LUNG TRANSPLANTATION CURRENT STATUS

Iskander Al-Githmi, MD, FRCSC-GS, FRCSC -Ts , FRCSC-CDs, FACS, FCCP Division of Cardiothoracic SurgeryKing Abdulaziz University Hospital

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE

5 7 36 78190

419

704

922

10871223

13581338145014601491

16281690

187919302071

23862448

2708

0

250

500

750

1000

1250

1500

1750

2000

2250

2500

2750

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

Nu

mb

er

of

Tra

ns

pla

nts

Bilateral/Double LungSingle Lung

ISHLTNOTE: 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.

2009

AVERAGE CENTER VOLUMELung Transplants: January 1, 2000 - June 30, 2008

46

2533

22 17730

10

20

30

40

50

60

1-4 5-9 10-19 20-29 30-39 40-49 50+

Average number of lung transplants per year

Nu

mb

er

of

ce

nte

rs

0

5

10

15

20

25

30

Number of centers Percentage of transplants

Per

cen

tag

e o

f tr

ansp

lan

ts

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 survivedMortality 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)

0

5

10

15

20

25

30

35

0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+

Recipient Age

% o

f tr

an

sp

lan

ts

ISHLT

2009

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

0

5

10

15

20

25

30

35

0-11 12-17 18-29 30-39 40-49 50-59 60-65 66+

Donor Age

% o

f tr

an

sp

lan

ts

ISHLT

2009

LUNG TRANSPLANTS: Transplant Recipient Age by Year of Transplant

Transplants: January 1, 1987 – June 30, 2008

0%

20%

40%

60%

80%

100%

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

0

10

20

30

40

50

60

0-11 12-17 18-34 35-49 50-59 60-65 66+ Mean Age

Mea

n r

ecip

ien

t ag

e (y

ears

)

% o

f T

ran

sp

lan

tsrs

Year of Transplant

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 strategiesA. Marginal donors

Do not fill these criteria:-1- Age < 55 yrs2- Clear Chest X-ray3- No smoking history

` 4- Sputum gram stain negative5- Normal gas exchange

Donor Supply

B. 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

C. 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

D. XenotransplantationInitial enthusiasm – unlimited donor supply

Hardening factors1. Severe immune response2. Apparent incompatibilities between the

coagulation systems of the two species

European resp.journal 2003;supp

Donor Supply

Reconditioning Lung Donor

Toronto Xvivo Lung Perfusion System

Shaf Keshavjee, MD,FRCSCDirector of Lung Transplant ProgramUniversity 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)

ISHLT

*Other includes:

Sarcoidosis: 2.1%

Bronchiectasis: 0.4%

Congenital Heart Disease: 0.2%

LAM: 0.8%

OB (non-ReTx): 0.5%

Miscellaneous: 6.3%

49%

29%

3%1%

2%

6%

10%

Alpha-1 COPD CF IPF IPAH Re-Tx Other*

2009

ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1995 - June 2008)

26%

14%2%5%

26%

8%

19%

Alpha-1 COPD CF IPF IPAH Re-Tx Other*

ISHLT

*Other includes:

Sarcoidosis: 2.9%

Bronchiectasis: 4.5%

Congenital Heart Disease: 1.1%

LAM: 1.2%

OB (non-ReTx): 1.1%

Miscellaneous: 7.7%

2009

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival (Transplants: January 1994 - June 2007)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al

(%)

.

Bilateral/Double Lung (N=12,246)

Single Lung (N=10,081)

All Lungs (N=22,328)

Double lung: 1/2-life = 6.6 Years; Conditional 1/2-life = 9.0 YearsSingle lung: 1/2-life = 4.6 Years; Conditional 1/2-life = 6.4 YearsAll lungs: 1/2-life = 5.4 Years; Conditional 1/2-life = 7.4 Years

P < 0.0001

ISHLT

2009

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type and Era

(Transplants: January 1990 – June 2007) Diagnosis: Idiopathic Pulmonary Fibrosis, Single Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al

(%)

IPF/Single lung/1990-1994 (N=456)

IPF/Single lung/1995-1999 (N=823)

IPF/Single lung/2000-6/2007 (N=1,775)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.51591990-1994 vs. 2000-6/2007: p = 0.00281995-1999 vs. 2000-6/2007: p = 0.0066

N=14

N=62

N=52

ISHLT

2009

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type and Era

(Transplants: January 1990 – June 2007) Diagnosis: Idiopathic Pulmonary Fibrosis, Double Lung

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al

(%)

IPF/Double lung/1990-1994 (N=67)

IPF/Double lung/1995-1999 (N=263)

IPF/Double lung/2000-6/2007 (N=1,310)

Survival comparisons1990-1994 vs. 1995-1999: p = 0.55111990-1994 vs. 2000-6/2007: p =0.02871995-1999 vs. 2000-6/2007: p < 0.0001

N=11

N=33

N=10

ISHLT

2009

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2007)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12Years

Su

rviv

al

(%)

Alpha-1 (N=2,085) CF (N=3,746) COPD (N=8,812)

IPF (N=4,695) IPAH (N=1,065) Sarcoidosis (N=597)

HALF-LIFE Alpha-1: 6.1 Years; CF: 7.0 Years; COPD: 5.1 Years; IPF: 4.3 Years; IPAH: 5.6 Years; Sarcoidosis: 5.3 Years

ISHLT

Survival comparisonsAlpha-1 vs. CF: p < 0.0001Alpha-1 vs. COPD: p < 0.0001 Alpha-1 vs. IPF: p < 0.0001Alpha-1 vs. Sarcoidosis: p = 0.0380CF vs. COPD: p < 0.0001CF vs. IPF: p < 0.0001CF vs. IPAH: p < 0.0001CF vs. Sarcoidosis: p < 0.0001IPAH vs. IPF: p = 0.0046COPD vs. IPF: p < 0.0001

2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Gender (Transplants: January 1990 – June 2007)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al

(%)

Male (N=13,251)

Female (N=11,981)

HALF-LIFE Male: 5.0 years; Female: 5.4 Years

p = 0.0006

N at risk at 5 years=3,456

N at risk = 783N at risk at 5 years=3,311

N at risk = 762

ISHLT

2009

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2007)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al

(%)

.

18-34 (N = 4,420)35-49 (N = 6,629)50-59 (N = 9,229)60-65 (N = 4,262)66+ (N = 694)

Survival comparisonsAll p-values significant at p < 0.0001 except 18-34 vs. 35-49: p = 0.7127; 60-65 vs. 66+: p = 0.0007

HALF-LIFE 18-34: 5.9 Years; 35-49: 6.3 Years; 50-59: 5.1 Years; 60-65: 4.2 Years; 66+: 3.2 Years

ISHLT

2009

Eur J Cardiothorac Surg 2006;30:846-851

Novalung

Novalung Technical Data

ataGas 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