Prediction the outcome of Lung Transplantation within the COLT cohort
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This document discusses the COLT cohort study of lung transplantation patients. The study aims to predict outcomes of lung transplantation, specifically chronic lung allograft dysfunction, within the COLT cohort of over 500 lung transplant recipients prospectively followed since 2009 across 13 centers in France and other European countries. The study utilizes a systems approach, collecting extensive clinical, environmental, omics, and other data from donors, recipients, and outcomes to develop predictive models of outcomes up to 3 years post-transplant.
![Biomarkers in transplantation
Why do we fail?
§ 15,000 studies on biomarkers in transplantation, 2 registred..
§ ImmuKnow®, Cylex,[ATP] blood CD4+
Kowalski et al. Transplantation 2006;82:663-8
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Prediction the outcome of Lung Transplantation within the COLT cohort
- 1. Prediction the outcome of Lung Transplantation within the COLT cohort Pr. Christophe Pison Pr. Antoine Magnan Pr. Laurent Nicod Consortium COLT Consortium SysCLAD Inserm1055, Grenoble European Institute for Systems Biology and Medicine - EISBM CHU Grenoble Univ. J. Fourier
- 2. Outline § Scope and limitations to success in Lung Transplantation (LT) § Chronic Lung Allograft Dysfunction (CLAD) § Biomarkers in transplantation: why do we fail? § From COLT to SysCLAD § Perspectives
- 3. Burden of Respiratory Diseases § World, 50.5 M deaths / year, 9.4 millions , 18.7 % § 4.30 M, Respiratory infections § 2.75 M, COPD § 1.6 M, Tuberculosis § 0.95 M, Bronchial carcinoma § Very poor prognosis median survival 1-5 years if hypoxemia at rest, no cure § Costs in Europe : 100 billions € § Indications for Lung Transplantation > 40,000 LTx worldwide § COPD § Cystic fibrosis § Interstitial lung diseases § Pulmonary hypertension 3
- 4. Anastomosis Pulmonary veins – left Auricle 4
- 5. QALY - Quality Adjusted Life Years 1 Qualité de vie ajusté sur la survie 123 4 5 6 7 8 9 0,5 1 2 3 Année 5 Résultats de la transplantation pulmonaire, S. Quêtant, T. Rochat, C. Pison. RMR 2010; 27:921-938
- 6. Achilles' tendons in Lung Transplantation § Shortage of grafts, Primary Graft Dysfunction § Chronic Lung Allograft Dysfunction -15%, 3 months § BOS in 50% at 5 years § different patterns - 4% / year § 30% cause of death > 1 year § median survival 1.5 years, if early onset 6
- 7. Survival in Grenoble VI-90 to VI-12 1 § 184 recipients before XII-2001, n = 70 190 procedures after XII-2001, n = 114 ,8 p: 0.0003 § 7 HL, 57 SL, 120 DL All § 121 male, 63 females ,6 § 77 COPD 50 CF ,4 40 ILD 18 PH ,2 0 0 12 24 36 48 60 72 84 96 108 120 7
- 8. Chronic Lung Allograft Dysfunction § 2 phenotypes BOS / RAS § risks factors 8
- 9. Chronic Lung Allograft Dysfunction § Risks factors § compliance to treatments § pollution Nawrot et al. Thorax 2011;66:748-54 9
- 10. Biomarkers in transplantation Why do we fail? § 15,000 studies on biomarkers in transplantation, 2 registred.. § AlloMap®, XDx, 11 informative genes transcripts from PBMC, a high negative prediction for acute rejection after heart transplantation Pham et al. N Engl J Med 2010;362:1890-900 10
- 11. Biomarkers in transplantation Why do we fail? § 15,000 studies on biomarkers in transplantation, 2 registred.. § ImmuKnow®, Cylex,[ATP] blood CD4+ Kowalski et al. Transplantation 2006;82:663-8 11
- 12. Roedder et al. Genome Medicine 2011;3:37
- 13. COLT - COhort in Lung Transplantation COLT § 4 May 2012, 11 French centres coordinated by Institut Thorax de Nantes, Pr. Antoine Magnan : Bichat, Bordeaux, Foch, Grenoble, HEGP, Lyon, Marie Lannelongue, Marseille, Nantes, Strasbourg, Toulouse § 766 candidates to lung transplantation since 2009 § 532 LT recipients prospectively followed for 5 years § Funds PHRC, VLM § Karine Botturi, PhD: SOPs, e-CRF, biobank > 30,000 samples, lung tissues D/R, blood, fresh PBMC, BAL, induced sputum, exhaled air § Proteomics, CHU Grenoble, Pr. M. Sève, C. Trocmé PhD 13
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- 18. Design- Methods in SysCLAD § Prospective cohort > 500 lung transplant recipients, since 2009 in 13 centres COLT and Lausanne, Bruxelles § Donors: day 0 § clinics § HLA § lung tissue § Recipients: before Tx, lung Tx, M6-M12 post LTx § clinics, e.CRF § Blood: HLA, transcriptomics x 2, proteomics x 2, miRNA x 1, subpopulations, polymorphism key genes, Toll r.. § BAL: microbiote, proteomics x 2 § Outcomes: to predict CLAD @ 3 years by year 1 18
- 19. 21 mois IE 18 mois Tech Mise Purif au SELDI1 (175 LTR) biomarqueurs point communs SELDI Mise au iTRAQ1 point SELDI2 (175 LTR) iTRAQ2 Rendu biomarqueurs WP3-5 sur 175 LTR sur 350 LTR Mise au point dosages biomarqueurs communs SELDI iTRAQ (150 LTR) : modif modèle Janvier 2013 Avril Juin 2013 Janvier 2014 Juin 2014 Janvier 2015 Phénotype Phénotype Phénotype Cohorte de caractérisation 220 LTR 350 LTR 500 LTR Cohorte de validation
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- 21. Perspectives § Strengths § COLT > 550 LT recipients by June 2012 § Systems approach § Prediction before function decline § Integration D / R clinical events, environmental x polymorphisms, omics § multilevel / scale signature ? § Weakness § limited time frame § collection data from 13 clinical centres § .. 21
- 22. Perspectives § Opportunities § first attempt to predict CLAD on a personal basis § interactions with AirPROM, U-BIOPRED, MeDALL § eTRIKS, BioAster § Public knowledge tool in Lung transplantation § consolidate a sustainable network to improve outcome predictions in a continuous way for personalized decisions § design specific RCTs § Use case for other solid organ transplantation § Threats § bottle necks § time.. 22
- 23. Acknowledgements § Charles Auffray & EISBM colleagues § David Koubi & Kevin Deplanche, Finovatis § Jean-Pierre & François Boissel, Novadiscovey § Dieter Maier, Biomax § Karine Botturi, Institut du Thorax, Nantes § Candice Trocmé & Michel Sève, Grenoble § Colleagues from COLT & Grenoble Lung Transplantation group § PHRC, VLM 23