Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients

Antoine Deschildre,David Romero-Cubero,Philippe Gosset,Caroline Thumerelle,Irina Decleyre-Badiu,Anny Dewilde,Stéphanie Lejeune,Ilka Engelmann,Clémence Mordacq,Sophie Boileau,Véronique Néve,Elodie Drumez,Guillaume Pouessel,Carole Langlois,Muriel Pichavant,Didier Hober

doi:10.1186/s12931-017-0672-0

Abstract

BackgroundViruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function.MethodsVirus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells.ResultsViruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state.ConclusionOur results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation.Trial registrationThis multicenter prospective study was approved by the regional investigational review board (ref: 08/07).

Highlights

Viruses are important triggers of asthma exacerbations
As our results showed that an infection with a different virus is frequently detected in asthmatic patients at steady state [15, 16], we focused on the virus-infected patients at exacerbation in order to compare patients infected at both times to those only infected at the exacerbation
In re-infected patients, the inflammatory reaction was characterized by a strong secretion of IL-1β, which might be involved in the neutrophil recruitment observed at steady state. This feature was a Conclusion Our results support a more pronounced defect in IFN-γ and IFN-λ secretion during virus-triggered exacerbation in the asthmatic children prone to viral re-infection. This defect is associated with an overexpression of virus sensors, a defective response to the corresponding ligands and with a specific airway inflammation

Summary

Introduction

Viruses are important triggers of asthma exacerbations. They are detected outside of exacerbation. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. We hypothesized that alteration of the expression and/or function of virus sensors is associated with impaired innate immune response during virus-induced asthma exacerbation. These alterations might impact on clinical and inflammatory profiles. To test this hypothesis, the anti-viral response and the expression and function of the virus sensors in blood mononuclear cells were explored in a cohort of allergic asthmatic children admitted to hospital with a diagnosis of severe exacerbation. As our results showed that an infection with a different virus is frequently detected in asthmatic patients at steady state [15, 16], we focused on the virus-infected patients at exacerbation in order to compare patients infected at both times to those only infected at the exacerbation

Objectives

Methods

Results

Discussion

Conclusion