Periodic Reporting for period 2 - REMEDIA (Impact of exposome on the course of lung diseases)
Periodo di rendicontazione: 2021-07-01 al 2022-12-31
Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are two very debilitating non-communicable diseases that are of particular interest to consider in parallel in a human exposome study. Their roots are opposite: COPD is currently considered to be mainly related to the external exposome, while factors outside of the exposome play a major role in CF. However, COPD and CF share common characteristics such as high phenotypic variability of unknown origin, which prevents good therapeutic efficacy. The overall picture must thus be supplemented by considering additional components of the exposome. The overall objective of the REMEDIA project is to extend the understanding of the contribution of the exposome, taken as a complex set of different components, to COPD and CF diseases. We will exploit data from existing cohorts and population registries to create a unified global database gathering phenotype and exposome information; we will develop a handy individual sensor device combining environmental and biomarker toolkits; and use a versatile atmospheric simulation chamber to simulate the health effects of complex exposomes.
Thanks to machine learning supervised analyses and causal inference models we will identify relevant risk factors; and develop econometric and cost-effectiveness models to assess the costs, performance, and cost-effectiveness of a selection of prevention strategies. Based on that we will develop guidelines to better predict disease risks and create a REMEDIA toolbox (global unified database, sensor device, versatile atmospheric simulation chamber, machine learning supervised analyses, causal inference model, Pan-European multi-criteria risk assessment tool, econometric and cost-effectiveness models, new guidelines and recommendations).
REMEDIA is also part of the European Human Exposome Network established between the 9 projects funded within the Human Exposome programme call H2020-SC1-BHC-2018-2020.
Thanks to machine learning supervised analyses and causal inference models we will identify relevant risk factors; and develop econometric and cost-effectiveness models to assess the costs, performance, and cost-effectiveness of a selection of prevention strategies. Based on that we will develop guidelines to better predict disease risks and create a REMEDIA toolbox (global unified database, sensor device, versatile atmospheric simulation chamber, machine learning supervised analyses, causal inference model, Pan-European multi-criteria risk assessment tool, econometric and cost-effectiveness models, new guidelines and recommendations).
REMEDIA is also part of the European Human Exposome Network established between the 9 projects funded within the Human Exposome programme call H2020-SC1-BHC-2018-2020.
WP1: The coordination has continued to closely monitor the progress of the project. A consortium meeting was organised in Patras in March 2022 and an amendment was prepared to organise the exit of P07 - CEGX.
WP2: Data gathering work has been focused on the REMEDIA database environment building, on standardization to allow replication of results between cohorts, on increasing the number of biological samples to be analyzed in OMICS as formalized by an accepted amendment and pursuing the data collection of environmental data. Access to databases has been achieved for most cohorts allowing the initiation of the statistical analyses for unsupervised approaches and exposome-phenotype associations, with associated publications (4) and congress communications (4).
WP3: The environmental toolbox prototype has been successfully developed, tested and miniaturized to a portable device. It is capable of measuring several pollutants, including particulate matter, several gases (CO, O3, NO2 and SO2) as well as temperature, humidity plus sound and light. The biomarker toolbox was developed and tested in a small study with healthy patients, measuring exhaled breath condensate after an ozone challenge.
WP4: Taking into account the advances of the first period, we managed to implement more complex simulated atmospheres at the laboratory (urban pollution + fresh/aged plume of biomass burning), and to expose preclinical models (naïve, CF and COPD) to these simulated atmospheres for 3 days. Biological results (analyses still ongoing) regarding lung function and bio-diagnoses have been issued and promising in establishing the links between components of the exposome and health impacts. In parallel, WP4 team had made significant advances on: Implementation of more complex simulated external exposome, by developing innovative protocols to simulate noise and stress components of the exposome; Development of in vitro studies, that will take place in synergy with in vivo studies: in a nutshell in vivo studies are dedicated to establish the links between exposome components and health effects, when in vitro studies will contribute to identify the nature of these links.
WP5: Task 5.3 which led to deliverable D5.3 submitted at M30. Task 5.3 consisted on the development of a synthetic exposome risk indicator in order to compare the 27 EU members. For this purpose specifically programmed multi-dimensional analyses have been carried out allowing to project n dimensions (the n variables) into one single factorial axis. The quality of the aggregation is represented by the level of inertia. The following synthetic indicators have been constructed: Synthetic air pollutant indicator; Synthetic burden of disease indicator (Period 2); Synthetic land use indicator; Synthetic environmental taxes indicator (period 2). Then feasibility of using concentration data of air pollutants have been investigated.
WP6: During period 2, task 6.1 explored additional time series using both EUROSTAT and the Danish registry investigating both COPD and cystic fibrosis in the EU. Task 6.2 started end of period 2 by developing a semi directive questionnaire for interviewing legal and ethics experts in key member states.
WP7: The REMEDIA LinkedIn and YouTube were set up. All the social media accounts are regularly updated. The WP7 activities include the publication of 7 articles, the presentations of the project at conferences and summer school, publication of 2 internal newsletters, the preparation of communication tools (video, kakemono, goodies, REMEDIA’s business card). Young researchers have been invited to share what they are working on in the news of the website.
WP8: Concerning the activities with EHEN, REMEDIA has been active in several ways: participation to the organizations of the EHEN meeting in Barcelona, contribution to the update of the Science to Policy Strategy, participation to the EHEN events and the EHEN working groups, collaboration with EPHOR on the EHEN virtual toolbox, inventory of EHEN projects tools.
WP2: Data gathering work has been focused on the REMEDIA database environment building, on standardization to allow replication of results between cohorts, on increasing the number of biological samples to be analyzed in OMICS as formalized by an accepted amendment and pursuing the data collection of environmental data. Access to databases has been achieved for most cohorts allowing the initiation of the statistical analyses for unsupervised approaches and exposome-phenotype associations, with associated publications (4) and congress communications (4).
WP3: The environmental toolbox prototype has been successfully developed, tested and miniaturized to a portable device. It is capable of measuring several pollutants, including particulate matter, several gases (CO, O3, NO2 and SO2) as well as temperature, humidity plus sound and light. The biomarker toolbox was developed and tested in a small study with healthy patients, measuring exhaled breath condensate after an ozone challenge.
WP4: Taking into account the advances of the first period, we managed to implement more complex simulated atmospheres at the laboratory (urban pollution + fresh/aged plume of biomass burning), and to expose preclinical models (naïve, CF and COPD) to these simulated atmospheres for 3 days. Biological results (analyses still ongoing) regarding lung function and bio-diagnoses have been issued and promising in establishing the links between components of the exposome and health impacts. In parallel, WP4 team had made significant advances on: Implementation of more complex simulated external exposome, by developing innovative protocols to simulate noise and stress components of the exposome; Development of in vitro studies, that will take place in synergy with in vivo studies: in a nutshell in vivo studies are dedicated to establish the links between exposome components and health effects, when in vitro studies will contribute to identify the nature of these links.
WP5: Task 5.3 which led to deliverable D5.3 submitted at M30. Task 5.3 consisted on the development of a synthetic exposome risk indicator in order to compare the 27 EU members. For this purpose specifically programmed multi-dimensional analyses have been carried out allowing to project n dimensions (the n variables) into one single factorial axis. The quality of the aggregation is represented by the level of inertia. The following synthetic indicators have been constructed: Synthetic air pollutant indicator; Synthetic burden of disease indicator (Period 2); Synthetic land use indicator; Synthetic environmental taxes indicator (period 2). Then feasibility of using concentration data of air pollutants have been investigated.
WP6: During period 2, task 6.1 explored additional time series using both EUROSTAT and the Danish registry investigating both COPD and cystic fibrosis in the EU. Task 6.2 started end of period 2 by developing a semi directive questionnaire for interviewing legal and ethics experts in key member states.
WP7: The REMEDIA LinkedIn and YouTube were set up. All the social media accounts are regularly updated. The WP7 activities include the publication of 7 articles, the presentations of the project at conferences and summer school, publication of 2 internal newsletters, the preparation of communication tools (video, kakemono, goodies, REMEDIA’s business card). Young researchers have been invited to share what they are working on in the news of the website.
WP8: Concerning the activities with EHEN, REMEDIA has been active in several ways: participation to the organizations of the EHEN meeting in Barcelona, contribution to the update of the Science to Policy Strategy, participation to the EHEN events and the EHEN working groups, collaboration with EPHOR on the EHEN virtual toolbox, inventory of EHEN projects tools.
On completion of the project, we will have advanced the understanding on the global burden of COPD and CF diseases attributable to environmental factors, and more specifically to external and internal exposome components. Deciphering the impact of environmental components throughout life on the phenotypic variability of COPD and CF could represent a major breakthrough in reducing morbidity and mortality associated with these two non-curable diseases and would lead to the identification of modifiable risk factors on which preventive action could be implemented.
The findings obtained in REMEDIA project will be relevant to populations that are largely beyond patients with COPD or CF. Indeed, these two diseases are only iconic examples of small airway diseases (SAD), and SAD are associated with other (non)-communicable diseases of major importance, reaching the pulmonary system (asthma, bronchiolitis, connective tissue diseases - interstitial lung diseases, pleural diseases), but also other organs (rheumatoid arthritis, Sjögren’s syndrome and inflammatory bowel diseases to name a few). Therefore, the identification of exposome components as essential modifiers of COPD and CF phenotypes should be applicable to other SAD, and thus could have a global impact on several diseases of high burden.
The findings obtained in REMEDIA project will be relevant to populations that are largely beyond patients with COPD or CF. Indeed, these two diseases are only iconic examples of small airway diseases (SAD), and SAD are associated with other (non)-communicable diseases of major importance, reaching the pulmonary system (asthma, bronchiolitis, connective tissue diseases - interstitial lung diseases, pleural diseases), but also other organs (rheumatoid arthritis, Sjögren’s syndrome and inflammatory bowel diseases to name a few). Therefore, the identification of exposome components as essential modifiers of COPD and CF phenotypes should be applicable to other SAD, and thus could have a global impact on several diseases of high burden.