• Air pollution;
  • Environmental epidemiology;
  • Generalized least squares;
  • Mixed models;
  • Semiparametric regression;
  • Time series;
  • Unmeasured confounding


Traditional studies of short-term air pollution health effects use time series data, while cohort studies generally focus on long-term effects. There is increasing interest in exploiting individual level cohort data to assess short-term health effects in order to understand the mechanisms and time scales of action. We extend semiparametric regression methods used to adjust for unmeasured confounding in time series studies to the cohort setting. Time series methods are not directly applicable since cohort data are typically collected over a prespecified time period and include exposure measurements on days without health observations. Therefore, long-time asymptotics are not appropriate, and it is possible to improve efficiency by exploiting the additional exposure data. We show that flexibility of the semiparametric adjustment model should match the complexity of the trend in the health outcome, in contrast to the time series setting where it suffices to match temporal structure in the exposure. We also demonstrate that pre-adjusting exposures concurrent with the health endpoints using trends in the complete exposure time series results in unbiased health effect estimation and can improve efficiency without additional confounding adjustment. A recently published article found evidence of an association between short-term exposure to ambient fine particulate matter (PM2.5) and retinal arteriolar diameter as measured by retinal photography in the Multi-Ethnic Study of Atherosclerosis (MESA). We reanalyze the data from this article in order to compare the methods described here, and we evaluate our methods in a simulation study based on the MESA data.