Inflammation and upper airway remodelling in natural and induced models of allergic rhinitis
File(s)
Author(s)
Orban, Nara T
Type
Thesis
Abstract
Introduction: Alterations in basement membrane thickness, collagen deposition, angiogenic and lymphangiogenic markers and changes in TGF- pathways, are features of remodelling seen in asthma. Such changes are not well-established in persistent allergic rhinitis (PAR).
Aims: To establish whether upper airway remodelling is a feature of PAR using two models of allergic rhinitis: natural seasonal allergen exposure (NAE) and repetitive allergen challenge (RAC) model.
Methods: Total nasal symptoms scores, nasal biopsies, and Th1 and Th2 cytokines from nasal secretions were assessed in subjects with severe PAR (n = 46), healthy control subjects (n = 19), and nasal polyp (NP) participants (n=11) who acted as positive controls. Angiolymphangiogenesis was examined using immunohistochemistry staining against CD31 (vascular endothelial cells), vascular endothelial growth factor-A, and D2-40 (lymphatic endothelial cells). Collagen and extracellular matrix proteins, such as heat shock protein-47 (collagen synthesis), matrix metalloproteinase-9, and tissue inhibitor metalloproteinase-1, and alpha-smooth muscle actin (myofibroblasts) were evaluated as markers of upper airway remodelling using image analysis. Submucosal effector inflammatory cells as well as TGF-, activin, ALK-4 and SMAD2 were measured using immunohistochemistry.
Results: Total nasal symptoms scores and quality of life were higher in PAR compared with healthy controls (P< 0.0001) in both NAE and RAC. Nasal secretion IL-4 (P< 0.01), IL-5, and IL-13 (P< 0.001) were significantly higher in PAR compared with healthy controls, with IL-5 increasing only in RAC. Submucosal eosinophils (P = 0.06) were increased in both NAE and RAC and neutrophils (p< 0.01) only in RAC. No differences were observed in angiogenesis, lymphangiogenesis, deposition of extracellular matrix, collagen markers, reticular basement membrane thickness, or glandular percentage area between PAR and healthy control subjects in either NAE or RAC models. TGF-p=0.04) and activin (p=0.01) were significantly raised in RAC with only TGF- (p=0.02) increasing in NAE.
Conclusions: Although TGF- pathway markers may be altered, remodelling is not a feature of moderate-severe persistent allergic rhinitis.
Aims: To establish whether upper airway remodelling is a feature of PAR using two models of allergic rhinitis: natural seasonal allergen exposure (NAE) and repetitive allergen challenge (RAC) model.
Methods: Total nasal symptoms scores, nasal biopsies, and Th1 and Th2 cytokines from nasal secretions were assessed in subjects with severe PAR (n = 46), healthy control subjects (n = 19), and nasal polyp (NP) participants (n=11) who acted as positive controls. Angiolymphangiogenesis was examined using immunohistochemistry staining against CD31 (vascular endothelial cells), vascular endothelial growth factor-A, and D2-40 (lymphatic endothelial cells). Collagen and extracellular matrix proteins, such as heat shock protein-47 (collagen synthesis), matrix metalloproteinase-9, and tissue inhibitor metalloproteinase-1, and alpha-smooth muscle actin (myofibroblasts) were evaluated as markers of upper airway remodelling using image analysis. Submucosal effector inflammatory cells as well as TGF-, activin, ALK-4 and SMAD2 were measured using immunohistochemistry.
Results: Total nasal symptoms scores and quality of life were higher in PAR compared with healthy controls (P< 0.0001) in both NAE and RAC. Nasal secretion IL-4 (P< 0.01), IL-5, and IL-13 (P< 0.001) were significantly higher in PAR compared with healthy controls, with IL-5 increasing only in RAC. Submucosal eosinophils (P = 0.06) were increased in both NAE and RAC and neutrophils (p< 0.01) only in RAC. No differences were observed in angiogenesis, lymphangiogenesis, deposition of extracellular matrix, collagen markers, reticular basement membrane thickness, or glandular percentage area between PAR and healthy control subjects in either NAE or RAC models. TGF-p=0.04) and activin (p=0.01) were significantly raised in RAC with only TGF- (p=0.02) increasing in NAE.
Conclusions: Although TGF- pathway markers may be altered, remodelling is not a feature of moderate-severe persistent allergic rhinitis.
Version
Open Access
Date Issued
2019-06
Date Awarded
2021-02
Copyright Statement
Creative Commons Attribution NonCommercial No Derivatives Licence
Advisor
Durham, Stephen
Publisher Department
Allergy and Clinical Immunology Section & Leukocyte Biology Section
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)