Abstract
INTRODUCTION: Field studies for allergic rhinitis (AR) commonly have inconsistent allergen concentrations and subject exposure patterns due to varying environmental conditions and subject behaviors. A technical and clinical validation study was conducted for the Allergen BioCube(®) using timothy grass to confirm uniform allergen concentration and clinically relevant subject symptom responses. METHODS: Allergen concentrations were verified by laser particle counts. Subjects (N = 14) with positive skin test reactions and no symptoms at screening received four 3-h timothy grass exposures in the BioCube over consecutive days. Subjects evaluated nasal itching, sneezing, rhinorrhea, and nasal congestion while in the BioCube; Total Nasal Symptom Score (TNSS) was computed. Peak Nasal Inspiratory Flow (PNIF), Peak Expiratory Flow Rate (PEFR), sIgE blood tests, and Nasal Inflammation Score (NIS) were assessed. A correlation analysis was conducted for mean sIgE, skin test, and TNSS. RESULTS: Uniform timothy grass concentrations were achieved in the BioCube, both spatially and temporally, at all subject positions. Mean TNSS increased substantially from pre-exposure levels (0.36 ± 0.74 to 1.86 ± 2.14) to maximums of 7.07 ± 2.76 at 1.5 h and 6.71 ± 2.70 at 3 h BioCube exposure. Twelve (86%) subjects had TNSS increases ≥6 units. PNIF decreased 12-24% from baseline at 3-h BioCube exposure. NIS increased (baseline = 0) to 3.7 (maximum score = 4). A low/moderate correlation (r = 0.485) occurred between mean sIgE blood levels and mean skin tests; neither sIgE or skin tests correlated with mean TNSS. However, subjects with high skin test scores or positive blood IgE tended to also have higher TNSS. CONCLUSIONS: The Allergen BioCube achieved technical and clinical validation for uniform timothy grass concentration and clinically meaningful AR sign and symptom responses. The Allergen BioCube can be used to assess the efficacy of therapies for reduction of AR signs and symptoms resulting from grass exposure.