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 (PM2.5), 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 75th to the 99th 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 1st and 99th 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 PM2.5 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.

Braun School of Public Health and Community Medicine The Hebrew University of Jerusalem Israel

Center for Environmental and Respiratory Health Research University of Oulu Oulu Finland

Climate Research Foundation Madrid Spain; Spanish Consortium for Research on Epidemiology and Public Health Spain

Department of Environmental Health Harvard T H Chan School of Public Health Boston MA USA

Department of Environmental Health Instituto Nacional de Saúde Dr Ricardo Jorge Porto Portugal; EPIUnit Instituto de Saúde Pública Universidade do Porto Porto Portugal; Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional Porto Portugal

Department of Environmental Health National Institute of Public Health Cuernavaca Morelos Mexico

Department of Environmental Health School of Public Health Fudan University Shanghai China

Department of Environmental Health University of São Paulo São Paulo Brazil

Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Australia

Department of Epidemiology Instituto Nacional de Saúde Dr Ricardo Jorge Lisbon Portugal

Department of Epidemiology Lazio Region Health Service ASL Roma 1 Via C Colombo 112 00147 Rome Italy

Department of Family Medicine and Public Health University of Tartu Tartu Estonia

Department of Geography Geoinformatics and Meteorology University of Pretoria Pretoria South Africa

Department of Global Health Policy Graduate School of Medicine The University of Tokyo Tokyo Japan

Department of Hygiene Epidemiology and Medical Statistics National and Kapodistrian University of Athens Greece

Department of Hygiene Epidemiology and Medical Statistics National and Kapodistrian University of Athens Greece; Environmental Research Group School of Public Health Faculty of Medicine Imperial College London London United Kingdom

Department of Pathology Faculty of Medicine University of São Paulo São Paulo Brazil

Department of Primary Care and Population Health University of Nicosia Medical School Nicosia Cyprus

Department of Public Health and Clinical Medicine Umeå University Sweden

Department of Public Health Environments and Society London School of Hygiene and Tropical Medicine London United Kingdom

Department of Public Health Environments and Society London School of Hygiene and Tropical Medicine London United Kingdom; Department of Statistics Computer Science and Applications G Parenti University of Florence Florence Italy

Department of Public Health Universidad de los Andes Santiago Chile

Department of Statistics and Computational Research Universitat de València València Spain

Directorate for Health Information and Research Malta

Environmental and Occupational Medicine and Institute of Environmental and Occupational Health Sciences National Taiwan University and NTU Hospital Taipei Taiwan

Estonian Environmental Research Centre Tallinn Estonia

Faculty of Geography and Environmental Sciences Hakim Sabzevari University Sabzevar 9617916487 Khorasan Razavi Iran

Faculty of Geography Babes Bolay University Cluj Napoca Romania

Gangarosa Department of Environmental Health Rollins School of Public Health Emory University Atlanta USA

Graduate School of Public Health Seoul National University Seoul Republic of Korea

IBE Chair of Epidemiology LMU Munich Munich Germany

Institute of Atmospheric Physics Czech Academy of Sciences Prague Czech Republic; Faculty of Environmental Sciences Czech University of Life Sciences Prague Czech Republic

Institute of Environmental Assessment and Water Research Barcelona Spain

Institute of Epidemiology Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Institute of Social and Preventive Medicine University of Bern Bern Switzerland; Oeschger Center for Climate Change Research University of Bern Bern Switzerland

Institute of Tropical Medicine Alexander von Humboldt Universidad Peruana Cayetano Heredia Lima Peru

National Institute of Environmental Health Science National Health Research Institutes Zhunan Taiwan

Norwegian Institute of Public Health Oslo Norway

Queen Mary University of London London United Kingdom

Santé Publique France Department of Environmental Health French National Public Health Agency Saint Maurice France

School of Epidemiology and Public Health Faculty of Medicine University of Ottawa Ottawa Canada; Environmental Health Science and Research Bureau Health Canada Ottawa Canada

School of Public Health and Community Medicine University of Gothenburg Gothenburg Sweden

School of Public Health and Social Work Queensland University of Technology Brisbane Australia

School of the Environment Yale University New Haven CT USA

Swiss Tropical and Public Health Institute Basel Switzerland

See more in PubMed

Analitis A, Michelozzi P, D’Ippoliti D, de’Donato F, Menne B, Matthies F, Atkinson RW, Iñiguez C, Basagaña X, Schneider A, Lefranc A, Paldy A, Bisanti L, Katsouyanni K, 2014. Effects of heat waves on mortality: effect modification and confounding by air pollutants. Epidemiology 25 (1), 15–22. PubMed

Anderson BG, Bell ML, 2009. Weather-related mortality: how heat, cold, and heat waves affect mortality in the United States. Epidemiology 20, 205–213. PubMed PMC

Anenberg SC, Haines S, Wang E, Nassikas N, Kinney PL, 2020. Synergistic health effects of air pollution, temperature, and pollen exposure: a systematic review of epidemiological evidence. Environ. Health 19, 130. PubMed PMC

Basu R, 2009. High ambient temperature and mortality: a review of epidemiologic studies from 2001 to 2008. Environ. Health 8, 40. PubMed PMC

Bouchama A, Dehbi M, Mohamed G, Matthies F, Shoukri M, Menne B, 2007. Prognostic factors in heat wave related deaths: a meta-analysis. Arch. Intern. Med. 167, 2170–2176. PubMed

Chen F, Fan Z, Qiao Z, Cui Y, Zhang M, Zhao X, Li X, 2017. Does temperature modify the effect of PM10 on mortality? A systematic review and meta-analysis. Environ. Pollut. 224, 326–335. PubMed

Chen K, Wolf K, Breitner S, Gasparrini A, Stafoggia M, Samoli E, Andersen ZJ, Bero-Bedada G, Bellander T, Hennig F, Jacquemin B, Pekkanen J, Hampel R, Cyrys J, Peters A, Schneider A, 2018. Two-way effect modifications of air pollution and air temperature on total natural and cardiovascular mortality in eight European urban areas. Environ. Int. 116, 186–196. PubMed

Chen K, Vicedo-Cabrera AM, Dubrow R, 2020. Projections of ambient temperature- and air pollution-related mortality burden under combined climate change and population aging scenarios: a review. Curr. Environ. Heal Reports 7 (3), 243–255. PubMed

Dominski FH, Lorenzetti Branco JH, Buonanno G, Stabile L, Gameiro da Silva M, Andrade A, 2021. Effects of air pollution on health: A mapping review of systematic reviews and meta-analyses. Environ. Res. 201, 111487. PubMed

Gasparrini A, Guo Y, Hashizume M, Lavigne E, Zanobetti A, Schwartz J, Tobias A, Tong S, Rocklöv J, Forsberg B, Leone M, De Sario M, Bell ML, Guo Y-L, Wu C. f., Kan H, Yi S-M, de Sousa Zanotti Stagliorio Coelho M, Saldiva PHN, Honda Y, Kim H.o., Armstrong B, 2015. Mortality risk attributable to high and low ambient temperature: a multicountry observational study. Lancet 386 (9991), 369–375. PubMed PMC

Gasparrini A, Guo Y, Hashizume M, Kinney PL, Petkova EP, Lavigne E, Zanobetti A, Schwartz JD, Tobias A, Leone M, Tong S, Honda Y, Kim H.o., Armstrong BG, 2015. Temporal variation in heat-mortality associations: a multicountry study. Environ. Health Perspect. 123 (11), 1200–1207. PubMed PMC

Gordon CJ, 2003. Role of environmental stress in the physiological response to chemical toxicants. Env Res 92 (1), 1–7. PubMed

Guo Y, Gasparrini A, Armstrong B, Li S, Tawatsupa B, Tobias A, Lavigne E, de Sousa Zanotti Stagliorio Coelho M, Leone M, Pan X, Tong S, Tian L, Kim H.o., Hashizume M, Honda Y, Guo Y-L, Wu C-F, Punnasiri K, Yi S-M, Michelozzi P, Saldiva PHN, Williams G, 2014. Global variation in the effects of ambient temperature on mortality: a systematic evaluation. Epidemiology 25 (6), 781–789. PubMed PMC

IPCC. Climate Change 2022: Impacts, Adaptation and Vulnerability. Technical Summary. 2022. https://report.ipcc.ch/ar6wg2/pdf/IPCC_AR6_WGII_FinalDraft_TechnicalSummary.pdf.

Jhun I, Fann N, Zanobetti A, Hubbell B, 2014. Effect modification of ozone-related mortality risks by temperature in 97 US cities. Environ. Int. 73, 128–134. PubMed

Kinney PL, 2018. Interactions of climate change, air pollution, and human health. Curr Environ Health Reports 5 (1), 179–186. PubMed

Lavigne E, Gasparrini A, Wang X, Chen H, Yagouti A, Fleury MD, Cakmak S, 2014. Extreme ambient temperatures and cardiorespiratory emergency room visits: assessing risk by comorbid health conditions in a time series study. Env Health 13 (1), 5. PubMed PMC

Li J, Woodward A, Hou X-Y, Zhu T, Zhang J, Brown H, Yang J, Qin R, Gao J, Gu S, Li J, Xu L, Liu X, Liu Q, 2017. Modification of the effects of air pollutants on mortality by temperature: A systematic review and meta-analysis. Sci Total Env 575, 1556–1570. PubMed

Liu C, Chen R, Sera F, Vicedo-Cabrera AM, Guo Y, Tong S, Coelho MSZS, Saldiva PHN, Lavigne E, Matus P, Valdes Ortega N, Osorio Garcia S, Pascal M, Stafoggia M, Scortichini M, Hashizume M, Honda Y, Hurtado-Díaz M, Cruz J, Nunes B, Teixeira JP, Kim H.o., Tobias A, Íñiguez C, Forsberg B, Åström C, Ragettli MS, Guo Y-L, Chen B-Y, Bell ML, Wright CY, Scovronick N, Garland RM, Milojevic A.i., Kyselý J, Urban A, Orru H, Indermitte E, Jaakkola JJK, Ryti NRI, Katsouyanni K, Analitis A, Zanobetti A, Schwartz J, Chen J, Wu T, Cohen A, Gasparrini A, Kan H, 2019. Ambient particulate air pollution and daily mortality in 652 cities. N. Engl. J. Med. 381 (8), 705–715. PubMed PMC

Meng X, Liu C, Chen R, et al. Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities. BMJ 2021; 372: n534. PubMed PMC

Orellano P, Reynoso J, Quaranta N, Bardach A, Ciapponi A, 2020. Short-term exposure to particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), and ozone (O3) and all-cause and cause-specific mortality: systematic review and meta-analysis. Environ. Int. 142, 105876. PubMed

Rai M, Stafoggia M, de’Donato F, Scortichini M, Zafeiratou S, Vazquez Fernandez L, Zhang S, Katsouyanni K, Samoli E, Rao S, Lavigne E, Guo Y, Kan H, Osorio S, Kyselý J, Urban A, Orru H, Maasikmets M, Jaakkola JJK, Ryti N, Pascal M, Hashizume M, Fook Sheng Ng C, Alahmad B, Hurtado Diaz M, De la Cruz Valencia C, Nunes B, Madureira J, Scovronick N, Garland RM, Kim H.o., Lee W, Tobias A, Íñiguez C, Forsberg B, Åström C, Maria Vicedo-Cabrera A, Ragettli MS, Leon Guo Y-L, Pan S-C, Li S, Gasparrini A, Sera F, Masselot P, Schwartz J, Zanobetti A, Bell ML, Schneider A, Breitner S, 2023. Heat-related cardiorespiratory mortality: effect modification by air pollution across 482 cities from 24 countries. Environ. Int. 174, 107825. PubMed

Ren C, Williams GM, Morawska L, Mengersen K, Tong S, 2008. Ozone modifies associations between temperature and cardiovascular mortality: analysis of the NMMAPS data. Occup. Env. Med. 65 (4), 255–260. PubMed

Romanello M, McGushin A, Di Napoli C, Drummond P, Hughes N, Jamart L, Kennard H, Lampard P, Solano Rodriguez B, Arnell N, Ayeb-Karlsson S, Belesova K, Cai W, Campbell-Lendrum D, Capstick S, Chambers J, Chu L, Ciampi L, Dalin C, Dasandi N, Dasgupta S, Davies M, Dominguez-Salas P, Dubrow R, Ebi KL, Eckelman M, Ekins P, Escobar LE, Georgeson L, Grace D, Graham H, Gunther SH, Hartinger S, He K, Heaviside C, Hess J, Hsu S-C, Jankin S, Jimenez MP, Kelman I, Kiesewetter G, Kinney PL, Kjellstrom T, Kniveton D, Lee JKW, Lemke B, Liu Y, Liu Z, Lott M, Lowe R, Martinez-Urtaza J, Maslin M, McAllister L, McMichael C, Mi Z, Milner J, Minor K, Mohajeri N, Moradi-Lakeh M, Morrissey K, Munzert S, Murray KA, Neville T, Nilsson M, Obradovich N, Sewe MO, Oreszczyn T, Otto M, Owfi F, Pearman O, Pencheon D, Rabbaniha M, Robinson E, Rocklöv J, Salas RN, Semenza JC, Sherman J, Shi L, Springmann M, Tabatabaei M, Taylor J, Trinanes J, Shumake-Guillemot J, Vu B, Wagner F, Wilkinson P, Winning M, Yglesias M, Zhang S, Gong P, Montgomery H, Costello A, Hamilton I, 2021. The 2021 report of the Lancet Countdown on health and climate change: code red for a healthy future. Lancet 398 (10311), 1619–1662. PubMed PMC

Rückerl R, Schneider A, Breitner S, Cyrys J, Peters A, 2011. Health effects of particulate air pollution: A review of epidemiological evidence. Inhal. Toxicol. 23 (10), 555–592. PubMed

Scortichini M, De Sario M, de’Donato F, Davoli M, Michelozzi P, Stafoggia M, 2018. Short-Term Effects of Heat on Mortality and Effect Modification by Air Pollution in 25 Italian Cities. Int. J. Environ. Res. Public Health 15 (8), 1771. PubMed PMC

Sera F, Armstrong B, Tobias A, Vicedo-Cabrera AM, Åström C, Bell ML, Chen B-Y, de Sousa Zanotti Stagliorio Coelho M, Matus Correa P, Cruz JC, Dang TN, Hurtado-Diaz M, Do Van D, Forsberg B, Guo YL, Guo Y, Hashizume M, Honda Y, Iñiguez C, Jaakkola JJK, Kan H, Kim H.o., Lavigne E, Michelozzi P, Ortega NV, Osorio S, Pascal M, Ragettli MS, Ryti NRI, Saldiva PHN, Schwartz J, Scortichini M, Seposo X, Tong S, Zanobetti A, Gasparrini A, 2019. How urban characteristics affect vulnerability to heat and cold: a multi-country analysis. Int. J. Epidemiol. 48 (4), 1101–1112. PubMed

Shi W, Sun Q, Du P, Tang S, Chen C, Sun Z, Wang J, Li T, Shi X, 2020. Modification effects of temperature on the ozone-mortality relationship: a nationwide multicounty study in China. Environ. Sci. Tech. 54 (5), 2859–2868. PubMed

Song X, Wang S, Hu Y, Yue M, Zhang T, Liu Y.u., Tian J, Shang K, 2017. Impact of ambient temperature on morbidity and mortality: An overview of reviews. Sci. Total Environ. 586, 241–254. PubMed

Stafoggia M, Forastiere F, Faustini A, Biggeri A, Bisanti L, Cadum E, Cernigliaro A, Mallone S, Pandolfi P, Serinelli M, Tessari R, Vigotti MA, Perucci CA, 2010. Susceptibility factors to ozone-related mortality: A population-based case-crossover analysis. Am. J. Respir. Crit. Care Med. 182 (3), 376–384. PubMed

Vicedo-Cabrera AM, Sera F, Liu C, et al. Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries. BMJ 2020; 368: m108. PubMed PMC

Vicedo-Cabrera AM, Scovronick N, Sera F, Royé D, Schneider R, Tobias A, Astrom C, Guo Y, Honda Y, Hondula DM, Abrutzky R, Tong S, Coelho M.d.S. Z.S., Saldiva PHN, Lavigne E, Correa PM, Ortega NV, Kan H, Osorio S, Kyselý J, Urban A, Orru H, Indermitte E, Jaakkola JJK, Ryti N, Pascal M, Schneider A, Katsouyanni K, Samoli E, Mayvaneh F, Entezari A, Goodman P, Zeka A, Michelozzi P, de’Donato F, Hashizume M, Alahmad B, Diaz MH, Valencia CDLC, Overcenco A, Houthuijs D, Ameling C, Rao S, Di Ruscio F, Carrasco-Escobar G, Seposo X, Silva S, Madureira J, Holobaca IH, Fratianni S, Acquaotta F, Kim H, Lee W, Iniguez C, Forsberg B, Ragettli MS, Guo YLL, Chen BY, Li S, Armstrong B, Aleman A, Zanobetti A, Schwartz J, Dang TN, Dung DV, Gillett N, Haines A, Mengel M, Huber V, Gasparrini A, 2021. The burden of heat-related mortality attributable to recent human-induced climate change. Nat. Clim. Chang. 11 (6), 492–500. PubMed PMC

WHO. WHO global air quality guidelines. Particulate matter (PM2.5 and PM10), ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide. 2021; published online Oct. DOI:10.1016/S0140-6736(06)69530-5. PubMed DOI

Zhang Y, Bi P, Hiller JE, 2010. Climate variations and Salmonella infection in Australian subtropical and tropical regions. Sci. Total Environ. 408 (3), 524–530. PubMed

Zhao Q.i., Guo Y, Ye T, Gasparrini A, Tong S, Overcenco A, Urban A, Schneider A, Entezari A, Vicedo-Cabrera AM, Zanobetti A, Analitis A, Zeka A, Tobias A, Nunes B, Alahmad B, Armstrong B, Forsberg B, Pan S-C, Íñiguez C, Ameling C, De la Cruz Valencia C, Åström C, Houthuijs D, Dung DV, Royé D, Indermitte E, Lavigne E, Mayvaneh F, Acquaotta F, de’Donato F, Di Ruscio F, Sera F, Carrasco-Escobar G, Kan H, Orru H, Kim H.o., Holobaca I-H, Kyselý J, Madureira J, Schwartz J, Jaakkola JJK, Katsouyanni K, Hurtado Diaz M, Ragettli MS, Hashizume M, Pascal M, de Sousa Zanotti Stagliorio Coélho M, Valdés Ortega N, Ryti N, Scovronick N, Michelozzi P, Matus Correa P, Goodman P, Nascimento Saldiva PH, Abrutzky R, Osorio S, Rao S, Fratianni S, Dang TN, Colistro V, Huber V, Lee W, Seposo X, Honda Y, Guo YL, Bell ML, Li S, 2021. Global, regional, and national burden of mortality associated with non-optimal ambient temperatures from 2000 to 2019: a three-stage modelling study. Lancet Planet Health 5 (7), e415–e425. PubMed