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)

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Title: 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)
Authors: Tunstall, T
Kon, OM
Bartlett, N
Hansel, TT
Johnston, SL
Mallia, P
Jackson, DJ
Walton, R
Edwards, M
Trujillo-Torralbo, MB
Del-Rosario, A
Shamji, B
Dhariwal, J
Kirk, P
Stumpf, M
Koopmann, JO
Telcian, A
Aniscenko, J
Gogsadze, L
Bakhsoliani, E
Stanciu, L
Hunt, TM
Hunt, TL
Hunt, DG
Westwick, J
Edwards, M
Item Type: Journal Article
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.
Issue Date: 28-Mar-2017
Date of Acceptance: 24-Mar-2017
URI: http://hdl.handle.net/10044/1/45996
DOI: https://dx.doi.org/10.​1016/​j.​ebiom.​2017.​03.​033
ISSN: 2352-3964
Publisher: Elsevier
Start Page: 128
End Page: 138
Journal / Book Title: EBioMedicine
Volume: 19
Copyright Statement: © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: British Lung Foundation
Asthma UK
Asthma UK
Asthma UK
Commission of the European Communities
Commission of the European Communities
Asthma UK
Asthma UK
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: P04/13
02/027
08/048
08/048
233015
260895
CH11SJ
CH11SJ
G1000758
DHRBA_P26095
Keywords: Absorption of mucosal lining fluid
Asthma
Interferons
Mucosal immunology
Rhinovirus
Type II inflammation
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine
Faculty of Natural Sciences



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