akciğer nakli: tarihçe ve genel bakış

Akciğer Nakli: Tarihçe Akciğer Nakli: Tarihçe ve Genel Bakışve Genel Bakış

Dr. Levent DalarDr. Levent Dalar

Yedikule Göğüs Hastalıkları ve Yedikule Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Göğüs Cerrahisi Eğitim ve

Araştırma HastanesiAraştırma Hastanesi

Herhangi bir kişi ya da Herhangi bir kişi ya da kurumla çıkar ilişkim kurumla çıkar ilişkim ve çatışmam yoktur.ve çatışmam yoktur.

TarihçeTarihçe

ÖncülerÖncüler İlk nakillerİlk nakiller Kırılma noktaları Kırılma noktaları YeniliklerYenilikler

Genel BakışGenel Bakış

Neler değişti?Neler değişti?

EndikasyonlarEndikasyonlar

TekniklerTeknikler SonuçlarSonuçlar Sağkalım Sağkalım

Öncüler: 1900’lerÖncüler: 1900’ler

NeptuneNeptune

Öncüler: MarcusÖncüler: Marcus

İlk Nakiller: Hardyİlk Nakiller: Hardy

İlk akciğer nakli hastası: İlk akciğer nakli hastası: J.R.J.R.

1963-19781963-1978

Nakil denemeleri devam ediyor, Nakil denemeleri devam ediyor, yapılan 38 nakilin tamamı yapılan 38 nakilin tamamı kaybediliyor. Sadece;kaybediliyor. Sadece;

1969 Fritz Derom’un sağ AC nakli 10 ay 1969 Fritz Derom’un sağ AC nakli 10 ay yaşadıyaşadı

Derom F, Barbier F, Ringoir S. Ten month survival Derom F, Barbier F, Ringoir S. Ten month survival after lung homotransplantation in man after lung homotransplantation in man J Thorac Cardiovasc Surg 1971; 61: 835-846J Thorac Cardiovasc Surg 1971; 61: 835-846

Bruce Reitz ilk uzun Bruce Reitz ilk uzun yaşayan kalp akciğer yaşayan kalp akciğer

naklini gerçekleştiriyornaklini gerçekleştiriyor

Reitz B, Wallwork J, Hunt S. N Eng J Med 1982; 306: 557

Toronto 1983: Tom HallToronto 1983: Tom Hall

Toronto 1986: İlk Toronto 1986: İlk Bilateral NakilBilateral Nakil

REGISTRY DATABASE:REGISTRY DATABASE:Number of Transplants Number of Transplants

ReportedReported

ORGANTransplants Reported from 7/1/2009 through

6/30/2010

Total Transplants Reported through

6/30/2010

Heart 3,608 100,210

Heart-Lung 69 4,248

Lung 3,168 38,119

ISHLT 2011ISHLTJ Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

REGISTRY DATABASE:REGISTRY DATABASE:Number of Centers Reporting Lung TransplantsNumber of Centers Reporting Lung Transplants

0

25

50

75

100

125

150

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Year of Transplant

# o

f C

en

ters

Re

po

rtin

g


REGISTRY DATABASE:REGISTRY DATABASE:Number of Centers Reporting Lung TransplantsNumber of Centers Reporting Lung Transplants

0

25

50

75

100

125

150

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Year of Transplant

# o

f C

en

ters

Re

po

rtin

g

Other

North America

Europe


NUMBER OF LUNG TRANSPLANTS REPORTED NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPEBY YEAR AND PROCEDURE TYPE

5 7 38 89204

449

758

972

11601291

13891509 1548 1559

16991783

19712008

2216

2567

2791

3272

2972

1411

2917

0

500

1000

1500

2000

2500

3000

3500

Nu

mb

er

of

tra

ns

pla

nts

Bilateral/Double LungSingle Lung

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.


AVERAGE CENTER VOLUMEAVERAGE CENTER VOLUMELung Transplants: January 1, 2000 - June 30, 2010Lung Transplants: January 1, 2000 - June 30, 2010

54

39

2316

7

28

70

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

4

8

12

16

20

24

Number of centers Percentage of transplants

Per

cen

tag

e o

f tr

ansp

lan

ts


LUNG TRANSPLANTS:LUNG TRANSPLANTS: Transplant Recipient Age by Year of TransplantTransplant Recipient Age by Year of Transplant

Transplants: January 1, 1987 – June 30, 2010Transplants: January 1, 1987 – June 30, 2010

0%

20%

40%

60%

80%

100%

0

12

24

36

48

60

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

Med

ian

rec

ipie

nt

age

(yea

rs)

% o

f tr

an

sp

lan

tsrs

Year of Transplant


AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS (1/1985-6/2010)(1/1985-6/2010)

0

5

10

15

20

25

30

35

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

Recipient Age

% o

f tr

an

sp

lan

ts


AGE DISTRIBUTION OF LUNG TRANSPLANT AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS BY ERARECIPIENTS BY ERA

0

5

10

15

20

25

30

35

40

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

% o

f tr

ansp

lan

ts

1985-1994 (N = 4,975)

1995-1999 (N = 7,412)

2000-6/2010 (N = 25,716)

p < 0.0001

Transplants with unknown recipient age were excluded from this tabulation.ISHLT 2011ISHLT

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

LUNG TRANSPLANTS: LUNG TRANSPLANTS: Donor Age by Year of TransplantDonor Age by Year of Transplant

Transplants: January 1, 1987 – June 30, 2010 Transplants: January 1, 1987 – June 30, 2010

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

2009

2010

Year of Transplant

0

10

20

30

40

50

0-11 12-17 18-34 35-49 50-59 60+ Median Donor Age

% o

f tr

ansp

lan

ts

Med

ian

do

no

r ag

e (y

ears

)


AGE DISTRIBUTION OF ADULT LUNG AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS BY ERATRANSPLANT RECIPIENTS BY ERA

0

2

4

6

8

10

12

14

16

18

20

18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 >65

1985-1995 (N = 6,059)

1996-6/2010 (N = 30,380)

p < 0.0001

Median age by era1985-1995 = 47 years1996-6/2010 = 53 years

% o

f tr

ansp

lan

ts


AGE DISTRIBUTION OF ADULT LUNG AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS BY ERATRANSPLANT RECIPIENTS BY ERA

0

2

4

6

8

10

12

14

16

18

20

22

18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 >65

1985-1994 (N=4,742)1995-1999 (N=6,970)2000-6/2010 (N=24,727)

p < 0.0001

Median age by era1985-1994 = 47 years1995-1999 = 50 years2000-6/2010 = 54 years

% o

f tr

ansp

lan

ts


ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival Kaplan-Meier Survival (Transplants: January 1994 - June 2009)(Transplants: January 1994 - June 2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years

Bilateral/Double Lung (N=16,628)

Single Lung (N=12,085)

All Lungs (N= 28,727)

Double lung: 1/2-life = 6.8 Years; Conditional 1/2-life = 9.3 YearsSingle lung: 1/2-life = 4.7 Years; Conditional 1/2-life = 6.5 YearsAll lungs: 1/2-life = 5.5 Years; Conditional 1/2-life = 7.8 Years

P < 0.0001

Su

rviv

al (

%)


ADULT LUNG TRANSPLANTATION: Indications for Single Lung ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants Transplants (Transplants: January 1995 - June 2010)(Transplants: January 1995 - June 2010)

*Other includes:

Pulmonary Fibrosis, Other: 3.4%

Sarcoidosis: 1.9%

Bronchiectasis: 0.4%

Congenital Heart Disease: 0.3%

LAM: 0.8%

Connective Tissue Disease: 1.0%

OB (non-ReTx): 0.6%

Miscellaneous: 0.9%

47%

32%

3%

1%2%

6%

10%

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


ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants Lung Transplants (Transplants: January 1995 - June 2010)(Transplants: January 1995 - June 2010)

26%

16%

17%

7%

27%

5% 2%

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

*Other includes:

Pulmonary Fibrosis, Other: 2.9%

Sarcoidosis: 3.0%

Bronchiectasis: 4.4%

Congenital Heart Disease: 1.2%

LAM: 1.1%

Connective Tissue Disease: 1.3%

OB (non-ReTx): 1.3%

Miscellaneous: 1.7%


ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONMajor Indications By Year (Number)Major Indications By Year (Number)

0

10

20

30

40

50

60

70

Myopathy

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

19940

250

500

750

1000

1250

1500

1750

2000

2250

2500

2750

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Transplant Year

Nu

mb

er

of

tra

ns

pla

nts

CF IPF COPD Alpha-1 IPAH Re-Tx


ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By DiagnosisKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2009)(Transplants: January 1990 – June 2009)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14Years

Su

rviv

al (

%)

Alpha-1 (N=2,349) CF (N=4,828) COPD (N=10,741)IPF (N=6,478) IPAH (N=1,189) Sarcoidosis (N=756)

HALF-LIFE Alpha-1: 6.3 Years; CF: 7.4 Years; COPD: 5.3 Years; IPF: 4.5 Years; IPAH: 4.9 Years; Sarcoidosis: 5.3 Years

Survival comparisonsAll comparisons with Alpha-1 and CF are statistically significant at < 0.01

COPD vs. IPF: p < 0.0001


ADULT LUNG TRANSPLANTS ADULT LUNG TRANSPLANTS (1997-6/2009)(1997-6/2009) Risk Factors for 1 Year MortalityRisk Factors for 1 Year Mortality

(N=13,937)

ISHLT 2011

DONOR CHARACTERISTICSDONOR CHARACTERISTICS NN RelativRelative Riske Risk

P-P-valuevalue

95% Conf. 95% Conf. IntervalInterval

Donor history of diabetesDonor history of diabetes 560560 1.441.44 <.000<.00011

1.21 -1.21 - 1.721.72

RECIPIENT CHARACTERISTICSRECIPIENT CHARACTERISTICS

Recipient on dialysisRecipient on dialysis 6161 2.662.66 <.000<.00011

1.84 -1.84 - 3.843.84

IV inotropesIV inotropes 4949 1.741.74 0.00760.0076 1.16 -1.16 - 2.602.60

Hospitalized (including ICU)Hospitalized (including ICU) 1,511,5133

1.701.70 <.000<.00011

1.50 -1.50 - 1.931.93

VentilatorVentilator 491491 1.571.57 <.000<.00011

1.31 -1.31 - 1.881.88

ISHLTJ Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

(N=13,937)

*Other = All diagnoses other than COPD, IPAH, IPF, cystic fibrosis, pulmonary fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, retransplant and LAM.

Reference group = COPD/Emphysema, Single lung

ISHLT 2011

RECIPIENT CHARACTERISTICSRECIPIENT CHARACTERISTICS NN RelativRelative Riske Risk

P-valueP-value 95% Conf. 95% Conf. IntervalInterval

Diagnosis = BronchiectasisDiagnosis = Bronchiectasis 273273 1.341.34 0.05820.0582 0.99 0.99 --

1.801.80

Prior SternotomyPrior Sternotomy 319319 1.221.22 0.08100.0810 0.98 0.98 --

1.521.52

Diagnosis = COPD/Emphysema, Diagnosis = COPD/Emphysema, double lungdouble lung

1,9401,940 1.161.16 0.05170.0517 1.00 1.00 --

1.341.34

Recipient history of diabetesRecipient history of diabetes 1,7481,748 1.111.11 0.09270.0927 0.98 0.98 --

1.251.25

Chronic steroid useChronic steroid use 6,6066,606 1.091.09 0.05060.0506 1.00 1.00 --

1.181.18

ADULT LUNG TRANSPLANTS ADULT LUNG TRANSPLANTS (1997-6/2009)(1997-6/2009) Borderline SignificantBorderline Significant Risk Factors for 1 Year Mortality Risk Factors for 1 Year Mortality


ADULT LUNG TRANSPLANTSADULT LUNG TRANSPLANTS (1/1997-6/2009)(1/1997-6/2009) Risk Factors for 1 Year MortalityRisk Factors for 1 Year Mortality

ISHLT 2011

Continuous Factors (see figures)Continuous Factors (see figures)

Recipient ageRecipient age BilirubinBilirubin

Transplant center Transplant center volume volume

Recipient oxygen Recipient oxygen required at restrequired at rest

Cardiac outputCardiac output Height differenceHeight difference

Recipient FVC % Recipient FVC % predictedpredicted


ADULT LUNG RECIPIENTSADULT LUNG RECIPIENTSCross-Sectional AnalysisCross-Sectional Analysis

Functional Status of Surviving RecipientsFunctional Status of Surviving Recipients(Follow-ups: April 1994 – June 2010)(Follow-ups: April 1994 – June 2010)

0%

20%

40%

60%

80%

100%

1 Year (N = 6,882) 3 Year (N = 4,423) 5 Year (N = 2,544)

No Activity Limitations Performs with Some Assistance Requires Total Assistance


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

(Deaths: January 1992 - June 2010)(Deaths: January 1992 - June 2010)

0

10

20

30

40

50

0-30 Days (N=2,204)

31 Days – 1Year

(N=3,781)

>1 Year – 3Years

(N=3,425)

>3 Years – 5Years

(N=1,962)

>5 Years – 10Years

(N=2,336)

>10 Years (N=675)

Bronchiolitis Malignancy (non-Lymph/PTLD)

Infection (non-CMV) Graft Failure

Cardiovascular

Pe

rce

nta

ge

of

De

ath

s


akciğer nakli: tarihçe ve genel bakış

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