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Background: Several studies have shown an association between nitrogen dioxide (NO2) and mortality. In Italy, the EpiAir multicentric study, "Air Pollution and Health: Epidemiological Surveillance and Primary Prevention," investigated short-term health effects of air pollution, including NO2. Objectives: To study the individual susceptibility, we evaluated the association between NO2 and cause-specific mortality, investigating individual sociodemographic features and chronic/acute medical conditions as potential effect modifiers. Methods: We considered 276,205 natural deaths of persons > 35 years of age, resident in 10 Italian cities, and deceased between 2001 and 2005. We chose a time-stratified case-crossover analysis to evaluate the short-term effects of NO2 on natural, cardiac, cerebrovascular, and respiratory mortality. For each subject, we collected information on sociodemographic features and hospital admissions in the previous 2 years. Fixed monitors provided daily concentrations of NO2, particulate matter ≤10 µm in aerodynamic diameter (PM10) and ozone (O3). Results: We found statistically significant associations with a 10-µg/m3 increase of NO2 for natural mortality [2.09% for lag 0-5; 95% confidence interval (CI), 0.96-3.24], for cardiac mortality (2.63% for lag 0-5; 95% CI, 1.53-3.75), and for respiratory mortality (3.48% for lag 1-5; 95% CI, 0.75-6.29). These associations were independent from those of PM10 and O3. Stronger associations were estimated for subjects with at least one hospital admission in the 2 previous years and for subjects with three or more specific chronic conditions. Some cardiovascular conditions (i.e., ischemic heart disease, pulmonary circulation impairment, heart conduction disorders, heart failure) and diabetes appeared to confer a strong susceptibility to air pollution. Conclusions: Our results suggest significant and likely independent effects of NO2 on natural, cardiac, and respiratory mortality, particularly among subjects with specific cardiovascular preexisting chronic conditions and diabetes. [ABSTRACT FROM AUTHOR]