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Background  Exposure to heat, air pollution, and pollen are associated with health outcomes, including cardiovascular and respiratory disease. Studies assessing the health impacts of climate change have considered increased exposure to these risk factors separately, though they may be increasing simultaneously for some populations and may act synergistically on health.  Our objective is to systematically review epidemiological evidence for interactive effects of multiple exposures to heat, air pollution, and pollen on human health.    Methods  We systematically searched electronic literature databases (last search, April 29, 2019) for studies reporting quantitative measurements of associations between at least two of the exposures and mortality from any cause and cardiovascular and respiratory morbidity and mortality specifically. Following the Navigation Guide systematic review methodology, we evaluated the risk of bias of individual studies and the overall quality and strength of evidence.    Results  We found 56 studies that met the inclusion criteria. Of these, six measured air pollution, heat, and pollen; 39 measured air pollution and heat; 10 measured air pollution and pollen; and one measured heat and pollen. Nearly all studies were at risk of bias from exposure assessment error. However, consistent exposure-response across studies led us to conclude that there is overall moderate quality and sufficient evidence for synergistic effects of heat and air pollution. We concluded that there is overall low quality and limited evidence for synergistic effects from simultaneous exposure to (1) air pollution, pollen, and heat; and (2) air pollution and pollen. With only one study, we were unable to assess the evidence for synergistic effects of heat and pollen.    Conclusions  If synergistic effects between heat and air pollution are confirmed with additional research, the health impacts from climate change-driven increases in air pollution and heat exposure may be larger than previously estimated in studies that consider these risk factors individually.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12940-020-00681-z.

Synergistic health effects of air pollution, temperature, and pollen exposure: a systematic review of epidemiological evidence