Periodic Reporting for period 2 - EPHOR (Exposome project for health and occupational research)
Reporting period: 2021-07-01 to 2022-12-31
Workplace exposure can lead to many diseases, such as cancer, cardiovascular and respiratory disease. The total burden of disease caused by occupational exposure is estimated at 5-7% of global mortality. Given the large societal and economic impact, ensuring a healthy work environment is an important goal for society, government, and industry. Current risk reduction policies and strategies are informed by existing scientific evidence, which is limited due to the challenges of studying the complex relationship between co-occurring multiple occupational and environmental exposures during the working life and health.
The human exposome is a promising concept for elucidating the complex relationships between environment and disease. We define the working-life exposome as all occupational and related non-occupational exposures throughout the course of life. Taking a working-life exposome approach will help address the current limitations by providing better insights into the relationships between a variety of exposures at work and disease at different life stages. Novel approaches and methods are needed to apply the working life exposome.
The EPHOR objective is to reduce the burden of occupationally related diseases by making available a working-life exposome toolbox:
• Better and more complete knowledge on how multiple exposures within the working-life exposome are related to non-communicable diseases, including complex interactions of exposures, biological pathways and early signs of health damages, and vulnerability at different life-stages;
• Innovative methods for collection, storage, and interpretation of working-life exposome data, including its economic and societal impact for scientists, policy makers and occupational health practitioners.
The human exposome is a promising concept for elucidating the complex relationships between environment and disease. We define the working-life exposome as all occupational and related non-occupational exposures throughout the course of life. Taking a working-life exposome approach will help address the current limitations by providing better insights into the relationships between a variety of exposures at work and disease at different life stages. Novel approaches and methods are needed to apply the working life exposome.
The EPHOR objective is to reduce the burden of occupationally related diseases by making available a working-life exposome toolbox:
• Better and more complete knowledge on how multiple exposures within the working-life exposome are related to non-communicable diseases, including complex interactions of exposures, biological pathways and early signs of health damages, and vulnerability at different life-stages;
• Innovative methods for collection, storage, and interpretation of working-life exposome data, including its economic and societal impact for scientists, policy makers and occupational health practitioners.
Within EPHOR we develop methods and tools to characterise the working-life exposome. We achieve this by 1) large-scale pooling of existing data to investigate associations between multiple exposures and disease outcomes and 2) collection of new internal and external exposome data in two case studies.
Up to date, an inventory of relevant European cohorts has been made (>150), of which 29 cohorts are included to form the initial EPHOR mega cohort. Outcome working groups of studied diseases (cancer, cardiovascular/metabolic, neurodegenerative, musculoskeletal, mental, and respiratory) and work participation have reviewed the existing literature to define critical knowledge gaps. Based on these, data analyses plans for the EPHOR mega cohort are being made. The main scientific objectives will be achieved by meta-analyses. A proof of concept of decentralised analyses via DataSHIELD is also being pursued but will not be feasible for all cohorts due to technical challenges. Protocols for cohort data harmonisation and for coding and cross-walking of occupational histories have been developed. A first version of EuroJEM has been developed consisting of harmonised existing job exposure matrices (JEMs) for 10 different exposures of main interest for work-related mortality and morbidity: respirable crystalline silica, nickel, wood dust, diesel engine exhaust, fast breathing due to heavy work, forward bent posture, heavy lifting, job demands, decision authority and noise and two newly developed JEMs for UV-light and precarious employment. A protocol was developed to include new data in EuroJEM through text and data mining.
In addition, new data collection is ongoing for two case studies which investigate the effects of respiratory health in the general population and general health in night shift workers. For the collection of external exposome data, a wearable sensor system including environmental sensors, activity and heart rate monitor, was developed. Also, samplers for (s)VOCs (wearable) and microbial diversity in dust (stationary) and a questionnaire app were developed or adapted. These were combined in an external exposome protocol that is being applied in the case studies. A stakeholder consultation on acceptability, advantages, and challenges of applying sensors among occupational health practitioners and a feasibility study has guided this development. For collection of the internal exposome, harmonised protocols were prepared including pre-processing and storage of blood, saliva, exhaled breath, exhaled breath aerosols and exhaled breath condensate. Due to the evolving COVID-19 situation, there has been a shift in focus towards self-sampling methods as an alternative to traditional sampling methods. Methods for the analyses of exposome markers were adapted. For the latter, a pilot study is ongoing. With respect to storage and interpretation of exposome data in the case studies, an existing data platform (YODA) has been customized for the EPHOR project.
Several methods for analyses of exposome data in the Mega Cohort and case studies have been developed and/or summarized: a) a tutorial of handling multiple exposures in exposure-response analyses b) an inventory of models for exposure time response analyses for estimating time dependent effects and c) three approaches to explore unknown exposure-disease associations, including a penalization model, a two-level Bayesian hierarchical regression model, and a three-level Bayesian hierarchical regression model. A plan for a generic workflow based on in silico data that enables the mechanistic linking of occupational stressors of WP6 to the adverse outcome pathway for allergic asthma has been developed. In addition, a simulation study protocol has been developed for incorporating exposome data in health impact assessments, which will investigate the effect of combined exposures and decay and timing of exposures, including the use of alternative end points for impact assessment such as working life expectancy, healthy working life expectancy and working years lost.
The WE-EXPOSE toolbox (www.we-expose.eu) currently contains the following tools: a database of European cohorts, a protocol for biological sampling, the protocols for the respiratory health case study and for the night shift work case study and the Substance Information System. The toolbox will be expanded with more tools. For the developments of specific tools, stakeholders were consulted, and we adopted a co-creation process with OSH professionals.
Up to date, an inventory of relevant European cohorts has been made (>150), of which 29 cohorts are included to form the initial EPHOR mega cohort. Outcome working groups of studied diseases (cancer, cardiovascular/metabolic, neurodegenerative, musculoskeletal, mental, and respiratory) and work participation have reviewed the existing literature to define critical knowledge gaps. Based on these, data analyses plans for the EPHOR mega cohort are being made. The main scientific objectives will be achieved by meta-analyses. A proof of concept of decentralised analyses via DataSHIELD is also being pursued but will not be feasible for all cohorts due to technical challenges. Protocols for cohort data harmonisation and for coding and cross-walking of occupational histories have been developed. A first version of EuroJEM has been developed consisting of harmonised existing job exposure matrices (JEMs) for 10 different exposures of main interest for work-related mortality and morbidity: respirable crystalline silica, nickel, wood dust, diesel engine exhaust, fast breathing due to heavy work, forward bent posture, heavy lifting, job demands, decision authority and noise and two newly developed JEMs for UV-light and precarious employment. A protocol was developed to include new data in EuroJEM through text and data mining.
In addition, new data collection is ongoing for two case studies which investigate the effects of respiratory health in the general population and general health in night shift workers. For the collection of external exposome data, a wearable sensor system including environmental sensors, activity and heart rate monitor, was developed. Also, samplers for (s)VOCs (wearable) and microbial diversity in dust (stationary) and a questionnaire app were developed or adapted. These were combined in an external exposome protocol that is being applied in the case studies. A stakeholder consultation on acceptability, advantages, and challenges of applying sensors among occupational health practitioners and a feasibility study has guided this development. For collection of the internal exposome, harmonised protocols were prepared including pre-processing and storage of blood, saliva, exhaled breath, exhaled breath aerosols and exhaled breath condensate. Due to the evolving COVID-19 situation, there has been a shift in focus towards self-sampling methods as an alternative to traditional sampling methods. Methods for the analyses of exposome markers were adapted. For the latter, a pilot study is ongoing. With respect to storage and interpretation of exposome data in the case studies, an existing data platform (YODA) has been customized for the EPHOR project.
Several methods for analyses of exposome data in the Mega Cohort and case studies have been developed and/or summarized: a) a tutorial of handling multiple exposures in exposure-response analyses b) an inventory of models for exposure time response analyses for estimating time dependent effects and c) three approaches to explore unknown exposure-disease associations, including a penalization model, a two-level Bayesian hierarchical regression model, and a three-level Bayesian hierarchical regression model. A plan for a generic workflow based on in silico data that enables the mechanistic linking of occupational stressors of WP6 to the adverse outcome pathway for allergic asthma has been developed. In addition, a simulation study protocol has been developed for incorporating exposome data in health impact assessments, which will investigate the effect of combined exposures and decay and timing of exposures, including the use of alternative end points for impact assessment such as working life expectancy, healthy working life expectancy and working years lost.
The WE-EXPOSE toolbox (www.we-expose.eu) currently contains the following tools: a database of European cohorts, a protocol for biological sampling, the protocols for the respiratory health case study and for the night shift work case study and the Substance Information System. The toolbox will be expanded with more tools. For the developments of specific tools, stakeholders were consulted, and we adopted a co-creation process with OSH professionals.
The EPHOR project is the first large project that applies the exposome concept to lay a scientific foundation for improving working-life health related to multifactorial chronic disease, vulnerable life stages and complex exposure situations.
The WE-EXPOSE toolbox containing developed tools, methods and knowledge will be made available to scientists, policymakers, and occupational health practitioners. By providing a knowledge base for evidence-based prevention, EPHOR will eventually contribute to reducing the burden of non-communicable diseases on EU healthcare systems, improving the health and wellbeing of EU citizens and productivity of the EU workforce, and increasing the competitiveness of EU industry.
The results of EPHOR are being communicated through the following websites: www.ephor-project.eu; www.we-expose.eu; www.humanexposome.eu and through https://www.linkedin.com/company/ephor-project-eu/.
The WE-EXPOSE toolbox containing developed tools, methods and knowledge will be made available to scientists, policymakers, and occupational health practitioners. By providing a knowledge base for evidence-based prevention, EPHOR will eventually contribute to reducing the burden of non-communicable diseases on EU healthcare systems, improving the health and wellbeing of EU citizens and productivity of the EU workforce, and increasing the competitiveness of EU industry.
The results of EPHOR are being communicated through the following websites: www.ephor-project.eu; www.we-expose.eu; www.humanexposome.eu and through https://www.linkedin.com/company/ephor-project-eu/.