Relationship between antihistamine residues in wastewater and airborne pollen concentrations: Insights into population-scale pollinosis response

Pollinosis is the most prevalent allergic disorder. Assessing the impact of real-world pollen exposure on symptoms remains challenging due to extensive patient-level efforts required. This study explores the potential of wastewater-based epidemiology (WBE) to investigate the relationship between airborne pollen concentrations and antihistamine residues in wastewater as an indicator of pollinosis symptom treatment at the population-scale. In Zurich (Switzerland), 279 wastewater samples were collected during 2021-2023. Each sample represents a 24-h period with excreta from approximately 471,000 individuals. Eleven antihistamine markers were analyzed in the samples using liquid chromatography high-resolution mass spectrometry. The relationship between antihistamine loads in wastewater and airborne pollen concentrations (47 taxa and miscellaneous pollen) was investigated by determining seasonal components of antihistamine loads and exploring pollen-specific contributions using Non-Negative Least Squares (NNLS) optimization. Four antihistamines were detected in quantifiable amounts in wastewater. The first-generation antihistamine, diphenhydramine, demonstrated rather constant levels. In contrast, the three second-generation antihistamines - bilastine, cetirizine, and fexofenadine - showed pronounced day-to-day variation with strong correlations among each other. For fexofenadine, which was investigated in detail for its correlation with airborne pollen concentrations, approximately 50 % of the annual wastewater loads were associated with acute pollen exposure. Another 20 % related to baseline consumption during the pollen season, while the remaining 30 % seems unrelated to pollen. Birch, grasses, hazel, hornbeam, plane, and plantain explained most of the variance in wastewater loads (R² = 0.82), with grass pollen alone accounting for a quarter of the annual loads. Increased fexofenadine loads during periods without elevated concentrations of common allergenic pollen suggests the presence of additional triggers for allergy symptoms, potentially yew pollen. Our study demonstrates that WBE can effectively reveal substantial day-to-day variation in antihistamine use related to pollen exposure. Thus, WBE presents an objective and questionnaire-independent method for investigating pollinosis symptom treatment at a population-scale.