LUNG TRANSPLANTATION CURRENT STATUS Iskander Al-Githmi, MD, FRCSC-GS, FRCSC -Ts , FRCSC-CDs, FACS, FCCP Division of Cardiothoracic Surgery King Abdulaziz University Hospital

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. Therefore, these numbers should not be interpreted as the rate of change in lung procedures performed worldwide. NOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as representing changes in the number of lung transplants performed worldwide. ISHLT 2009

AVERAGE CENTER VOLUME Lung Transplants: January 1, 2000 - June 30, 2008 ISHLT 2009

Lung Transplantation in KSA 4 transplants at KFH – Jeddah 1991 - 1994 1996 ,first single lung transplant at KFSH & RC (Riyadh ) First bilateral lung transplant at KFSH & RC (Riyadh ) 1998 2001 , the lung transplant unit was established at KFSH & RC ( Jeddah) Dec. 23,2001, the first successful bilateral lung transplant in the Middle East was performed at KFSH & RC (Jeddah)

KFSH&RC – Jeddah Lung Transplantation Program Patients with end-stage lung diseases, N=13 Indications: Pulmonary fibrosis (n=8) Bronchiectasis (n=2) Pulmonary HTN (n=1) COPD (n=1) LAM (n=1)

Types of transplantation: Single lung (n=10) Bilateral lung (n=3) Results: 10/13 survived Mortality 3/13 (n=1 liver failure, n=1 stroke, n=1 T.B.) 1 year survival 95 %

Lung transplantation in KSA KFSH & RC ( Jeddah ) is the only active hospital performing lung transplantation in the Middle East IPF is the commonest indication followed by Broncheictasis 95% 1 year survival

AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS (1/1985-6/2008) ISHLT 2009

DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS (1/1985-6/2008) ISHLT 2009

LUNG TRANSPLANTS: Transplant Recipient Age by Year of Transplant Transplants: January 1, 1987 – June 30, 2008 ISHLT 2009

Lung transplantation evaluation process Cardiothoracic Transplant Surgeon Transplant Pulmonologist Transplant Coordinator Transplant Anesthiologist Infectious Disease Nutritionist Social services Psychologist Physiotherapist

Recipient Selective Criteria: End-stage pulmonary disease with life expectancy < 2 yrs. Absence of severe extra pulmonary diseases. Strong motivation towards the idea of lung transplantation. Severe functional limitation, but potential for rehabilitation. Excellent psychosocial support. No current smoking or substances abuse

Indications: Obstructive air way disease (29%) - COPD - Alpha 1 antitrypsin deficiency Idiopathic pulmonary fibrosis (19%) Septic pulmonary disease (16%) - Bronchiectasis - cystic fibrosis Primary pulmonary hypertension (11%)

Other Varieties (11%) e.g. - sarcoidosis - lymphangioliomyomatosis (LAM) - eosinophilic granuloma

Contra-indications: Age > 65 years Active smoking Poor compliance with the treatment Severe active infections (HIV, Hepatitis B & C)

Con’t. Active malignancy within the past two years. Drugs or alcohol abuse. Dysfunction of major other organs - renal dysfunction - untreatable CAD or LV dysfunction - liver dysfunction Ventilator dependence - high mortality BMI < 16 and BMI > 30 Severe osteoporosis

Donor Selection Criteria (Standard): Age < 55 years ABO blood group compatibility No significant lung diseases Absence of chest trauma Smoking Hx < 20 pack years Clear CXR PaO2 > 300mm Hg on F102 1.0 and PEEP 5 cm for 5 min. Bronchoscopy – clear Sputum gram stain- Absence of organisms

Donor-Recipient Matching Issues ABO blood group is the most antigen system Panel reactive antibodies Size matching Undesized: persistent pneumothorax and increase work of breathing. Oversized: atelectasis and distortion of anatomy

Donor Supply Increasing gap between demand and supply Newer strategies A. Marginal donors Do not fill these criteria:- 1- Age < 55 yrs 2- Clear Chest X-ray 3- No smoking history ` 4- Sputum gram stain negative 5- Normal gas exchange

Donor Supply Living lobar transplantation Harvesting left lower lobe from one healthy donor & right lower lobe from another ( 25% of TLC for each) Pioneered by University of southern California (Vaughn Starns). Impressive result in both children & adults Associated with Significant morbidity but no fatalities reported

Donor Supply Non -heart beating donor (NHBD) A donor whose death is defined by irreversible cessation of circulatory and respiratory functions (UDDA) Period of time between a systole and retrieval is controversial , recommendation is 2-5min NHBD contributes < 1% of the numbers of transplants in USA In Holland 50% of cadaveric transplants are from NHBD

Non-heart beating donor

Donor Supply Xenotransplantation Initial enthusiasm – unlimited donor supply Hardening factors 1. Severe immune response 2. Apparent incompatibilities between the coagulation systems of the two species European resp.journal 2003;supp

Reconditioning Lung Donor Donor Supply Reconditioning Lung Donor

Toronto Xvivo Lung Perfusion System

Shaf Keshavjee, MD,FRCSC Director of Lung Transplant Program University of Toronto

Lung transplantation Single or double lung Wait time -Blood Type -Size Severity of illness -Life expectancy while on the waiting list -Outcome post transplant Surgical time (6-8 hours) Hospital stay (14-21 days) Follow up ( life long, frequent office visits)

ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: January 1995 - June 2008) *Other includes: Sarcoidosis: 2.1% Bronchiectasis: 0.4% Congenital Heart Disease: 0.2% LAM: 0.8% OB (non-ReTx): 0.5% Miscellaneous: 6.3% ISHLT 2009

ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1995 - June 2008) *Other includes: Sarcoidosis: 2.9% Bronchiectasis: 4.5% Congenital Heart Disease: 1.1% LAM: 1.2% OB (non-ReTx): 1.1% Miscellaneous: 7.7% ISHLT 2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival (Transplants: January 1994 - June 2007) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow- up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period. Survival rates were compared using the log-rank test statistic. ISHLT 2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Procedure Type and Era (Transplants: January 1990 – June 2007) Diagnosis: Idiopathic Pulmonary Fibrosis, Single Lung Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow- up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Survival rates were compared using the log-rank test statistic. ISHLT 2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Procedure Type and Era (Transplants: January 1990 – June 2007) Diagnosis: Idiopathic Pulmonary Fibrosis, Double Lung Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow- up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Survival rates were compared using the log-rank test statistic. ISHLT 2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2007) Survival comparisons Alpha-1 vs. CF: p < 0.0001 Alpha-1 vs. COPD: p < 0.0001 Alpha-1 vs. IPF: p < 0.0001 Alpha-1 vs. Sarcoidosis: p = 0.0380 CF vs. COPD: p < 0.0001 CF vs. IPF: p < 0.0001 CF vs. IPAH: p < 0.0001 CF vs. Sarcoidosis: p < 0.0001 IPAH vs. IPF: p = 0.0046 COPD vs. IPF: p < 0.0001 Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow- up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. Survival rates were compared using the log-rank test statistic. ISHLT 2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Gender (Transplants: January 1990 – June 2007) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow- up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. Survival rates were compared using the log-rank test statistic. ISHLT 2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2007) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow- up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. Survival rates were compared using the log-rank test statistic. ISHLT 2009

Eur J Cardiothorac Surg 2006;30:846-851

Novalung

Novalung Technical Data ata Gas exchange by diffusion across a plasma tight membrane Heparin coated surface (ACT 120 – 140s) Low shear stress (blood trauma) Low resistance (6mmHg at 1.5 l/min) Blood flow 0.5 – 4.5 L/min Filling volume = 250 ml saline

Novalung as a bridge to lung transplantation J Thorac Cardiovasc Surg 2006;131:719

Initianal experience with novalung as a bridge to lung transplant- Hannover Medical School N=12 patients Patients with refractory respiratory failure Hypercapnea and acidosis despite maximal conventional ventilation Placed on Novalung as a bridge to lung transplantation

Initianal experience with novalung as a bridge to lung transplant- Hannover Medical School J Thorac Cardiovasc Surg 2006;131:719

Initianal experience with novalung as a bridge to lung transplant- Hannover Medical Schoo 10/12 patients successfully bridged to transplantation 8/10 survived lung transplant Cause of death : multi-organ failure 2 prior, 2 after lung transplant

Conclusions Lung transplantation is life saving procedure for end-stage lung diseases Mortality on the waiting list remains a major problem Reduce the gap between demands and supply i.e increase donor supply will decrease mortality on the waiting list Novalung is a safe and valuable option to bridge patients to lung transplantation.

Thank you