Elsevier

EBioMedicine

Volume 19, May 2017, Pages 128-138
EBioMedicine

Research Paper
A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-γ and IFN-λ) and Type 2 Inflammation (IL-5 and IL-13)

https://doi.org/10.1016/j.ebiom.2017.03.033Get rights and content
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Highlights

  • Following rhinovirus infection asthmatics have increased interferons and type 2 inflammation in airway mucosal lining fluid.

  • Nasosorption cytokines and chemokines showed distinct pathways of interferon and type 2 inflammation in asthma.

  • Precision mucosal sampling has potential for stratifying molecular endotypes of asthma.

  • Validation of nasosorption and bronchosorption will be required for selection of asthmatics for therapy with biologics.

Experimental human rhinovirus (HRV) infection causes more severe upper and lower respiratory tract symptoms in allergic asthmatics than in healthy controls. There is greater induction of cytokines and chemokines in nasal and bronchial mucosal lining fluid (MLF) of asthmatics: with distinct pathways of type 2 and anti-viral/regulatory inflammation.

Subject to further validation, analysis of MLF may prove useful in stratification of patients with asthma, and the definition of molecular endotypes.

Interpretation

Nasosorption and bronchosorption are precision sampling methods with potential for widespread application in respiratory and other mucosal diseases (e.g. gastrointestinal diseases).

Biomarkers identified in nasosorption and bronchosorption samples will need to be validated compared to established airway sampling methods, in a range of asthma phenotypes, and with current and novel therapies.

Abstract

Background

Rhinovirus infection is a major cause of asthma exacerbations.

Objectives

We studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations.

Methods

We used nasosorption on days 0, 2–5 and 7 and bronchosorption at baseline and day 4 to sample mucosal lining fluid to investigate airway mucosal responses to rhinovirus infection in patients with allergic asthma (n = 28) and healthy non-atopic controls (n = 11), by using a synthetic absorptive matrix and measuring levels of 34 cytokines and chemokines using a sensitive multiplex assay.

Results

Following rhinovirus infection asthmatics developed more upper and lower respiratory symptoms and lower peak expiratory flows compared to controls (all P < 0.05). Asthmatics also developed higher nasal lining fluid levels of an anti-viral pathway (including IFN-γ, IFN-λ/IL-29, CXCL11/ITAC, CXCL10/IP10 and IL-15) and a type 2 inflammatory pathway (IL-4, IL-5, IL-13, CCL17/TARC, CCL11/eotaxin, CCL26/eotaxin-3) (area under curve day 0–7, all P < 0.05). Nasal IL-5 and IL-13 were higher in asthmatics at day 0 (P < 0.01) and levels increased by days 3 and 4 (P < 0.01). A hierarchical correlation matrix of 24 nasal lining fluid cytokine and chemokine levels over 7 days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-γ, CXCL10/IP10, CXCL11/ITAC, IL-15 and IL-5 increased in bronchial lining fluid following viral infection (all P < 0.05).

Conclusions

Precision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation.

Keywords

Rhinovirus
Asthma
Mucosal immunology
Absorption of mucosal lining fluid
Interferons
Type II inflammation

Cited by (0)

1

DJJ and SLJ contributed equally as Senior Investigators.