title: Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes.
abstract: Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis due to inhalant allergens. We aimed to develop a reproducible technique for grass pollen nasal allergen challenge and to study biomarkers within nasal secretions. 20 Grass pollen allergic individuals underwent nasal challenges with purified Timothy grass allergen. An initial dose-titration challenge was used to determine dose-response characteristics. Subsequently, volunteers underwent 3 further challenges using individualised threshold doses. Symptom scores, visual analogue scores, and peak nasal inspiratory flow (PNIF) were recorded at baseline and up to 6h after challenge. Nasal secretions were collected at each time point using synthetic filter papers or absorptive polyurethane sponges and analysed for IL-4, -5, -10, -13, IFN-γ, Tryptase and Eosinophil Cationic Protein (ECP). Challenges gave reproducible symptom scores and decreased PNIF. Tryptase levels in nasal fluid peaked at 5 min after challenge and returned to baseline levels at 1h. ECP, IL-5, IL-13 and IL-4 levels were increased from 2-3 h and showed progressive increases to 5-6 h. Sponges proved the superior nasal fluid sampling technique. We have developed a reproducible nasal allergen challenge technique. This may be used as a surrogate clinical endpoint in trials assessing the efficacy of treatments for allergic rhinitis. Tryptase in local nasal secretions is a potential biomarker of the early phase response; ECP and the Th2 cytokines IL-5, -13 and -4 markers of late phase allergic responses. Our model allows correlation between clinical responses and local biomarkers following nasal allergen challenge.
authors: Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, UK. g.scadding@imperial.ac.uk
authors: Guy W
authors: GW
authors: Scadding
authors: Moises A
authors: MA
authors: Calderon
authors: Virginia
authors: V
authors: Bellido
authors: Gitte Konsgaard
authors: GK
authors: Koed
authors: Niels-Christian
authors: NC
authors: Nielsen
authors: Kaare
authors: K
authors: Lund
authors: Alkis
authors: A
authors: Togias
authors: Deborah
authors: D
authors: Phippard
authors: Laurence A
authors: LA
authors: Turka
authors: Trevor T
authors: TT
authors: Hansel
authors: Stephen R
authors: SR
authors: Durham
authors: Peter Adler
authors: PA
authors: Wurtzen
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D047150:Eosinophil Cationic Protein / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009299:Nasal Provocation Tests / Q000379:methods*; D031784:Phleum / Q000276:immunology / Q000378:metabolism; D011058:Pollen / Q000276:immunology* / Q000378:metabolism; D015203:Reproducibility of Results; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013997:Time Factors; D053802:Tryptases / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000485:Allergens; D018793:Interleukin-13; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D047150:Eosinophil Cationic Protein; D053802:Tryptases