title: Severe Persistent Allergic Rhinitis. Inflammation but No Histologic Features of Structural Upper Airway Remodeling.
abstract: BACKGROUND
  Increases in airway smooth muscle, extracellular matrix, and vascularity are prominent features of airway remodeling in asthma, whereas the extent of such remodeling in patients with persistent allergic rhinitis (PAR) is unknown.
  
  
  OBJECTIVE
  To test the hypothesis that upper airway remodeling is a feature of PAR.
  
  
  METHODS
  Total nasal symptoms scores, nasal biopsies, and Th1 and Th2 cytokines from nasal lavage were assessed in subjects with severe PAR (n = 46) and healthy control subjects (n = 19). 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 (markers of collagen synthesis), matrix metalloproteinase-9, and tissue inhibitor metalloproteinase-1, and α-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of upper airway remodeling using image analysis, together with reticular basement membrane thickness, mucus gland area, collagen area, and submucosal effector inflammatory cells.
  
  
  RESULTS
  Total nasal symptoms scores, visual analog scale, and total quality of life were significantly higher in PAR compared with healthy control subjects (P < 0.0001). Nasal lavage cytokine levels of IL-4 (P < 0.01), IL-5, and IL-13 (P < 0.001, respectively) were significantly higher in PAR compared with healthy control subjects. In addition there was an increase in submucosal eosinophils (P = 0.06). No statistical difference in terms of angiogenesis, lymphangiogenesis, deposition of extracellular matrix, collagen markers, reticular basement membrane thickness, or glandular percentage area was observed between PAR and healthy control subjects.
  
  
  CONCLUSIONS
  Our data suggest that tissue remodeling is not a feature of PAR and argues that in contrast to asthma, targeting remodeling in allergic rhinitis may not be appropriate as a therapeutic approach.
authors.affiliation: 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, United Kingdom.
authors.forename: Aarif O
authors.identifier: http://orcid.org/0000-0003-4098-4211
authors.initials: AO
authors.lastname: Eifan
authors.affiliation: 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, United Kingdom.
authors.forename: Nara T
authors.initials: NT
authors.lastname: Orban
authors.affiliation: 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, United Kingdom.
authors.forename: Mikila R
authors.identifier: http://orcid.org/0000-0002-2921-6169
authors.initials: MR
authors.lastname: Jacobson
authors.affiliation: 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, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D000293:Adolescent; D000328:Adult; D056151:Airway Remodeling; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism; D065631:Rhinitis, Allergic / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D050958:HSP47 Heat-Shock Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D020780:Matrix Metalloproteinase 9
keywords: allergen; allergic rhinitis; angiogenesis; collagen; lymphangiogenesis