Repetitive nasal allergen challenge in allergic rhinitis: priming and Th2-type inflammation but no evidence of remodelling.
File(s)
Supporting information
Supporting information
Author(s)
Orban, Nara
Jacobson, Mikila R
Nouri-Aria, Kayhan T
Durham, Stephen R
Eifan, Aarif O
Type
Journal Article
Abstract
BACKGROUND: Local tissue eosinophilia and Th2-cytokines are characteristic features of seasonal allergic rhinitis. Airway-remodelling is a feature of asthma whereas evidence for remodelling in allergic rhinitis (AR) is conflicting. OBJECTIVE: By use of a novel human repetitive nasal allergen challenge (RAC) model, we evaluated the relationship between allergic inflammation and features of remodelling in AR. METHODS: Twelve patients with moderate-severe AR underwent 5-alternate day challenges with diluent which after 4-weeks were followed by 5-alternate day challenges with grass pollen extract. Nasal symptoms, Th1/Th2 cytokines in nasal secretion and serum were evaluated. Nasal biopsies were taken 24 hours after the 1st and 5th challenges with diluent and with allergen. Sixteen healthy controls underwent a single challenge with diluent and with allergen. Using immunohistochemistry, epithelial and sub-mucosal inflammatory cells, and remodelling markers were evaluated by computed image analysis. RESULTS: There was an increase in early and late-phase symptoms after every allergen challenge compared to diluent (both p<0.05) with evidence of both clinical and immunological priming. Nasal tissue eosinophils and IL-5 in nasal secretion increased significantly after RAC compared to corresponding diluent challenges (p<0.01, p=0.01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r=0.79, p=0.007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r=0.69, p=0.06) in allergic rhinitis. No differences were observed after RAC with regards to epithelial integrity, reticular basement membrane thickness, glandular area, expression of markers of activation of airway-remodelling including α-SMA, HSP-47, extracellular matrix (MMP7, 9 and TIMP-1), angiogenesis and lymphangiogenesis for AR compared to healthy controls. CONCLUSION: Novel repetitive nasal allergen challenge in participants with severe persistent seasonal allergic rhinitis resulted in tissue eosinophilia and increases in IL-5 but no structural changes. Our data support no link between robust Th2-inflammation and development of airway-remodelling in AR.
Date Issued
2021-02
Date Acceptance
2020-10-28
Citation
Clinical and Experimental Allergy, 2021, 51 (2), pp.329-338
ISSN
0954-7894
Publisher
Wiley
Start Page
329
End Page
338
Journal / Book Title
Clinical and Experimental Allergy
Volume
51
Issue
2
Copyright Statement
© 2020 John Wiley & Sons Ltd. This is the accepted version of the following article: Orban, N, Jacobson, MR, Nouri‐Aria, KT, Durham, SR, Eifan, AO. Repetitive nasal allergen challenge in allergic rhinitis: Priming and Th2‐type inflammation but no evidence of remodelling. Clin Exp Allergy. 2021; 51: 329– 338, which has been published in final form at https://doi.org/10.1111/cea.13775
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33141493
Subjects
Allergic
angiogenesis
early and late phase response
eosinophils
inflammation
lymphangiogenesis
mast cells
priming
remodelling
repetitive allergen challenge
rhinitis
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2020-11-03