Nara T Orban1,2, Mikila R Jacobson1,2, Kayhan T Nouri-Aria1,2, Stephen R Durham1,2, Aarif O Eifan1,2. 1. Allergy and Clinical Immunology, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, Faculty of Medicine, Imperial College London, London, UK. 2. Allergy Department, Royal Brompton and Harefield Hospitals NHS Trust, Imperial College London, London, UK.
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 submucosal 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 < .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 < .01, P = .01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r = 0.79, P = .007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r = 0.69, P = .06) in allergic rhinitis. No differences were observed after RAC with regard 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 with 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.
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 submucosal 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 < .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 < .01, P = .01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r = 0.79, P = .007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r = 0.69, P = .06) in allergic rhinitis. No differences were observed after RAC with regard 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 with 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.
Authors: Pavel Kolkhir; Daniel Elieh-Ali-Komi; Martin Metz; Frank Siebenhaar; Marcus Maurer Journal: Nat Rev Immunol Date: 2021-10-05 Impact factor: 53.106
Authors: Jonathan Corren; Sarbjit S Saini; Remi Gagnon; Mark H Moss; Gordon Sussman; Joshua Jacobs; Elizabeth Laws; Elinore S Chung; Tatiana Constant; Yiping Sun; Jennifer Maloney; Jennifer D Hamilton; Marcella Ruddy; Claire Q Wang; Meagan P O'Brien Journal: J Asthma Allergy Date: 2021-08-16