Lung Transplant for Interstitial Lung Disease

Lung Transplant for Interstitial Lung Disease

Isabel Neuringer, MD

Living with IPF Patient SymposiumSeptember 15, 2012

[email protected]

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Diffuse Lung Parenchymal Diseases

• Heterogeneous disorders• Auto-immune disease, environmental/

exposure• 30-40% idiopathic• Prevalence ~ 70 per 100,000• Median survival ~ 3-5 years• If disease progresses – lung

transplantation remains an appropriate treatment

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Lung Transplantation for ILD• 1983 Toronto Lung Transplant Group performed

1st single lung transplant on a patient with idiopathic pulmonary fibrosis

• Now ~ 3000 lung transplants performed per year for all end-stage lung diseases

• Lung transplant for IPF has been increasing• IPF and diffuse parenchymal diseases now >

50% of all transplants in US• ~ 7000 lung transplants performed for IPF

between 1995 - 2010

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NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE

0

500

1000

1500

2000

2500

3000

3500

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

3272

297229172791

2567

2216

20081971

17831699

15591548150913891411

12911160

972

758

449

204893875

Num

ber o

f tra

nspl

ants

Single LungBilateral/Double LungTotal

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

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

0

5.0000

10.0000

15.0000

20.0000

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

% o

f tr

ansp

lant

s

Recipient Age


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ADULT LUNG TRANSPLANTATIONMajor Indications By Year (Number)

0

17.50

35.00

52.50

70.00

Myopathy CAD

198219831984198519861987198819891990199119921993199419951996

0

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

Num

ber o

f tra

nspl

ants

Transplant Year

CF IPF COPD Alpha-1 IPAH Re-Tx


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Lung Transplantation for ILD

• 3 potential types of procedures: heart/lung, double lung, single lung

• Heart/lung transplantation 1980s now uncommon

• Double lung – if chronic suppurative infection or if pulmonary hypertension, will lessen graft dysfunction upon implantation

• Increasing trend for double lung transplant • Increased mortality on wait list

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ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type

(Transplants: January 1990 – June 2009)Diagnosis: Idiopathic Pulmonary Fibrosis

0

20.0000

40.0000

60.0000

80.0000

100.0000

0 3 6 9 12 15

Surv

ival

(%)

Years

IPF/Single lung (N=3,947)IPF/Double lung (N=2,529)N at risk (IPF/Single lung)N at risk (IPF/Double lung)

N=36

N=19

p < 0.0001

N at risk at 5 years = 430

N at risk at 5 years = 912


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Contra-indications for Lung Transplantation

• Malignancy/cancer within 2 years• Untreatable dysfunction of other organ

system• Chronic incurable extra-pulmonary

infection• Chest deformity• Non-adherence• Substance addiction –tobacco, alcohol,

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Relative Contra-indications for Lung Transplantation

• Age ? • Severely limited functional status• Colonization with resistant bacteria, fungi,

mycobacteria• Body mass index > 30 kg/m2• Mechanical ventilation• Other medical comorbidities – need to be

optimized – diabetes, hypertension, gastroesophageal reflux, coronary artery disease

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• Early evaluation • Progression of disease can be

unpredictable• More difficult to accomplish urgent/

emergent work-up when critically ill• Patients expected to participate in

pulmonary rehab program• Medical and psychosocial assessment

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• Risk factors and prognoses unique to ILD patients awaiting transplant– Fibrosis score on chest CT scan– Pulmonary function testing may not always

correlate with outcome– 10% decline forced vital capacity identifies

high risk – Drop in oxygen with exercise– “Acute exacerbations”

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• Improved peri-operative outcomes• Improved donor management, operative

techniques, critical care • Cardiopulmonary techniques to manage

critically ill patients• Patients often sicker at time transplant in

current era

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• Lung allocated by blood group, size• Lung Allocation Score (LAS)

– DOB, height, weight– Diagnosis– Functional status, six minute walk distance– Diabetes, kidney tests– Ventilation, supplemental oxygen, breathing

tests, carbon dioxide– Pulmonary artery pressure

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• Transplant team members– surgeon (MD)– pulmonologist (MD)– coordinators (RN, NP, PA)– psychologist– social worker– infectious diseases (MD)– financial coordinator– transplant administrators

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• Extensive testing – blood counts – kidney and liver function – CT scan of chest and abdomen – perfusion scanning – right and left heart catheterization – serologies to common viruses – CMV, EBV– blood types, antibodies to donor proteins

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• Recovery – Intensive care unit (ICU) with breathing tube,

ventilator and chest tubes– Regular hospital ward – nutrition, airway

clearance, incentive spirometer, chest tubes– Education about medical regimen and active

learning about self-care– Length of stay may vary anticipate 14-21 days

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• Primary Graft Dysfunction– Early re-implantation and perfusion– Cold preservation solution to warm re-

perfusion– Reactive oxygen – Severity graded by oxygenation– Higher incidence in ILD and high pulmonary

circulation pressures

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Lung Transplantation for ILD• Early events –

– Infection – hospitalization, donor, community– Anti-viral and anti-fungal prophylaxis

• Life-long immunosuppression– Deplete immune cells at the time of transplant– Steroids– Calcineurin inhibitor (tacrolimus or cyclosporin)– Anti-metabolite (azathioprine or mycophenolate

mofetil)

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http://pharmaceuticals.indiabizclub.com/catalog/261604~mycepttm+(mycophenolate+mofetil)~new+delhi


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Lung Transplant for ILD• Acute rejection

– Present with cough, fatigue, shortness of breath– 30-40 % within 1st year– Acute rejection - foreign proteins on the donor lungs

and the recipient’s immune system response– Diagnosed with tissue sample read by pathologist– Treat acute rejection with steroids– If persistent, add stronger biological therapy to

deplete immune cells

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Lung Transplant for ILD

• Chronic lung allograft dysfunction– Recipient response to donor lungs over time

causing scarring– ~ 45 % of patients develop by 5 years time– Diagnosed by following pulmonary function

testing– Multiple causes – repeated acute rejection,

antibodies to the donor lungs, chronic aspiration, responses to viral infections

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• Long term complications– Chronic lung allograft rejection– Kidney insufficiency and high blood pressure– Diabetes– Anemia– Skin cancers and post-transplant lymphoma– Osteoporosis

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

0

25.0000

50.0000

75.0000

100.0000

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)Number at risk (bilateral/double)Number at risk (single)Number at risk(all)

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

Surv

ival

(%)


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ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2009)

0

20.0000

40.0000

60.0000

80.0000

100.0000

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

Years

18-34 (N = 5,523)35-49 (N = 7,980)50-59 (N = 11,389)60-65 (N = 5,685)>65 (N = 1,217)N at risk (18-34)N at risk (35-49)N at risk (50-59)N at risk (60-65)N at risk (66+)

Survival comparisonsAll p-values significant at p < 0.0001 except 18-34 vs. 35-49: p =0.1708

HALF-LIFE 18-34: 6.4 Years; 35-49: 6.7 Years; 50-59: 5.3 Years; 60-65: 4.4 Years; >65: 3.5 Years

Surv

ival

(%)


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ADULT LUNG RECIPIENTSCross-Sectional Analysis

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

0%

25%

50%

75%

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


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Lung Transplantation for ILD• Heterogeneous disease• Difficult to predict timing of transplant• IPF now > 50 % of lung transplants• Early referral best• Keep in shape, wear oxygen, exercise, nutrition• Support groups• Education• THANK YOU !!

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Lung Transplant for Interstitial Lung Disease

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