. 2023 Oct 4:383:e075203.

doi: 10.1136/bmj-2023-075203.

Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis

Cong Liu¹, Renjie Chen¹, Francesco Sera², Ana Maria Vicedo-Cabrera^{3

4}, Yuming Guo^{5

6}, Shilu Tong^{7

8

9

10}, Eric Lavigne^{11

12}, Patricia Matus Correa¹³, Nicolás Valdés Ortega¹³, Souzana Achilleos¹⁴, Dominic Roye^{15

16}, Jouni Jk Jaakkola^{17

18}, Niilo Ryti^{17

18}, Mathilde Pascal¹⁹, Alexandra Schneider²⁰, Susanne Breitner^{20

21}, Alireza Entezari^{6

22}, Fatemeh Mayvaneh²², Raanan Raz²³, Yasushi Honda²⁴, Masahiro Hashizume²⁵, Chris Fook Sheng Ng²⁶, Vânia Gaio^{27

28}, Joana Madureira^{27

29

30}, Iulian-Horia Holobaca³¹, Aurelio Tobias^{26

32}, Carmen Íñiguez^{16

33}, Yue Leon Guo^{34

35

36}, Shih-Chun Pan³⁵, Pierre Masselot^{37

38}, Michelle L Bell³⁹, Antonella Zanobetti⁴⁰, Joel Schwartz⁴⁰, Antonio Gasparrini^{37

38

41}, Haidong Kan^{42

43}

Affiliations

¹ School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
² Department of Statistics, Computer Science and Applications "G. Parenti," University of Florence, Florence, Italy.
³ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁴ Oeschger Centre for Climate Change Research, University of Bern, Bern, Switzerland.
⁵ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁶ Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁷ National Institute of Environmental Health, Chinese Centre for Disease Control and Prevention, Beijing, China.
⁸ School of Public Health and Institute of Environment and Human Health, Anhui Medical University, Hefei, China.
⁹ Centre for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
¹⁰ School of Public Health and Social Work, Queensland University of Technology, Brisbane, QLD, Australia.
¹¹ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹² Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
¹³ Department of Public Health, Universidad de los Andes, Santiago, Chile.
¹⁴ Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus.
¹⁵ Climate Research Foundation, Madrid, Spain.
¹⁶ Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
¹⁷ Centre for Environmental and Respiratory Health Research (CERH), University of Oulu, Oulu, Finland.
¹⁸ Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹⁹ Santé Publique France, Department of Environmental and Occupational Health, French National Public Health Agency, Saint Maurice, France.
²⁰ Institute of Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany.
²¹ IBE-Chair of Epidemiology, LMU Munich, Munich, Germany.
²² Faculty of Geography and Environmental Sciences, Hakim Sabzevari University, Sabzevar, Khorasan Razavi, Iran.
²³ Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Israel.
²⁴ Centre for Climate Change Adaptation, National Institute for Environmental Studies, Tsukuba, Japan.
²⁵ Department of Global Health Policy, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
²⁶ School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
²⁷ Department of Environmental Health, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal.
²⁸ NOVA National School of Public Health, Public Health Research Center, Universidade NOVA de Lisboa, Lisbon, Portugal.
²⁹ EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.
³⁰ Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Porto, Portugal Porto, Portugal.
³¹ Faculty of Geography, Babes-Bolay University, Cluj-Napoca, Romania.
³² Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Barcelona, Spain.
³³ Department of Statistics and Computational Research, University of Valencia, Valencia, Spain.
³⁴ Environmental and Occupational Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
³⁵ National Institute of Environmental Health Science, National Health Research Institutes, Zhunan, Taiwan.
³⁶ Graduate Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan.
³⁷ Department of Public Health Environments and Society, London School of Hygiene and Tropical Medicine, London, UK.
³⁸ Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK.
³⁹ School of the Environment, Yale University, New Haven, CT, USA.
⁴⁰ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴¹ Centre for Statistical Methodology, London School of Hygiene and Tropical Medicine, London, UK.
⁴² School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China kanh@fudan.edu.cn.
⁴³ Children's Hospital of Fudan University, National Centre for Children's Health, Shanghai, China.

PMID: 37793695
PMCID: PMC10548261
DOI: 10.1136/bmj-2023-075203

Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis

Cong Liu et al. BMJ. 2023.

. 2023 Oct 4:383:e075203.

doi: 10.1136/bmj-2023-075203.

Authors

Affiliations

¹ School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
² Department of Statistics, Computer Science and Applications "G. Parenti," University of Florence, Florence, Italy.
³ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁴ Oeschger Centre for Climate Change Research, University of Bern, Bern, Switzerland.
⁵ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁶ Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁷ National Institute of Environmental Health, Chinese Centre for Disease Control and Prevention, Beijing, China.
⁸ School of Public Health and Institute of Environment and Human Health, Anhui Medical University, Hefei, China.
⁹ Centre for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
¹⁰ School of Public Health and Social Work, Queensland University of Technology, Brisbane, QLD, Australia.
¹¹ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹² Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
¹³ Department of Public Health, Universidad de los Andes, Santiago, Chile.
¹⁴ Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus.
¹⁵ Climate Research Foundation, Madrid, Spain.
¹⁶ Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
¹⁷ Centre for Environmental and Respiratory Health Research (CERH), University of Oulu, Oulu, Finland.
¹⁸ Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹⁹ Santé Publique France, Department of Environmental and Occupational Health, French National Public Health Agency, Saint Maurice, France.
²⁰ Institute of Epidemiology, Helmholtz Zentrum München - German Research Centre for Environmental Health, Neuherberg, Germany.
²¹ IBE-Chair of Epidemiology, LMU Munich, Munich, Germany.
²² Faculty of Geography and Environmental Sciences, Hakim Sabzevari University, Sabzevar, Khorasan Razavi, Iran.
²³ Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Israel.
²⁴ Centre for Climate Change Adaptation, National Institute for Environmental Studies, Tsukuba, Japan.
²⁵ Department of Global Health Policy, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
²⁶ School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
²⁷ Department of Environmental Health, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal.
²⁸ NOVA National School of Public Health, Public Health Research Center, Universidade NOVA de Lisboa, Lisbon, Portugal.
²⁹ EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.
³⁰ Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Porto, Portugal Porto, Portugal.
³¹ Faculty of Geography, Babes-Bolay University, Cluj-Napoca, Romania.
³² Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Barcelona, Spain.
³³ Department of Statistics and Computational Research, University of Valencia, Valencia, Spain.
³⁴ Environmental and Occupational Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
³⁵ National Institute of Environmental Health Science, National Health Research Institutes, Zhunan, Taiwan.
³⁶ Graduate Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan.
³⁷ Department of Public Health Environments and Society, London School of Hygiene and Tropical Medicine, London, UK.
³⁸ Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK.
³⁹ School of the Environment, Yale University, New Haven, CT, USA.
⁴⁰ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴¹ Centre for Statistical Methodology, London School of Hygiene and Tropical Medicine, London, UK.
⁴² School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China kanh@fudan.edu.cn.
⁴³ Children's Hospital of Fudan University, National Centre for Children's Health, Shanghai, China.

PMID: 37793695
PMCID: PMC10548261
DOI: 10.1136/bmj-2023-075203

Abstract

Objective: To investigate potential interactive effects of fine particulate matter (PM_2.5) and ozone (O₃) on daily mortality at global level.

Design: Two stage time series analysis.

Setting: 372 cities across 19 countries and regions.

Population: Daily counts of deaths from all causes, cardiovascular disease, and respiratory disease.

Main outcome measure: Daily mortality data during 1994-2020. Stratified analyses by co-pollutant exposures and synergy index (>1 denotes the combined effect of pollutants is greater than individual effects) were applied to explore the interaction between PM_2.5 and O₃ in association with mortality.

Results: During the study period across the 372 cities, 19.3 million deaths were attributable to all causes, 5.3 million to cardiovascular disease, and 1.9 million to respiratory disease. The risk of total mortality for a 10 μg/m³ increment in PM_2.5 (lag 0-1 days) ranged from 0.47% (95% confidence interval 0.26% to 0.67%) to 1.25% (1.02% to 1.48%) from the lowest to highest fourths of O₃ concentration; and for a 10 μg/m³ increase in O₃ ranged from 0.04% (-0.09% to 0.16%) to 0.29% (0.18% to 0.39%) from the lowest to highest fourths of PM_2.5 concentration, with significant differences between strata (P for interaction <0.001). A significant synergistic interaction was also identified between PM_2.5 and O₃ for total mortality, with a synergy index of 1.93 (95% confidence interval 1.47 to 3.34). Subgroup analyses showed that interactions between PM_2.5 and O₃ on all three mortality endpoints were more prominent in high latitude regions and during cold seasons.

Conclusion: The findings of this study suggest a synergistic effect of PM_2.5 and O₃ on total, cardiovascular, and respiratory mortality, indicating the benefit of coordinated control strategies for both pollutants.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at URL www.icmje.org/disclosure-of-interest/ and declare: support from the National Natural Science Foundation of China and the Italian Ministry of University and Research; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

**Fig 1**
Percentage changes (central estimates and 95% confidence interval) in total, cardiovascular, and respiratory mortality associated with a 10 μg/m³ increase in PM_2.5 and O₃ in stratified analyses and in high and low latitude regions. High latitude (n=186), latitude above median (absolute value of 40.3°) across all cities; low latitude (n=186), latitude below median across all cities. P values for interactions were obtained from likelihood ratio tests. CI=confidence interval; CVD=cardiovascular mortality; O₃=ozone; PM_2.5=fine particular matter with an aerodynamic diameter ≤2.5 μm

**Fig 2**
Percentage changes (central estimates and 95% confidence interval) in total, cardiovascular, and respiratory mortality associated with a 10 μg/m³ increase in PM_2.5 and O₃ in stratified analyses and in warm and cold seasons. Warm season is March to August for the northern hemisphere and September to February for the southern hemisphere; Cold season is September to February for the northern hemisphere and March to August for the southern hemisphere. P values for interactions were obtained from likelihood ratio tests. CI=confidence interval; CVD=cardiovascular mortality; O₃=ozone; PM_2.5=fine particular matter with an aerodynamic diameter ≤2.5 μm

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Comment in

Protecting populations from the health harms of air pollution.
Sullivan J, Sorensen C. Sullivan J, et al. BMJ. 2023 Oct 4;383:2020. doi: 10.1136/bmj.p2020. BMJ. 2023. PMID: 37793680 No abstract available.

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Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis

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Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis

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