The project is coordinated by the respiratory medicine department of the Nantes University Hospital.
The respiratory medicine Department of the Nantes University Hospital is located at the Laënnec Hospital in the city of Saint-Herblain. It is headed since 2015 by Professor François-Xavier Blanc. The respiratory medicine department also belongs to “’L’institut du thorax” which gathers the departments of cardiology, thoracic surgery, vascular surgery, hemodynamics, endocrinology and respiratory medicine around care, training/teaching and research.
The respiratory medicine Department includes 66 beds in 4 conventional medical care units (Thoracic Oncology; Cystic Fibrosis, Pulmonary Hypertension and Transplantation; Pulmonary Diseases and Intensive Care). A day care department shared with other specialties of l’institut du thorax, a day care dedicated to thoracic oncology, 4 weekday hospital beds for short check-ups, 4 shared sleep recording beds, an endoscopy suite with daily access to interventional bronchoscopy, a smoking cessation unit and a clinical research unit into the “Centre d’Investigations Cliniques -CIC Thorax” are also part of this department. An allergy and clinical immunology unit is attached to this department and is located on the Hôtel Dieu site (center of Nantes).
The Department includes 21 permanent senior physicians, of whom 4 are empowered to lead researches and 5 have a PhD. Four new residents in respiratory medicine and two in oncology are trained every year. Most of them get a Master’s degree by the end of their training (5 years). The Department covers all fields of respiratory medicine with a special focus on lung cancer (from diagnosis to treatment), cystic fibrosis (Cystic Fibrosis Resource and Skills Center, Nantes-Roscoff Constitutive Center), pulmonary hypertension (competence center), asthma, infectious diseases and lung transplantation. It is a pioneer center in the management of severe asthma for the West of France and one of the 6 lung transplant centers outside the Paris region.
The Thoracic oncology unit coordinated by Prof. Jaafar Bennouna participates to the interdisciplinary care for lung cancer and malignant mesothelioma in coordination with other departments: radiology and interventional radiologist team, anatomopathology, molecular biology, thoracic surgery, palliative and supportive care. The patient path is clearly defined with pivotal nurses considering the patient in his/her globality. In 2018, 254 patients with lung cancer (+ 11.9 % versus 2017) were treated, corresponding to 2236 cycles of chemo and/or immunotherapy (+27.9 % versus 2017). Additionally, between June 2017 and June 2018, 54 patients were included in clinical trials, including phase I. Since 2017, eleven clinical trials have been opened in the unit: 3 Phases III, 4 Phase II and 4 Phase I studies. Since 2019, some patients treated in the outpatient unit by chemotherapy, immunotherapy or targeted therapies are followed for their symptoms via smartphone or tablet computers. The Thoracic Oncology unit closely works with the molecular and anatomopathology department for the monitoring treatment of patients with ctDNA.
The respiratory team of CIC Thorax is composed of 2 project managers, 3 technicians and 2 dedicated clinical research nurses who support Phases I to IV clinical trials in respiratory diseases.
LUNG O2 brings together several research units around the Department of respiratory medicine :
Team III “Signaling in vascular and pulmonary pathophysiology” led by Gervaise Loirand of the institut du thorax (UMR 1087),
The “Vascular and pulmonary signalling and pathophysiology” team at the Institute of Thorax (UMR Inserm 1087/Cnrs 6291) is interested in understanding the cellular and molecular mechanisms involved in the development and progression of allergic asthma and pulmonary arterial hypertension. The projects developed aim to identify the events and actors responsible for alterations in the structure and function of the cells of the bronchial wall in asthma and of the pulmonary arteries in pulmonary arterial hypertension. The approaches and strategies put in place are designed to bring together fundamental and translational aspects, as illustrated by the NaRacAS project. The achievement of our projects should lead to the generation of relevant experimental models for the study of these pathologies, the discovery of targets of interest for the development of new therapeutic strategies, and biomarkers for the evaluation of the disease and the efficacy of treatments.
Team IV “Immunoregulation And Immunointervention in Transplantation and Autoimmunity” led by Sophie Brouard of the Center for Researche in Transplantation and Immunology (UMR 1064)
Team IV“Immunoregulation and Immunointervention in Transplantation and Autoimmunity” of the Centre de Recherche en Transplantation et Immunologie (CRTI-UMR 1064) co-directed by Dr. Sophie BROUARD and Pr. David LAPLAUD, brings together scientists and clinicians to address issues in kidney, liver and lung transplantation and the pathophysiology of autoimmune diseases, such as multiple sclerosis and autoimmune hepatitis, with a fundamental and translational approach. Through the development of bio-collections (DIVAT-Biocoll, CENTAURE, COLT) and databases (DIVAT), the team is focusing on immune and lymphocyte regulation mechanisms in these different pathological contexts and the search for diagnostic and prognostic companion biomarkers. The team IV headed by Sophie BROUARD is thus co-leader of a major hospital-university project aimed at improving and drastically modifying the management of transplanted patients.
Finally, the aim of this research is to develop innovative therapeutic strategies in these different fields of application. This allows this team to have significant experience in industrial development through the filing of several patents, some of which are currently under license, and has also contributed to the foundation of several startups and spin-offs (TcLand, Xenothera, Effimune and Osé-immunotherapeutics).
Team V ” Translational ImmunoGenetic in AutoImmunity and Transplantation ” directed by Pr Pierre-Antoine Gourraud of the Center for Research in Transplantation and Immunology (UMR 1064)
Team V from the CRTI “Translational ImmunoGenetics in Autoimmunity and Transplantation” led by Pr Pierre Antoine Gourraud: The ATIP/Avenir team was created in September 2015. Its research interests focus on immunogenomics and precision medicine approaches for complex immune-related traits and diseases, including multiple sclerosis, infectious diseases and transplantation. By combining scientists from diverse fields of expertise (biology, bioinformatics, statistics, immunogenomics, epidemiology), our team’s main objective is to tackle complex immune-related diseases and traits by integrating multiple large datasets (genomics, biological, and clinical) into precision medicine applications. Our research projects are divided into two major axes: (1) Immunogenomics and epidemiology and (2) Precision medicine applications.
Team IV « Immunogenic cell death and mesothelioma therapy » led by Marc Gregoire from the CRCINA INSERM UMR 1232.
Malignant pleural mesothelioma (MPM), a cancer related to asbestos exposure, and non-small cell lung cancer (NSCLC) are two types of aggressive thoracic cancers for which conventional treatments lack efficacy. Although the recent development of immunotherapy has improved the clinical prognosis of many patients, many patients unfortunately do not benefit from these new strategies.
Base on a collection of patient samples (tumor explants, pleural fluids, blood and cell lines), our team develops research projects that aim to better characterize tumor cells and the microenvironment of these cancers in order to propose appropriate therapeutic strategies. In particular, we are studying the expression of markers in patient samples as well as the cells constituting the tumor microenvironment, in particular tumor-associated macrophages (TAMs) which have immunosuppressive properties.
In parallel, the therapeutic approaches we are developing aim to modify this microenvironment in order to promote the establishment of anti-tumor immune responses. We are evaluating the use of combinations of epigenetic agents, as well as oncolytic viruses (OVs), whose capacity to induce immunogenic death of tumor cells has been demonstrated in our previous work.
Our short and medium term projects are I) to continue the study of the tumor microenvironment on the basis of our collection and the development of 3-dimensional co-culture models, II) to improve epigenetic therapeutic approaches by the study of new combinations but also through the development of new vectorization tools, III) to develop and optimize OV for the treatment of thoracic cancers.
All this work should make it possible to propose innovative and adapted therapeutic strategies to modulate the tumor microenvironment and improve the treatment of thoracic cancers.
Our integration within the LUNG O2 facilitates discussions and exchanges of materials between researchers and clinicians, thus optimizing the orientation of research projects for clinical transfer.
Laboratory EA3826: “Impact of acute inflammation on host-pathogen interactions and pulmonary homeostasis” directed by Pr Antoine Roquilly
We have shown that acute inflammation leaves an immunological scar in the lungs, mainly characterized by functional alterations of mononuclear phagocytes. The main goal of our team is to dissect the mechanisms of this so-called “trained” immunity, and its consequences on pulmonary homeostasis and susceptibility to diseases such as bacterial and viral pneumonia. We rely on large biocollections from hospitalized patients and matched healthy controls. We follow a cyclical strategy to align animal and human studies using cutting-edge functional genomics and validation studies. We are developing translational projects in three complementary axes based on the study of the interaction between the pulmonary microbiota and mucosal immunity during and after inflammation.
Axis 1: Host-pathogen interactions in the lungs.
Axis 2: The inflammatory state and its role in human physiopathology.
Axis 3: Development of immunotherapies and precision medicine approaches.
The molecular genetics platform for cancer at the Nantes University Hospital and the ICO (Western Cancer Institute), directed by Prof. Marc Denis,
The platform
The Regional Tumor Molecular Biology Platform was funded by the National Cancer Institute (INCa) in 2008. Since then, we have developed numerous approaches to perform molecular tests on lung and colorectal tumors as well as melanomas. In particular, we have developed Next Generation Sequencing or NGS approaches to perform a detailed analysis of lung tumors. Current efforts are mainly focused on tumor characterization at the RNA level (RNA sequencing), and on the detection/characterization of molecular alterations in circulating DNA (deep sequencing and digital PCR). This organization has allowed us to create a network at the regional level, and to develop translational research projects both at the regional (ELUCID) and national (MELROSE) levels, which are part of the LUNG O2 cluster.
The MIHAR laboratory: Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes, led by Pr Emmanuel Montassier,
MiHAR lab research focuses on antimicrobial resistance. According to the World Health Organization, antimicrobial resistance is one of the most prominent health threats for the next decades. Currently, antimicrobial resistance is responsible for 700,000 deaths annually; and without policies to counteract this burden, in 2050, AMR is predicted to become a devastating problem with 10 million deaths each year. This number is larger than the number of people that died in 2018 from cancer.
Numerous factors influence the emergence and spread of bacterial resistance. Among these latter, the exposure of bacteria, and especially bacteria of the intestinal microbiota, to antibacterial agents favors the emergence of bacteria that are resistant to these antibiotics, and also to other antibiotics. Basically, we study how interactions between Microbiotas, Hosts and Antibiotics may influence the emergence and spread of Resistant bacteria. We also study how microbiome can predict the emergence of antimicrobial resistance using “Omics” technologies, including metagenomics, transcriptomics, proteomics and metabolomics.
In the LUNG O2 cluster, MiHAR will work on the discovery of microbiome biomarkers in hospital-acquired pneumonias, leading cause of death from nosocomial infections in critically ill patients. Our objective is to bring our computational skills in “Omics” to find signatures and biomarkers that will be predictive of the subsequent hospital-acquired pneumonia in critically ill patients. Our computational microbiology team develops methods and softwares that will bring precision medicine to the respiratory research on the territory. We will apply those methods and softwares to find patterns in microbial communities that will predict the onset of hospital-acquired pneumonia
The Nantes Science and Numerics Laboratory (LS2N) with Emilie Poirson,
Health of the future is one of the 3 major economic and societal challenges addressed by the Ecole Centrale de Nantes both in research and training. These 2 activities are represented within the LUNG O2 cluster by Emilie Poirson and Thomas Lechevallier, who are in close on-going collaborations with the University Hospital in the field of connected healthcare.
Emilie Poirson
University professor, member of the Nantes science and Numerics laboratory (LS2N), within the PACCE team (Perception, Action Cognition for Design and Ergonomics). She works particularly on the place of the human being in the design of products (perceptions, emotions, interfaces…), especially on applications in the field of health (connected home devices for health).
Thomas Lechevallier
He is in charge of a Health Engineering course thanks to his large experience in engineering in the field of health especially at the Nantes University Hospital. He is also in charge of the Environment, Mobility, Health option at the Ecole Centrale de Nantes, which is part of the LUNG O2 cluster.
The Data Clinic Service (Pr Pierre-Antoine Gourraud), of the Nantes University Hospital
The Nantes University Hospital Data Warehouse combines both structured (coded) and unstructured data (text from reports). It includes 17 million stays/visits concerning 2.4 million patients admitted to Nantes University Hospital, the majority of them since 2000, with 128 million structured data and more than 27 million documents, such as reports. An update is carried out on a weekly basis. The data is collected from a number of sources: PMSI (Program for medicalization of the information systems): diagnosis and procedure codes, Plain-text reports (consultation, hospitalization, imaging, genetics, biology, surgery, laboratory results) and structured lab-work results (numerically coded variables).
Methodologically, the project will benefit from the expertise of the Data Clinic Service of CHUN (CHUN, INSERM, CIC 1413, Clinique des données, Nantes, France). The Data-Clinic legally and scientifically facilitates access to health data from institutional sources including the university hospital and promotes the deployment of the appropriate epidemiological and computational methods to deliver the highest level of interpretations for complex data.
The Data Clinic provides support to hospital researchers in the Nantes University Hospital community by assisting clinical research in data extraction and computer analysis.
The Data Clinic team from left to right : Pr PA Gourraud, Delphine Toublant, Adrien Bazoges, Sandrine Coudol, Olivia Rousseau, Thomas Goronflot, Matilde Karakachoff, Dr Matthieu Wargny.
The Department of Training Institutes (DIF) of the Nantes University Hospital led by Nathalie Alglave.
The Department of Training Institutes (DIF) of the Nantes University Hospital Center (CHU) is attached to the Human Resources Department.
The DIF of CHUN includes 11 institutes or schools that prepare for diplomas ranging from level V to Master 2, in the field of health and social work.
Their mission is to provide initial and continuing education for health professionals in order to meet the health needs of the population. The DIF is developing a true regional policy adapted to the needs of the healthcare territory’s job market and, more specifically, to those of hospital and non-hospital institutions.
Approximately 1,200 students benefit from these training courses.
Dynamic pedagogical teams, associating specialized professionals from health structures, the social sector and the university, follow students and pupils throughout their training.
During his or her studies, the student or trainee benefits from qualified internships in the care units of the Nantes University Hospital but also in other structures in the Pays de Loire region as well as nationally and internationally.
The DIF of Nantes University Hospital offers a study framework perfectly suited to the realization of professional projects in the health and social fields thanks to its experience, values and human resources.
Human and social sciences (HSS), which are very important in paramedical training, form a set of disciplines that study various aspects of human reality at both the individual and collective levels. The purpose of these disciplines is to analyze human activity (education and training, management and administration, information and communication, health, work, law…) and to focus on issues shared by several disciplines. This allows an evidence-based return to the issues addressed by the actors of health in three fast-evolving fields that are genetics and personalized medicine, applications of neuroscience and cognitive sciences and new technologies encompassing the cultural, political, economic, ethical and epistemic outcomes. On this last point, the emerging nursing sciences in France will allow to widen and better understand the human/patient perception of health and disease in a holistic outcome. Indeed, the theories of “care” are re-examining the approach of public health institutions through the growing role of new actors and uses, as well as through the recognition of patients as “expert- uninitiated”. Thus, the HHS and nursing sciences will be able to shed the necessary light on the “LUNG innOvatiOn” project, in particular through a holistic approach to the healthcare user in terms of a psychosocial approach in a transdisciplinary dynamic at the service of personalized care in a city-hospital relay system, by making the link with the emergence of new professions such as nurses in advanced practices.
We are therefore in a transdisciplinary research network combining life sciences, technology, HHS and nursing sciences, enriching each-other reciprocally.
And the Gustave Eiffel University (formerly IFSTTAR) with Andry Razakamanantsoa.
The actions of the Gustave Eiffel University are coordinated by the Geomaterial and Geotechnic Modelling (GMG) laboratory, of the Geotechnical engineering, Environment, Natural hazards and Earth sciences Department (GERS). The activities of this laboratory are part of a context of resource saving applied to infrastructures, cities and territories, taking into account the societal issues related to climate change. Part of the research activities is dedicated to the study of soil-atmosphere interactions.
Within the scope of LUNG O2, Gustave Eiffel University researchers contribute to research activities and knowledge transfer actions related to the analysis of environmental impacts on the development of respiratory diseases. To date, the correlations between particles emissions on air quality at local and regional scales, lung diseases and pathogens carried by particles have not been fully established. Thus, Gustave Eiffel University is seeking to provide an engineering-environmental perspective in order to explain the various mechanisms involved, in particular on the emissions of fine particles 1) in urban areas and/or in connection with road traffic, 2) during construction activities, 3) in the various ways of mobility and their impacts on respiratory health, but also the analysis of the mechanisms of pollutants emission and suspension such as nanoparticles; emerging pollutants including radon or radioactive gases …
To do so, the Gustave Eiffel University carries out measurements of emissions and environmental parameters in situ. This work is carried out by identifying areas where individuals are prone to develop lung diseases due to significant exposure to pollution: cities, public transport, construction sites, etc.
We also carry out physical modeling in the laboratory using an aeraulic chamber, a suspension chamber and a 3D high-frequency particle velocymeter (3D HF PIV). The Gustave Eiffel University, in collaboration with the Ecole Centrale de Nantes, also contributes to training activities for engineer students in issues related to the environment, e-health and mobility.
