Survival after single versus bilateral lung Survival after single versus bilateral lung transplantation for COPD and pulmonary transplantation for COPD and pulmonary

fibrosisfibrosis

University Hospital GasthuisbergLeuvenBelgium

A. Demir, D. Van Raemdonck, G. Verleden, L. A. Demir, D. Van Raemdonck, G. Verleden, L. Dupont, W. Coosemans, H. Decaluwé, P. De Leyn, Dupont, W. Coosemans, H. Decaluwé, P. De Leyn,

P. Nafteux, T. LerutP. Nafteux, T. Lerut

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

ADULT LUNG TRANSPLANTATION: IndicationsADULT LUNG TRANSPLANTATION: Indications (1/1995-6/2008)(1/1995-6/2008)

DIAGNOSISDIAGNOSIS SLT (N = SLT (N = 10,19010,190)) BLT (N = BLT (N = 13,33813,338)) TOTAL (N = TOTAL (N = 23,52823,528))

COPD/EmphysemaCOPD/Emphysema 4,994 ( 49.0% )4,994 ( 49.0% ) 3,423 ( 25.7% )3,423 ( 25.7% ) 8,417 ( 35.8% )8,417 ( 35.8% )

Idiopathic Pulmonary FibrosisIdiopathic Pulmonary Fibrosis 2,967 ( 29.1% )2,967 ( 29.1% ) 1,930 ( 14.5% )1,930 ( 14.5% ) 4,897 ( 20.8% )4,897 ( 20.8% )

Cystic FibrosisCystic Fibrosis 191 ( 1.9% )191 ( 1.9% ) 3,552 ( 26.6% )3,552 ( 26.6% ) 3,743 ( 15.9% )3,743 ( 15.9% )

Alpha-1Alpha-1 662 ( 6.5% )662 ( 6.5% ) 1,017 ( 7.6% )1,017 ( 7.6% ) 1,679 ( 7.1% )1,679 ( 7.1% )

Idiopathic Pulmonary Arterial HypertensionIdiopathic Pulmonary Arterial Hypertension 74 ( 0.7% )74 ( 0.7% ) 714 ( 5.4% )714 ( 5.4% ) 788 ( 3.3% )788 ( 3.3% )

SarcoidosisSarcoidosis 212 ( 2.1% )212 ( 2.1% ) 391 ( 2.9% )391 ( 2.9% ) 603 ( 2.6% )603 ( 2.6% )

BronchiectasisBronchiectasis 40 ( 0.4% )40 ( 0.4% ) 596 ( 4.5% )596 ( 4.5% ) 636 ( 2.7% )636 ( 2.7% )

LAMLAM 80 ( 0.8% )80 ( 0.8% ) 157 ( 1.2% )157 ( 1.2% ) 237 ( 1.0% )237 ( 1.0% )

Congenital Heart DiseaseCongenital Heart Disease 19 ( 0.2% )19 ( 0.2% ) 144 ( 1.1% )144 ( 1.1% ) 163 ( 0.7% )163 ( 0.7% )

Re-Transplant: Obliterative BronchiolitisRe-Transplant: Obliterative Bronchiolitis 160 ( 1.6% )160 ( 1.6% ) 134 ( 1.0% )134 ( 1.0% ) 294 ( 1.2% )294 ( 1.2% )

Obliterative Bronchiolitis Obliterative Bronchiolitis

(Not Re-Transplant)(Not Re-Transplant)

53 ( 0.5% )53 ( 0.5% ) 150 ( 1.1% )150 ( 1.1% ) 203 ( 0.9% )203 ( 0.9% )

Re-Transplant: Not Obliterative BronchiolitisRe-Transplant: Not Obliterative Bronchiolitis 105 ( 1.0% )105 ( 1.0% ) 97 ( 0.7% )97 ( 0.7% ) 202 ( 0.9% )202 ( 0.9% )

Connective Tissue DiseaseConnective Tissue Disease 68 ( 0.7% )68 ( 0.7% ) 113 ( 0.8% )113 ( 0.8% ) 181 ( 0.8% )181 ( 0.8% )

Interstitial PneumonitisInterstitial Pneumonitis 32 ( 0.3% )32 ( 0.3% ) 29 ( 0.2% )29 ( 0.2% ) 61 ( 0.3% )61 ( 0.3% )

CancerCancer 6 ( 0.1% )6 ( 0.1% ) 17 ( 0.1% )17 ( 0.1% ) 23 ( 0.1% )23 ( 0.1% )

OtherOther 527 ( 5.2% )527 ( 5.2% ) 874 ( 6.6% )874 ( 6.6% ) 1,401 ( 6.0% )1,401 ( 6.0% )

ISHLT

2009

ADULT LUNG TRANSPLANTATION: ADULT LUNG TRANSPLANTATION: Distribution of Procedure Type for Major IndicationsDistribution of Procedure Type for Major Indications (1992-2007)(1992-2007)

ISHLT

Year of Year of TXTX

Alpha-1Alpha-1 COPDCOPD Cystic FibrosisCystic Fibrosis IPFIPF IPAHIPAH

DoubleDouble SingleSingle DoubleDouble SingleSingle DoubleDouble SingleSingle DoubleDouble SingleSingle DoubleDouble SingleSingle

19921992 28.128.1 71.971.9 16.416.4 83.683.6 97.097.0 3.03.0 10.210.2 89.889.8 26.626.6 73.473.4

19931993 38.738.7 61.361.3 16.016.0 84.084.0 94.994.9 5.15.1 16.516.5 83.583.5 53.853.8 46.246.2

19941994 43.043.0 57.057.0 18.918.9 81.181.1 86.186.1 13.913.9 13.913.9 86.186.1 64.364.3 35.735.7

19951995 46.246.2 53.853.8 21.421.4 78.678.6 89.789.7 10.310.3 27.927.9 72.172.1 89.389.3 10.710.7

19961996 47.347.3 52.752.7 26.826.8 73.273.2 87.087.0 13.013.0 27.327.3 72.772.7 82.082.0 18.018.0

19971997 46.446.4 53.653.6 26.326.3 73.773.7 92.992.9 7.17.1 22.222.2 77.877.8 90.090.0 10.010.0

19981998 48.548.5 51.551.5 28.828.8 71.271.2 92.692.6 7.47.4 20.120.1 79.979.9 86.886.8 13.213.2

19991999 47.047.0 53.053.0 28.128.1 71.971.9 90.890.8 9.29.2 23.023.0 77.077.0 86.086.0 14.014.0

20002000 58.158.1 41.941.9 29.029.0 71.071.0 94.794.7 5.35.3 31.831.8 68.268.2 92.692.6 7.47.4

20012001 59.959.9 40.140.1 28.628.6 71.471.4 94.094.0 6.06.0 30.030.0 69.769.7 89.889.8 10.210.2

20022002 56.656.6 43.443.4 38.538.5 61.561.5 96.296.2 3.83.8 35.135.1 64.964.9 89.989.9 10.110.1

20032003 65.465.4 34.634.6 42.242.2 57.857.8 95.195.1 4.94.9 41.841.8 58.258.2 95.495.4 4.64.6

20042004 73.973.9 26.126.1 45.345.3 54.754.7 96.296.2 3.83.8 44.044.0 56.056.0 94.494.4 5.65.6

20052005 77.877.8 22.222.2 49.749.7 50.350.3 97.797.7 2.32.3 46.246.2 53.853.8 90.590.5 9.59.5

20062006 76.376.3 23.723.7 58.558.5 41.541.5 99.299.2 0.80.8 49.349.3 50.750.7 100.0100.0 0.00.0

20072007 86.986.9 13.113.1 64.564.5 35.535.5 97.197.1 2.92.9 48.848.8 51.251.2 94.194.1 5.95.9

2009

ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONProcedure Type within Indication, by YearProcedure Type within Indication, by Year

0

10

20

30

40

50

60

70

80

90

100

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

% o

f tr

ansp

lan

ts

Bilateral/Double Lung Transplant Single Lung Transplant

AT Def COPD IPF IPAH

ISHLT 2009

ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: (Transplants: January 1995 - June 2008)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 ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1995 - June 2008)(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 TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival Kaplan-Meier Survival (Transplants: January 1994 - June 2007)(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

AimAim

Whether single lung transplantation (SLTx) or Whether single lung transplantation (SLTx) or bilateral lung transplantation (BLTx) should be bilateral lung transplantation (BLTx) should be preferred for patients with end-stage pulmonary preferred for patients with end-stage pulmonary fibrosis and COPD remains unknown. fibrosis and COPD remains unknown.

The objective of this retrospective study was to The objective of this retrospective study was to analyze factors recorded in a prospective analyze factors recorded in a prospective database that are predictive fordatabase that are predictive for long-term long-term survival in our lung transplant cohorsurvival in our lung transplant cohort t

Patients and MethodsPatients and Methods

Between July 1991 and December 2009Between July 1991 and December 2009

329 LTx with COPD and Fibrotic patients, 329 LTx with COPD and Fibrotic patients,

193 M and 136 F, Mean age:54.5 years [23-69] 193 M and 136 F, Mean age:54.5 years [23-69]

COPD patients (n=226)COPD patients (n=226)– BLTx (65%)BLTx (65%)– SLTx (35%) SLTx (35%)

FFibrotic patients (n=103)ibrotic patients (n=103)– SLTx (56%) SLTx (56%) – BLTx (44%) BLTx (44%)

The overall 5 and 10-year survival rate was 65% and 51% for The overall 5 and 10-year survival rate was 65% and 51% for recipients with COPD and 57% and 41% recipients with recipients with COPD and 57% and 41% recipients with pulmonary fibrosis (p=0.09)pulmonary fibrosis (p=0.09)..

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

YearYear ALPHA-1 ALPHA-1 (N=2,085)(N=2,085)

CF CF (N=3,746)(N=3,746)

COPD COPD (N=8,812)(N=8,812)

IPF IPF (N=4,695)(N=4,695)

IPAH IPAH (N=1,065)(N=1,065)

SARCOIDOSIS SARCOIDOSIS (N=597)(N=597)

11 78.778.7 82.682.6 82.482.4 74.174.1 71.171.1 72.272.2

33 64.864.8 67.567.5 65.365.3 58.558.5 60.360.3 57.857.8

55 55.755.7 57.457.4 50.850.8 45.945.9 51.751.7 51.951.9

77 45.945.9 5050 38.538.5 35.435.4 44.544.5 43.543.5

1010 32.632.6 39.639.6 22.922.9 22.322.3 32.432.4 31.931.9

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

Note: Other comparisons are not statistically different.

ISHLT

2009

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

0

25

50

75

100

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

Years

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

Diagnosis: Emphysema/COPDDiagnosis: 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

Overall 5-year survival rate was higher after BLTX compared to Overall 5-year survival rate was higher after BLTX compared to SLTx in recipients with COPD (77% vs. 49%;SLTx in recipients with COPD (77% vs. 49%; p p < 0.001) < 0.001)

ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure TypeKaplan-Meier Survival by Procedure Type

(Transplants: January 1990 – June 2007)(Transplants: January 1990 – June 2007)

Diagnosis: Idiopathic Pulmonary FibrosisDiagnosis: Idiopathic Pulmonary Fibrosis

0

25

50

75

100

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

Years

Su

rviv

al (

%)

IPF/Single lung (N=3,054)

IPF/Double lung (N=1,640) N=66

N=27

p = 0.0004

N at risk at 5 years = 241

N at risk at 5 years = 659

ISHLT

2009

Overall 5-year survival rate wasOverall 5-year survival rate wasn’t n’t after BLTX compared to after BLTX compared to SLTxSLTx in recipients with in recipients with fibrosis (55% versus 56%; p=0.35) fibrosis (55% versus 56%; p=0.35)

Bilateral versus single lung transplantation Bilateral versus single lung transplantation was not a predictor of early (30 day) and was not a predictor of early (30 day) and late (60 day) mortality after LTx in late (60 day) mortality after LTx in recipients with COPD and pulmonary recipients with COPD and pulmonary fibrosis (fibrosis (pp>0.05). >0.05).

The length of the ICU stay in the bilateral The length of the ICU stay in the bilateral group was significantly longer after LTx in group was significantly longer after LTx in recipients with COPD (recipients with COPD (pp=0.03). =0.03).

ConclusionConclusion

Mortality, morbidity and long-term sMortality, morbidity and long-term survival urvival did not differ between BLTx vs SLTx in did not differ between BLTx vs SLTx in patients with pulmonary fibrosis.. patients with pulmonary fibrosis.. However, BLTx leads to better long-term However, BLTx leads to better long-term survival in recipients with COPD. SLTx survival in recipients with COPD. SLTx may result in fatal complications in the may result in fatal complications in the remaining native emphysematous lungremaining native emphysematous lung. .

Potential advantages for SSLTxPotential advantages for SSLTx

No more native lung presentNo more native lung present– Specific native lung problems may be avoidedSpecific native lung problems may be avoided

Acute Acute hhyperinflationyperinflation Chronic hyperinflation Chronic hyperinflation Infectıon Infectıon Effect of Effect of aaspergillus pneumonia native lung spergillus pneumonia native lung TTumour of the natıve lungumour of the natıve lung

Survival benefit (?)Survival benefit (?)– Early postoperativeEarly postoperative– Late: BOS developmentLate: BOS development– Better QOL and performance? Better QOL and performance?

Potential disadvantages Potential disadvantages

Increasing waiting listsIncreasing waiting lists– Why using two lungs if one may be sufficient?Why using two lungs if one may be sufficient?– Increasing waiting list mortalityIncreasing waiting list mortality