A causal exposure response function with local adjustment for confounding: Estimating health effects of exposure to low levels of ambient fine particulate matter.

In the last two decades, ambient levels of air pollution have declined substantially. At the same time, the Clean Air Act mandates that the National Ambient Air Quality Standards (NAAQS) must be routinely assessed to protect populations based on the latest science. Therefore, researchers should continue to address the following question: is exposure to levels of air pollution below the NAAQS harmful to human health? Furthermore, the contentious nature surrounding environmental regulations urges us to cast this question within a causal inference framework. Several parametric and semi-parametric regression approaches have been used to estimate the exposure-response (ER) curve between long-term exposure to ambient air pollution concentrations and health outcomes. However, most of the existing approaches are not formulated within a formal framework for causal inference, adjust for the same set of potential confounders across all levels of exposure, and do not account for model uncertainty regarding covariate selection and the shape of the ER. In this paper, we introduce a Bayesian framework for the estimation of a causal ER curve called LERCA (Local Exposure Response Confounding Adjustment), which a) allows for different confounders different strength of confounding at the different exposure levels; and b) propagates model uncertainty regarding confounders' selection and the shape of the ER. Importantly, LERCA provides a principled way of assessing the observed covariates' confounding importance at different exposure levels, providing researchers with important information regarding the set of variables to measure and adjust for in regression models. Using simulation studies, we show that state of the art approaches perform poorly in estimating the ER curve in the presence of local confounding. LERCA is used to evaluate the relationship between long-term exposure to ambient PM, a key regulated pollutant, and cardiovascular hospitalizations for 5,362 zip codes in the continental U.S. and located near a pollution monitoring site, while adjusting for a potentially varying set of confounders across the exposure range. Our data set includes rich health, weather, demographic, and pollution information for the years of 2011-2013. The estimated exposure-response curve is increasing indicating that higher ambient concentrations lead to higher cardiovascular hospitalization rates, and ambient PM was estimated to lead to an increase in cardiovascular hospitalization rates when focusing at the low exposure range. Our results indicate that there is no threshold for the effect of PM on cardiovascular hospitalizations.