1. Advances in Lung Transplantation: A Patient Guide David J. Lederer, M.D., M.S. Assistant Professor of Medicine New York Presbyterian Lung Transplant Program Columbia University College of Physicians and Surgeons

2. Outline The past The past History of Transplantation History of Transplantation The present The present Recent Advances Recent Advances The future The future Current Research at Columbia Current Research at Columbia

3. History of Lung Transplantation The Past

4. History of Lung Transplantation 1963 1963 First attempt at lung transplantation First attempt at lung transplantation Patient lived for 18 days Patient lived for 18 days 1960s – early 1980s: 1960s – early 1980s: 45 attempts at lung transplantation 45 attempts at lung transplantation Longest survivor: 10 months Longest survivor: 10 months

5. History of Lung Transplantation 1982 1982 First report of long-term success (heart-lung) First report of long-term success (heart-lung) 1986 1986 First successful double lung transplantation First successful double lung transplantation Both lungs together attached at the trachea Both lungs together attached at the trachea 1989 1989 First successful double lung transplantation First successful double lung transplantation One lung at a time One lung at a time

6. NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE 15 48 89 192 415 706 908 1079 1202 1323 1340 1472 1450 1478 1552 1599 1725 1699 ISHLT 2006 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. 1815 J Heart Lung Transplant 2006;25:880-892

7. ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 – June 2004) Survival comparisons by era 1988-94 vs. 1995-99: p = 0.0294 1988-94: vs. 2000-6/03: p <0.0001 1995-99 vs. 2000-6/03: p <0.0001 ISHLT 2006 J Heart Lung Transplant 2006;25:880-892

8. Question: Why don’t people live longer after a lung transplant?

9. Answer: There are complications after transplantation Infection Infection Rejection Rejection Acute rejection Acute rejection Chronic rejection (BOS) Chronic rejection (BOS) Cancer Cancer Heart disease Heart disease

10. Question: How can we help prevent and treat these problems?

11. Answer: Patients: Patients: Take your medicine Take your medicine Adhere to lifestyle recommendations Adhere to lifestyle recommendations Call us immediately with any new problems Call us immediately with any new problems Doctors: Doctors: Do all that stuff, and Do all that stuff, and Study new treatments Study new treatments

12. Recent Advances in Lung Transplant Care The Present

13. FACT 1 out of 2 lung transplant patients develop chronic rejection (also called BOS) within 5 years of transplantation 1 out of 2 lung transplant patients develop chronic rejection (also called BOS) within 5 years of transplantation There are very few treatments for BOS There are very few treatments for BOS

14. NEW STUDY Inhaled cyclosporine Inhaled cyclosporine The active ingredient in Neoral The active ingredient in Neoral May cut the risk of chronic rejection by half! May cut the risk of chronic rejection by half! Preliminary study Preliminary study Small study at one center Small study at one center Inhaled cyclosporine is not available (Don’t try this at home!!!) Inhaled cyclosporine is not available (Don’t try this at home!!!)

15. NEW STUDY Everolimus Everolimus A new immunosuppresant A new immunosuppresant May help prevent chronic rejection May help prevent chronic rejection 10% lower risk in the first year 10% lower risk in the first year Preliminary study Preliminary study No difference in chronic rejection after 1 year No difference in chronic rejection after 1 year

16. NEW STUDIES Azithromycin (Zithromax) Azithromycin (Zithromax) May slow the progression of chronic rejection May slow the progression of chronic rejection Preliminary studies only Preliminary studies only No “randomized” studies yet No “randomized” studies yet Randomized studies provide the strongest evidence in favor or against new treatments. Randomized studies provide the strongest evidence in favor or against new treatments.

17. FACT Bone health gets worse after transplantation Bone health gets worse after transplantation 3 out of 4 lung transplant patients have osteoporosis!! 3 out of 4 lung transplant patients have osteoporosis!!

18. NEW STUDY Resistance exercise Resistance exercise Helps improve bone density Helps improve bone density Should be done with medication Should be done with medication Fosamax, Boniva, etc. Fosamax, Boniva, etc. Doesn’t have to end with rehab ends Doesn’t have to end with rehab ends Keep exercising! Keep exercising!

19. That’s it?!

20. What you can do Write to your representative and senators Write to your representative and senators Increase National Institutes of Health funding!! Increase National Institutes of Health funding!! Consider participation in research studies Consider participation in research studies We owe everything we know about medicine to patients who volunteer in research studies. We owe everything we know about medicine to patients who volunteer in research studies. Ask your pulmonologist and lung transplant doctor about research studies!!! Ask your pulmonologist and lung transplant doctor about research studies!!!

21. Key Concepts about Research Do no harm Do no harm 100% voluntary 100% voluntary “Informed consent” “Informed consent” Experimental therapy!!! Experimental therapy!!!

22. Current Research Studies at Columbia The Future

23. Ongoing studies at Columbia: Before Transplantation Viagra for COPD/emphysema Viagra for COPD/emphysema 9 week study for patients with emphysema 9 week study for patients with emphysema 4 weeks of Viagra 4 weeks of Viagra 4 weeks of placebo 4 weeks of placebo 1 week with no pills 1 week with no pills We are trying to see if Viagra helps breathing We are trying to see if Viagra helps breathing Men and women are eligible Men and women are eligible

24. Ongoing studies at Columbia: Before Transplantation Bronchial fenestration for COPD/emphysema (EASE study) Bronchial fenestration for COPD/emphysema (EASE study) Bronchoscopic procedure Bronchoscopic procedure Like a lung volume reduction without surgery Like a lung volume reduction without surgery Decompress big lungs Decompress big lungs

25. Ongoing studies at Columbia: Before Transplantation Aspirin and Simvastatin for Pulmonary Hypertension Aspirin and Simvastatin for Pulmonary Hypertension We are studying these drugs as treatments for pulmonary hypertension We are studying these drugs as treatments for pulmonary hypertension This is the 1 st NIH-funded clinical trial in pulmonary hypertension This is the 1 st NIH-funded clinical trial in pulmonary hypertension

26. Ongoing studies at Columbia: Before Transplantation Pirfenidone for Pulmonary Fibrosis Pirfenidone for Pulmonary Fibrosis Treatment trial of pirfenidone Treatment trial of pirfenidone Enrollment is closed Enrollment is closed

27. Ongoing studies at Columbia: After Transplantation Genetic Analysis to Predict Rejection of Lung Transplants (LARGO) Genetic Analysis to Predict Rejection of Lung Transplants (LARGO) This study is looking for a blood test to diagnose rejection This study is looking for a blood test to diagnose rejection Might save people from having bronchoscopies in the future!! Might save people from having bronchoscopies in the future!!

28. Ongoing studies at Columbia: After Transplantation Evaluating the Safety and Efficacy of Intravenous Immunoglobulin Evaluating the Safety and Efficacy of Intravenous Immunoglobulin We are studying whether an infusion of IVIG helps prevent infections after transplantation We are studying whether an infusion of IVIG helps prevent infections after transplantation

29. Ongoing studies at Columbia: After Transplantation Genetic Predictors of Primary Graft Dysfunction after Lung Transplant Genetic Predictors of Primary Graft Dysfunction after Lung Transplant 10-20% of the time, the lungs don’t work right away after transplantation. 10-20% of the time, the lungs don’t work right away after transplantation. We are trying to predict who will develop this complication We are trying to predict who will develop this complication This study will lead to studies of new treatments for this complication This study will lead to studies of new treatments for this complication

30. Summary We’ve come a long way… We’ve come a long way… But there is a long way to go. But there is a long way to go. New treatments are on the horizon New treatments are on the horizon Consider enrolling in research studies Consider enrolling in research studies Be fully informed Be fully informed Understand the risks Understand the risks 100% voluntary 100% voluntary