Model misspecification, measurement error, and apparent supralinearity in the concentration-response relationship...

A growing number of studies have produced results that suggest the shape of the concentration-response (C-R) relationship between PM2.5 exposure and mortality is "supralinear" such that incremental risk is higher at the lowest exposure levels than at the highest exposure levels. If the C-R function is in fact supralinear, then there may be significant health benefits associated with reductions in PM2.5 below the current US National Ambient Air Quality Standards (NAAQS), as each incremental tightening of the PM2.5 NAAQS would be expected to produce ever-greater reductions in mortality risk. In this paper we undertake a series of tests with simulated cohort data to examine whether there are alternative explanations for apparent supralinearity in PM2.5 C-R functions. Our results show that a linear C-R function for PM2.5 can falsely appear to be supralinear in a statistical estimation process for a variety of reasons, such as spatial variation in the composition of total PM2.5 mass, the presence of confounders that are correlated with PM2.5 exposure, and some types of measurement error in estimates of PM2.5 exposure. To the best of our knowledge, this is the first simulation-based study to examine alternative explanations for apparent supralinearity in C-R functions.