasal Mucosa ,PRIMARY RSV BRONCHIOLITIS ,DISEASE SEVERITY ,RISK-FACTORS ,Cytokines ,Female ,Chemokines ,Respiratory Insufficiency ,Transcriptome ,Life Sciences & Biomedicine - Abstract
RATIONALE: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is thought to result from uncontrolled viral replication, an excessive immune response, or both. OBJECTIVES: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. METHODS: Infants with viral bronchiolitis necessitating admission (n=55) were recruited from a paediatric centre during 2016/17. Of these, 30 were RSV infected (18 'moderate', and 12 mechanically ventilated 'severe'). Nasal fluids were sampled frequently over time using nasosorption devices and nasophayngeal aspiration (NPA). Hierarchical clustering of time weighted averages (TWA) was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. MEASUREMENTS AND MAIN RESULTS: Unexpectedly, cases of severe RSV bronchiolitis had lower nasal viral loads and reduced interferon (IFN)-γ and CCL5/RANTES levels compared to those with moderate disease, especially when allowance was made for disease duration (all P
- Published
- 2018