The extent and robustness of the interaction between exposures to heat and ambient PM2.5 is unclear and little is known of the interaction between exposures to cold and ambient PM2.5. Clarifying these interactions, if any, is crucial due to the omnipresence of PM2.5 in the atmosphere and increasing scope and frequency of extreme temperature events. To investigate both of these interactions, we merged 6 073 575 individual-level mortality records from thirteen states spanning seventeen years with 1 km daily PM2.5 predictions from sophisticated prediction model and 1 km meteorology from Daymet V4. A time-stratified, bidirectional case-crossover design was used to control for confounding by individual-level, long-term and cyclic weekly characteristics. We fitted conditional logistic regressions with an interaction term between PM2.5 and extreme temperature events to investigate the potential interactive effects on mortality. Ambient PM2.5 exposure has the greatest effect on mortality by all internal causes in the 2 d moving average exposure window. Additionally, we found consistently synergistic interactions between a 10 μg m-3 increase in the 2 d moving average of PM2.5 and extreme heat with interaction odds ratios of 1.013 (95% CI: 1.000, 1.026), 1.024 (95% CI: 1.002, 1.046), and 1.033 (95% CI: 0.991, 1.077) for deaths by all internal causes, circulatory causes, and respiratory causes, respectively, which represent 75%, 156%, and 214% increases in the coefficient estimates for PM2.5 on those days. We also found evidence of interactions on the additive scale with corresponding relative excess risks due to interaction (RERIs) of 0.013 (95% CI: 0.003, 0.021), 0.020 (95% CI: 0.008, 0.031), and 0.017 (95% CI: -0.015, 0.036). Interactions with other PM2.5 exposure windows were more pronounced. For extreme cold, our results were suggestive of an antagonistic relationship. These results suggest that ambient PM2.5 interacts synergistically with exposure to extreme heat, yielding greater risks for mortality than only either exposure alone.
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