title: Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge.
abstract: BACKGROUND
  Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments.
  
  
  OBJECTIVE
  To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study.
  
  
  METHODS
  We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a nonatopic control group (n = 14). Volunteers underwent a standardized NAC with 2000 biological units of timothy grass allergen (equivalent to 1.3 μg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed.
  
  
  RESULTS
  Immunotherapy-treated patients had lower symptom scores (P = 0.04) and higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective seasonal symptom scores (P < 0.0001). Compared to untreated allergics, immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL-9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison), and trends for reduced IL-13 (P = 0.07, area under the curve) and early-phase tryptase levels (P = 0.06).
  
  
  CONCLUSIONS
  Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: G W
authors.initials: GW
authors.lastname: Scadding
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: A O
authors.initials: AO
authors.lastname: Eifan
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Lao-Araya
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Penagos
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: S Y
authors.initials: SY
authors.lastname: Poon
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Steveling
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Yan
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Switzer
authors.affiliation: Immune Tolerance Network, Bethesda, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Phippard
authors.affiliation: The National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Togias
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Shamji
authors.affiliation: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D012634:Bodily Secretions / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology*; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D031784:Phleum / Q000276:immunology*; D010936:Plant Extracts / Q000627:therapeutic use*; D011058:Pollen / Q000276:immunology*; D065631:Rhinitis, Allergic / Q000188:drug therapy* / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology; D063729:Sublingual Immunotherapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016207:Cytokines; D010936:Plant Extracts
keywords: Th2; allergic rhinitis; chemokine; cytokine; tryptase