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Aims Air pollution and climate change are intrinsically linked to emerging hazards for global health. High air particulate matter (PM) levels may trigger out-of-hospital cardiac arrest (OHCA). High temperature could act synergistically with PM in determining OHCA. The aim of the present study was to investigate the effect of PM exposure alone, and in combination with temperature, on the risk of OHCA, in a large European metropolitan area with population >4 million. Methods We evaluated the association between short-term PM exposure, temperature, and the risk of OHCA over a two-year study period, allowing us to investigate 5761 events using a time-stratified case-crossover design combined with a distributed lag non-linear model. Results Higher risk of OHCA was associated with short-term exposure to PM10. The strongest association was experienced three days before the cardiac event where the estimated change in risk was 1.70% (0.48-2.93%) per 10 mu g/m(3) of PM. The cumulative exposure risk over the lags 0-6 was 8.5% (0.0-17.9%). We observed a joint effect of PM and temperature in triggering cardiac arrests, with a maximum effect of 14.9% (10.0-20.0%) increase, for high levels of PM before the cardiac event, in the presence of high temperature. Conclusion The present study helps to clarify the controversial role of PM as OHCA determinant. It also highlights the role of increased temperature as a key factor in triggering cardiac events. This evidence suggests that tackling both air pollution and climate change might have a relevant impact in terms of public health.