Association between long-term exposure to air pollution and cause-specific mortality within five Italian longitudinal metropolitan studies

Background: Extensive epidemiological literature has documented adverse effects of ambient air pollution on human health. However, in Italy, no multicenter longitudinal studies on chronic exposure to air pollution and mortality have been conducted. Within the BIGEPI project, we aimed to investigate the association between longterm exposure to air pollution and cause-specific mortality in large Italian population-based cohorts. Methods: Five administrative cohorts from Turin, Bologna, Rome, Taranto, and Brindisi (Italy) were included. Subjects aged 30+ were enrolled from the 2011 Census, followed-up until 2018 (2019 for Bologna), and linked with population and health registries. Annual mean concentrations of particulate matter ≤10 and 2.5 μm (PM10 and PM2.5), dioxide nitrogen (NO2), and warm-season ozone (O3w) were assigned to each participant’s geocoded residential address at baseline. Long-term associations between pollutants and non-accidental, cardiovascular, and respiratory mortality were investigated through single- and two-pollutant Cox proportional hazard models. Effect modification by sex and age was tested. Cohort-specific estimates were pooled in a random-effects metaanalysis. Results: 2,709,903 subjects (contributing over 18 million person-years) generated 266,821 non-accidental deaths. Each increment of 5 μg/m3 of PM10, 1 μg/m3 of PM2.5 and 10 μg/m3 of NO2 was associated with an increased risk of non-accidental mortality, with pooled Hazard Ratios (HR) of 1.018 (95% CI: 1.005–1.030), 1.004 (95% CI: 1.001–1.007) and 1.010 (95% CI: 1.002–1.018), respectively. HRs for cardiovascular and respiratory mortality were higher, the latter with CIs including the null. The associations remained quite stable after adjustment for the other pollutants. O3w was negatively associated with mortality but estimates were not statistically significant and reduced to unity upon adjustment for NO2. No consistent statistically significant effect modifications by sex and age emerged. Conclusions: Updated evidence implicates a continued risk of mortality in Italy due to long-term air pollution exposure, despite declining levels of exposure during the last years.