Advanced Medicine 2016 Lung Transplantation. Paul A Corris Newcastle University Newcastle Upon Tyne UK

Transcription

1 Advanced Medicine 2016 Lung Transplantation Paul A Corris Newcastle University Newcastle Upon Tyne UK

2 First Human Lung Transplantation 1963 JAMA 1963;186: The lung donor was a NHBD who died from myocardial infarction! J.D. Hardy Jackson, MS Recipient was a 58yr old male prisoner with lung cancer and emphysema Donor was non heart beating donor (DCD)

3 Adult Lung Transplants Number of Transplants by Year and Procedure Type Number of Transplants Bilateral/Double Lung Single Lung JHLT Oct; 34(10): 33(10):

4 Adult Lung Transplants Procedure Type within Indication, by Year 100% 90% 80% Bilateral/Double Lung Transplant Single Lung Transplant % of Transplants 70% 60% 50% 40% 30% 20% 10% 0% AT Def COPD IPF IPAH 2015 JHLT Oct; 34(10): 33(10):

5 Adult Lung Transplants Kaplan-Meier Survival by Procedure Type Median survival (years): Bilateral/Double lung: 7.1; Conditional=9.7 Single lung: 4.5; Conditional=6.4 Survival (%) p < Bilateral/Double Lung (N=28,135) Single Lung (N=17,099) JHLT Oct; 34(10): 33(10): Years

6 Adult Lung Transplants Kaplan-Meier Survival by Era Median survival (years): : 4.2; Conditional= : 6.0; Conditional= /2013: NA; Conditional=NA Survival (%) N at risk = 2,065 All pair-wise comparisons were significant at p <0.001 except vs /2013 (p=0.1211) (N=9,783) (N=21,593) /2013 (N=16,006) N at risk = 252 N at risk = Years JHLT Oct; 34(10): 33(10):

7 Lung transplant Survival Newcastle in 1069 patients Newcastle Lung/heart-lung Transplantation (n=1069) Post 2000 (n=778) Pre 2000 (n=291) p=0.0005

8 Adult Lung Transplants Functional Status of Surviving Recipients (Follow-ups: ) 100% 80% 60% 40% 20% FC % 20% 30% 40% 50% 60% 70% 80% 90% 0% 1 Year (N=8,010) 2 Years (N=6,567) 5 Years (N=5,446) 100% 2015 JHLT Oct; 34(10): 33(10):

9 Obliterative Bronchiolitis FEV 1 / FVC = 0.89/1.52 FEF = 0.46 Lymphocytes CD8 Neutrophils Macrophages OB (Myo)fibroblasts Collagen Deposition Remodelling BOS Airflow Obstruction

10 CT of OB showing central airway dilatation

11 Adult Lung Transplants Freedom from Bronchiolitis Obliterans Syndrome 2015 JHLT Oct; 33(10):

12 Randomised trial of de novo Azithromycin Double blind randomized controlled trial of azithromycin (n=40) or placebo (n=43) de novo after LTx for 2 years Vos et al. Eur Respir J 2011;37:164-72

13 Case Reports regarding Azithromycin in BOS 120 Repetitive rejection/infection FEV1%BL FEF25-75%BL BOS 1 Azithromycin

14 Case Reports regarding Azithromycin in BOS 120 Repetitive rejection/infection FEV1%BL FEF25-75%BL BOS 1 Azithromycin

15 Azithromycin 250 mg three times a week improves lung function in patients with BOS post lung Transplantation Thorax Lung transplantation Original article A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation Paul A Corris, Victoria A Ryan,Therese Small, James Lordan, Andrew J Fisher, Gerard Meachery, Gail Johnson, Chris Ward Trial registration number EU-CTR, /GB Thorax 2015;0:1 9.

16 Azithromycin improves FEV1 in BOS.. P=

17 Restrictive Allograft Dysfunction CT appearance: - Interstitial opacity - Traction bronchiectasis - Ground glass opacity - Upper-lobe dominant fibrosis (in 40%) Sato et al, 2011 JHLTx,

18 Evidence Based Guidelines European Respiratory Journal Dec 2014, 44 (6) ; Environmental pollution GORD Infection Lymphocytic bronchitis DSA Phenotyping Fundoplication TLI Photophoresis Azithromycin

19 Source: Transplant activity in the UK, , NHS Blood and Transplant

20 Living donors Source: Transplant activity in the UK, , NHS Blood and Transplant

21 Donor Lung use variability Donors of >1 organ PMP Lung donors (%) USA UK Australia USA UK Australia Snell et al, Journal of Heart and Lung Transplant 2007

22 UK Worldwide Lung Transplant Rates 2013 (per million population)

23 UK DBD Organ transplantation

24 UK DCD Organ Transplantation

25 Primary graft dysfunction

26 Fundamental Problems with the Current Approach to Donor Organ Management 1. Focus has been on slowing down death, rather than on facilitating recovery / regeneration 2. Cold preservation hinders the possibility of active metabolic processes / repair 3. Unable to assess DCD or DBD properly and predict how the organ works AFTER we implant it 4. Leads to safe practice with turn down of useable organs

27 How do we increase quantity and quality of lungs Ex vivo Perfusion Evaluation Treatment Resuscitation Stable and reliable ex vivo maintenance perfusion technique the treatment platform Reliable lung evaluation Develop a Treatment Arsenal Injury - Specific Repair Personalized Medicine Immunological pre-preparation (tolerance)

28 EVLP

29

30 Commercial developments in EVLP

31 Treatment during EVLP Treatment during EVLP Cypel et al. Thorac Surg Clin 2015; 25: 27-33

32 FUNCTIONAL REPAIR OF HUMAN DONOR LUNGS BY IL-10 GENE THERAPY Change from Baseline (mmhg) PaO 2 /FiO * (dynes.sec.cm -5 ) PVR * EVLP/AdIL-10 EVLP M. Cypel, M. Liu, M. Rubacha, J. C. Yeung, S. Hirayama, M. Anraku, M. Sato, J. Medin, B. L. Davidson, M. de Perrot, T. K. Waddell, A. S. Slutsky, S. Keshavjee SCIENCE Translational Medicine 2009 October 28; 1(4) :4ra9.

33 First EVLP recipient Newcastle Donor lung PaO2 20 Kpa on 100% O2

34 Options for bridging to transplant Novalung lung assist device AV for CO2 PA to LA in PAH Awake ECMO

35 New face of ECMO

36 Awake patients on support NOVALUNG ECMO

37 Take Home messages 1. Long term results continue to improve 2. Quality of life good 3. Technology and biology should improve number and quality of organs 4. Technology and biology affording ability to bridge recipients to safe transplantation 5. 4 depends on successful 3