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Accounting for measurement error to assess the effect of air pollution on omic signals.

ABSTRACT: Studies on the effects of air pollution and more generally environmental exposures on health require measurements of pollutants, which are affected by measurement error. This is a cause of bias in the estimation of parameters relevant to the study and can lead to inaccurate conclusions when evaluating associations among pollutants, disease risk and biomarkers. Although the presence of measurement error in such studies has been recognized as a potential problem, it is rarely considered in applications and practical solutions are still lacking. In this work, we formulate Bayesian measurement error models and apply them to study the link between air pollution and omic signals. The data we use stem from the "Oxford Street II Study", a randomized crossover trial in which 60 volunteers walked for two hours in a traffic-free area (Hyde Park) and in a busy shopping street (Oxford Street) of London. Metabolomic measurements were made in each individual as well as air pollution measurements, in order to investigate the association between short-term exposure to traffic related air pollution and perturbation of metabolic pathways. We implemented error-corrected models in a classical framework and used the flexibility of Bayesian hierarchical models to account for dependencies among omic signals, as well as among different pollutants. Models were implemented using traditional Markov Chain Monte Carlo (MCMC) simulative methods as well as integrated Laplace approximation. The inclusion of a classical measurement error term resulted in variable estimates of the association between omic signals and traffic related air pollution measurements, where the direction of the bias was not predictable a priori. The models were successful in including and accounting for different correlation structures, both among omic signals and among different pollutant exposures. In general, more associations were identified when the correlation among omics and among pollutants were modeled, and their number increased when a measurement error term was additionally included in the multivariate models (particularly for the associations between metabolomics and NO2).

SUBMITTER: Ponzi E

PROVIDER: S-EPMC6940143 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Accounting for measurement error to assess the effect of air pollution on omic signals.

Ponzi Erica E Vineis Paolo P Chung Kian Fan KF Blangiardo Marta M

PloS one 20200102 1

Studies on the effects of air pollution and more generally environmental exposures on health require measurements of pollutants, which are affected by measurement error. This is a cause of bias in the estimation of parameters relevant to the study and can lead to inaccurate conclusions when evaluating associations among pollutants, disease risk and biomarkers. Although the presence of measurement error in such studies has been recognized as a potential problem, it is rarely considered in applica ...[more]

PMID: 31896134

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Project description:BackgroundTwo distinctly different types of measurement error are Berkson and classical. Impacts of measurement error in epidemiologic studies of ambient air pollution are expected to depend on error type. We characterize measurement error due to instrument imprecision and spatial variability as multiplicative (i.e. additive on the log scale) and model it over a range of error types to assess impacts on risk ratio estimates both on a per measurement unit basis and on a per interquartile range (IQR) basis in a time-series study in Atlanta.MethodsDaily measures of twelve ambient air pollutants were analyzed: NO2, NOx, O3, SO2, CO, PM10 mass, PM2.5 mass, and PM2.5 components sulfate, nitrate, ammonium, elemental carbon and organic carbon. Semivariogram analysis was applied to assess spatial variability. Error due to this spatial variability was added to a reference pollutant time-series on the log scale using Monte Carlo simulations. Each of these time-series was exponentiated and introduced to a Poisson generalized linear model of cardiovascular disease emergency department visits.ResultsMeasurement error resulted in reduced statistical significance for the risk ratio estimates for all amounts (corresponding to different pollutants) and types of error. When modelled as classical-type error, risk ratios were attenuated, particularly for primary air pollutants, with average attenuation in risk ratios on a per unit of measurement basis ranging from 18% to 92% and on an IQR basis ranging from 18% to 86%. When modelled as Berkson-type error, risk ratios per unit of measurement were biased away from the null hypothesis by 2% to 31%, whereas risk ratios per IQR were attenuated (i.e. biased toward the null) by 5% to 34%. For CO modelled error amount, a range of error types were simulated and effects on risk ratio bias and significance were observed.ConclusionsFor multiplicative error, both the amount and type of measurement error impact health effect estimates in air pollution epidemiology. By modelling instrument imprecision and spatial variability as different error types, we estimate direction and magnitude of the effects of error over a range of error types.

Project description:Spatiotemporal air pollution models are increasingly being used to estimate health effects in epidemiological studies. Although such exposure prediction models typically result in improved spatial and temporal resolution of air pollution predictions, they remain subject to shared measurement error, a type of measurement error common in spatiotemporal exposure models which occurs when measurement error is not independent of exposures. A fundamental challenge of exposure measurement error in air pollution assessment is the strong correlation and sometimes identical (shared) error of exposure estimates across geographic space and time. When exposure estimates with shared measurement error are used to estimate health risk in epidemiological analyses, complex errors are potentially introduced, resulting in biased epidemiological conclusions. We demonstrate the influence of using a three-stage spatiotemporal exposure prediction model and introduce formal methods of shared, multiplicative measurement error (SMME) correction of epidemiological health risk estimates. Using our three-stage, ensemble learning based nitrogen oxides (NOx) exposure prediction model, we quantified SMME. We conducted an epidemiological analysis of wheeze risk in relation to NOx exposure among school-aged children. To demonstrate the incremental influence of exposure modeling stage, we iteratively estimated the health risk using assigned exposure predictions from each stage of the NOx model. We then determined the impact of SMME on the variance of the health risk estimates under various scenarios. Depending on the stage of the spatiotemporal exposure model used, we found that wheeze odds ratio ranged from 1.16 to 1.28 for an interquartile range increase in NOx. With each additional stage of exposure modeling, the health effect estimate moved further away from the null (OR=1). When corrected for observed SMME, the health effects confidence intervals slightly lengthened, but our epidemiological conclusions were not altered. When the variance estimate was corrected for the potential "worst case scenario" of SMME, the standard error further increased, having a meaningful influence on epidemiological conclusions. Our framework can be expanded and used to understand the implications of using exposure predictions subject to shared measurement error in future health investigations.

Project description:BackgroundSpatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health.MethodsOur study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally.ResultsIn general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1.ConclusionWhile our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models.

Dataset Information

Accounting for measurement error to assess the effect of air pollution on omic signals.

Publications

Accounting for measurement error to assess the effect of air pollution on omic signals.

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