Multicenter Study

. 2020 Feb 10:368:m108.

doi: 10.1136/bmj.m108.

Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries

Ana M Vicedo-Cabrera^{1

2

3}, Francesco Sera⁴, Cong Liu⁵, Ben Armstrong⁴, Ai Milojevic⁴, Yuming Guo⁶, Shilu Tong^{7

8

9}, Eric Lavigne^{10

11}, Jan Kyselý^{12

13}, Aleš Urban¹², Hans Orru¹⁴, Ene Indermitte¹⁴, Mathilde Pascal¹⁵, Veronika Huber^{16

17}, Alexandra Schneider¹⁸, Klea Katsouyanni^{19

20}, Evangelia Samoli¹⁹, Massimo Stafoggia²¹, Matteo Scortichini²¹, Masahiro Hashizume²², Yasushi Honda²³, Chris Fook Sheng Ng²⁴, Magali Hurtado-Diaz²⁵, Julio Cruz²⁵, Susana Silva²⁶, Joana Madureira^{27

28}, Noah Scovronick²⁹, Rebecca M Garland^{30

31

32}, Ho Kim³³, Aurelio Tobias³⁴, Carmen Íñiguez^{35

36}, Bertil Forsberg³⁷, Christofer Åström³⁷, Martina S Ragettli^{38

39}, Martin Röösli^{38

39}, Yue-Liang Leon Guo⁴⁰, Bing-Yu Chen⁴⁰, Antonella Zanobetti⁴¹, Joel Schwartz⁴¹, Michelle L Bell⁴², Haidong Kan⁴³, Antonio Gasparrini^{4

44

45}

Affiliations

¹ Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK ana.vicedo-cabrera@lshtm.ac.uk.
² Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
³ Oeschger Centre for Climate Change Research, University of Bern, Bern, Switzerland.
⁴ Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK.
⁵ School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, China.
⁶ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁷ Shanghai Children's Medical Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁸ School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei, China.
⁹ School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia.
¹⁰ Air Health Science Division, Health Canada, Ottawa, Canada.
¹¹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
¹² Institute of Atmospheric Physics, Czech Academy of Sciences, Prague, Czech Republic.
¹³ Faculty of Environmental Sciences, Czech University of Life Sciences, Prague, Czech Republic.
¹⁴ Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
¹⁵ Santé Publique France, French National Public Health Agency, Saint Maurice, France.
¹⁶ Department of Physical, Chemical and Natural Systems, Universidad Pablo de Olavide, Sevilla, Spain.
¹⁷ Potsdam Institute for Climate Impact Research, Potsdam, Germany.
¹⁸ Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
¹⁹ Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Greece.
²⁰ School of Population Health and Environmental Sciences, King's College London, London, UK.
²¹ Department of Epidemiology, Lazio Regional Health Service/ASL Roma 1, Rome, Italy.
²² Department of Global Health Policy, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
²³ Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan.
²⁴ School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
²⁵ Department of Environmental Health, National Institute of Public Health, Cuernavaca Morelos, Mexico.
²⁶ Department of Epidemiology, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
²⁷ EPIUnit-Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.
²⁸ Department of Environmental Health, Instituto Nacional de Saúde Dr Ricardo Jorge, Porto, Portugal.
²⁹ Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, USA.
³⁰ Natural Resources and the Environment Unit, Council for Scientific and Industrial Research, Pretoria 0001, South Africa.
³¹ Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa.
³² Department of Geography, Geo-informatics and Meteorology, University of Pretoria, Pretoria, South Africa.
³³ Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.
³⁴ Institute of Environmental Assessment and Water Research, Spanish Council for Scientific Research, Barcelona, Spain.
³⁵ Department of Statistics and Computational Research, University of Valencia, Valencia, Spain.
³⁶ Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
³⁷ Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
³⁸ Swiss Tropical and Public Health Institute, Basel, Switzerland.
³⁹ University of Basel, Basel, Switzerland.
⁴⁰ Environmental and Occupational Medicine, National Taiwan University and NTU Hospital, Taiwan.
⁴¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴² School of Forestry and Environmental Studies, Yale University, New Haven, CT, USA.
⁴³ Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Fudan University, Shanghai, China.
⁴⁴ Centre for Statistical Methodology, London School of Hygiene and Tropical Medicine, London, UK.
⁴⁵ Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK.

PMID: 32041707
PMCID: PMC7190035
DOI: 10.1136/bmj.m108

Multicenter Study

Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries

Ana M Vicedo-Cabrera et al. BMJ. 2020.

. 2020 Feb 10:368:m108.

doi: 10.1136/bmj.m108.

Authors

Affiliations

¹ Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK ana.vicedo-cabrera@lshtm.ac.uk.
² Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
³ Oeschger Centre for Climate Change Research, University of Bern, Bern, Switzerland.
⁴ Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK.
⁵ School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, China.
⁶ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁷ Shanghai Children's Medical Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁸ School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei, China.
⁹ School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia.
¹⁰ Air Health Science Division, Health Canada, Ottawa, Canada.
¹¹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
¹² Institute of Atmospheric Physics, Czech Academy of Sciences, Prague, Czech Republic.
¹³ Faculty of Environmental Sciences, Czech University of Life Sciences, Prague, Czech Republic.
¹⁴ Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
¹⁵ Santé Publique France, French National Public Health Agency, Saint Maurice, France.
¹⁶ Department of Physical, Chemical and Natural Systems, Universidad Pablo de Olavide, Sevilla, Spain.
¹⁷ Potsdam Institute for Climate Impact Research, Potsdam, Germany.
¹⁸ Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
¹⁹ Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Greece.
²⁰ School of Population Health and Environmental Sciences, King's College London, London, UK.
²¹ Department of Epidemiology, Lazio Regional Health Service/ASL Roma 1, Rome, Italy.
²² Department of Global Health Policy, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
²³ Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan.
²⁴ School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
²⁵ Department of Environmental Health, National Institute of Public Health, Cuernavaca Morelos, Mexico.
²⁶ Department of Epidemiology, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal.
²⁷ EPIUnit-Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.
²⁸ Department of Environmental Health, Instituto Nacional de Saúde Dr Ricardo Jorge, Porto, Portugal.
²⁹ Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, USA.
³⁰ Natural Resources and the Environment Unit, Council for Scientific and Industrial Research, Pretoria 0001, South Africa.
³¹ Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa.
³² Department of Geography, Geo-informatics and Meteorology, University of Pretoria, Pretoria, South Africa.
³³ Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.
³⁴ Institute of Environmental Assessment and Water Research, Spanish Council for Scientific Research, Barcelona, Spain.
³⁵ Department of Statistics and Computational Research, University of Valencia, Valencia, Spain.
³⁶ Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
³⁷ Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
³⁸ Swiss Tropical and Public Health Institute, Basel, Switzerland.
³⁹ University of Basel, Basel, Switzerland.
⁴⁰ Environmental and Occupational Medicine, National Taiwan University and NTU Hospital, Taiwan.
⁴¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴² School of Forestry and Environmental Studies, Yale University, New Haven, CT, USA.
⁴³ Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Fudan University, Shanghai, China.
⁴⁴ Centre for Statistical Methodology, London School of Hygiene and Tropical Medicine, London, UK.
⁴⁵ Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK.

PMID: 32041707
PMCID: PMC7190035
DOI: 10.1136/bmj.m108

Abstract

Objective: To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide.

Design: Two stage time series analysis.

Setting: 406 cities in 20 countries, with overlapping periods between 1985 and 2015, collected from the database of Multi-City Multi-Country Collaborative Research Network.

Population: Deaths for all causes or for external causes only registered in each city within the study period. MAIN OUTCOME MEASURES: Daily total mortality (all or non-external causes only).

Results: A total of 45 165 171 deaths were analysed in the 406 cities. On average, a 10 µg/m³ increase in ozone during the current and previous day was associated with an overall relative risk of mortality of 1.0018 (95% confidence interval 1.0012 to 1.0024). Some heterogeneity was found across countries, with estimates ranging from greater than 1.0020 in the United Kingdom, South Africa, Estonia, and Canada to less than 1.0008 in Mexico and Spain. Short term excess mortality in association with exposure to ozone higher than maximum background levels (70 µg/m³) was 0.26% (95% confidence interval 0.24% to 0.28%), corresponding to 8203 annual excess deaths (95% confidence interval 3525 to 12 840) across the 406 cities studied. The excess remained at 0.20% (0.18% to 0.22%) when restricting to days above the WHO guideline (100 µg/m³), corresponding to 6262 annual excess deaths (1413 to 11 065). Above more lenient thresholds for air quality standards in Europe, America, and China, excess mortality was 0.14%, 0.09%, and 0.05%, respectively.

Conclusions: Results suggest that ozone related mortality could be potentially reduced under stricter air quality standards. These findings have relevance for the implementation of efficient clean air interventions and mitigation strategies designed within national and international climate policies.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from UK Medical Research Council, China Medical Board Collaborating Program, Fundação para a Ciência e a Tecnologia, Spanish Ministry of Economy, Industry and Competitiveness, German Federal Ministry of Education and Research, Czech Science Foundation, Estonian Ministry of Education and Research, Japanese Society for the Promotion of Science, Australian National Health and Medical Research Council, Science and Technology Commission of Shanghai Municipality, Global Research Laboratory, through the National Research Foundation of Korea, Future Planning and Korea Ministry of Environment, CSIR parliamentary grant, and the National Institute of Environmental Health Sciences funded HERCULES Centre; no financial relationships with any organisations 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**
Geographical distribution of city specific average annual means of ozone (O₃, maximum eight hour average) of 406 cities of the Multi-City Multi-Country Collaborative Research Network included in the study

**Fig 2**
Overall and country specific short term ozone-mortality association, expressed as relative risk per 10 µg/m³ increase in ozone (O₃, maximum eight hour average) (lag 01)

**Fig 3**
Overall and country specific excess mortality (%) associated with ozone by specific ranges defined between thresholds consistent with current air quality standards. (No excess mortality associated with ozone was found in Australia, as daily ozone levels were below the maximum background level of 70 µg/m³). 100 µg/m³, World Health Organization guideline; 120 µg/m³, European Union directive; 140 µg/m³ (about 0.070 parts per million); National Ambient Air Quality Standard (NAAQS) in the US; 160 µg/m³ Chinese Ambient Air Quality Standard (CAAQS)

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Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries

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Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries

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