Peak nasal inspiratory flow as outcome for provocation studies in allergen exposure chambers: a GA²LEN study

Background: The GA²LEN chamber has been developed as a novel mobile allergen exposure chamber (AEC) allowing standardized multicenter trials in allergy. Hitherto, subjective nasal symptom scores have been the most often used outcome parameter, but in standardized modern trials objective parameters are preferred. Despite its practicability, the objective parameter peak nasal inspiratory flow (PNIF) has been rarely used for allergy trials in the setting of allergen exposure chambers. This study aims to evaluate PNIF as an outcome parameter for provocation studies in AECs. Methods: In a randomized controlled blinded setting subjects suffering from allergic rhinitis were exposed to grass pollen, birch pollen, house dust mite and/or placebo in the GA²LEN chamber. Different allergen concentrations were used to evaluate symptom severities. Patients had to perform PNIF before and every 30 min during a challenge using a portable PNIF meter. Results: 86 subjects participated in 203 challenges, altogether. House dust mite provocations caused the greatest reduction in PNIF values, followed by grass pollen and birch pollen. Provocations with every allergen or pollen concentration led to a significant decrease (p < 0.05) in PNIF compared to baseline. Furthermore, positive correlations were obtained between PNIF and peak expiratory flow, height and weight, and inverse correlations between PNIF and total nasal symptom score, nasal congestion score and visual analog scale of overall subjective symptoms. Conclusion: PNIF is a helpful and feasible tool for conducting provocation trials with allergens, especially grass pollen and house dust mite, in an AEC

Development, Alteration and Real Time Dynamics of Conjunctiva-Associated Lymphoid Tissue

Purpose: Conjunctiva-associated lymphoid tissue (CALT) is thought to play a key role in initiating ocular surface related immune responses. This study was planned to get first profound insights into the function of CALT related to development, cellular dynamics and morphological alteration using a novel mouse model. Methods: Expression and morphology of CALT were investigated using BALB/c mice kept under different housing conditions, after topical antigen-stimulation and following lymphadenectomy and splenectomy. Particles and bacteria were applied topically to study antigen-transport. Intravital visualization was performed using two-photon microscopy. Results: Postnatal development and ultrastructure of CALT in the mouse is similar to humans. Topical antigen-challenge significantly alters CALT expression. Bacterial translocation is demonstrated via lymphoepithelium whereas cellular velocities within follicles were approximately 8 mu m/min. Conclusions: CALT in the mouse is an immunological interface of the ocular surface, featuring dynamic processes such as morphological plasticity, particle/bacteria transport and cellular migration

MOESM7 of Peak nasal inspiratory flow as outcome for provocation studies in allergen exposure chambers: a GA2LEN study

Additional file 7: Figure S3. Comparison of different allergens and their PNIF outcome. PNIF development compared between the different allergens and placebo. Both grass pollen and house dust mite (HDM) elicited significantly greater PNIF% reductions at each associated time of measurement than placebo (p < 0.001) and birch pollen (p < 0.01). PNIF% is displayed as medians and boxplots. Outliers are presented as degree sign, extreme outliers as asterisk

Validation of the Global Allergy and Asthma European Network (GA(2)LEN) chamber for trials in allergy: Innovation of a mobile allergen exposure chamber

BACKGROUND: Field clinical trials of pollen allergy are affected by the impossibility of predicting and determining individual allergen exposure because of many factors (eg, pollen season, atmospheric variations, pollutants, and lifestyles). Environmental exposure chambers, delivering a fixed amount of allergen in a controlled environmental setting, can overcome these limitations. Environmental exposure chambers are currently already used in phase 2, 3, and even 4 trials. Unfortunately, few chambers exist in the world, and this makes it difficult to perform large, multicenter clinical trials. The new Global Allergy and Asthma European Network (GA(2)LEN) mobile exposure chamber is a step forward because the mobility of the chamber makes it convenient for patients to participate in clinical testing. OBJECTIVE: This study was made to validate the reproducibility, sensitivity, and specificity of the results obtained in the new GA(2)LEN chamber. METHODS: Seventy-two adult patients (19-61 years old) with allergic rhinitis with or without asthma caused by grass pollen were included in different clinical validation tests. Total symptom scores and total nasal symptom scores were recorded at time zero (0) and every 10 minutes during exposures, along with nasal and respiratory parameters. RESULTS: Exposure tests confirmed the reproducibility between subsequent runs and the sensitivity (P < .00001 vs patients exposed to placebo) and specificity (very low score in nonallergic subjects) in the GA(2)LEN chamber. No adverse reactions were recorded during the tests. CONCLUSIONS: The mobility of the GA(2)LEN chamber provides a new, potentially effective, and safe way of generating reliable data in allergy multicenter clinical trials