EBioMedicine (May 2017)

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)

  • Trevor T. Hansel,
  • Tanushree Tunstall,
  • Maria-Belen Trujillo-Torralbo,
  • Betty Shamji,
  • Ajerico del-Rosario,
  • Jaideep Dhariwal,
  • Paul D.W. Kirk,
  • Michael P.H. Stumpf,
  • Jens Koopmann,
  • Aurica Telcian,
  • Julia Aniscenko,
  • Leila Gogsadze,
  • Eteri Bakhsoliani,
  • Luminita Stanciu,
  • Nathan Bartlett,
  • Michael Edwards,
  • Ross Walton,
  • Patrick Mallia,
  • Toby M. Hunt,
  • Trevor L. Hunt,
  • Duncan G. Hunt,
  • John Westwick,
  • Matthew Edwards,
  • Onn Min Kon,
  • David J. Jackson,
  • Sebastian L. Johnston

DOI
https://doi.org/10.1016/j.ebiom.2017.03.033
Journal volume & issue
Vol. 19, no. C
pp. 128 – 138

Abstract

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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.

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