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).
abstract: BACKGROUND
  Rhinovirus infection is a major cause of asthma exacerbations.
  
  
  OBJECTIVE
  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 7days 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.
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK; Imperial College Healthcare NHS Trust, UK; Imperial Clinical Respiratory Research Unit (ICRRU), UK. Electronic address: t.hansel@imperial.ac.uk.
authors.forename: Trevor T
authors.initials: TT
authors.lastname: Hansel
authors.affiliation: Imperial College Healthcare NHS Trust, UK; Imperial Clinical Respiratory Research Unit (ICRRU), UK.
authors.forename: Tanushree
authors.initials: T
authors.lastname: Tunstall
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK; Imperial College Healthcare NHS Trust, UK.
authors.forename: Maria-Belen
authors.initials: MB
authors.lastname: Trujillo-Torralbo
authors.affiliation: Novartis Institute for Biomedical Research, Horsham, UK.
authors.forename: Betty
authors.initials: B
authors.lastname: Shamji
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK; Imperial College Healthcare NHS Trust, UK.
authors.forename: Ajerico
authors.initials: A
authors.lastname: Del-Rosario
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK; Imperial College Healthcare NHS Trust, UK.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Dhariwal
authors.affiliation: MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK.
authors.forename: Paul D W
authors.initials: PDW
authors.lastname: Kirk
authors.affiliation: Dept. of Theoretical Systems Biology at IC, UK.
authors.forename: Michael P H
authors.initials: MPH
authors.lastname: Stumpf
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; Medimmune, Cambridge, UK.
authors.forename: Jens
authors.initials: J
authors.lastname: Koopmann
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Aurica
authors.initials: A
authors.lastname: Telcian
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Aniscenko
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Gogsadze
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Eteri
authors.initials: E
authors.lastname: Bakhsoliani
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Luminita
authors.initials: L
authors.lastname: Stanciu
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Nathan
authors.initials: N
authors.lastname: Bartlett
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK.
authors.forename: Ross
authors.initials: R
authors.lastname: Walton
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK; Imperial College Healthcare NHS Trust, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.affiliation: Hunt Developments (UK) Ltd, Midhurst, West Sussex, UK.
authors.forename: Toby M
authors.initials: TM
authors.lastname: Hunt
authors.affiliation: Hunt Developments (UK) Ltd, Midhurst, West Sussex, UK.
authors.forename: Trevor L
authors.initials: TL
authors.lastname: Hunt
authors.affiliation: Hunt Developments (UK) Ltd, Midhurst, West Sussex, UK.
authors.forename: Duncan G
authors.initials: DG
authors.lastname: Hunt
authors.affiliation: Novartis Institute for Biomedical Research, Horsham, UK.
authors.forename: John
authors.initials: J
authors.lastname: Westwick
authors.affiliation: Novartis Institute for Biomedical Research, Horsham, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Imperial College Healthcare NHS Trust, UK; Imperial Clinical Respiratory Research Unit (ICRRU), UK.
authors.forename: Onn Min
authors.initials: OM
authors.lastname: Kon
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK; Guy's and St Thomas' NHS Trust.
authors.forename: David J
authors.initials: DJ
authors.lastname: Jackson
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College (IC), London, UK; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, UK; Imperial College Healthcare NHS Trust, UK.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000821:virology; D001980:Bronchi / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000821:virology; D010850:Picornaviridae Infections / Q000276:immunology*; D012229:Rhinovirus; D019562:Viral Load; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Absorption of mucosal lining fluid; Asthma; Interferons; Mucosal immunology; Rhinovirus; Type II inflammation