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Background: The prevalence of asthma has increased in recent decades. Among the reasons for this increase is environmental pollution. Pollutants cause bronchial inflammation and introduce modifications in the pollen, making it more allergenic. Objective: Assess symptoms and medication requirements of asthmatic patients with grass allergies in Madrid (high urban pollution) and Ciudad Real (low pollution), and simultaneously evaluate the in vitro effects that pollen collected in both areas has on the immune cells of patients. Methods: During two pollen seasons, patients from both cities were included. The patients recorded their symptoms and the asthma medication they took daily. In both cities, pollen data, pollutants and meteorological variables were evaluated. The response to different cell populations from patients in both areas were analysed after "in vitro" stimulation with pollen from both cities. Results: The symptoms and medication use of the patients in Madrid was 29.94% higher. The NO2 concentration in Madrid was triple that of Ciudad Real (33.4 vs. 9.1 µg/m3 of air). All other pollutants had very similar concentrations during the study period. Pollen from the high pollution area caused a significant enhancement of T‐CD8+ and NK cells proliferation compared with pollen of low pollution area, independently of the patient's origin. Conclusion: Asthmatic patients from Madrid have a worse clinical evolution than those from Ciudad Real because of higher levels of urban pollution, and this could be driven by the higher capacity of pollen of Madrid to activate T‐CD8+ and NK cells. [ABSTRACT FROM AUTHOR]