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Systems Medicine of Respiratory Diseases an actual breakthrough

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1 Systems Medicine of Respiratory Diseases an actual breakthrough
Pr. Christophe Pison, MD, PhD Clinique Universitaire de Pneumologie Pole Thorax et Vaisseaux Inserm1050 Biologie Environnementale et Systémique - BEeSY European Institute for Systems Biology and Medicine - EISBM CHU Grenoble Université Grenoble Alpes INRIA, Lyon, 11th of February 2014

2 www.eisbm.org www.bioaster.com www.biovision.org Institut de Recherche
Technologique

3 Consortium International Systemoscope
« Repenser la recherche, comprendre le vivant, améliorer la santé  »

4 Conflicts Of Interests, 3 last years
Actélion Astra Zeneca Bayer Boehringer Ingelheim GlaxoSmithKline Lilly Novartis Nutricia-Danone Pfizer Gilead Therakos PneumRx, Medwin, Aeris, Holaira Vitalaire, Orkyn, SOS 4

5 Contents Non communicable diseases and “health crisis”
Burden of respiratory diseases and unmet needs Systems medicine for respiratory health in Rhône-Alpes and Europe Biotechnology Journal 2012; 7 special issue on Systems biology and personalized medicine 5

6 Non Communicable Diseases - NCDs
6

7 New paradigms irruption
“Health crisis” Uncontrolled increase in health costs Efficacy  Justice decline Increase incidence in Non Communicable Diseases - NCDs Limitations in present treatments and majors problems in new drug registrations New paradigms irruption « Exposome » & « Omics » data accumulation and how use it for better patient cares? Specialized versus Systems Medicine Reactive versus proactive Medicine? 7

8 Uncontrolled increases in health costs
USA 18% GIP 2009 to 30% by 2030 & last OECD France, 12% GIP 2009, life expectancy 81 years in 2009 8

9 Efficacy & Justice decline
NEJM 2010;362:460-5 9

10 Burden of Respiratory Diseases and Unmet Needs
5.2 million disability life years lost annually in the EU 300 billions € / year in the EU Cystic fibrosis 1st genetic lethal disease Asthma one of the most common chronic diseases in children COPD 4th cause of death, 2nd cause disability life year by 2008 in USA Lung cancer 1st cause of death by cancer in men, 2nd in women No cure for any! 10 10

11 N Engl J Med 2013;369:448-57 11

12 Stratégies personnalisées et participatives
Médecine 4P: L’opportunité Stratégies personnalisées et participatives Prédiction de la maladie Prédiction de la réponse Prévention de la maladie Traitement ciblé 12

13 Médecine systémique en pratique
Agir là Changer le cours de la vie Ou la ? Changer le cours de la maladie Guérir Ou encore la ? Contrôler Thérapie ciblée Hood L, RMMJ 2013 adapté du Pr. A. Magnan

14 to integrate multi-scale space-time dimensions
Challenge to integrate multi-scale space-time dimensions Peter Hunter, University of Auckland – Denis Noble, Oxford University 14 14

15 Achilles' tendons in Lung Transplantation
Shortage of grafts, Primary Graft Dysfunction Chronic Lung Allograft Dysfunction - CLAD BOS in 50% at 5 years different patterns 30% cause of death > 1 year median survival 1.5 years, if early onset -15%, 3 months - 4% / year 15

16 QALY - Quality Adjusted Life Years
0,5 1 Année Qualité de vie ajusté sur la survie 16 Résultats de la transplantation pulmonaire, S. Quêtant, T. Rochat, C. Pison. RMR 2010; 27:

17 Signature to predict chronic dysfunction
17

18 CLAD prediction: The clock is always ticking!
Time 18 Transplantation Jul 27;86(2):192-9.

19 Roedder et al. Genome Medicine 2011;3:37

20 20 SysCLAD Progress Meeting. ENS de Lyon, FR. November 12th, 2013

21 Design  Methods in SysCLAD
COLT French prospective cohort since centres + Bruxelles Swiss Transplant Cohort Study, STCS since 2008 in Lausanne- Genève, Zurich VIII-2013, : 1050 transplanted, 512 reached year 2, 215 year 3 Donors: day 0 clinics HLA lung tissue Recipients: before Tx, day-0 Tx, M6-M12 post LTx Clinics, e.CRF Pollution Blood: HLA, transcriptomics x 2, proteomics x 2, miRNA x 1, lymphocytes subpopulations, exome sequencing BAL: microbiote  macrophages polarization, proteomics x 2 Outcomes: to predict year-3 as soon as year-1 21 21

22 22

23 Air pollution model (Ineris)
Collaboration with Ineris (National Institute for Industrial Environment and Risks) to get access to the up-to date national-wide exposure model with high spatial and temporal resolutions (1x1km) 23

24 Alveolar macrophage polarization Lung transplant recipients
Pulmonary microbiota and Alveolar macrophage polarization in Lung transplant recipients Service de Pneumologie Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland Laboratory: Ben Marsland, PhD Eric Bernasconi, PhD Clinical supervision: Prof. Laurent Nicod Prof. John-David Aubert Research coordination: Dr. Angela Koutsokera Present the complementary approach of studying lung microbiota and alveolar macrophage polarization Adapted from SciencePhotoLibrary 24

25 NEJM 2013,369:20-31 25

26 Editorial Prediction of chronic lung allograft dysfunction: a systems medicine challenge Christophe Pison, Antoine Magnan, Karine Botturi, Michel Sève, Sophie Brouard, Benjamin J. Marsland, Florian Ernst, Tobias Paprotka, Kevin Deplanche, Andreas Fritz, Valérie Siroux, Jean-Pierre Boissel, Paul A. Corris, Charles Auffray, Laurent P. Nicod and the SysCLAD consortium Eur Respir J 2014, in press 26 26

27 SysCLAD Consortium Cohort  Of Lung Transplantation-COLT (associating surgeons; anaesthetists,-intensivists, physicians, research staff) Bordeaux: J. Jougon, J.-F. Velly; H. Rozé; E. Blanchard, C. Dromer; Bruxelles: M. Antoine, M. Cappello, M. Ruiz, Y. Sokolow, F. Vanden Eynden, G. Van Nooten;  L. Barvais, J. Berré, S. Brimioulle, D. De Backer, J. Créteur, E. Engelman, I. Huybrechts, B. Ickx, T. J.C. Preiser,  T. Tuna, L. Van Obberghe, N. Vancutsem, J.-L. Vincent; P. De Vuyst, I. Etienne, F. Féry, F. Jacobs, C. Knoop, J.L. Vachiéry, P. Van den Borne, I. Wellemans ; G. Amand, L. Collignon, M. Giroux; Grenoble: E. Arnaud-Crozat, V. Bach, P.-Y. Brichon, P. Chaffanjon, O. Chavanon, A. de Lambert, S. Guigard, K. Hireche, A. Pirvu, P. Porcu, R. Hacini ; P. Albaladejo, C. Allègre, D. Anglade, D. Bedague, P. Bouzat, E. Briot, O. Carle, M. Casez-Brasseur, D. Colas, G. Dessertaine, M. Durand, J. Duret, M.C. Fèvre, G. Francony, S. Gay, M.R Marino, D. Protar, D. Rehm, S. Robin, M. Rossi-Blancher, L. Saunier; P. Bédouch, A. Boignard, H. Bouvaist, A. Briault, B. Camara, S. Chanoine, M. Dubuc, S. Lantuéjoul, S. Quêtant, J. Maurizi, P. Pavèse,  C. Pison, C. Saint-Raymond, N. Wion; C. Chérion; Lyon: R. Grima, O. Jegaden, J.-M. Maury, F. Tronc; C. Flamens, S. Paulus; J.-F. Mornex, F. Philit, A. Senechal, J.-C. Glérant, S. Turquier; D. Gamondes; L. Chalabresse, F. Thivolet-Bejui; C Barnel, C. Dubois, A. Tiberghien; Paris, Hôpital Européen Georges Pompidou: F. Le Pimpec-Barthes, A.  Bel, P. Mordant, P.  Achouh; V. Boussaud; R. Guillemain, D. Méléard, M.O. Bricourt, B. Cholley ; V. Pezella; Marseille: M. Adda, M. Badier, F. Bregeon, B. Coltey, X.B. D’Journo, S. Dizier, C. Doddoli, N. Dufeu, H. Dutau, JM. Forel, JY. Gaubert, C. Gomez, M. Leone, A. Nieves, B. Orsini, L. Papazian L, C. Picard, M. Reynaud-Gaubert, A. Roch, JM. Rolain, E. Sampol, V. Secq, P. Thomas, D. Trousse; Yahyaoui M ; Nantes: O. Baron, P. Lacoste, C. Perigaud, J.C. Roussel; I. Danner, A Haloun A. Magnan, A Tissot; T. Lepoivre, M. Treilhaud; K. Botturi-Cavaillès, S. Brouard, R. Danger, J. Loy M. Morisset, M. Pain, S. Pares, D. Reboulleau, P.-J. Royer ; Hôpital Marie Lanelongue: P. Dartevelle, E. Fadel, S. Mussot, D. Fabre, O. Mercier; P. Viard, F. Stéphan; J. Cerrina, P. Hervé, J. Le Pavec,  F. Le Roy Ladurie ; l. lamrani Paris Hôpital Bichat: Y. Castier, P. Cerceau, F. Francis, G. Lesèche; N. Allou, P. Augustin, S. Boudinet, M. Desmard, G. Dufour, P. Montravers ; O. Brugière, G. Dauriat, G. Jébrak, H. Mal, A. Marceau, A.-C. Métivier, G. Thabut ; B. Ait Ilalne; Strasbourg: P. Falcoz, G. Massard, N. Santelmo; G. Ajob, O. Collange O. Helms, J. Hentz, A. Roche; B. Bakouboula, T. Degot, A. Dory,  S. Hirschi, S. Ohlmann-Caillard, L. Kessler , R. Kessler, A. Schuller; K. Bennedif, S. Vargas; Suresnes: P. Bonnette,  A. Chapelier, P. Puyo, E. Sage;  J. Bresson, V. Caille, C. Cerf, J. Devaquet, V. Dumans-Nizard, ML. Felten, M. Fischler,  AG. Si Larbi, M. Leguen, L. Ley, N. Liu, G. Trebbia; S. De Miranda, B. Douvry, F. Gonin, D. Grenet, A.M. Hamid, H. Neveu, F. Parquin, C. Picard, A. Roux;  F. Bouillioud, P. Cahen, M. Colombat, C. Dautricourt, M. Delahousse, B. D’Urso, J. Gravisse, A. Guth, S. Hillaire, P. Honderlick, M. Lequintrec, E. Longchampt, F. Mellot, A. Scherrer, L. Temagoult, L. Tricot; M. Vasse, C. Veyrie, L. Zemoura; Toulouse: J. Berjaud, L. Brouchet, M. Dahan; F. Le Balle, O. Mathe ; H. Benahoua, A. Didier, A.L. Goin, M. Murris; L. Crognier, O. Fourcade. Swiss Transplant  Cohort Study-STCS  Genève-Lausanne: T. Krueger, H.B. Ris, J.H. Robert, J. Wellinger; J.-D. Aubert, C. Blanc L.P. Nicod, B.J. Marsland, T. Rochat, P. Soccal; Ph Jolliet,  A Koutsokera, C. Marcucci, O. Manuel; E. Bernasconi, M. Chollet, F. Gronchi, B. Marsland; Zurich: S. Hillinger, I. Inci, P. Kestenholz, W. Weder; M. Zalunardo;  C. Benden, U. Buergi, L.C. Huber; B. Isenring, T. Rechsteiner, M. Schuurmans; T. Muller, A. Gaspert, D. Holzmann, N. Müller,  S. Nicca, C. Schmid. SME and Platforms Biomax, Germany: A. Fritz, D. Maier; Finovatis, Lyon, France: K. Desplanche, D. Koubi; GATC, Germany: T. Paprotka, F. Ernst, B. Wahl; Novasdicovery, Lyon, France: J.-P. Boissel, G. Olivera-Botello; Prométhée Proteomics Platform, CHU Grenoble: C. Trocmé, B. Toussaint, S. Bourgoin-Voillard, M. Séve; Inserm U823, Université Joseph Fourier, Grenoble, France: M. Benmerad, V. Siroux, R. Slama; European Institute for Systems Biology & Medicine: C. Auffray, D. Charron, J. Pellet, C. Pison 27 27

28 Respiratory Systems Medicine - ReSyM
Objectives build a multidisciplinary network to define within 2 years 3 use cases of systems biology / medicine in the context of respiratory medicine, using preexisting set of data successfully apply to European frame programme Horizon-2020 28

29 29

30 Basic Clinical and Biomedical Questions
Long-life dimension repeated measurements to refine phenotypes Adapted from R. Slama group 30

31 Basic Clinical and Biomedical Questions
Mechanisms Shared and non-shared mechanisms in COPD-Asthma / Lung Cancer / Interstitial Pulmonary Fibrosis Respective weights of risk factors to develop a specific chronic respiratory disease: Environmental factors [pollution, smoking, physical activity, nutrition, stress, sleep] Age, Gender, Socio-economic class and Occupation Genetic susceptibility 31

32 Basic Clinical and Biomedical Questions
Taxonomy New classification of old diseases as Asthma, COPD, Lung fibrosis, Lung cancer Associations with other chronic respiratory conditions: Asthma-COPD COPD-Lung Cancer Emphysema-IPF IPF-Lung Cancer Association with other chronic conditions: mainly cardiovascular and metabolic chronic diseases 32

33 33

34 Clinique Universitaire de Pneumologie Université Grenoble Alpes
IRC Mucoviscidose HTAP Transplantation Oncologie Thoracique Maladies Chroniques Respiratoires Promouvoir Bien-Etre Médecine 4P Mécanismes communs maladies chroniques respiratoires et cancer bronchqiue (miRNA, épigénétiques, effet Warburg), patients communs, technologies communes, approches systémiques Coûts efficacité Médecine “pro-active” Proportion de patients pris en charge Médecine “reactive” type CHU 34

35

36 Intégration des données
Médecine 4P Biologie des Systèmes Participation Biologie Personnalisation Technologie Prévention Intégration des données Prédiction Signatures complexes Modélisation Biomarqueurs Adapté du Pr. A. Magnan 36


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