Advances in Lung Transplantation: Advances in Lung Transplantation: A Patient GuideA 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

OutlineOutline

The past The past History of TransplantationHistory of Transplantation

The present The present Recent AdvancesRecent Advances

The future The future Current Research at ColumbiaCurrent Research at Columbia

History of Lung History of Lung TransplantationTransplantation

The PastThe Past

History of Lung TransplantationHistory of Lung Transplantation

19631963 First attempt at lung transplantationFirst attempt at lung transplantation Patient lived for 18 daysPatient lived for 18 days

1960s – early 1980s:1960s – early 1980s: 45 attempts at lung transplantation45 attempts at lung transplantation Longest survivor: 10 monthsLongest survivor: 10 months

History of Lung TransplantationHistory of Lung Transplantation

19821982 First report of long-term success (heart-lung)First report of long-term success (heart-lung)

19861986 First successful double lung transplantationFirst successful double lung transplantation Both lungs together attached at the tracheaBoth lungs together attached at the trachea

19891989 First successful double lung transplantationFirst successful double lung transplantation One lung at a timeOne lung at a time

NUMBER OF LUNG TRANSPLANTS REPORTED NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPEBY YEAR AND PROCEDURE TYPE

0

200

400

600

800

1000

1200

1400

1600

1800

Nu

mb

er o

f T

ran

spla

nts

Bilateral/Double LungSingle Lung

15 15 48 89192

415

706

908

1079

12021323

13401472

14501478

15521599

17251699

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

ADULT LUNG TRANSPLANTATIONADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Era Kaplan-Meier Survival by Era (Transplants: January 1988 – June 2004)(Transplants: January 1988 – June 2004)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10

Years

Su

rviv

al (

%)

.

1988-1994 (N=4,345)1995-1999 (N=6,668)2000-6/2004 (N=7,217)

1988-1994: 1/2-life = 3.9 Years; Conditional 1/2-life = 7.0 Years1995-1999: 1/2-life = 4.5 Years; Conditional 1/2-life = 7.0 Years2000-6/2004: 1/2-life = 5.0 Years; Conditional 1/2-life = 5.3 Years

Survival comparisons by era1988-94 vs. 1995-99: p = 0.02941988-94: 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

Question: Question:

Why don’t people live longer Why don’t people live longer after a lung transplant?after a lung transplant?

Answer: There are complications Answer: There are complications after transplantationafter transplantation

InfectionInfection RejectionRejection

Acute rejectionAcute rejection Chronic rejection (BOS)Chronic rejection (BOS)

CancerCancer Heart diseaseHeart disease

Question: Question:

How can we help prevent and How can we help prevent and treat these problems?treat these problems?

Answer: Answer:

Patients:Patients: Take your medicineTake your medicine Adhere to lifestyle recommendationsAdhere to lifestyle recommendations Call us immediately with any new Call us immediately with any new

problemsproblems Doctors:Doctors:

Do all that stuff, andDo all that stuff, and Study new treatmentsStudy new treatments

Recent Advances in Recent Advances in Lung Transplant CareLung Transplant Care

The PresentThe Present

FACTFACT

1 out of 2 lung transplant patients 1 out of 2 lung transplant patients develop chronic rejection (also called develop chronic rejection (also called BOS) within 5 years of BOS) within 5 years of transplantationtransplantation

There are very few treatments for There are very few treatments for BOSBOS

NEW STUDYNEW STUDY

Inhaled cyclosporineInhaled cyclosporine The active ingredient in NeoralThe active ingredient in Neoral May cut the risk of chronic rejection by May cut the risk of chronic rejection by

half! half! Preliminary studyPreliminary study

Small study at one centerSmall study at one center Inhaled cyclosporine is not available (Don’t Inhaled cyclosporine is not available (Don’t

try this at home!!!)try this at home!!!)

NEW STUDYNEW STUDY

EverolimusEverolimus A new immunosuppresantA new immunosuppresant May help prevent chronic rejectionMay help prevent chronic rejection

10% lower risk in the first year 10% lower risk in the first year Preliminary studyPreliminary study

No difference in chronic rejection after 1 No difference in chronic rejection after 1 yearyear

NEW STUDIESNEW STUDIES

AzithromycinAzithromycin (Zithromax) (Zithromax) May slow the progression of chronic May slow the progression of chronic

rejectionrejection Preliminary studies onlyPreliminary studies only No “randomized” studies yetNo “randomized” studies yet

Randomized studies provide the strongest Randomized studies provide the strongest evidence in favor or against new treatments.evidence in favor or against new treatments.

FACTFACT

Bone health gets worse after Bone health gets worse after transplantationtransplantation

3 out of 4 lung transplant patients 3 out of 4 lung transplant patients have osteoporosis!!have osteoporosis!!

NEW STUDYNEW STUDY

Resistance exerciseResistance exercise Helps improve bone density Helps improve bone density Should be done with medicationShould be done with medication

Fosamax, Boniva, etc.Fosamax, Boniva, etc. Doesn’t have to end with rehab endsDoesn’t have to end with rehab ends

Keep exercising!Keep exercising!

That’s it?!That’s it?!

What you can doWhat you can do

Write to your representative and senatorsWrite to your representative and senators Increase National Institutes of Health funding!!Increase National Institutes of Health funding!!

Consider participation in research studiesConsider participation in research studies We owe everything we know about medicine to We owe everything we know about medicine to

patients who volunteer in research studiespatients who volunteer in research studies.. Ask your pulmonologist and lung transplant doctor Ask your pulmonologist and lung transplant doctor

about research studies!!!about research studies!!!

Key Concepts about ResearchKey Concepts about Research

Do no harmDo no harm100% voluntary100% voluntary““Informed consent”Informed consent”Experimental therapy!!!Experimental therapy!!!

Current Research Studies at Current Research Studies at ColumbiaColumbia

The FutureThe Future

Ongoing studies at Columbia: Ongoing studies at Columbia: Before TransplantationBefore Transplantation

Viagra for COPD/emphysemaViagra for COPD/emphysema 9 week study for patients with emphysema9 week study for patients with emphysema

4 weeks of Viagra4 weeks of Viagra 4 weeks of placebo4 weeks of placebo 1 week with no pills1 week with no pills

We are trying to see if Viagra helps We are trying to see if Viagra helps breathingbreathing

Men and women are eligibleMen and women are eligible

Ongoing studies at Columbia: Ongoing studies at Columbia: Before TransplantationBefore Transplantation

Bronchial fenestration for Bronchial fenestration for COPD/emphysema (EASE study)COPD/emphysema (EASE study) Bronchoscopic procedureBronchoscopic procedure Like a lung volume reduction without Like a lung volume reduction without

surgerysurgery Decompress big lungsDecompress big lungs

Ongoing studies at Columbia: Ongoing studies at Columbia: Before TransplantationBefore Transplantation

Aspirin and Simvastatin for Pulmonary Aspirin and Simvastatin for Pulmonary HypertensionHypertension We are studying these drugs as We are studying these drugs as

treatments for pulmonary hypertensiontreatments for pulmonary hypertension This is the 1This is the 1stst NIH-funded clinical trial in NIH-funded clinical trial in

pulmonary hypertensionpulmonary hypertension

Ongoing studies at Columbia: Ongoing studies at Columbia: Before TransplantationBefore Transplantation

Pirfenidone for Pulmonary FibrosisPirfenidone for Pulmonary Fibrosis Treatment trial of pirfenidoneTreatment trial of pirfenidone Enrollment is closedEnrollment is closed

Ongoing studies at Columbia: Ongoing studies at Columbia: After TransplantationAfter Transplantation

Genetic Analysis to Predict Rejection Genetic Analysis to Predict Rejection of Lung Transplants (LARGO)of Lung Transplants (LARGO) This study is looking for a blood test to This study is looking for a blood test to

diagnose rejectiondiagnose rejection Might save people from having Might save people from having

bronchoscopies in the future!!bronchoscopies in the future!!

Ongoing studies at Columbia: Ongoing studies at Columbia: After TransplantationAfter Transplantation

Evaluating the Safety and Efficacy of Evaluating the Safety and Efficacy of Intravenous Immunoglobulin Intravenous Immunoglobulin We are studying whether an infusion of We are studying whether an infusion of

IVIG helps prevent infections after IVIG helps prevent infections after transplantationtransplantation

Ongoing studies at Columbia: Ongoing studies at Columbia: After TransplantationAfter Transplantation

Genetic Predictors of Primary Graft Genetic Predictors of Primary Graft Dysfunction after Lung TransplantDysfunction after Lung Transplant 10-20% of the time, the lungs don’t 10-20% of the time, the lungs don’t

work right away after transplantation.work right away after transplantation. We are trying to predict who will We are trying to predict who will

develop this complication develop this complication This study will lead to studies of new This study will lead to studies of new

treatments for this complicationtreatments for this complication

SummarySummary

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 horizonNew treatments are on the horizon Consider enrolling in research studies Consider enrolling in research studies

Be fully informedBe fully informed Understand the risksUnderstand the risks 100% voluntary100% voluntary