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External exposome & longitudinal accelerated design for lung function

Investigador:
Jelle Vlaanderen
Institució:
Associate Professor, Utrecht University (UU)

BACKGROUND

In addition to genomic inherited profile, health is shaped by environmental factors that we humans are exposed to on a daily basis: what we eat, the air we breathe, our social interactions and lifestyle choices such as smoking and exercising. The environment we live in has a significant impact on our health, explaining an estimated 70% of the (non-communicable chronic disease burden). As most of the aspects of our environment are modifiable, this provides a huge potential for disease prevention. Leading scientists in Europe and the USA have formalized this perspective as the Exposome concept. Derived from the term exposure, the Exposome is the sum of all non-genetic drivers of health and diseases. Interacting with the genome, it defines individual health at different stages throughout the life course, including foetal life.

The European initiative for exposome mapping and disease evaluation impact in urban populations, EXPANSE, focuses on describing the links of the urban exposome, the complex interplay between the built, social, physico-chemical, food, and lifestyle aspects of the urban environment and health. Our health is shaped by environmental factors that we humans are exposed to on a daily basis: what we eat, the air we breathe, our social interactions and lifestyle choices such as smoking and exercising.

In the context of EXPANSE project, it has been planned to perform an accelerated analysis directed to measure the effect of external exposome in lung function, among the available cohorts of WP1-EXPANSE, including GCAT cohort.

GCAT represents a population based adult cohort with a large urban composition basis. The cohort will enable well-powered analyses using state-of-the art methods linking the External and Internal Exposome to primary diseases endpoints, including but not limited to FEV1, FVC, as well as disease-specific mortality estimates.

HYPOTHESIS

We hypothesize that the complex mixture External Exposome may alter the physiology and predispose individuals to developing FEV1, FVC.

OBJECTIVES

METHODOLOGY (Subjects, Ethics, Confidentiality, Return Of Results and Incidental Findings management)

This analysis will include subjects from European administrative, adult and birth matured cohorts. From IGTP, the subjects included in this project belong to the GCAT study. All participants were informed of the general objectives for the study of the genetic profile and environmental impact on the development of chronic diseases. The project has been evaluated and approved by the CEIC of the Germans Trias i Pujol Hospital (2014). We will produce and report pooled results so that they ensure confidentiality.

1.Study design. Matured birth cohorts (MBC) as well as adult cohorts will be included in this analysis to have a life-course perspective. Data will be pooled altogether for the statistical analysis. We plan to do this using the ANDREA research environment. ANDREA is the secure, online research environment of EXPANSE. The system is GDPR compliant and adheres to the FAIR principles (see https://support.mydre.org/portal/en/kb/andrea-organization/compliance).

2. Outcomes of interest All recorded spirometry measurements:

pre-bronchodilation forced vital capacity (FVC)

pre-bronchodilation forced expiratory volume 1s (FEV1)

3. Exposures This study focuses on long-term exposure, so only annual exposure generated from WP1 will be used. These EXPANSE surfaces are available for the year 2000 and later. For the years 1990-1999 a back extrapolation factor is provided.

We will assign the annual exposure at the year before the spirometry measurement to the measurement. So, measurements from the cohort from the year 2002 get assigned the annual average at that location in the year 2001, 1995 will get 1994 assigned etc. If a cohort has measurements before 1990, we assign the earliest available calendar year of exposure, i.e. 1990 using back extrapolation (see surfaces rollout V3).

A detailed document will be attached including: exposures of interest WP1 exposure surfaces EXPANSE (version 3); covariates considered and statistical analysis to be done.

REFERENCES