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Clinical Transplantation Lung

Clinical Transplantation Lung. Howard University Hospital Department of Transplantation Clive O. Callender, MD. Arturo Hernandez, MD. Objective. Current Status of Lung Transplantation. No of Transplanted Organs vs Waiting List 2004.

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Clinical Transplantation Lung

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  1. Clinical TransplantationLung Howard University Hospital Department of Transplantation Clive O. Callender, MD. Arturo Hernandez, MD

  2. Objective • Current Status of Lung Transplantation

  3. No of Transplanted Organs vs Waiting List 2004 Recovered Transplanted Waiting List • Total 25,237 26,539 86,378 • Kidney 12,575 15,671 (9,025) 57,910 • PTA 2,021 132 504 • PAK 418 973 • K-P 879 2,410 • Liver 6,405 5,780 (5,457) 17,133 • Intestine 167 52 196 • Heart 2,096 1,961 3,237 • Lung 1,973 1,168 3,852 • Heart-lung 37 171 • Source: 2005 OPTN/SRTR Annual Report,

  4. Graft Survival Follow-up Period 1 Year 10 Years Tx 2002-2003 Tx 1993-2003 Kidney Deceased Donor • Graft Survival 89.0% 40.5% • Patient Survival 94.6% 60.7% Kidney: Living Donor • Graft Survival 95.1% 56.4% • Patient Survival 97.9% 76.4% Kidney-Pancreas Kidney Graft Survival 91.7% 52.5% Pancreas Graft Survival 85.8% 53.6% Liver Deceased Donor • Graft Survival 82.2% 52.5% • Patient Survival 81.7% 67.0% Intestine Graft Survival 73.8% 22.0% Heart Graft Survival 86.8% 51.1% Lung Graft Survival 81.4% 22.1% Heart-Lung Graft Survival 55.8% 24.6% UNOS/SRTR, 2003

  5. Current Status of Lung Transplantation • Long term survival—50% die by 5 years • Bronchiolitis obliterans (chronic rejection)—primary cause of poor survival • Future of lung transplantation is prevent bronchiolitis obliterans

  6. Lung TransplantationPre-Cyclosporine Era, Pre-1983 100 At risk: (38) 80 (28) 60 % free from death (19) 40 (12) 20 (4) 0 0 50 100 150 200 250 Time (days)

  7. Worldwide Lung Transplantation Numbers Lung transplants performed worldwide, by year Primary diagnosis, 01/1995 - 06/2003 1706 1655 1.8% 2.6% 4.2% 1537 1508 1410 10.4% 1413 1417 1337 1342 39.0% 9.0% 1206 1069 16.0% 17.0% 902 685 Emphysema/COPD Idiopathic pulmonary fibrosis Cystic fibrosis Alpha-1 antitrypsin deficiency Primary pulmonary hypertension Sarcoidosis Retransplant/graft failure Other 408 185 80 47 13 15 Source: International Society of Heart and Lung Transplantation (ISHLT); UNOS

  8. Chiron Briefing Document Figure 2.2-1 Comparative Transplantation Survival Rates Primary lung transplant by underlying diagnosis Primary kidney, liver, and heart transplant *Kidney, liver, and heart data extrapolated from OPTN Annual Report, 2003.

  9. Clinical Manifestations of Chronic Rejection • Two methods for the diagnosis of chronic rejection • Histologically through transbronchial biopsy (OB) • Clinically through sustained decline in pulmonary function (Bronchiolitis Obliterans Syndrome, BOS) • OB and BOS are histologic and clinical manifestations of the same process • Patients develop progressive shortness of breath, graft failure, airflow obstruction, recurrent pulmonary infections • Once chronic rejection develops, airway damage is progressive and irreversible • Patients die of graft failure/pneumonia

  10. Causes of Death Following Lung Transplantation

  11. Despite Best Current Systemic Treatment and Patient Management, Chronic Rejection Eventually Affects Most Patients % chronic rejection-free survival % ofpatients 100 100 80 80 Tac 60 MMF 60 40 40 Despite best available therapy CsA AZA 20 20 0 0 0 1 2 3 4 5 6 7 Calcineurin inhibitors Anti-metabolites Prednisone Years from transplant Plus induction, plus pulsed intensifications prn Source: ISHLT, market research

  12. New Concept: Avoid Increasing Systemic Immunosuppression Non alloimmune factors: • Infection • GERD • Others Immune activation Increase systemic immune suppression BOS

  13. Pathway to Chronic Rejection Non-alloimmune stimuli Airway ischemia Viruses Bacterial - PSEUDOMONAS Oxidant stress Reflux Alloimmune stimuli Recurrent acute vascular rejection Lymphocytic bronchitis Epithelial injury Inflammation Fibroblastic repair

  14. Lymphocytic Bronchitis/Bronchiolitis

  15. Acute Rejection Acute rejection is a perivascular processdiagnosed by transbronchial biopsy

  16. Separate Interventions for Separate Processes rejection and ongoing injury, inflammation and fibrosis ending in bronchiolitis obliterans Systemic immunosuppression Systemic administration to avert vascular rejection, halting lymphocytic recruitment and activation

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