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J Epidemiol Community Health. 2007 September; 61(9): 838.
PMCID: PMC2660011

Authors' response

Hänninen and Jantunen argued that an analysis of effect modification by temperature can be properly conducted only after the effects of meteorology on exposure have been thoroughly quantified.

Interaction or effect modification refers to the extent to which the joint effect of two risk factors on disease or mortality differs from the independent effect of each of the factors. In essence, heterogeneous data should not be pooled and homogeneity and linearity are two assumptions that should be tested in a well‐conducted statistical analysis. In our study,1 the association between mortality and daily concentrations of fine particulate air pollution was not linear at lower temperatures. Therefore, using all data would have biased the overall estimate. Moreover, there was a clear rationale for interaction testing because the literature shows that both high and low temperatures increase mortality2,3,4 and that air pollution is associated with temperature.5

With our analysis, we can only speculate about the mechanisms underlying the much stronger association found between mortality and PM10 during warmer periods, even though the PM10 levels reach higher values in winter. As we discussed in our paper, three explanations can be proposed. First, as postulated by Hänninen and Jantunen, the higher relative effects during the summer might be a consequence of spending more time outdoors or because of indoor and outdoor PM10 are more similar in the summer. Hänninen and Jantunen argue that the strong seasonal pattern may be influenced by the times windows are kept open, with median times in Helsinki of 0.3 h/day in winter compared with 24 h/day in summer. Such large differences, however, probably do not apply in Belgium, which has a temperate climate, with a mean average temperature of 2.6°C in January. Two other potential explanations, which we discussed in our paper, include the lower background mortality in summer, resulting in a larger pool of susceptible people in summer, and the component‐specific toxicity of PM10, which may differ across the temperature range. The discussion on the interaction between meteorology and particulate air pollution on acute health effects in terms of triggering mortality will continue for some time until appropriate experimental studies in animals or human volunteers have been completed. An experimental study that exposed isolated rat macrophages to ambient particulate matter collected during winter, spring and summer (in Amsterdam, Lodz, Oslo and Rome) showed that PM10 samples collected in summer were more potent at inducing inflammatory cytokines.6

Since exposure estimates are also based on assumptions, with many uncertainties, there is an urgent need for simple valid biomarkers of internal particle exposure. Carbon load in lung macrophages7 might represent such a measure to test the underlying reason(s) for the larger health effects in the summer than in winter. However, whatever the uncertainty of exposure measures might be, this is not by itself a reason to ignore heterogeneity and effect modification within data.


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2. Michelozzi P, De Sario M, Accetta G. et al Temperature and summer mortality: geographical and temporal variations in four Italian cities. J Epidemiol Community Health 2006. 60417–423.423 [PMC free article] [PubMed]
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5. Katsouyanni K, Touloumi G, Spix C. et al Short‐term effects of ambient sulphur dioxide and particulate matter on mortality in 12 European cities: results from time series data from the APHEA project. Air Pollution and Health: a European Approach, BMJ 1997. 3141658–1663.1663 [PMC free article] [PubMed]
6. Hetland R B, Cassee F R, Lag M. et al Cytokine release from alveolar macrophages exposed to ambient particulate matter: heterogeneity in relation to size, city and season. Part Fibre Toxicol 2005. 172–4.4 [PMC free article] [PubMed]
7. Kulkarni N, Pierse N, Rushton L. et al Carbon in airway macrophages and lung function in children. N Engl J Med 2006. 35521–30.30 [PubMed]

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