LUNG TRANSPLANTATION

2012

דר' לקסר אורימכון הראה

בית החולים האוניברסיטאי הדסה

INDICATION

Lung transplantation is indicated for patients with

chronic, end-stage lung disease who are failing maximal

medical therapy, or for whom no effective medical

therapy exists.

•COPD

•IPF

•PPH

•CF

.

.

The Journal of Heart and Lung TransplantationJuly 2006

Ideally, listing for transplantation should occur when

life expectancy is greatly reduced but nonetheless

greater than the expected waiting time for a suitable

organ, and transplantation should be performed when

life expectancy after transplantation exceeds life expectancy without the procedure.

TIMING

The Journal of Heart and Lung TransplantationJuly 2006

AIMS

Survival benefit

Quality of life

Palliation

Absolute contraindications

• Malignancy in the last 2 years.

•. Untreatable advanced dysfunction of another major organ system •. Non-curable chronic extrapulmonary infection including HBV HCV HIV•. Significant chest wall/spinal deformity.•. Documented nonadherence •. Untreatable psychiatric or psychologic condition •. Absence of a consistent or reliable social support•. Substance addiction (e.g., alcohol, tobacco, or narcotics) The Journal of Heart and Lung Transplantation

July 2006

Relative contraindications

• Age >65y• Unstable condition• Limited functional condition• 18 >bmi>30• Colonization with resistant organism• Ventilation • Osteoporosis• IHD,D.M.,GERD,HTN….

The Journal of Heart and Lung Transplantation

July 2006

COPD

Guidelines for Referral

•. BODE index exceeding 5

Guidelines for Transplantation

•. Patients with a BODE index* of 7 to 10 or at least 1

of the following:

•. History of hospitalization for exacerbation associated

with acute hypercapnia (PCO2 exceeding 50 mm Hg).

• Pulmonary hypertension or cor pulmonale, or both,

despite oxygen therapy.

•. FEV1 of less than 20% and either DLCO of less than 20%

or homogenous distribution of emphysema.

The Journal of Heart and Lung Transplantation

July 2006

Cystic fibrosis and bronchiectasis

Guidelines for Referral

•. FEV1 below 30% predicted or a rapid decline in FEV1.

•. Exacerbation of pulmonary disease requiring ICU stay.

•. Increasing frequency of exacerbations requiring antibiotic

therapy.

•. Refractory and/or recurrent pneumothorax.

•. Recurrent hemoptysis not controlled by embolization.

Guideline for Transplantation

•. Oxygen-dependent respiratory failure.

•. Hypercapnia.

•. Pulmonary hypertension. The Journal of Heart and Lung TransplantationJuly 2006

PULMONARY FIBROSISGuideline for Referral early,do not wait to treatment•. Histologic or radiographic evidence of UIP irrespective of vital capacity.

•. Histologic evidence of fibrotic NSIP.

Guideline for Transplantation

•. Histologic or radiographic evidence of UIP and any of the following:

•. A DLCO of less than 39% predicted.

•. A 10% or greater decrement in FVC during 6 months of follow-up.

•. A decrease in pulse oximetry below 88% during 6-MWT.

•. Honeycombing on HRCT (fibrosis score of 2).

•. Histologic evidence of NSIP and any of the following:

•. A DLCO of less than 35% predicted.

• . A 10% or greater decrement in FVC or 15% decrease

in DLCO during 6 months of follow-up.

The Journal of Heart and Lung Transplantation

July 2006

PULMONARY ARTERIAL HYPERTENSION

Guideline for Referral•. NYHA functional class III or IV, irrespective of ongoing therapy.

•. Rapidly progressive disease.

Guideline for Transplantation•. Persistent NYHA class III or IV on maximal medical therapy.

•. Low (350 meter) or declining 6-MWT.

•. Failing therapy with intravenous epoprostenol, or equivalent.

•. Cardiac index of less than 2 liters/min/m2.

•. Right atrial pressure exceeding 15 mm Hg.

The Journal of Heart and Lung Transplantation

July 2006

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

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

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

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 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 TRANSPLANTATIONKaplan-Meier Survival by Procedure Type (Transplants: January 1990 – June 2007)

Diagnosis: Emphysema/COPD

0

25

50

75

100

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

Years

Su

rviv

al

(%)

COPD/Single lung (N=5,683)

COPD/Double lung (N=3,129) N=138

N=60

P < 0.0001

N at risk at 5 years = 744

N at risk at 5 years = 1,786

ISHLT

2009

ADULT LUNG TRANSPLANTS (1/1995-6/2007) Risk Factors for 1 Year Mortality

Recipient Age

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65

Recipient Age

Re

lati

ve

Ris

k o

f 1

Ye

ar

Mo

rta

lity

p < 0.0001

ISHLT

2009

ADULT LUNG RECIPIENTSFunctional Status of Surviving Recipients

(Follow-ups: April 1994 – June 2008)

0%

20%

40%

60%

80%

100%

1 Year (N = 6,820) 3 Year (N = 4,333) 5 Year (N = 2,492) 10 Years (N = 422)

No Activity Limitations Performs with Some Assistance Requires Total Assistance

ISHLT

2009

ADULT LUNG RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: April 1994 – June 2008)

0%

20%

40%

60%

80%

100%

1 Year (N=8,937) 3 Year (N=5,452) 5 Year (N=3,386) 10 year (N=704)

Working (FT/PTStatus unknown)

Working Part Time

Working Full Time

Retired

Not Working

ISHLT

2009

0

20

40

60

80

100

Year 1 (N = 6,105) Year 5 (N = 2,573)

% o

f P

atie

nts

Other

Rapa + Cellcycle

Rapa + Calcineurin

Tacrolimus

Tacrolimus + MMF

Tacrolimus + AZA

Cyclosporine + MMF

Cyclosporine + AZA

ADULT LUNG RECIPIENTS Maintenance Immunosuppression Drug Combinations at Time of Follow-up

For follow-ups between January 2002 through June 2008 Analysis limited to patients receiving prednisone

ISHLT

Analysis is limited to patients who were alive at the time of the follow-up

2009

POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 10 Years Post-Transplant (Follow-ups: April

1994 - June 2008)

Outcome Within 10

Years

Total number with known response

Hypertension 97.30% (N = 337)

Renal Dysfunction 42.10% (N = 484)

Abnormal Creatinine < 2.5 mg/dl 24.20% Creatinine > 2.5 mg/dl 7.40% Chronic Dialysis 7.60% Renal Transplant 2.90%

Hyperlipidemia 68.50% (N = 410)

Diabetes 37.40% (N = 374)

Bronchiolitis Obliterans Syndrome 50.20% (N = 297)

ISHLT

2009

FREEDOM FROM BRONCHIOLITIS OBLITERANS SYNDROME

For Adult Lung Recipients (Follow-ups: April 1994-June 2008)Conditional on Survival to 14 days

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

Freedom from Bronchiolitis ObliteransSyndrome (N = 10,835)

N at risk at 5 years = 1,329

N at risk = 61

% F

ree

do

m f

rom

Bro

nc

hio

litis

O

blit

era

ns

Sy

nd

rom

e

ISHLT

2009

FREEDOM FROM SEVERE RENAL DYSFUNCTION*For Adult Lung Recipients (Follow-ups: April 1994-June 2008)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Years

% F

ree

do

m f

rom

Se

ve

re R

en

al

Dy

sfu

nc

tio

n

Freedom from Severe RenalDysfunction (N=11,463)

N at risk at 5 years = 1,910

N at risk = 110

* Severe renal dysfunction = Creatinine > 2.5 mg/dl (221 μmol/L), dialysis or renal transplant

ISHLT

2009

FREEDOM FROM MALIGNANCYFor Adult Lung Recipients (Follow-ups: April 1994-June 2008)

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Years

% F

ree

fro

m M

ali

gn

an

cy

All malignancy Lymph Skin Other

ISHLT

2009

ADULT LUNG TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death

(Deaths: January 1992 - June 2008)

0

10

20

30

40

50

0-30 Days (N= 1,621 )

31 Days – 1Year (N =

3,110)

>1 Year – 3Years (N=2,776 )

>3 Years – 5Years (N =

1,593 )

>5 Years – 10Years (N=1,797 )

>10 Years (N= 392)

Bronchiolitis Malignancy (non-Lymph/PTLD)

Infection (non-CMV) Graft Failure

Cardiovascular

Pe

rce

nta

ge

of

De

ath

s

ISHLT

2009

?מה קורה בישראל

: שקלול -LAS SCOREרשימה ארצית לפי • חומרת המחלה וסכויי הצלחת ההשתלה

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