Epidemiology & burden of disease

A conceptual model of life-course disease risk
Population studies of chronic diseases have traditionally recruited middle-aged subjects. However, there is strong evidence that:
  • the risk of disease is influenced by early exposures, including in utero; 
  • life-stages include critical (bearing long-term effects) and sensitive periods (susceptible to large effects).
The idea of a sequence of critical and sensitive periods leads to the concept of "chain of risk", i.e. the interplay of early exposures and late exposures. To use this concept in practice implies having access to multiple life-stages in exposure assessment and epidemiological studies, and repeated measurements of biomarkers at different time windows. This approach requires an inter-generational epidemiological study design and novel statistical analyses.
 
Risk analyses

The calibration algorithms and estimates of measurement error and inter-individual differences in biological responses are used to perform updated risk analyses in the short and long-term effect studies, using standard parametric and non-parametric risk functions and advanced risk analysis procedures that account for the contributing effects of often-correlated exposures (e.g. partial least square regression, ridge regression, and Bayesian mixture models). In the short-term studies (such as the Oxford Street Randomized Trial), EXPOsOMICS relates the external and internal exposome markers and profiles to acute outcomes such as pulmonary function measures, other patho-physiological outcomes, heart function and asthma episodes. For PISCINA, correlations between external and internal exposome markers are investigated together with genotoxicity outcomes. In the long-term studies the calibrated exposure estimates and internal exposure markers are applied to study the association between subfractions of air pollution (PMs, UFP, and oxidative stress potential), water contaminants and health outcomes in different areas of Europe.

The idea of a sequence of critical and sensitive periods leads to the concept of "chain of risk", i.e. the interplay of early exposures and late exposures. To use this concept in practice implies having access to multiple life-stages in exposure assessment and epidemiological studies, and repeated measurements of biomarkers at different time windows. This approach requires an inter-generational epidemiological study design and novel statistical analyses.