title: 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.
abstract: BACKGROUND
  Spatially-resolved air pollution models can be developed in large areas. The resulting increased exposure contrasts and population size offer opportunities to better characterize the effect of atmospheric pollutants on respiratory health. However the heterogeneity of these areas may also enhance the potential for confounding. We aimed to discuss some analytical approaches to handle this trade-off.
  
  
  METHODS
  We modeled NO2 and PM10 concentrations at the home addresses of 1082 pregnant mothers from EDEN cohort living in and around urban areas, using ADMS dispersion model. Simulations were performed to identify the best strategy to limit confounding by unmeasured factors varying with area type. We examined the relation between modeled concentrations and respiratory health in infants using regression models with and without adjustment or interaction terms with area type.
  
  
  RESULTS
  Simulations indicated that adjustment for area limited the bias due to unmeasured confounders varying with area at the costs of a slight decrease in statistical power. In our cohort, rural and urban areas differed for air pollution levels and for many factors associated with respiratory health and exposure. Area tended to modify effect measures of air pollution on respiratory health.
  
  
  CONCLUSIONS
  Increasing the size of the study area also increases the potential for residual confounding. Our simulations suggest that adjusting for type of area is a good option to limit residual confounding due to area-associated factors without restricting the area size. Other statistical approaches developed in the field of spatial epidemiology are an alternative to control for poorly-measured spatially-varying confounders.
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Parc de Recerca Biomèdica de Barcelona, Doctor Aiguader 88, 08003 Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Passeig Marítim 25-29, 08003 Barcelona, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), Spain; INSERM, U823, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute Albert Bonniot, 38042 Grenoble, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Pedersen
authors.forename: Valérie
authors.initials: V
authors.lastname: Siroux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pin
authors.forename: Marie Aline
authors.initials: MA
authors.lastname: Charles
authors.forename: Anne
authors.initials: A
authors.lastname: Forhan
authors.forename: Agnés
authors.initials: A
authors.lastname: Hulin
authors.forename: Julien
authors.initials: J
authors.lastname: Galineau
authors.forename: Johanna
authors.initials: J
authors.lastname: Lepeule
authors.forename: Lise
authors.initials: L
authors.lastname: Giorgis-Allemand
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
authors.forename: Isabella
authors.initials: I
authors.lastname: Annesi-Maesano
authors.forename: Rémy
authors.initials: R
authors.lastname: Slama
mesh_terms: D000393:Air Pollutants / Q000032:analysis* / Q000633:toxicity; D000397:Air Pollution / Q000032:analysis; D001249:Asthma / Q000139:chemically induced / Q000453:epidemiology*; D015331:Cohort Studies; D003198:Computer Simulation; D015986:Confounding Factors, Epidemiologic; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008956:Models, Chemical; D015233:Models, Statistical; D009585:Nitrogen Dioxide / Q000032:analysis* / Q000633:toxicity; D052638:Particulate Matter / Q000032:analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D015995:Prevalence; D012307:Risk Factors; D012424:Rural Population / Q000706:statistics & numerical data; D018401:Sample Size; D011795:Surveys and Questionnaires; D014504:Urban Health; D014505:Urban Population
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D009585:Nitrogen Dioxide
keywords: ADMS; Air pollution; BMI; Bias; CI; Children's respiratory health; Confounding; ETS; ISAAC; LUR; NO(2); O(3); OR; PM(10); Prenatal exposure; atmospheric dispersion modeling system; body mass index; confidence interval; environmental tobacco smoke; international study of asthma and allergies; land-use regression; nitrogen dioxide; odds ratio; ozone; particulate matter with an aerodynamic diameter below 10μm