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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-?, IFN-?/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 7days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-?, 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.
SUBMITTER: Hansel TT
PROVIDER: S-EPMC5440599 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Hansel Trevor T TT Tunstall Tanushree T Trujillo-Torralbo Maria-Belen MB Shamji Betty B Del-Rosario Ajerico A Dhariwal Jaideep J Kirk Paul D W PDW Stumpf Michael P H MPH Koopmann Jens J Telcian Aurica A Aniscenko Julia J Gogsadze Leila L Bakhsoliani Eteri E Stanciu Luminita L Bartlett Nathan N Edwards Michael M Walton Ross R Mallia Patrick P Hunt Toby M TM Hunt Trevor L TL Hunt Duncan G DG Westwick John J Edwards Matthew M Kon Onn Min OM Jackson David J DJ Johnston Sebastian L SL
EBioMedicine 20170328
<h4>Background</h4>Rhinovirus infection is a major cause of asthma exacerbations.<h4>Objectives</h4>We studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations.<h4>Methods</h4>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 ...[more]