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

BMJ 2020; 368 doi: (Published 10 February 2020) Cite this as: BMJ 2020;368:m108
  1. Ana M Vicedo-Cabrera, assistant professor1 2 3,
  2. Francesco Sera, research fellow1,
  3. Cong Liu, PhD student4,
  4. Ben Armstrong, professor1,
  5. Ai Milojevic, assistant professor1,
  6. Yuming Guo, professor5,
  7. Shilu Tong, professor6 7 8,
  8. Eric Lavigne, adjunct professor9 10,
  9. Jan Kyselý, associate professor11 12,
  10. Aleš Urban, postdoctoral researcher11,
  11. Hans Orru, associate professor13,
  12. Ene Indermitte, lecturer13,
  13. Mathilde Pascal, project manager14,
  14. Veronika Huber, research fellow15 16,
  15. Alexandra Schneider, senior scientist17,
  16. Klea Katsouyanni, professor18 19,
  17. Evangelia Samoli, associate professor18,
  18. Massimo Stafoggia, senior researcher20,
  19. Matteo Scortichini, researcher20,
  20. Masahiro Hashizume, professor21,
  21. Yasushi Honda, professor22,
  22. Chris Fook Sheng Ng, lecturer23,
  23. Magali Hurtado-Diaz, researcher24,
  24. Julio Cruz, researcher24,
  25. Susana Silva, researcher25,
  26. Joana Madureira, postdoctoral research fellow26 27,
  27. Noah Scovronick, assistant professor28,
  28. Rebecca M. Garland, principal researcher29 30 31,
  29. Ho Kim, professor32,
  30. Aurelio Tobias, senior researcher33,
  31. Carmen Íñiguez, senior researcher34 35,
  32. Bertil Forsberg, professor36,
  33. Christofer Åström, senior research assistant36,
  34. Martina S Ragettli, senior scientific collaborator37 38,
  35. Martin Röösli, professor37 38,
  36. Yue-Liang Leon Guo, professor39,
  37. Bing-Yu Chen, professor39,
  38. Antonella Zanobetti, principal research scientist40,
  39. Joel Schwartz, professor40,
  40. Michelle L Bell, professor41,
  41. Haidong Kan, professor42,
  42. Antonio Gasparrini, professor1 43 44
  1. 1Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK
  2. 2Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  3. 3Oeschger Centre for Climate Change Research, University of Bern, Bern, Switzerland
  4. 4School 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
  5. 5Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
  6. 6Shanghai Children’s Medical Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  7. 7School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei, China
  8. 8School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia
  9. 9Air Health Science Division, Health Canada, Ottawa, Canada
  10. 10School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
  11. 11Institute of Atmospheric Physics, Czech Academy of Sciences, Prague, Czech Republic
  12. 12Faculty of Environmental Sciences, Czech University of Life Sciences, Prague, Czech Republic
  13. 13Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia
  14. 14Santé Publique France, French National Public Health Agency, Saint Maurice, France
  15. 15Department of Physical, Chemical and Natural Systems, Universidad Pablo de Olavide, Sevilla, Spain
  16. 16Potsdam Institute for Climate Impact Research, Potsdam, Germany
  17. 17Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
  18. 18Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Greece
  19. 19School of Population Health and Environmental Sciences, King’s College London, London, UK
  20. 20Department of Epidemiology, Lazio Regional Health Service/ASL Roma 1, Rome, Italy
  21. 21Department of Global Health Policy, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  22. 22Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan
  23. 23School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
  24. 24Department of Environmental Health, National Institute of Public Health, Cuernavaca Morelos, Mexico
  25. 25Department of Epidemiology, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal
  26. 26EPIUnit–Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
  27. 27Department of Environmental Health, Instituto Nacional de Saúde Dr Ricardo Jorge, Porto, Portugal
  28. 28Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, USA
  29. 29Natural Resources and the Environment Unit, Council for Scientific and Industrial Research, Pretoria 0001, South Africa
  30. 30Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa
  31. 31Department of Geography, Geo-informatics and Meteorology, University of Pretoria, Pretoria, South Africa
  32. 32Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea
  33. 33Institute of Environmental Assessment and Water Research, Spanish Council for Scientific Research, Barcelona, Spain
  34. 34Department of Statistics and Computational Research, University of Valencia, Valencia, Spain
  35. 35Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain
  36. 36Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
  37. 37Swiss Tropical and Public Health Institute, Basel, Switzerland
  38. 38University of Basel, Basel, Switzerland
  39. 39Environmental and Occupational Medicine, National Taiwan University and NTU Hospital, Taiwan
  40. 40Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  41. 41School of Forestry and Environmental Studies, Yale University, New Haven, CT, USA
  42. 42Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Fudan University, Shanghai, China
  43. 43Centre for Statistical Methodology, London School of Hygiene and Tropical Medicine, London, UK
  44. 44Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to: A M Vicedo-Cabrera ana.vicedo-cabrera{at}
  • Accepted 17 December 2019


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.


  • Contributors: AG and HK are senior authors and contributed equally to this work. AG, YG, MH, and BA set up the collaborative network. AMV-C, AG, FS, and HK designed the study. AMV-C coordinated the work and took the lead in drafting the manuscript and interpreting the results. AG and FS developed the statistical methods. AMV-C conducted the statistical analysis. BA, AH, FS, AG, KK, ES, MS, AT, CI, VH, AS, JS, NS, RG, and EL provided substantial scientific input in interpreting the results and drafting the manuscript. CL, AM, YG, ST, EL, JK, AU, HO, EI, MP, VH, AS, KK, ES, MS, MS, MH, YH, CFSN, MH, JC, SS, JM, NS, RG, HK, AT, CI, BF, CA, MSR, MR, YLLG, BYC, AZ, JS, MB, and HK provided the data and contributed to the interpretation of the results and to the submitted version of the manuscript. AMV-C, AG, and HK are the guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This work was primarily supported by the UK Medical Research Council (MR/M022625/1 and MR/R013349/1) and by the UK Natural Environment Research Council (NE/R009384/1). HaK was supported by the National Natural Science Foundation of China (91843302 and 91643205) and China Medical Board Collaborating Program (16-250). JM was supported by the Fundação para a Ciência e a Tecnologia (FCT) through the scholarship SFRH/BPD/115112/2016. VH was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO, PCIN-2017-046) and the German Federal Ministry of Education and Research (BMBF, 01LS1201A2). AU and JK were supported by the Czech Science Foundation (18-22125S). HO and EI were supported by the Estonian Ministry of Education and Research (IUT34-17). AT was supported by the Japanese Society for the Promotion of Science invitational fellowships for research in Japan (S18149). YG was supported by the career development fellowship of the Australian National Health and Medical Research Council (APP1107107 and APP1163693). ST was supported by the Science and Technology Commission of Shanghai Municipality (18411951600). HoK was supported by the Global Research Laboratory (#K21004000001-10A0500-0710) through the National Research Foundation of Korea and by the Future Planning and Korea Ministry of Environment as the “Climate Change Correspondence R&D Program” (2013001310002). RMG was supported by a CSIR parliamentary grant. NS is supported by the National Institute of Environmental Health Sciences funded HERCULES Centre (P30ES019776). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of this manuscript.

  • This publication was developed under assistance agreement No RD835871 awarded by the US Environmental Protection Agency to Yale University (MLB). It has not been formally reviewed by EPA. The views expressed in this document are solely those of the authors of the publication and do not necessarily reflect those of the Agency. EPA does not endorse any products or commercial services mentioned in this publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at 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.

  • Ethical approval: Not required.

  • Data sharing: Data have been collected within the MCC (Multi-City Multi-Country) Collaborative Research Network ( under a data sharing agreement and cannot be made publicly available. Researchers can refer to MCC participants listed as coauthors for information on accessing the data for each country. The R code for the analysis is available from the corresponding author.

  • The lead authors (AG and HK) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Dissemination to participants and related patient and public communities: Dissemination of the findings will be carried out through press releases by the research institutions of the contributing authors.

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