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I Dear Editor i , This mono-centre, randomized, open-label, observer-blinded parallel-group study (clinicaltrials.gov; NCT03315611) was initiated to study effects of emollients on skin inflammation in atopic dermatitis (AD) upon grass pollen exposure in moderately to highly grass pollen IgE-sensitized patients (approved by the Ethics committee MHH, no. 7586). Taken together, this is the first study to elucidate effects of basic therapy on allergen-induced skin inflammatory immune responses and on the skin microbiome in AD. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Allergic rhinitis has the greatest prevalence of any respiratory disease and affects about 20% of the population in North America and Europe. There is an increasing need for allergen challenge systems to test anti-allergic drugs under well-controlled conditions. The allergen challenge chamber ( ACC) is a room that enables reproducible challenges with controlled levels of inhalant allergens, temperature and humidity for several hours. ACCs have been used in Europe, North America and Japan to evaluate symptomatic and anti-inflammatory medications for the treatment of allergic rhinitis. This review summarizes the experience with a typical ACC in Germany, the Fraunhofer Challenge Chamber, and describes the stability and reproducibility of the allergen exposure in the chamber. It further provides data for the specificity and reproducibility of clinical read-out parameters, such as nasal symptom scores, nasal flow rates and nasal secretions, as well as of nasal biomarkers obtained in different validation studies. Typical study designs for testing the acute and prophylactic treatment effects of anti-allergic substances are discussed. Regulatory authorities, such as the FDA and EMA, recommend the use of ACCs in drug development to evaluate the optimal dose and onset of action during early clinical development. In combination with natural-exposure Phase III studies, they provide supportive evidence of superiority over placebo as an additional pharmacodynamic assessment tool. In particular, ACC studies may be of additional value in the clinical development of immunotherapy, because the variability of natural allergen exposure hampers the demonstration of efficacy in clinical trials. [ABSTRACT FROM AUTHOR]

Allergic rhinitis has the greatest prevalence of any respiratory disease and affects about 20% of the population in North America and Europe. There is an increasing need for allergen challenge systems to test anti-allergic drugs under well-controlled conditions. The allergen challenge chamber (ACC) is a room that enables reproducible challenges with controlled levels of inhalant allergens, temperature and humidity for several hours. ACCs have been used in Europe, North America and Japan to evaluate symptomatic and antiinflammatory medications for the treatment of allergic rhinitis. This review summarizes the experience with a typical ACC in Germany, the Fraunhofer Challenge Chamber, and describes the stability and reproducibility of the allergen exposure in the chamber. It further provides data for the specificity and reproducibility of clinical read-out parameters, such as nasal symptom scores, nasal flow rates and nasal secretions, as well as of nasal biomarkers obtained in different validation studies. Typical study designs for testing the acute and prophylactic treatment effects of anti-allergic substances are discussed. Regulatory authorities, such as the FDA and EMA, recommend the use of ACCs in drug development to evaluate the optimal dose and onset of action during early clinical development. In combination with natural-exposure Phase Ill studies, they provide supportive evidence of superiority over placebo as an additional pharmacodynamic assessment tool. In particular, ACC studies may be of additional value in the clinical development of immunotherapy, because the variability of natural allergen exposure hampers the demonstration of efficacy in clinical trials. [ABSTRACT FROM AUTHOR]

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. The aim of this study was to validate an environmental exposure unit for controlled human pollen inhalation studies in participants with seasonal allergic rhinitis. 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. 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. 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. [ABSTRACT FROM AUTHOR]