title: Safety, efficacy and repeatability of a novel house dust mite allergen challenge technique in the Fraunhofer allergen challenge chamber.
abstract: Efficacy testing of immunotherapy in field studies is often hampered by variation of airborne allergens. Standardized allergen exposure in challenge chamber settings might be an alternative. Therefore, we developed a universal technique to create an atmosphere loaded with allergen particles of adjustable size from aqueous solutions of licensed allergen extracts.
  
  
  
  The aim of this study was to apply this technique and test the safety and efficacy of challenges with house dust mite (HDM) allergen in the Fraunhofer allergen challenge chamber.
  
  
  
  Aerosol particles carrying HDM allergen were produced by spray-drying of an aqueous solution containing HDM allergen and lactose. In a monocenter, placebo-controlled, single-blind, dose-escalation pilot study, 18 subjects with perennial allergic rhinitis and sensitization to HDM were exposed to HDM allergen for 4 h at either 250, 500, 1000 SQE/m3or lactose alone (0 SQE/m3) 7 days apart. The dose of 500 SQE/m³ was repeated to investigate reproducibility. Total nasal symptom score (TNSS) was the primary endpoint.
  
  
  
  Exposure to HDM increased TNSS (mean ± SD) to 3.4 ± 1.8, 3.3 ± 2.1, and 3.6 ± 2.0 at 250, 500 and 1000 SQE/m3, respectively, while lactose alone did not change TNSS (0.7 ± 0.6). The results were reproducible at 500 SQE/m3. Pulmonary function and adverse event frequency did not change with escalation of allergen dose.
  
  
  
  This HDM allergen particle generation is safe, specific and reproducible and can therefore be used for efficacy testing of immunotherapy and for basic clinical research.
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Lueer
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Biller
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Casper
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Windt
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Badorrek
authors.affiliation: Allergopharma GmbH & Co. KG, Reinbek, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Haefner
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Framke
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Koch
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Ziehr
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease - Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Krug
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Koch
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.|Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease - Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Hohlfeld
mesh_terms: D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003888:Desensitization, Immunologic; D045853:Exhalation; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D012129:Respiratory Function Tests; D065631:Rhinitis, Allergic / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D012307:Risk Factors; D055815:Young Adult
chemical_list: D039741:Antigens, Dermatophagoides; D009569:Nitric Oxide; D007073:Immunoglobulin E
keywords: aerosol generation; allergen challenge; allergic rhinitis; clinical trial; immunotherapy