Reduced nasal viral load and IFN responses in infants with RSV bronchiolitis and respiratory failure

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Title: Reduced nasal viral load and IFN responses in infants with RSV bronchiolitis and respiratory failure
Authors: 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
Item Type: Journal Article
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<0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of NPA samples (n=43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A. CONCLUSIONS: Infants with severe RSV bronchiolitis have lower nasal viral load, IP-10/CXCL10 and type-I IFNs levels compared to moderately ill children, but enhanced MUC5AC and IL17A gene expression in nasal cells.
Issue Date: 24-Apr-2018
Date of Acceptance: 23-Apr-2018
URI: http://hdl.handle.net/10044/1/60334
DOI: https://doi.org/10.1164/rccm.201712-2567OC
ISSN: 1073-449X
Publisher: American Thoracic Society
Start Page: 1074
End Page: 1084
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 198
Issue: 8
Copyright Statement: © 2018 by the American Thoracic Society.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Funder's Grant Number: RDA02
NF-SI-0513-10150
Keywords: Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
viral bronchiolitis
respiratory syncytial virus
nasosorption
interferon
innate immunity
PRIMARY RSV BRONCHIOLITIS
T-CELL EXHAUSTION
DISEASE SEVERITY
YOUNG-CHILDREN
RISK-FACTORS
INFECTION
CYTOKINE
INTERFERONS
ASSOCIATION
NEUTROPHILS
innate immunity
interferon
nasosorption
respiratory syncytial virus
viral bronchiolitis
innate immunity
interferon
nasosorption
respiratory syncytial virus
viral bronchiolitis
11 Medical and Health Sciences
Respiratory System
Publication Status: Published
Conference Place: United States
Open Access location: https://www.atsjournals.org/doi/10.1164/rccm.201712-2567OC
Online Publication Date: 2018-04-24
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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