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Background: The epidemiological evidence on the interaction between heat and ambient air pollution on mortality is still inconsistent.

Objectives: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries.

Methods: We used daily data on all-cause mortality, air temperature, particulate matter ≤ 10 μm (PM₁₀), PM ≤ 2.5 μm (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) from 620 cities in 36 countries in the period 1995–2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants.

Results: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75^th to the 99^th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM₁₀ was equal to 10 or 90 μg/m³, respectively. Corresponding estimates when daily O3 concentrations were 40 or 160 μg/m³ were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 μg/m³ increment in PM₁₀ was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1^st and 99^th city-specific percentiles, respectively. Corresponding mortality estimate for O₃ across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM_2.5 and NO₂.

Conclusions: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities.