Does consideration of larger study areas yield more accurate estimates of air pollution health effects? An illustration of the bias-variance trade-off in air pollution epidemiology
Introduction
The respiratory system is vulnerable to exposure to airborne toxicants during development (Baïz et al., 2011, Bateson and Schwartz, 2008, Bråbäck and Forsberg, 2009, Clark et al., 2010, Latzin et al., 2009, Latzin et al., 2011, Mauad et al., 2008, Pinkerton and Joad, 2000, Pope, 1989, Sram et al., 2005, Woodruff et al., 2008, Wu et al., 2009). Early life exposure to ambient air pollution has been associated with cord blood immunologic parameters (Baïz et al., 2011, Latzin et al., 2011), decreased lung function in newborns (Latzin et al., 2009), asthma and asthma-related symptoms in the first year of life (Aguilera et al., 2013, Andersen et al., 2008, Bateson and Schwartz, 2008, Bråbäck and Forsberg, 2009, Brauer et al., 2002, Clark et al., 2010, Ebisu et al., 2011, Esplugues et al., 2011, Gehring et al., 2002, Gouveia and Fletcher, 2000, Karr et al., 2009, Morgenstern et al., 2007, Nordling et al., 2008, Orazzo et al., 2009, Pino et al., 2004, Pope, 1989, Ryan et al., 2005). Early studies relied on permanent monitoring stations to assess exposure (Andersen et al., 2008, Bateson and Schwartz, 2008, Bråbäck and Forsberg, 2009, Gouveia and Fletcher, 2000, Latzin et al., 2009, Latzin et al., 2011, Orazzo et al., 2009, Pino et al., 2004, Pope, 1989, Sram et al., 2005), an approach with a limited spatial resolution. Over the last decade, models with improved spatial resolution such as dispersion or land-use regression (LUR) models (Hoek et al., 2008) have been increasingly applied (Aguilera et al., 2013, Bråbäck and Forsberg, 2009, Brauer et al., 2002, Clark et al., 2010, Ebisu et al., 2011, Esplugues et al., 2011, Gehring et al., 2002, Karr et al., 2009, Morgenstern et al., 2007, Nordling et al., 2008, Ryan et al., 2005). Such approaches allow consideration of large study areas as a whole, including city centers, surrounding suburban and sometimes rural areas. Considering such large areas entails a potential increase in exposure contrasts and study size, which is a priori desirable in terms of statistical power.
However, the greater population heterogeneity may also increase the potential for confounding, in particular due to spatially-varying factors.
Indeed, not only do ambient air pollution levels vary largely over space, but also possibly other parameters such as exposure to infectious factors, to sources of allergens (e.g. pet ownership, dairy farms, pollen), health-care access and distribution of personal characteristics such as socioeconomic status, smoking and diet (Wright and Subramanian, 2007). Residual confounding may occur if these asthma risk factors are unevenly distributed across types of areas (rural and urbanized areas) and are not assessed, or are assessed with measured error or poorly taken into account in regression models. The alternative between studying small homogeneous areas with fewer subjects and expanding area size together with population heterogeneity and possibly resulting bias can be seen as an illustration of the classical epidemiological trade-off between bias and variance.
The present study aimed to document this bias-variance trade-off related to confounding, size and heterogeneity of study area that may occur in studies of air pollution health effects relying on exposure models that are applied to a large study area. We did not consider the impact on exposure misclassification of using models with a fine spatial resolution, compared e.g., to approaches resting on permanent air quality monitoring stations (Gulliver et al., 2011, Lepeule et al., 2010, Marshall, 2008). We illustrated this trade-off in a study of ambient air pollution effects on respiratory health in the first year of life using simulations and real data. First, we conducted a simulation study to estimate the bias and statistical power in studies with area-dependent unmeasured confounders, to illustrate the efficiency of various analytical approaches. Secondly, we assessed the association between air pollution levels and infant respiratory health in a mother–child cohort study using several analytical approaches to limit residual confounding.
Section snippets
Study population
This study relies on mother–child pairs from the EDEN mother–child cohort. The EDEN mother–child cohort study is a population-based prospective study on pre- and early postnatal nutritional, environmental and social determinants of the children's development and health (Baïz et al., 2011, Drouillet et al., 2009, Hampel et al., 2011, Slama et al., 2009). Between 2003 and 2006, pregnant women expecting singletons at the University Hospitals in Poitiers and Nancy, two middle-sized cities in West
Study population and prevalence of asthma-related outcomes
Approximately half (N = 1082) of EDEN mother–child study population lived in the modeling area of our air dispersion model, had follow-up data and could be included in this study (Fig. 1).
Excluded mothers more often lived in rural areas during pregnancy (Fig. 2) were less likely to breastfeed; their children less frequently attended day-care facilities with other children (Table S1, Supplementary material). The prevalence of recurrent wheeze was 10.5% among included and 7.1% among excluded
Discussion
We characterized the associations between air pollution levels estimated using a fine scale dispersion model and respiratory health in the first year of life within a mother–child cohort conducted in two middle-sized cities. A dispersion model enabled the inclusion of a relatively large area and allowed taking into account local sources of pollution and temporal variations. The areas, including city-centers, urban areas and rural areas appeared to be quite heterogeneous for many factors
Acknowledgment
We thank the midwife research assistants (L. Douhaud, S. Bedel, B. Lortholary, S. Gabriel, M. Rogeon, and M. Malinbaum) for data collection and to P. Lavoine for checking, coding, and data entry.
The EDEN study group includes M.A. Charles, M. de Agostini, A. Forhan, B. Heude, P. Ducimetière, M. Kaminski, M.J. Saurel-Cubizolles, P. Dargent, X. Fritel, B. Larroque, N. Lelong, L. Marchand, C. Nabet, I. Annesi-Maesano, R. Slama, V. Goua, G. Magnin, R. Hankard, O. Thiebaugeorges, M. Schweitzer, B.
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