Technical and clinical validation of a mobile chamber for allergen exposure tests

Rationale: The performance of a newly developed mobile allergen exposure chamber, allowing multicenter trials with exactly the same standard of procedure, had to be validated from the technical and clinical point of view. Technical parameters included particle (e.g. pollen) dispersion stability and spatial particle distribution at each subject position during a test period, temperature, O₂ and CO₂ and relative humidity stability. Since the chamber uses individual pollen exposure, each seating position has its own particle source, and all particle related parameters had to be measured at each seating position. To be accepted as an appropriate alternative to natural allergen exposure for clinical trials the clinical validation must document a high reliability of provoked symptoms in repeated provocations.                                                                                                                             Methods: Temperature, relative humidity, O2 and CO2 levels within the chamber have been monitored, with and without subjects being present in the chamber. These tests have been executed during several days, at outside temperatures ranging from -2^oC to 26^oC. The pollen distribution was validated using sedimentation measurements at 22 positions and at various particle concentrations. For all particle tests, grass pollen have been used. The chamber was used for exposure with grass and birch pollen in adult subjects with or without allergic symptoms due to birch and/or grass pollen during the last two seasons. Exposure for 90 - 240 min has been done outside the seasons. Nasal, conjunctival and bronchial symptoms were recorded as subjective parameters every 10 min. As objective parameters spirometry, peak-flow, exhaled nitrogen oxide (FeNO), peak nasal inspiratory flow and nasal secretion were obtained at baseline and after exposure.                                                                                                                               Results: Measurements showed a temperature variance of +/- 0.5K and humidity variance of +/- 3% with or without subjects being present. In a circular area with a diameter of 50 cm, the particle concentration is +/- 16% of the defined concentration and the accuracy remains over the course of 4 hours. No particles were found in the breathable air of non-active seating positions. Refloating measurements showed no particle concentration increase. The repeated exposures (up to four times) with birch and grass pollen in different concentrations elicited reproducible clinical symptoms on all the three organs and significant differences between placebo and verum pollen exposure. Generally, the symptoms started to occur after 10-30 min. and reached a plateau following 70 - 90 min of continuous exposure to pollen. Strongest symptoms were of nasal origin.                                                                 Conclusions: The novel Mobile Allergen Exposure Chamber fulfills the need for a reproducible and very well controlled pollen exposure and is regarded to be appropriate for allergen immunotherapy studies phase one and two, pharmaceutical drugs/anti-allergic drugs