1. Lung Transplantation Biology
Robert Padera, M.D., Ph.D.
HBTM 235
September 23, 2015

2. Goal
To teach you everything something about the many facets of lung transplantation

3. Outline Introduction The recipient The donor The transplant
The complications
Outcomes

4. NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE
This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. Therefore, these numbers should not be interpreted as the rate of change in lung procedures performed worldwide.
2010
ISHLT
J Heart Lung Transplant Oct; 29 (10):
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.

5. AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS (1/1985-6/2009)
2010
ISHLT
J Heart Lung Transplant Oct; 29 (10):

6. Outline Introduction The recipient The donor The transplant
The complications
Outcomes

7. The Recipient Respiratory failure of lung origin
Idiopathic pulmonary fibrosis/UIP
COPD/Emphysema
Cystic fibrosis
Primary pulmonary hypertension
Alpha-1 antitrypsin deficiency
Others
All other options exhausted

8. ADULT LUNG TRANSPLANTATION Major Indications By Year (Number)
2010
ISHLT
J Heart Lung Transplant Oct; 29 (10):

9. Usual Interstitial Pneumonia
Also known as idiopathic pulmonary fibrosis
UIP adds cells and fibrous tissue (scar) to the lung, thickening and stiffening it and restricting the elastic stretching, making inspiration harder
Manifestations include:
Decreased compliance – stiff lung
Decreased lung volumes – spirometry measurements
Impaired diffusion - DLCO measurement
Abnormal small airway function
Pulmonary hypertension

10. UIP - Gross
Honeycombing, most severe/earliest in lower zones, subpleural areas

11. UIP - Microscopic
End-stage lung
Normal lung
Fibroblastic foci

12. Emphysema

13. Cystic Fibrosis

14. Evaluation of Candidacy
Blood tests
Nicotine/cotine (6 months)
Blood type (ABO)
Tissue typing (HLA – major histocompatibility complex)
Infection/immunity
General hematology/chemistry
Imaging tests
Chest X-ray, chest computed tomography (CT)
Pulmonary function tests
Spirometry, 6 minute walk
Cardiac tests
EKG, coronary angiography, echocardiography

15. 15

16. Outline Introduction The recipient The donor The transplant
The complications
Outcomes

17. Donor Characteristics
Brain death
Medical history
Transmissible entities: infections, malignancy
Willingness to be organ donor
Imaging
Pneumonia, hemorrhage, underlying lung disease, pulmonary emboli, etc.
Function?

18. Ex Vivo Lung Perfusion Preservation during transport Evaluation
Treatment

19. Outline Introduction The recipient The donor The transplant
The complications
Outcomes

20. Procedure Multiorgan harvest Removed from donor Transport to recipient
Implantation and anastomosis
Bronchus
Pulmonary artery
Pulmonary veins

21. Lung Anatomy Vasculature21

22. Outline Introduction The recipient The donor The transplant
The complications
Outcomes

23. Rejection Hyperacute ABO mismatch Acute cellular HLA mismatch
Antibody mediated
Developed
Chronic

24. Acute Rejection
Vascular
Airway

25. Chronic Rejection
Vascular
Airway

26. Post-transplant Medications
30-40 pills/day
Immunosuppressants
Cyclosporine
Mycophenolate
Prednisone
Antibiotics
PCP, CMV
Vitamins/minerals

27. Infection Increased risk from Immunosuppression
Cytomegalovirus
Increased risk from
Immunosuppression
Cough reflex diminished
Mucociliary clearance impaired
Opportunistic infections common
Pneumocystis jiroveci
Aspergillus

28. Outline Introduction The recipient The donor The transplant
The complications
Outcomes

29. ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 – June 2008)
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.
2010
ISHLT
J Heart Lung Transplant Oct; 29 (10):

30. ADULT LUNG RECIPIENTS Employment Status of Surviving Recipients (Follow-ups: April 1994 – June 2009)
This figure shows the employment status reported on the 1-year, 3-year, 5-year and 10-year annual follow-ups. Because all follow-ups between April 1994 and June 2009 were included, the bars do not include the same patients.
2010
ISHLT
J Heart Lung Transplant Oct; 29 (10):

31. ADULT LUNG TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death (Deaths: January June 2009)
Only known causes of death are included in the tabulation.
2010
ISHLT
J Heart Lung Transplant Oct; 29 (10):