# Presentation: 361055

## Current Status of Lung Transplantation

**Jeff Golden, MD **
**Professor of Clinical Medicine and Surgery**
**Medical Director, Lung Transplantation****University of California, San Francisco**

## Current Status of Lung Transplantation

**Long term survival—50% die by 5 years**
**Bronchiolitis obliterans (chronic rejection)—primary cause of poor survival**
**Future of lung transplantation—****prevent bronchiolitis obliterans**

## Lung TransplantationPre-Cyclosporine Era, Pre-1983

**Time (days)**

**(4)**

**(12)**

**(19)**

**(28)**

**(38)**

**At risk:**

**0**

**50**

**100**

**150**

**200**

**250**

**0**

**20**

**40**

**60**

**80**

**100**

**% free from death**

## Worldwide Lung Transplantation Numbers

**Worldwide Lung Transplantation Numbers**

**Source: International Society of Heart and Lung Transplantation (ISHLT); UNOS **

**Lung transplants performed worldwide, by year**

**Emphysema/COPD**
**Idiopathic pulmonary fibrosis**
**Cystic fibrosis**
**Alpha-1 antitrypsin deficiency**
**Primary pulmonary hypertension**
**Sarcoidosis**
**Retransplant/graft failure**
**Other**

**1.8%**
**2.6%       **
**4.2%             **

**39.0%**

**10.4%**

**17.0%**

**16.0%**

**9.0%**

**Primary diagnosis, 01/1995 - 06/2003**

**1342**

**1337**

**1417**

**1413**

**1410**

**1508**

**1537**

**1706**

**1655**

**1206**

**1069**

**902**

**685**

**408**

**185**

**80**

**47**

**15**

**13**

## Comparative Transplantation Survival Rates

**Comparative Transplantation ****Survival Rates**

**Primary lung transplant by underlying diagnosis**

**Primary kidney, liver, and heart transplant**

***Kidney, liver, and heart data extrapolated from OPTN Annual Report, 2003.**

- Chiron Briefing Document Figure 2.2-1

## Slide 6

## Clinical Manifestations of Chronic Rejection

**Two methods for the diagnosis of chronic rejection**
**Histologically through transbronchial biopsy (OB)**
**Clinically through sustained decline in pulmonary function (Bronchiolitis Obliterans Syndrome, BOS)**
**OB and BOS are histologic and clinical manifestations of the same process**
**Patients develop progressive shortness of breath, graft failure, airflow obstruction, recurrent pulmonary infections**
**Once chronic rejection develops, airway damage is progressive and irreversible**
**Patients die of graft failure/pneumonia**

## Causes of Death Following Lung Transplantation

## Despite Best Current Systemic Treatment and Patient Management, Chronic Rejection Eventually Affects Most Patients

**0**

**20**

**40**

**60**

**80**

**100**

**0**

**1**

**2**

**3**

**4**

**5**

**6**

**7**

**Years from transplant**

**0**

**20**

**40**

**60**

**80**

**100**

**Calcineurin**** inhibitors**

**Anti-metabolites**

**Prednisone**

**CsA**

**Tac**

**AZA**

**MMF**

**% of****patients**

***Plus induction, plus pulsed intensifications prn***

**Source: ISHLT, market research**

***Despite best available therapy***

**% chronic rejection-free survival**

## New Concept: Avoid Increasing Systemic Immunosuppression  

**New Concept: Avoid Increasing ****Systemic Immunosuppression  **

** ****Infection**
** ****GERD**
** ****Others**

**Immune**
**activation**

**Increase**
**systemic **
**immune**
**suppression**

**BOS**

** ****Non**
**alloimmune**
**factors:**

## Pathway to Chronic Rejection

**Epithelial injury**
**Inflammation**
**Fibroblastic repair**

**Pathway to Chronic Rejection**

**Non-alloimmune stimuli **
**Airway ischemia **
**Viruses **
**Bacterial - *****PSEUDOMONAS ***
**Oxidant stress **
**Reflux**

**Alloimmune stimuli **
**Recurrent acute vascular rejection**
**Lymphocytic bronchitis**

## Lymphocytic Bronchitis/Bronchiolitis

## Acute Rejection

**Acute rejection is a perivascular process***** *****diagnosed by transbronchial biopsy**

## Separate Interventions for Separate Processes

**Cyclosporine by inhalation**

**Systemic immunosuppression**

**Epithelial administration to avert airway rejection and ongoing injury, inflammation and fibrosis ending in bronchiolitis obliterans**

**Systemic administration to avert vascular rejection, halting lymphocytic recruitment and activation**