Periodic Reporting for period 3 - REMEDIA (Impact of exposome on the course of lung diseases)
Período documentado: 2023-01-01 hasta 2023-12-31
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: In this third period, the coordination pursued its effort to closely monitor the progress of the project (resubmission of deliverables, revision and resubmission of RP2 technical report throughout the year, follow-up of cohorts’ access). The management team organised regular meetings to address the requests formulated by the EC and the advises from the SAB. A consortium meeting was organised in Copenhagen in February 2023. GA representatives voted in favour of an extension request for one year (February 2023), this vote was confirmed at the GA in December 2023.
WP2: In this third period of the project, work on data gathering and enrichment has been focused on the pursue of standardization work to allow replication of results between cohorts without actually merging the datasets (i.e. Pelagie and ALSPAC for assessing respiratory function in children/young adults and DCH/TROMSO/NOWAC/HUNT for assessing COPD risk in adults) and pursue of 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 and congress communications.
WP3: The developed environmental toolbox prototype is capable of measuring several pollutants, including particulate matter, several gases (CO, O3, NO2 and SO2) as well as temperature, humidity, sound and light. It is now in the validation phase. The biomarker toolbox was developed and tested in a small study with healthy patients, measuring exhaled breath condensate after an ozone challenge. Momentarily the sensor surfaces are optimized and validated.
WP4: We are now able to implement complex simulated atmospheres at the laboratory and to expose preclinical models (naïve, CF and COPD) to these simulated atmospheres. Biological results regarding lung function and bio-diagnoses are ongoing and promising in establishing the links between components of the exposome and health impacts (publications). In parallel, WP4 team had made significant advances on the implementation of more complex simulated external exposome (noise and stress) and the development of in vitro studies that will contribute to identify the nature of the links between exposome components and health effects.
WP5:The research activities related to WP5 are well advanced and in line with the planned schedule. Task 5.1 (Machine Learning Supervised Analyses and Prediction Models) was initiated at M30 and completed the selection of databases and candidate variables for predictive analyses. Task 5.2 (Causal Inference Modelling) was initiated at M36 by exploring appropriate techniques to establish causal inferences on the data from the French National CF Registry. Task 5.3 (Pan European Multicriteria Risk Assessment Analyses) was initiated at M6 and submitted the first deliverable of WP5 D5.3 on time (Accepted deliverable).
WP6: Period 3 was mainly devoted to developing, within the framework of Task 6.2 a semi-structured questionnaire to assess the legal and ethical aspects of public health interventions against exposome risks. Task 6.3 was also initiated during period 3 by evaluating methodologies and relevant indicators to develop robust cost-effectiveness models that could be applied to public health measures against respiratory risk factors exposure.
WP7: In period three, the REMEDIA LinkedIn, X and YouTube social media accounts have been regularly updated. The WP7 activities include the publication of 4 articles, the presentations of the project at conferences and summer school, publication of 2 internal newsletters, the preparation of communication tools. Young researchers have been invited to share what they are working on in the news of the website. Furthermore, REMEDIA integrated a Horizon Results Booster workshop in order to optimize communication and dissemination activities.
WP8:In the third period, concerning the activities with EHEN, REMEDIA has been active in several ways: preparation and start of the governance of the EHEN network by REMEDIA, EPHOR and HEDIMED, participation to the EHEN working groups
WP2: In this third period of the project, work on data gathering and enrichment has been focused on the pursue of standardization work to allow replication of results between cohorts without actually merging the datasets (i.e. Pelagie and ALSPAC for assessing respiratory function in children/young adults and DCH/TROMSO/NOWAC/HUNT for assessing COPD risk in adults) and pursue of 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 and congress communications.
WP3: The developed environmental toolbox prototype is capable of measuring several pollutants, including particulate matter, several gases (CO, O3, NO2 and SO2) as well as temperature, humidity, sound and light. It is now in the validation phase. The biomarker toolbox was developed and tested in a small study with healthy patients, measuring exhaled breath condensate after an ozone challenge. Momentarily the sensor surfaces are optimized and validated.
WP4: We are now able to implement complex simulated atmospheres at the laboratory and to expose preclinical models (naïve, CF and COPD) to these simulated atmospheres. Biological results regarding lung function and bio-diagnoses are ongoing and promising in establishing the links between components of the exposome and health impacts (publications). In parallel, WP4 team had made significant advances on the implementation of more complex simulated external exposome (noise and stress) and the development of in vitro studies that will contribute to identify the nature of the links between exposome components and health effects.
WP5:The research activities related to WP5 are well advanced and in line with the planned schedule. Task 5.1 (Machine Learning Supervised Analyses and Prediction Models) was initiated at M30 and completed the selection of databases and candidate variables for predictive analyses. Task 5.2 (Causal Inference Modelling) was initiated at M36 by exploring appropriate techniques to establish causal inferences on the data from the French National CF Registry. Task 5.3 (Pan European Multicriteria Risk Assessment Analyses) was initiated at M6 and submitted the first deliverable of WP5 D5.3 on time (Accepted deliverable).
WP6: Period 3 was mainly devoted to developing, within the framework of Task 6.2 a semi-structured questionnaire to assess the legal and ethical aspects of public health interventions against exposome risks. Task 6.3 was also initiated during period 3 by evaluating methodologies and relevant indicators to develop robust cost-effectiveness models that could be applied to public health measures against respiratory risk factors exposure.
WP7: In period three, the REMEDIA LinkedIn, X and YouTube social media accounts have been regularly updated. The WP7 activities include the publication of 4 articles, the presentations of the project at conferences and summer school, publication of 2 internal newsletters, the preparation of communication tools. Young researchers have been invited to share what they are working on in the news of the website. Furthermore, REMEDIA integrated a Horizon Results Booster workshop in order to optimize communication and dissemination activities.
WP8:In the third period, concerning the activities with EHEN, REMEDIA has been active in several ways: preparation and start of the governance of the EHEN network by REMEDIA, EPHOR and HEDIMED, participation to the EHEN working groups
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.