Overview of Lung Transplantation

Overview of Lung Transplantation

Luca Paoletti, MDAssistant Professor of Medicine

Medical University of South Carolina

Objectives

Define indications for lung transplantation Review guidelines for recipient selection for

lung transplantation Review surgical approaches for

transplantation Describe survival outcomes following

transplantation

Transplantation

IPFCF

History of Lung Transplantation

1963- First Transplant 1963-1981 over 40 attempted 1983- First long term successful lung

transplant 1990- First living donor transplant Early 2000’s - Double lung transplant

more common

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE

1985

1987

1989

1991

1993

1995

1997

1999

2001

2003

2005

2007

2009

0

500

1000

1500

2000

2500

3000

3500

4000

5 7 38 89204

450

758970

11601289

1412138915101547 1559

1700178419742012

2218

25692794

29202981

32783519

Total

Bilateral/Double Lung

Num

ber o

f Tra

nspl

ants

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 2012

J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

LUNG TRANSPLANTS Transplant Recipient Age by Year of Transplant

(Transplants: January 1, 1987 – June 30, 2011)

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

0%

20%

40%

60%

80%

100%

0

12

24

36

48

60

0-11 12-17 18-34 35-49 50-59 60-65 >65 Median AgeYear of Transplant

% o

f Tra

nspl

ants

Med

ian

reci

pien

t age

(yea

rs)

ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS (1/1985-6/2011)

18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 >650

5

10

15

20

Recipient Age

% o

f Tra

nspl

ants


DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS (1/1985-6/2011)

0-11 12-17 18-29 30-39 40-49 50-59 60-65 >650

5

10

15

20

25

30

35

Donor Age

% o

f Tra

nspl

ants


When to consider transplant

Untreatable, advanced stage lung disease

No other significant medical disease Limited life expectancy Poor quality of life Support system Must participate in rehab

J Heart Lung Transplant 2006. 25, 745-755

Absolute Contraindications Extrapulmonic disease HIV infection Malignancy within prior

2 years Hepatitis B antigen

positivity Hepatitis C biopsy

proven liver disease Severe Musculoskeletal

disease

Substance addiction in prior 6 months

Absence of reliable support system

Untreatable psychosocial problems

Non-compliance


Relative Contraindications

Age > 65 Critical or unstable

medical condition Systemic or

multisystem extrapulmonic disease

Pan resistant organisms

Symptomatic osteoporosis

Mechanical ventilation

BMI <17 or >30


Role of Rehab Pre-op

Dyspnea = inactivity = muscle weakness = difficulty with ADLs

Rehab = improvement in functional capacity

Rehab = comfort with staff pre and post Rehab = group therapy Rehab = assessment of patient and

their support

Role of Rehab post op

Continued muscle strengthening Continued endurance training Improvement in PFTs Improvement in 6MWT Prepares for home program

ADULT LUNG TRANSPLANTSIndications (Transplants: January 1995 - June 2011)

Diagnosis SLT (N = 13,271) BLT (N = 20,831) TOTAL (N = 34,102)COPD/Emphysema 6,048 ( 45.6% ) 5,539 ( 26.6% ) 11,587 ( 34.0% )Idiopathic Pulmonary Fibrosis 4,430 ( 33.4% ) 3,495 ( 16.8% ) 7,925 ( 23.2% )Cystic Fibrosis 219 ( 1.7% ) 5,469 ( 26.3% ) 5,688 ( 16.7% )Alpha-1 741 ( 5.6% ) 1,332 ( 6.4% ) 2,073 ( 6.1% )Idiopathic Pulmonary Arterial Hypertension 82 ( 0.6% ) 982 ( 4.7% ) 1,064 ( 3.1% )Pulmonary Fibrosis, Other 498 ( 3.8% ) 659 ( 3.2% ) 1,157 ( 3.4% )Bronchiectasis 54 ( 0.4% ) 891 ( 4.3% ) 945 ( 2.8% )Sarcoidosis 251 ( 1.9% ) 614 ( 2.9% ) 865 ( 2.5% )Re-Transplant: Obliterative Bronchiolitis 259 ( 2.0% ) 254 ( 1.2% ) 513 ( 1.5% )Connective Tissue Disease 140 ( 1.1% ) 281 ( 1.3% ) 421 ( 1.2% )Obliterative Bronchiolitis (Not Re-Transplant) 91 ( 0.7% ) 260 ( 1.2% ) 351 ( 1.0% )LAM 122 ( 0.9% ) 241 ( 1.2% ) 363 ( 1.1% )Re-Transplant: Not Obliterative Bronchiolitis 166 ( 1.3% ) 191 ( 0.9% ) 357 ( 1.0% )Congenital Heart Disease 45 ( 0.3% ) 248 ( 1.2% ) 293 ( 0.9% )Cancer 6 ( 0.0% ) 28 ( 0.1% ) 34 ( 0.1% )Other 119 ( 0.9% ) 347 ( 1.7% ) 466 ( 1.4% )


ADULT LUNG TRANSPLANTSMajor Indications By Year (Number)

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

0

250

500750

1,000

1,2501,5001,750

2,0002,2502,500

2,750CF IPF COPD Alpha-1 IPAH Re-Tx

Transplant Year

Num

ber o

f Tra

nspl

ants



COPD

Referral to transplant center:• BODE index of 5

Transplantation:• BODE index 7 – 10 or at least 1 of the following:

PaCO2 > 50mmHg Pulmonary hypertension or cor pulmonale despite O2

therapy FEV1 < 20% predicted and:

DLCO of less than 20% or homogenous emphysema on CT

J Heart Lung Transplant 2006;25:745–55.

BODE score

Variable Points on BODE Index 0 1 2 3

FEV1 (% predicted) ≥65 50-64 36-49 ≤35

6-Minute Walk Test (meters) ≥350 250-349 150-249 ≤149

MMRC Dyspnea

Scale0-1 2 3 4

Body Mass Index >21 ≤21

Idiopathic Pulmonary Fibrosis

Referral Histologic or radiographic evidence of UIP irrespective of

vital capacity Histologic evidence of fibrotic NSIP

Transplantation DLCO < 39% predicted 10% or greater decrease in FVC during 6 months of

follow-up A decrease in pulse oximetry below 88% during a 6-MWT Honeycombing on HRCT Reassess every 3 months


Cystic Fibrosis

Referral FEV1 < 30% predicted or a rapid decline in FEV1 Young, female patients refer early Exacerbation of pulmonary disease requiring ICU Increasing frequency of exacerbations requiring antibiotics Recurrent hemoptysis not controlled by embolization

Transplantation Oxygen-dependent respiratory failure Hypercapnia Pulmonary hypertension


Pulmonary Arterial Hypertension

Symptomatic progressive disease despite vasodilator treatment

WHO III-IV Right atrial pressure > 15mmHg Low or declining 6 minute walk test

Pre-transplant Evaluation

PFTs 6 minute walk test EKG Echocardiogram Cardiac cath HRCT

Chemistries LFTs Serologies- CMV,

HIV, Hepatitis, EBV V/Q scan Dexa scan GERD

Ideal Donor Selection Donor Age < 55 Smoking History < 20 pk/yrs No history of significant lung disease PaO2/FIO2 > 300 on PEEP of 5 cm H2O CXR clear BAL: No organisms on gram stain Normal endobronchial examination Absence of chest trauma ABO matched Size matched

Good vs. Bad

Bad

Donor Selection Donor Net Alert UNOS website• Potential donor evaluation

Absolutes• Blood type• Donor height• Serology

• HIV• Hepatitis

• Mucus• X-ray (pneumonia)• Antigens

Relative• PaO2 =• Bronchoscopy• Location• Smoking history• Laboratory

values

Provisional Yes

Conventional Mechanical Ventilation• Volume Control• Tidal Volume 8-10cc/kg OF ideal body

weight• Rate to achieve PCO2 35-45• PEEP of 5-8

Donor Ventilator Management

Prevent aspiration:• Inflate ETT cuff to 25 cm H20• Head of bed > 30 degrees

Airway Clearance• Bag ventilation and suction• Therapeutic Bronchoscopy

Donor Ventilator Management

Donor Selection:

Getting the Lungs

Lung Transplant Surgery

Sternotomy

Clamshell Incision

Thoracotomy

Cardiopulmonary Bypass

Anastomosis

Donor Lung

MUSC Team

OR

Possibly the futureEx Vivo Lung Perfusion

Costs

Varies from center to center Median cost in 2007: $140,000 Mean LOS -18 daysRemember… Annual infusion therapy for A1AT/Pulm

HTN is over $100,000

Organ Allocation

Organ Allocation Organ Allocation:

• Shall be based on sound medical judgment;• Shall seek to achieve the best use of donated organs;• Shall be designed to avoid wasting organs

Policies shall be designed to achieve equitable allocation of organs among patients by:• (1) Standardizing the criteria for determining suitable

transplant candidates• (2) Setting priority rankings

• These rankings shall be ordered from most to least medically urgent

Department of Health and Human Services

New Lung Allocation Scheme• Waitlist Urgency measure• Post-transplant survival measure• Transplant benefit (extra days of life) = post-transplant survival minus waitlist urgency• Normalize to scale of 1 - 100 = Lung Allocation Score (LAS)

LAS calculation

Diagnosis Age Height, Weight Diabetes Oxygen requirement 6MWT Functional Status

PA systolic pressure PA mean pressure PAOP Cr FVC Arterial CO2

Factors that Affect Outcomes

Donor Age Ischemia time Age of Recipient Diagnosis of Recipient Level of illness at transplant

ADULT LUNG TRANSPLANTSKaplan-Meier Survival

(Transplants: January 1994 - June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 160

25

50

75

100

Bilateral/Double Lung (N=19,566)Single Lung (N=13,276)All Lungs (N=32,842)

Years

Surv

ival

(%)

Double lung: 1/2-life = 6.7 Years; Conditional 1/2-life = 9.4 YearsSingle lung: 1/2-life = 4.6 Years; Conditional 1/2-life = 6.5 YearsAll lungs: 1/2-life = 5.5 Years; Conditional 1/2-life = 7.7 Years

p < 0.0001


ADULT LUNG TRANSPLANTSKaplan-Meier Survival by Era

(Transplants: January 1988 - June 2010)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 140

20

40

60

80

1001988-1995 (N=5,949)1996-2003 (N=12,632)2004-6/2010 (N=17,715)

Years

Surv

ival

(%)

N at risk = 1,055

N at risk = 192

N at risk = 5851988-1995: 1/2-life = 3.9 Years; Conditional 1/2-life = 7.0 Years1996-2003: 1/2-life = 5.3 Years; Conditional 1/2-life = 7.9 Years2004-6/2010: 1/2-life = 5.9 Years; Conditional 1/2-life = NA

1988-95 vs. 1996-2003: p < 0.00011988-95 vs. 2004-6/2010: p <0.0001 1996-2003 vs. 2004-6/2010: p <0.0001


Physiologic results

Near normal spirometry Improved gas exchange Single lung transplant• PFTs plateau at 3-6 months• Most perfusion goes to transplanted lung

Bilateral lung transplant• PFTs plateau at 6-9 months• Perfusion is equally split

ADULT LUNG RECIPIENTS Cross-Sectional Analysis

Functional Status of Surviving Recipients (Follow-ups: April 1994 – June 2011)

1 Year (N = 6,935) 3 Years (N = 4,448) 5 Years (N = 2,581)0%

20%

40%

60%

80%

100%

No Activity Limitations Performs with Assistance Total Assistance


ADULT LUNG RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: April 1994 – June 2011)

0%

20%

40%

60%

80%

100%

1 Year (N = 11,669)

3 Years (N = 7,276)

5 Years (N = 4,702)

Working (FT/PT Status unknown)

Working Part Time

Working Full Time

Retired

Not Working


Medications

Typically 10-15 different meds Take pills in AM and PM Take 3 different Immunosuppressants

POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 and 5 Years

Post-Transplant (Follow-ups: April 1994 - June 2008)

ISHLT

2009

ADULT LUNG TRANSPLANT RECIPIENTSCause of Death (Deaths: January 1992 – June 2011)

CAUSE OF DEATH 0-30 Days (N = 2,504)

31 Days - 1 Year

(N = 4,347)

>1 Year - 3 Years

(N = 3,910)

>3 Years - 5 Years

(N = 2,217)

>5 Years – 10 Years (N = 2,615)

>10 Years (N = 756)

BRONCHIOLITIS 8 (0.3%) 199 (4.6%) 1,018 (26.0%) 647 (29.2%) 659 (25.2%) 157 (20.8%)

ACUTE REJECTION 89 (3.6%) 77 (1.8%) 59 (1.5%) 11 (0.5%) 16 (0.6%) 1 (0.1%)

LYMPHOMA 1 (0.0%) 109 (2.5%) 82 (2.1%) 36 (1.6%) 60 (2.3%) 30 (4.0%)

MALIGNANCY, NON-LYMPHOMA 3 (0.1%) 117 (2.7%) 273 (7.0%) 218 (9.8%) 324 (12.4%) 90 (11.9%)

CMV 0 108 (2.5%) 38 (1.0%) 7 (0.3%) 4 (0.2%) 1 (0.1%)

INFECTION, NON-CMV 503 (20.1%) 1,561 (35.9%) 894 (22.9%) 434 (19.6%) 472 (18.0%) 127 (16.8%)

GRAFT FAILURE 652 (26.0%) 740 (17.0%) 727 (18.6%) 403 (18.2%) 466 (17.8%) 132 (17.5%)

CARDIOVASCULAR 268 (10.7%) 195 (4.5%) 154 (3.9%) 106 (4.8%) 133 (5.1%) 50 (6.6%)

TECHNICAL 262 (10.5%) 146 (3.4%) 35 (0.9%) 15 (0.7%) 25 (1.0%) 8 (1.1%)

OTHER 718 (28.7%) 1,095 (25.2%) 630 (16.1%) 340 (15.3%) 456 (17.4%) 160 (21.2%)

ISHLT 2012 Percentages represent % of deaths in the respective time period

J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

Referral to MUSC for Lung Transplantation Evaluation

Sarah Simon (843)792-4773 Email me at [email protected]

Documents

Overview of Lung Transplantation