Lung Transplantation A look Inside A Surgeon s Perspective Hassan Nemeh, MD Henry Ford Hospital Michigan Society of Respiratory Care Spring Conference 2016
Historical background Alexis Carrel 1905 Reported on heart and lung transplant in a cat model
Historical background Vladimir Demikhov Reported on 20 different techniques of heart and heartlung transplant in 1950
Historical background James Hardy, MD First human lung transplant 1964 by Hardy
Historical background Fritz Derom achieved a 10 months survival after lung transplant in a patient with pulmonary silicosis in 1971.
Historical background Bruce Reitz started a clinical trial in heart-lung transplant in 1981 after success in primate model in the lab
Historical background The Toronto group headed by Joel Cooper established lung transplant as we know it today
Adult Lung Transplants Number of Transplants by Year and Procedure Type Number of Transplants 4000 3500 3000 2500 2000 1500 1000 500 0 5 6 32 Bilateral/Double Lung Single Lung 69 160 384 664 874 2129 19011934 1711 1630 14171440 1483 12961301 1160 1055 2481 2699 28382901 3177 3450 3745 3750 3893 2015 NOTE: This figure includes only the adult lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as representing changes in the number of adult lung transplants performed worldwide. JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024
Indications Cystic fibrosis FEV1 <30%, or clinical worsening COPD FEV1<25% or PCO2 >55 with pul. HTN IPF Symptomatic, VC <60-70%, DLCO <50-60% PPH NYHA class III or IV on vasodilator Eisenmenger s NYHA class IIIorIV
Adult Lung Transplants Indications (Transplants: January 1995 June 2014) Diagnosis SLT (N=16,226) BLT (N=29,457) TOTAL (N=45,683) COPD/Emphysema 6,826 (42.1%) 7,856 (26.7%) 14,682 (32.1%) Idiopathic Pulmonary Fibrosis 5,561 (34.3%) 5,442 (18.5%) 11,003 (24.1%) Cystic Fibrosis 228 (1.4%) 7,191 (24.4%) 7,419 (16.2%) Alpha-1 792 (4.9%) 1,667 (5.7%) 2,459 (5.4%) Idiopathic Pulmonary Arterial Hypertension 91 (0.6%) 1,250 (4.2%) 1,341 (2.9%) Pulmonary Fibrosis, Other 758 (4.7%) 1,125 (3.8%) 1,883 (4.1%) Bronchiectasis 65 (0.4%) 1,167 (4.0%) 1,232 (2.7%) Sarcoidosis 301 (1.9%) 857 (2.9%) 1,158 (2.5%) Retransplant: Obliterative Bronchiolitis 338 (2.1%) 440 (1.5%) 778 (1.7%) Connective Tissue Disease 200 (1.2%) 481 (1.6%) 681 (1.5%) Obliterative Bronchiolitis (Not Retransplant) 110 (0.7%) 381 (1.3%) 491 (1.1%) LAM 142 (0.9%) 330 (1.1%) 472 (1.0%) Retransplant: Not Obliterative Bronchiolitis 210 (1.3%) 246 (0.8%) 456 (1.0%) Congenital Heart Disease 93 (0.6%) 333 (1.1%) 426 (0.9%) Cancer 7 (0.0%) 30 (0.1%) 37 (0.1%) Other 504 (3.1%) 661 (2.2%) 1,165 (2.6%) 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024 For some retransplants, a diagnosis other than retransplant was reported, so the total number and percentage of retransplants may be greater.
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% 1999 2001 2003 2005 2007 2009 2011 2013 1999 2001 2003 2005 2007 2009 2011 2013 1999 2001 2003 2005 2007 2009 2011 2013 1999 2001 2003 2005 2007 2009 2011 2013 AT Def COPD IPF IPAH 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024
Adult Lung Transplants Major Indications by Year (Number) 3,500 3,000 CF IPF COPD Alpha-1 IPAH Retx Number of Transplants 2,500 2,000 1,500 1,000 500 0 Transplant Year 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024 For some retransplants, a diagnosis other than retransplant was reported, so the total percentage of retransplants may be greater.
Adult Lung Transplants Kaplan-Meier Survival by Procedure Type for Primary Transplant Recipients (Transplants: January 1990 June 2013) 100 80 Median survival (years): Bilateral/Double lung: 7.1; Conditional=9.7 Single lung: 4.5; Conditional=6.4 Survival (%) 60 40 p < 0.0001 20 0 Bilateral/Double Lung (N=28,135) Single Lung (N=17,099) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024 Years
Adult Lung Transplants Kaplan-Meier Survival by Diagnosis (Transplants: January 1990 June 2013) 100 Alpha-1 (N=2,904) CF (N=7,336) COPD (N=15,064) Survival (%) 80 60 40 20 IPF (N=10,438) IPAH (N=1,584) Sarcoidosis (N=1,136) All pair-wise comparisons were significant at p < 0.05 except Alpha-1 vs. IPAH, Alpha-1 vs. Sarcoidosis, COPD vs. IPAH, COPD vs. Sarcoidosis, IPAH vs. Sarcoidosis Median survival (years): Alpha-1=6.5; CF=8.5; COPD=5.5; IPF=4.7; IPAH=5.7; Sarcoidosis=6.1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024 Years
Adult Lung Transplants Functional Status of Surviving Recipients (Follow-ups: January 2009 June 2014) 100% 10% 80% 20% 30% 60% 40% 50% 40% 60% 70% 20% 80% 90% 0% 1 Year (N=8,010) 2 Years (N=6,567) 3 Years (N=5,446) 100% 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024
Adult Lung Transplants Employment Status of Surviving Recipients (Follow-ups: January 2009 June 2014) 100% 80% 60% 40% Working (FT/PT Status unknown) Working Part Time Working Full Time Retired Not Working 20% 0% 1 Year (N=5,408) 3 Years (N=3,650) 5 Years (N=2,535) 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024
Adult Lung Transplants Rehospitalization Post Transplant of Surviving Recipients (Follow-ups: January 2009 June 2014) 100% 80% 60% 40% 20% Hospitalized, Rejection + Infection Hospitalized, Rejection Only No Hospitalization Hospitalized, Infection Only Hospitalized, Not Rejection/Not Infection 0% 1 Year (N=8,972) 3 Years (N=6,021) 5 Years (N=4,199) 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024
Adult Lung Transplants Cumulative Morbidity Rates in Survivors within 1 and 5 Years Post Transplant (Follow-ups: April 1994 June 2014) Outcome Within 1 Year Total number with known response Within 5 Years Total number with known response Hypertension 51.7% (N=17,813) 80.7% (N=5,293) Renal Dysfunction 22.5% (N=20,551) 53.3% (N=7,056) Abnormal Creatinine 2.5 mg/dl 15.7% 35.3% Creatinine > 2.5 mg/dl 5.0% 14.3% Chronic Dialysis 1.7% 3.0% Renal Transplant 0.1% 0.8% Hyperlipidemia 26.2% (N=18,510) 57.9% (N=5,643) Diabetes 23.0% (N=20,502) 39.5% (N=6,941) Bronchiolitis Obliterans Syndrome 9.3% (N=19,348) 41.1% (N=5,987) 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024
Adult Lung Transplants Cumulative Post Transplant Malignancy Rates in Survivors(Follow-ups: April 1994 June 2014) Malignancy/Type 1-Year Survivors 5-Year Survivors 10-Year Survivors No Malignancy 20,260 (96.3%) 6,191 (83.4%) 1,222 (70.9%) Malignancy (all types combined) 780 (3.7%) 1,234 (16.6%) 501 (29.1%) Malignancy Type* Skin 279 882 359 Lymphoma 272 111 47 Other 200 294 139 Type Not Reported 29 10 2 Other malignancies reported include: adenocarcinoma (2; 2; 1), bladder (2; 1; 0), lung (2; 4; 0), breast (1; 5; 2); prostate (0; 5; 1), cervical (1; 1; 0); liver (1; 1; 1); and colon (1; 1; 0). Numbers in parentheses represent the number of reported cases within each time period. * Recipients may have experienced more than one type of malignancy; therefore, the sum of individual malignancy types may be greater than the total number with malignancy. 2015 JHLT. 2015 2014 Oct; 34(10): 33(10): 1264-1277 1009-1024
Ex-vivo lung perfusion Future Direction Lung transplant Ambulatory ECMO Induction of tolerance Bioengineered lung tissue