Wastewater-Based Analysis of Antihistamines to Estimate Pollinosis Disease Burden at Population-Scale

BackgroundPollinosis, or hay fever, is the most prevalent allergic disorder. Assessing the impact of real-world pollen exposure on symptoms remains challenging due to the extensive efforts required at the patient level. ObjectivesWe explore the potential of wastewater-based epidemiology (WBE) to investigate the impact of exposure to specific pollen taxa on symptoms and to assess self-medication patterns of second-generation antihistamines at a population-scale. MethodsIn Zurich (Switzerland), 279 wastewater samples were collected from 2021-2023. Each sample represents a 24-hour 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 concentrations of airborne pollen (47 taxa) was investigated using multivariate linear regression analysis. ResultsThe loads of three second-generation antihistamines in wastewater showed strong day-to-day variation correlating with airborne pollen patterns. About 50% of the annual fexofenadine consumption was linked to acute pollen exposure, 20% to baseline consumption during pollen season, and 30% was independent of pollen. Alder, birch, grasses, hornbeam, plane, and plantain explained most of the variance in consumption (R2 = 0.82), with grass pollen alone causing a quarter of the annual consumption. Increased fexofenadine consumption during periods without elevated concentrations of common allergenic pollen suggests the presence of additional triggers for allergy symptoms, potentially yew pollen. ConclusionsOur study demonstrates that WBE can effectively capture substantial day-to-day variation in antihistamine consumption caused by pollen exposure symptoms. As such, WBE is an objective, cost-effective, and questionnaire-independent method for investigating pollinosis at a population-scale.