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Introduction: To determine threshold concentrations of pollen inducing symptoms in seasonal allergic rhinitis patients has been a challenge for decades. Allergen challenge chambers (ACC) allow a controlled, reproducible experimental design to address this problem. Hitherto, ACCs were only run with high pollen concentrations. Methods: The Fraunhofer ACC was technically modified to deploy very low pollen concentrations. Then, adults with birch pollen-induced allergic rhinitis were challenged with varying birch pollen concentrations using a patient-blinded, sham challenge-controlled, part-randomized, titrate-to-effect clinical study setting. Mean increase in Total Nasal Symptom Score (TNSS) ≥0.55 compared to sham challenge was regarded as minimal clinically important difference (MCID). Further endpoints were nasal secretion weight, exhaled nitric oxide (FeNO), and inflammatory cells from nasal lavage. Results: Fifteen participants with mild to moderate allergic rhinitis participated in the experimental study part (mean age 45 years [22–64]; 7 females). Mean TNSS was: 1.08 at 0 pollen/m3; 1.05 at 10 pollen/m3; 1.2 at 50 pollen/m3; 1.74 at 100 pollen/m3; 1.61 at 200 pollen/m3; 2.79 at 1,000 pollen/m3. MCID of TNSS was observed at 100, 200, and 1,000 pollen/m3. More than half of the study population showed a lack of response at 10, 50, and 200 pollen/m3. Nasal secretion increased slightly with concentration. No clinically meaningful results could be derived from FeNO and inflammatory cells. Conclusions: The applied technical modification of the Fraunhofer ACC produced stable, low pollen concentrations. Based on mean TNSS data, the threshold concentration for inducing symptoms with birch pollen was 50–100 pollen/m3. © 2025 The Author(s).
Introduction: Climate change may increase the spread of allergenic plants such as ragweed. Ragweed pollen is assumed to be more allergenic than birch pollen. Determining pollen threshold concentrations triggering symptoms is challenging. Technical modifications to the Fraunhofer allergen challenge chamber (ACC) now allow investigation of very low pollen concentrations. Based on Total Nasal Symptom Score (TNSS) data from 15 subjects with birch pollen allergic rhinitis (AR), a birch pollen threshold between 50 and 100 pollen grains/m3 of air was previously derived. This study explored threshold concentrations of ragweed pollen. Methods: Two ragweed pollen AR patients were exposed to varying concentrations of ragweed pollen for 4 h. TNSS was recorded every 20 min, and nasal secretion and peak nasal inspiratory flow hourly. Area under the curve (AUC0-240) values were calculated. Ex vivo basophil activation tests with varying concentrations of ragweed pollen, Amb a 1, birch pollen, and Bet v 1 were performed for both ragweed pollen AR patients and 6 of the 15 birch pollen AR patients. Mean effective concentrations (EC50) for CD63 expression were calculated. Results: Ragweed pollen exposure resulted in the following TNSS AUC0-240 values: 28/23 at 0, 18/17 at 50, 13/27 at 100, 40/40 at 200, 29/16 at 300, and 55/47 at 1,000 pollen grains/m3. For CD63 expression, the mean EC50 was 277 pollen/mL for ragweed pollen, 884 ng/mL for Amb a 1, 11 pollen/mL for birch pollen, and 0.13 ng/mL for Bet v 1. On average, the proportion of Amb a 1 in ragweed pollen was 0.17%, and the proportion of Bet v 1 in birch pollen 1.96%. Conclusion: The modified Fraunhofer ACC can investigate pollen threshold concentrations under defined conditions. The assumed differences in threshold concentrations of ragweed and birch pollen for triggering symptoms were not confirmed. To derive reliable threshold concentrations for ragweed pollen, larger studies have to be followed. © 2026 The Author(s).