overview of lung transplantation luca paoletti, md assistant professor of medicine medical...
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Overview of Lung Transplantation
Luca Paoletti, MD
Assistant 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
758
9701160
128914121389
15101547 1559
17001784
19742012
2218
2569
279429202981
3278
3519
Total
Bilateral/Double Lung
Nu
mb
er
of
Tra
ns
pla
nts
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 Age
Year of Transplant
% o
f T
ran
sp
lan
ts
Me
dia
n r
ec
ipie
nt
ag
e (
ye
ars
)
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 T
ran
sp
lan
ts
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
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 T
ran
sp
lan
ts
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
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
J Heart Lung Transplant 2006. 25, 745-755
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
J Heart Lung Transplant 2006. 25, 745-755
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% )
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
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
500
750
1,000
1,250
1,500
1,750
2,000
2,250
2,500
2,750CF IPF COPD Alpha-1 IPAH Re-Tx
Transplant Year
Nu
mb
er
of
Tra
ns
pla
nts
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
J Heart Lung Transplant 2006. 25, 745-755
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
J Heart Lung Transplant 2006;25:745–55.
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
J Heart Lung Transplant 2006;25:745–55.
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 days
Remember… 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
Su
rviv
al (
%)
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
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
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
Su
rviv
al (
%)
N at risk = 1,055
N at risk = 192
N at risk = 585
1988-1995: 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
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
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
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
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
ISHLT 2012J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095
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]