1. Overview of Lung Transplantation
Luca Paoletti, MD
Assistant Professor of Medicine
Medical University of South Carolina

2. Objectives Define indications for lung transplantation
Review guidelines for recipient selection for lung transplantation
Review surgical approaches for transplantation
Describe survival outcomes following transplantation

3. Transplantation CF
IPF

5. History of Lung Transplantation
1963- First Transplant
over 40 attempted
1983- First long term successful lung transplant
1990- First living donor transplant
Early 2000’s - Double lung transplant more common
1963 – prisoner, lung cancer, renal disease, pneumonia. Lived 18 days with O2 sat of 98%, died of pneumonia and renal failure. No rejection noted

6. NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE
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):

7. LUNG TRANSPLANTS Transplant Recipient Age by Year of Transplant (Transplants: January 1, 1987 – June 30, 2011)
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

8. AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS (1/1985-6/2011)
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

9. DONOR AGE DISTRIBUTION FOR LUNG TRANSPLANTS (1/1985-6/2011)
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

10. 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
High risk of death over 2 years
J Heart Lung Transplant ,

11. 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 ,

12. 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 ,

13. 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
Muscle strengthening, endurance training, and education and weight loss
The repetitive contact facilitates a patient’s comfort level to analyze and ask questions that may have been left suppressed during physician visits.  The opportunity to meet and converse with other patients “in the same boat” allow the patient to build self efficacy and motivation (1). Following pulmonary rehabilitation, preoperative transplant patients become informed health care consumers.  During the preoperative phase, patients enrolled in pulmonary rehabilitation are able to improve their functional capacity (4). 

14. Role of Rehab post op Continued muscle strengthening
Continued endurance training
Improvement in PFTs
Improvement in 6MWT
Prepares for home program

15. ADULT LUNG TRANSPLANTS Indications (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% )
Transplants with unknown diagnoses are excluded from this tabulation.
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

16. ADULT LUNG TRANSPLANTS Major Indications By Year (Number)
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

17. J Heart Lung Transplant 2006. 25, 745-755

18. COPD Referral to transplant center: Transplantation: BODE index of 5
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
BODE index published NEJM 2004
BODE index of 7 – 10 predicts a 50% 3 year survival
BODE is BMI, degree of obstruction, Dyspnea score, 6 minute walk test
J Heart Lung Transplant 2006;25:745–55.

19. 6-Minute Walk Test (meters)
BODE score
Variable
Points on BODE Index 1 2 3
FEV1 (% predicted)
≥65
50-64
36-49
≤35
6-Minute Walk Test (meters)
≥350
≤149
MMRC Dyspnea Scale
0-1 4
Body Mass Index
>21
≤21

20. 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.

21. 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.

22. Pulmonary Arterial Hypertension
Symptomatic progressive disease despite vasodilator treatment
WHO III-IV
Right atrial pressure > 15mmHg
Low or declining 6 minute walk test

23. 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

24. 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

25. Good vs. Bad

26. Bad

27. Donor Selection Donor Net Alert UNOS website
Potential donor evaluation
Absolutes
Blood type
Donor height
Serology
HIV
Hepatitis
Mucus
X-ray (pneumonia)
Antigens
Provisional Yes
Relative
PaO2 =
Bronchoscopy
Location
Smoking history
Laboratory values

28. Donor Ventilator Management
Conventional Mechanical Ventilation
Volume Control
Tidal Volume 8-10cc/kg OF ideal body weight
Rate to achieve PCO
PEEP of 5-8

29. 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

30. Donor Selection:

31. Getting the Lungs

32. Lung Transplant Surgery

33. Sternotomy

35. Clamshell Incision

37. Thoracotomy

39. Cardiopulmonary Bypass

40. Anastomosis

41. Donor Lung

42. MUSC Team

45. OR

46. Possibly the future Ex Vivo Lung Perfusion
Lung transplantation has become the mainstay of therapy for patients suffering from end-stage lung disease refractory to medical management. However, the number of patients listed for lung transplantation largely exceeds the donors available. Currently only 15 to 20% of the lungs that are offered from brain dead donors are used; while 80% of the remaining donor lungs are rejected by the transplant programs primarily due to “Poor Organ Function.”
Normothermic ex vivo lung perfusion (EVLP), assessment and evaluation of poorly functioning donor lungs permits a more rational utilization of potentially acceptable organs which are currently often discarded despite the relatively reversible nature of their imperfections. The ultimate objective of the EVLP procedure is to expand the donor organ pool and thus reduce or possibly eliminate mortality and morbidity on the transplant waiting list.
EVLP with STEEN Solution™ will help increase the pool of available organs by allowing assessment of marginal lungs in optimized conditions. Several mechanisms contribute to this:
1. The warming and reperfusion period allows time for the lung to re-establish its normal condition in an optimized and safer environment. The ex vivo perfusion is carefully controlled using a lung-protective strategy.
2. The physiological problems caused by neurogenic pulmonary edema in the organ donor with respect to electrolytic balance, colloid-osmotic pressure and temperature are restored during this protective reperfusion period.
3. Any remaining donor blood still in the lungs (containing coagulation factors, complement, activated white cells, inflammatory cytokines and non-physiological substances, including drugs used during donor management) is diluted and filtered away during the EVLP. This washing out benefit is not achieved with current hypothermic perfusion as the cold temperature induces vascular constriction within the lung, preventing complete flushing.
4. It facilitates removal of clots in the pulmonary circulation through the use of transient retrograde perfusion at the beginning of the procedure.
5. The ex vivo system provides an excellent environment for recruitment and re-expansion of atelectatic lung areas.
6. It allows time to assess and clean/suction bronchial secretions.
7. It allows for all ventilatory volumes and pressures to be transferred directly to the lungs without interference of the chest wall and diaphragm.
8. The dextran in the perfusate solution facilitates perfusion of the pulmonary micro-vasculature

50. 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

51. Organ Allocation

52. 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
Department of Health and Human Services

53. 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 = Lung Allocation Score (LAS)
LAS was initiated, prioritizing patients on the basis of the risk of death on the waiting list (urgency) and the chance of surviving 1 year after transplant (utility) (17). Accordingly, the LAS is, in part, a score based on severity of illness, which may have a significant impact on the characteristics of patients transplanted and survival outcomes

54. LAS calculation Diagnosis Age Height, Weight Diabetes
Oxygen requirement
6MWT
Functional Status
PA systolic pressure
PA mean pressure
PAOP Cr
FVC
Arterial CO2

55. Approximately 1800 people awaiting lung transplant as of October 21, 2010
Advantages of this newer system for the United States include greater efficiency in organ placement, so that fewer offers need to be made before organs are accepted for use; shorter waiting list of active patients; an apparent reduction in waiting time to transplantation; and an early indication of reduced waiting list mortality. The system clearly identifies some of the patients who are sicker and more in need of urgent transplants, yet reported survival has not been negatively impacted

57. Factors that Affect Outcomes
Donor Age
Ischemia time
Age of Recipient
Diagnosis of Recipient
Level of illness at transplant

58. ADULT LUNG TRANSPLANTS Kaplan-Meier Survival (Transplants: January 1994 - June 2010)
Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients.
The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period.
Survival rates were compared using the log-rank test statistic. A significant p-value means that at least one of the groups is different than the others but it doesn’t identify which group it is.
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

59. ADULT LUNG TRANSPLANTS Kaplan-Meier Survival by Era (Transplants: January 1988 - June 2010)
vs : p <
vs /2010: p <0.0001
vs /2010: p <0.0001
Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients.
The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period.
Survival rates were compared using the log-rank test statistic. No adjustments were made for multiple comparisons.
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

60. 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

61. ADULT LUNG RECIPIENTS Cross-Sectional Analysis Functional Status of Surviving Recipients (Follow-ups: April 1994 – June 2011)
This figure shows the functional status reported on the 1-year, 3-year and 5-year annual follow-ups. Because all follow-ups between April 1994 and June 2011 were included, the bars do not include the same patients.
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

62. ADULT LUNG RECIPIENTS Employment Status of Surviving Recipients (Follow-ups: April 1994 – June 2011)
This figure shows the employment status reported on the 1-year, 3-year and 5-year annual follow-ups. Because all follow-ups between April 1994 and June 2011 were included, the bars do not include the same patients.
ISHLT
2012
J Heart Lung Transplant.  2012 Oct; 31(10):

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

65. POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 and 5 Years Post-Transplant (Follow-ups: April June 2008)
This table shows the percentage of patients experiencing various morbidities as reported on the 1-year annual follow-up form and within 5 years following transplantation. The percentages are based on patients with known responses. To reduce bias, only patients with responses reported on every follow-up through the 5-year annual follow-up were included in the 5-year analysis. Because the outcomes are reported to be unknown at different rates the number with known responses for each outcome are also provided.
ISHLT
2009

66. ADULT LUNG TRANSPLANT RECIPIENTS Cause of Death (Deaths: January 1992 – June 2011)
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
108 (2.5%)
38 (1.0%)
7 (0.3%)
4 (0.2%)
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%)
Only known causes of death are included in the tabulation.
ISHLT
2012
Percentages represent % of deaths in the respective time period
J Heart Lung Transplant.  2012 Oct; 31(10):

67. Referral to MUSC for Lung Transplantation Evaluation
Sarah Simon (843)
me at