Outdoor Environmental Risk Factors for Paediatric Ragweed Sensitisation: A Formal Model Comparison

Background/Objectives: Ragweed (Ambrosia artemisiifolia) is a major aeroallergen in Central and Eastern Europe. Croatian children in regions with twofold difference in pollen exposure show near-identical sensitisation prevalence (the "Zagreb paradox"), and an earlier analysis found regional pollen and rural residence to be the only associated environmental factors. We re-examined whether air pollution, surrounding landscape and indoor environment contribute to it. Methods: This cross-sectional analysis used 3520 of the 4016 children recruited to the EU FP7 ATOPICA study, who had their complete data re-analysed within the EU Horizon Europe EDIAQI project. Sensitisation was defined as a skin prick test wheal of at least 2 mm. Environmental predictors (particulate matter, PM₁₀; nitrogen dioxide, NO₂; regional pollen; CORINE land cover within 5 km; rural residence; and indoor exposures) were compared using the Akaike Information Criterion (AIC) in logistic regression models, which were adjusted for age and parental atopy. Results: Sensitisation prevalence was 10.8%. PM₁₀ and categorical pollen area fitted the data equally well (ΔAIC 1.7): both describe the same inland-coastal contrast and cannot be distinguished with area-level data. NO₂ added nothing to either. Of the 16 landscape variables, only transitional woodland-shrub remained associated with sensitisation after Bonferroni correction (adjusted odds ratio, aOR 0.93 [95% confidence interval, CI 0.90-0.97]); total green area was nominally associated (aOR 0.92 [95% CI 0.87-0.98]; p = 0.009). Children in rural locations were less often sensitised (aOR 0.69 [95% CI 0.50-0.96]; p = 0.026), as previously reported; a mediation analysis could not determine whether broadleaved forest cover explains this association. Indoor exposures added little to model fit. Conclusions: Area-level data cannot separate particulate air pollution from pollen exposure, so a contribution of air pollution can be neither confirmed nor excluded. Rural residence and, with less certainty, surrounding green space were associated with less sensitisation, and the indoor environment added little to it.