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Cited by 110Air Quality and Health ImpactsClimate Change and Health ImpactsIndoor Air Quality and Microbial Exposure

Acute effects of ambient ozone on mortality in Europe and North America: results from the APHENA study

Open access
Peng, Roger D., Samoli, Evangelia, Pham, Luu, Dominici, Francesca, Touloumi, Giota, Ramsay, Tim, Burnett, Richard T., Krewski, Daniel +6 more·2013·Air Quality, Atmosphere & Health
DOI 10.1007/s11869-012-0180-9PMC PMC3668792
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Abstract

The "Air Pollution and Health: A Combined European and North American Approach" (APHENA) project is a collaborative analysis of multi-city time-series data on the association between air pollution and adverse health outcomes. The main objective of APHENA was to examine the coherence of findings of time-series studies relating short-term fluctuations in air pollution levels to mortality and morbidity in 125 cities in Europe, the US, and Canada. Multi-city time-series analysis was conducted using a two-stage approach. We used Poisson regression models controlling for overdispersion with either penalized or natural splines to adjust for seasonality. Hierarchical models were used to obtain an overall estimate of excess mortality associated with ozone and to assess potential effect modification. Potential effect modifiers were city-level characteristics related to exposure to other ambient air pollutants, weather, socioeconomic status, and the vulnerability of the population. Regionally pooled risk estimates from Europe and the US were similar; those from Canada were substantially higher. The pooled estimated excess relative risk associated with a 10 µg/m 3 increase in 1 h daily maximum O 3 was 0.26 % (95 % CI, 0.15 %, 0.37 %). Across regions, there was little consistent indication of effect modification by age or other effect modifiers considered in the analysis. The findings from APHENA on the effects of O 3 on mortality in the general population were comparable with previously reported results and relatively robust to the method of data analysis. Overall, there was no indication of strong effect modification by age or ecologic variables considered in the analysis.

AI snapshot

Written from the paper’s full text.

TL;DR

The APHENA study pooled multi-city time-series data from Europe, the US, and Canada and found that short-term ambient ozone exposure was associated with increased all-cause mortality. Pooled risk estimates were similar for Europe and the US but substantially higher for Canada, with little consistent evidence of effect modification by age or other city-level factors.

Key findings

  • The pooled estimated excess relative risk associated with a 10 µg/m³ increase in 1 h daily maximum O₃ was 0.26% (95% CI, 0.15%, 0.37%) using natural splines with 8 df per year.
  • Warm-season effects were higher than annual effects: for all-cause non-accidental mortality, all ages, per 10 µg/m³ increase in average lags 0–1 O₃, excess risks were 0.25% (95% CI, 0.10%, 0.40%) in Europe, 0.95% (95% CI, 0.65%, 1.2%) in Canada, and 0.57% (95% CI, 0.35%, 0.79%) in the US.
  • There was little consistent effect modification by age or other modifiers. In the US, temperature had a strong negative modifying effect, with the percent increase in mortality per 10 µg/m³ O₃ ranging from 0.27% to 0.00% between the 25th and 75th percentiles of temperature.
  • The exposure–response analysis did not support a threshold for O₃ and total mortality in any of the three centers.

Methods

  • Two-stage multi-city time-series analysis: first-stage city-specific log-linear Poisson regression models with overdispersion, controlling for seasonality using natural splines or penalized splines with 3, 8, or 12 df per year, temperature smooths, day-of-week, and holiday effects.
  • Main year-round O₃ analysis included 23 European cities, 50 US cities, and 12 Canadian cities; warm-season analysis used all 86 US cities. Exposure was daily 1 h maximum O₃; outcomes included all-cause mortality excluding external causes, overall and by age (<75 and ≥75 years).
  • Second-stage Bayesian hierarchical models pooled city-specific effects and assessed effect modification by city-level variables; threshold analyses used a grid from 0 to 75 µg/m³ in 5 µg/m³ increments and compared AIC values.

Limitations

  • Stated: data came from multiple countries and had not been collected under a uniform protocol across Europe and North America; European data came from 24 countries with varying collection methods, and a fully harmonized database was not possible, leaving differing measurement error structures as potential contributors to heterogeneity.
  • Stated: effect-modification analyses were limited by the restricted number of variables measured with sufficient commonality; the only socioeconomic indicator available across the full dataset was unemployment rate, and data were unavailable on health status, diabetes, housing characteristics, or air pollution source mix.
  • Stated: identifying a threshold is exceedingly difficult because the O₃–mortality association is inherently small and would likely require far more data than APHENA could assemble. Evident from the text: Canadian estimates were based on smaller cities with wider confidence intervals, Canadian O₃ concentrations were lowest and covered the narrowest range, and Canadian PM₁₀ was measured only every sixth day, making two-pollutant estimates not directly comparable.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s11869-012-0180-9

Cites

16 of 16 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 9 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The annual estimated effects of O3 on cardiovascular mortality for those above or below 75 years of age were generally slightly higher than those for total mortality.

    “The annual estimated effects of O3 on cardiovascular mortality for those above or below 75 years of age (data not shown) were generally slightly higher than those for total mortality.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the US, temperature had a strong negative modifying effect, with the percent increase in mortality for a 10 μg/m3 increase in O3 estimated to range from 0.27% to 0.00% between the 25th and 75th percentiles of temperature.

    “In the US, temperature had a strong negative modifying effect, with the percent increase in mortality for a 10 µg/m3 increase in O3 estimated to range from 0.27 % to 0.00 % between the 25th and 75th percentiles of temperature.”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was a statistically significant effect of O3 on total mortality for all ages in all three centers.

    “There was a statistically significant effect of O3 on total mortality for all ages in all three centers.”
    Quote in the paperSubstantial claim
  • Findingown data

    The highest effect of O3 in Europe was observed on cardiovascular mortality among those <75 years using the average of 2 days exposure (0.35%, 95% CI 0.12%, 0.58%).

    “The highest effect of O3 in Europe was observed on cardiovascular mortality among those <75 years using the average of 2 days exposure (0.35 %, 95 % CI, 0.12 %, 0.58 %).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Across regions, there was little consistent indication of effect modification by age or other effect modifiers considered in the analysis.

    “Across regions, there was little consistent indication of effect modification by age or other effect modifiers considered in the analysis.”
    • Also stated in: § Discussion · plain
      “There was no consistent pattern of effect modification for the association between O3 and mortality.”
    Quote in the paperSubstantial claim
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 4
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Regionally pooled risk estimates from Europe and the US were similar, whereas those from Canada were substantially higher.

    “Regionally pooled risk estimates from Europe and the US were similar; those from Canada were substantially higher.”
    • Also stated in: § Results · plain
      “The effects for Canada are generally larger but with wider confidence intervals due to the smaller sizes of the Canadian cities. With the exception of estimates based on 3 df per year, the estimates for Europe and the US are comparable.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Canada and the US, the largest effect of annual O3 was observed in the older age group; in Europe, the largest effect was seen among those <75 years of age.

    “In Canada and the US, the largest effect of annual O3 was observed in the older age group; in Europe, the largest effect was seen among those <75 years of age.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    All O3 effects were statistically significant during the warm period and higher than the annual effects.

    “All O3 effects were statistically significant during the warm period and higher than the annual effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Using warm months only, the percent increase in all-cause non-accidental mortality for all ages associated with a 10 μg/m3 increase in the average of lags 0-1 O3 was 0.25% (95% CI 0.10%, 0.40%) for Europe, 0.95% (95% CI 0.65%, 1.2%) for Canada, and 0.57% (95% CI 0.35%, 0.79%) for the US.

    “Using these warm months only, the percent increase in all-cause non-accidental mortality for all ages associated with at 10 µg/m3 increase in the average of lags 0–1 O3 was 0.25 % (95 % CI, 0.10 %, 0.40 %) for Europe, 0.95 % (95 % CI, 0.65 %, 1.2 %) for Canada, and 0.57 % (95 % CI, 0.35 %, 0.79 %) for the US.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Europe and the US, the largest effects were observed when exposure over 3 days was taken into account for all health outcomes analyzed, whereas the highest effects in Canada were observed for the average of lags 0-1.

    “In Europe and the US, the largest effects were observed when we took into account the exposure over 3 days for all the health outcomes analyzed, whereas the highest effects in Canada were observed when we took into account the average of lags 0–1.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The summer-only O3 effect estimates for cause-specific mortality were positive, except for cardiovascular mortality among those <75 years of age in Canada, and in most cases statistically significant.

    “The summer-only O3 effect estimates for cause-specific mortality were positive (except for cardiovascular mortality among those <75 years of age in Canada) and in most cases statistically significant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In Canada, the highest effects of summertime O3 were observed for respiratory mortality for all ages under all lag structures considered, while in Europe and the US the same was true only using lag 1 O3 exposure.

    “In Canada, the highest effects of summertime O3 were observed for respiratory mortality for all ages under all lag structures considered while, in Europe and the US, the same was true only using lag 1 O3 exposure.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The results for respiratory mortality were less consistent and not statistically significant in any case.

    “The results for respiratory mortality were less consistent and not statistically significant in any case.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was some indication of confounding by PM10 in the Canadian results, but the estimates with and without PM10 in the models are not directly comparable for Canada because PM10 measurements were only measured every sixth day.

    “There was some indication of confounding by PM10 in the Canadian results, but the estimates with and without PM10 in the models are not directly comparable for Canada, since PM10 measurements were only measured every sixth day.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Mortality risk estimates for O3 tended to decrease with increasing df in the smooth function of time and were generally higher for the average of lags 0 and 1 compared with lag 1 O3 concentration alone.

    “Mortality risk estimates for O3 tended to decrease with increasing df in the smooth function of time and were generally higher for the average of lags 0 and 1 compared with lag 1 O3 concentration alone.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For O3 and mortality, there was some variation in findings by whether results were considered for the full year or only for the summer months, pointing to higher effects when only the warm period was considered.

    “For O3 and mortality, there was some variation in findings by whether results were considered for the full year or only for the summer months, pointing to higher effects when only the warm period was considered.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The coefficient of variation for O3 was associated with mortality in both the US and Europe, but not in Canada.

    “The coefficient of variation for O3 was associated with mortality in both the US and Europe, but not in Canada.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    O3 concentrations were lowest in the Canadian data and also covered the narrowest range.

    “We note that O3 concentrations were lowest in the Canadian data and also covered the narrowest range.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was some evidence that the mean SO2 level and the percent of the population over age 75 years modified the O3 effect, but the evidence was not consistent across the US, Canada, and Europe.

    “Although there was some evidence that the mean SO2 level and the percent of the population over age 75 years modified the O3 effect, the evidence was not consistent across the US, Canada, and Europe.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The APHENA findings on the effects of O3 on mortality in the general population were comparable with previously reported results and relatively robust to the method of data analysis.

    “The findings from APHENA on the effects of O3 on mortality in the general population were comparable with previously reported results and relatively robust to the method of data analysis.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The smooth function of time removes long-term trends and seasonal patterns from the data to guard against confounding by smoothly varying unmeasured temporal confounders.

    “These functions remove long-term trends and seasonal patterns from the data to guard against confounding by smoothly varying unmeasured temporal confounders.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The smooth function of time serves as a proxy for any time-dependent outcome predictors or confounders with long-term trends and seasonal patterns not explicitly included in the model.

  • May combine two claims.

    Premisecitation

    Identifying a threshold in time-series models is exceedingly difficult, and numerous simulation studies bear this out.

    “However, identifying a threshold in time-series models is exceedingly difficult, and numerous simulation studies bear this out (Katsouyanni et al. 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Katsouyanni et al. 2009

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In previously reported analyses, the European and North American risk estimates were quite similar, whereas the estimates based on the Canadian data were somewhat higher.

    “In previously reported analyses, the European and North American risk estimates were quite similar, whereas the estimates based on the Canadian data were somewhat higher (Health Effects Institute 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Health Effects Institute 2003

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The Canadian, APHEA, and NMMAPS data sets consistently demonstrate an acute effect of O3 on mortality, although quantitative risk estimates have varied across the three data sets.

    “The Canadian, APHEA, and NMMAPS data sets have now been extensively analyzed, and, while the quantitative risk estimates have varied across the three data sets, these data sets consistently demonstrate an acute effect of O3 on mortality.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    In the United States and Canada, nationwide reference methods for air pollution data collection are in place, and deaths are captured and coded uniformly.

    “In the United States and Canada, nationwide reference methods for air pollution data collection are in place, and deaths are captured and coded uniformly.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Study design and conductreasoning

    It was not possible to assemble a fully harmonized database for the first-stage analysis, so differences in the time-series data and possible differing measurement error structures across the three sets of data remain potential contributors to heterogeneity.

    “Consequently, differences in the time-series data, as well as the possibility of differing measurement error structures across the three sets of data, remain as potential contributors to heterogeneity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The data came from multiple countries and had not been collected according to a uniform protocol across Europe and North America; however, all data had been edited and had undergone a quality assessment audit as part of the APHENA project.

    “The data came from multiple countries and had not been collected according to a uniform protocol across Europe and North America; however, all data had been edited and had undergone a quality assessment audit as part of the APHENA project.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    The data can be analyzed with multiple models to assess sensitivity of findings to model specification, and effect modification can be assessed using risk estimates coming from a common analytic approach.

    “The data can be analyzed with multiple models, so as to assess sensitivity of findings to model specification, and effect modification can be assessed using risk estimates coming from a common analytic approach.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Well-documented approaches were used to develop air pollution concentration values that would be as complete and uniform as possible.

    “Well-documented approaches were used to develop air pollution concentration values that would be as complete and uniform as possible.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Coordinated multi-city studies in four major Asian cities and 14 UK conurbations reported 0.38% and 0.30% increases in all-natural cause mortality, respectively, associated with a 10 μg/m3 increase in an 8-h average ozone.

    “Coordinated multi-city studies in four major Asian cities and 14 UK conurbations reported 0.38 % and 0.30 % increases in all-natural cause mortality, respectively, associated with a 10 µg/m3 increase in an 8-h average ozone (Health Effects Institute 2010; Pattenden et al. 2010).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Health Effects Institute 2010

      Not checked in the free run.

    • cites Pattenden et al. 2010 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    The European data came from 24 countries and methods for their collection varied among the countries, although they were assembled and edited with a common protocol.

    “The European data came from 24 countries and methods for their collection varied among the countries, although they were assembled and edited with a common protocol.”
    Quote in the paperNot a substantial claim
26 of 26

  • The authors state this as an assumption.

    In the second-stage model, city-specific effects βc are normally distributed around an overall effect and are independent observations with variances equal to the between-cities variance and the squared standard error of βc.

    “For the second stage of the analysis, we assumed the city-specific effects βc to be normally distributed around an overall effect.”
    “These models assumed that city-specific effects βc were a sample of independent observations from a normal distribution with the same mean and with variances equal to the between-cities variance and the squared standard error of βc.”

  • The authors state this as an assumption.

    The smooth function of time serves as a proxy for any time-dependent outcome predictors or confounders with long-term trends and seasonal patterns not explicitly included in the model.

    “The smooth function of time serves as a proxy for any time-dependent outcome predictors or confounders with long-term trends and seasonal patterns not explicitly included in the model.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • European city count is smaller than the reported country count

    Minor

    The paper says the European data came from 24 countries, but it reports only 23 European cities in the analysis. Twenty-three cities cannot represent 24 countries.

  • UK conurbation count differs from the cited study title

    Minor

    The discussion attributes a result to a study of 14 UK conurbations, but the cited Pattenden et al. reference identifies its study as covering 15 British conurbations.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Health Effects Institute (2003) Revised analyses of time-series studies of air pollution and health. Health Effects Institute, Cambridge
  2. Health Effects Institute (2010) Public Health and Air Pollution in Asia (PAPA): coordinated studies of short-term exposure to air pollution and daily mortality in four cities. HEI research report 154. Health Effects Institute, Boston
  3. World Health Organization (2006) Air quality guidelines: global ppdate 2005—particulate matter, ozone, nitrogen dioxide and sulfur dioxide. World Health Organization, Copenhagen

Cited by

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Related

Authors
Peng, R. D., Samoli, E., Pham, L., Dominici, F., Touloumi, G., Ramsay, T., Burnett, R. T., Krewski, D., Le Tertre, A., Cohen, A., Atkinson, R. W., Anderson, H. R., Katsouyanni, K., & Samet, J. M.
Affiliations
  • Johns Hopkins University (US)
  • National and Kapodistrian University of Athens (GR)
  • Harvard University (US)
  • University of Ottawa (CA)
  • Health Canada (CA)
  • Health Effects Institute (US)
  • St George's, University of London (GB)
  • University of Southern California (US)
Corresponding author
Peng, Roger D.
ORCID
Venue
Air Quality, Atmosphere & Health
Publisher
Springer Science and Business Media LLC
Published
2012-08-15
Volume
6
Issue
2
Pages
445-453
ISSN
  • 1873-9318 (ISSN-L)
  • 1873-9326
DOI
10.1007/s11869-012-0180-9
PMC
PMC3668792
OpenAlex
W2002527279
Cited by
110
References
16
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 16 · 2019: 9 · 2018: 10 · 2017: 15 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 3
FWCI
3.77
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Air Quality Atmosphere & Health (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
National Institute of Environmental Health Sciences (R21ES022585, R01ES019560)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Climate Change and Health Impacts
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Indoor Air Quality and Microbial Exposure
Keywords
ozone, ambient air pollution, mortality, excess relative risk, effect modification, air pollution and health

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