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Evangelia Samoli,¹ Antonis Analitis,¹ Giota Touloumi,¹ Joel Schwartz,² Hugh R. Anderson,³ Jordi Sunyer,⁴ Luigi Bisanti,⁵ Denis Zmirou,⁶ Judith M. Vonk,⁷ Juha Pekkanen,⁸ Pat Goodman,⁹ Anna Paldy,¹⁰ Christian Schindler,¹¹ and Klea Katsouyanni¹

¹Department of Hygiene and Epidemiology, University of Athens, Athens, Greece; ²Harvard School of Public Health, Boston, Massachusetts, USA; ³Community Health Sciences, St. George's Hospital Medical School, University of London, London, United Kingdom; ⁴Institut Municipal Investigacio Medica (IMIM), Barcelona, Spain; ⁵Azienda Sanitaria Locale della Città di Milano, Milano, Italy; ⁶INSERM U420, Nancy, France; ⁷Department of Epidemiology and Statistics, University of Groningen, Groningen, the Netherlands; ⁸National Public Health Institute, Unit of Environmental Epidemiology, Kuopio, Finland; ⁹Dublin Institute of Technology, Dublin, Ireland; ¹⁰National Institute of Environmental Health, Budapest, Hungary; ¹¹University of Basel, Institut fur Sozial-und Praventivmedizin, Basel, Switzerland

Abstract
Several studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of theses studies linear nonthreshold relations were assumed. We investigated the exposure-response association between ambient particles and mortality in the 22 European cities participating in the APHEA (Air Pollution and Health--A European Approach) project, which is the largest available European database. We estimated the exposure-response curves using regression spline models with two knots and then combined the individual city estimates of the spline to get an overall exposure-response relationship. To further explore the heterogeneity in the observed city-specific exposure-response associations, we investigated several city descriptive variables as potential effect modifiers that could alter the shape of the curve. We conclude that the association between ambient particles and mortality in the cities included in the present analysis, and in the range of the pollutant common in all analyzed cities, could be adequately estimated using the linear model. Our results confirm those previously reported in Europe and the United States. The heterogeneity found in the different city-specific relations reflects real effect modification, which can be explained partly by factors characterizing the air pollution mix, climate, and the health of the population. Key words: air pollution, exposure-response, heterogeneity, hierarchical modeling, mortality, splines. Environ Health Perspect 113:88-95 (2005) . doi:10.1289/ehp.7387 available via http://dx.doi.org/ [Online 21 October 2004]

Address correspondence to E. Samoli, Department of Hygiene and Epidemiology, University of Athens Medical School, 75 Mikras Asias St., 115 27 Athens, Greece. Telephone: 30-210-7462085. Fax: 30-210-7462205. E-mail: esamoli@med.uoa.gr

This work was funded by Environment and Climate Programme contracts ENV4-CT97-0534 and QLK4-CT-2001-30055 from the European Commission.

The authors declare they have no competing financial interests.

Received 5 July 2004 ; accepted 21 October 2004.

An erratum was published in Environ Health Perspect 113:A297 (2005) .