Clinical validation of controlled exposure to birch pollen in the Environmental Exposure Unit (EEU)

The Environmental Exposure Unit (EEU) operation

The EEU allows for reliable allergen exposure of up to 140 participants at once while controlling the environment regardless of the outdoor weather conditions. A custom-engineered computer and laser-aided system controls the dispersion of a predetermined concentration of pollen from a single point of delivery. The pollen is propelled using directional fans over the seating area. Rotorod^® samplers (Sampling Technologies Inc, Minnetonka, Minnesota), placed in seven specific locations around the seating area, typically sample the pollen in the air every 30 min, allowing for the assessment of pollen concentration at each location (Fig. 1) [13–15]. Custom microcontroller regulated rotorods developed by the Allergy Research Unit team monitor and transmit their revolutions per minute (RPM) data, along with date and time stamp, wirelessly to the research data management system, and store information locally on secure digital storage. Sensors that monitor RPM, battery condition and rotorod spindle movement provide visual and audible feedback on-screen and through warning LED lights as well as a speaker in order to be able to alert of any potential operational issues. If required, environmental sensors can be fitted to the microcontroller to provide additional point source data of that particular location [15].

Through minor adjustments in the pollen dispersion system or directional fans during the exposure visit, pollen concentration remains consistent throughout the unit [16]. A special ventilation system effectively controls the indoor environment, providing 100 % filtered fresh outdoor air, while controlling humidity (adjusted between 40 and 60 %) and temperature (18–22 °C), and the CO₂-laden air is exhausted outdoors [8]. The system is capable of replacing the volume of the room with filtered fresh air once every 12 min, while maintaining the pre-set temperature and humidity.

Due to the geographical location of the EEU and the high prevalence of ragweed allergy in Kingston, ON, ragweed has been extensively used as the allergen of choice during clinical trials [10, 17, 18]. Recently, there has been a growing need to validate and use other allergens for the evaluation of allergen specific immunotherapies in facilities like the EEU, as opposed to previous studies of anti-histamines and intranasal corticosteroids, where the specific allergen used is not as critical [10, 17–19]. Since different pollens have varying physical properties such as weight and air dynamics, which would affect their suspension in the air and ultimately the concentration, there is a need to evaluate the distribution and clinical effects of different pollens within the EEU before incorporating their use into future clinical studies. The use of grass pollen was most recently evaluated in the EEU, providing clinical validation of its use, and determining the pollen concentration and distribution requirements needed to reach predetermined symptom scores [16].

Ragweed pollen has a barbed and spiky surface giving it a “sticky” property and the clumping of pollen grains together may cause it to remain aloft during increased air current velocities (Fig. 2). Birch pollen, which has a comparable particle size to ragweed (20–22 microns compared to 18–20 microns for ragweed), would be expected to share similar air suspension characteristics. Having three raised pores on its surface, birch pollen may be able to remain suspended in the air for longer periods before “falling out” of air currents and coming to rest, similar to the effect of spikes on ragweed pollen. A birch pollen concentration of 3500 ± 500 grains was targeted for this study, similar to previous ragweed studies [8]. Preliminary studies in the EEU while fully setup, but without human participants, have confirmed the capability of the system equipment to release, disperse and maintain birch pollen concentrations [20].

Topographic features of birch and ragweed pollen on microscopic examination (not to scale). Birch pollen (left) have smoother surfaces with three pores compared to ragweed pollen which have spiky and barbed surfaces that causes the pollen grain to clump together. Both pollen are of comparable size, 20–22 microns in the case of birch pollen and 18–20 microns for ragweed pollen

We aimed to clinically evaluate the use of European White Birch pollen (Betula pendula) to challenge birch allergic participants and establish the change in symptom scores and nasal air flow at different time points throughout and following pollen exposure.