Safety, efficacy and repeatability of a novel house dust mite allergen challenge technique in the Fraunhofer allergen challenge chamber.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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/m3 or 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. RESULTS: 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. CONCLUSION: 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.

A combination of cetirizine and pseudoephedrine has therapeutic benefits when compared to single drug treatment in allergic rhinitis.

UNLABELLED: Antihistamines and nasal decongestants are well-established therapeutics in allergic rhinitis. However, no data are available which directly compare the effect size of the single substances with their combination in a single study including placebo (PLA) treatment. OBJECTIVE: The aim of this study was to evaluate the effect of a combination of cetirizine (CET) and pseudoephedrine (PSE) and to compare it to treatment with CET or PSE alone and to PLA during grass pollen allergen challenge in an environmental challenge chamber (ECC). MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled, four-way crossover study the effect of a combination of 10 mg CET with 120 mg PSE (CET + PSE) versus CET or PSE alone or PLA on symptoms, nasal flow, and nasal secretions was investigated in 49 patients with intermittent allergic rhinitis. Subjects underwent four 6-h pollen exposures in an ECC with administration of the drugs after 2 h. RESULTS: The induction of nasal symptoms, nasal secretion and nasal obstruction (measured as nasal flow) during the first 2 h of pollen exposure was highly reproducible at the 4 consecutive exposures. The symptom of nasal obstruction was significantly reduced after treatment with CET + PSE compared to the treatment with CET or PSE alone or PLA (p < 0.0001). Furthermore, the combination treatment significantly reduced the total nasal symptom score (TNSS) and visual analogue scale score (VAS) compared to the single treatments or PLA. Nasal flow was significantly increased after treatment with CET + PSE and PSE and nasal secretions were significantly reduced by CET + PSE and CET without significant additional improvement of the combination therapy. CONCLUSION: The combination treatment with CET and PSE is more effective than treatment with single substances in subjects with allergic rhinitis.

Validation of an environmental exposure unit for controlled human inhalation studies with grass pollen in patients with seasonal allergic rhinitis.

BACKGROUND: There is an increasing need for allergen inhalation systems to perform basic clinical research and test anti-allergic drugs under well-controlled conditions. This requires stability of environmental conditions like temperature and humidity, as well as allergen concentration and reproducible induction of allergic symptoms. OBJECTIVE: The aim of this study was to validate an environmental exposure unit for controlled human pollen inhalation studies in participants with seasonal allergic rhinitis. METHODS: Temperature, relative humidity, and air flow rate were kept constant with an air conditioning system. Pollen atmosphere was generated using a specially designed feeding system and monitored online by laser counter and offline using rotating rod samplers. Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and safety (lung function) parameters were evaluated at different pollen concentrations and repeated allergen challenges. RESULTS: Temperature, humidity, and air flow rate in the environmental exposure unit remained constant within a range of <2%. The spatial distribution and the temporal stability of the pollen concentration varied only slightly over 4 h (+/-10% and <4%, respectively). Dose-dependent induction of allergic rhinitis symptoms, reduction in nasal air flow rate, and increase in nasal secretion were observed over time. These effects were reproducible from day to day. Lung function remained clinically normal at all concentrations and from day to day. CONCLUSIONS: Thus, pollen exposure in the environmental exposure unit is an effective, reproducible, safe, and suitable method for single-centre clinical studies on the efficacy of anti-allergic treatment or basic clinical research.