Update in Lung Transplant

Kapil Patel, MD

Clinical Assistant Professor of Medicine

Center for Advanced Lung Disease

Stanford University Medical Center

• Introduction

• Referral and Evaluation

• Lung Allocation Score

• Infections

• Diabetes

• Gastroenterology related diseases

• Sinus Disease

• Malignancy

• Conclusion

Introduction

• 3500 lung transplants performed annually worldwide

• In 1983, UPMC performed the first lung transplant in a cystic fibrosis patient

• 3rd most common indication for bilateral lung

transplant • 5688 performed (Jan 1995 – July 2011)

• Highest long-term survival in lung transplant

ADULT LUNG TRANSPLANTSKaplan-Meier Survival by Diagnosis(Transplants: January 1990 - June 2010)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Su

rviv

al (

%)

Years

Alpha-1 (N=2,490) CF (N=5,608) COPD (N=11,948)

IPF (N=7,540) IPAH (N=1,308) Sarcoidosis (N=849)

HALF-LIFE Alpha-1: 6.2 Years; CF: 7.5 Years; COPD: 5.3

Years; IPF: 4.4 Years; IPAH: 5.0 Years; Sarcoidosis: 5.3 Years

ISHLT

Introduction

• Advances in medical therapy have lead to a steady rise in the life expectancy in CF

• Despite therapeutic advances, respiratory failure accounts for most morbidity and mortality

• Lung transplant is the only treatment option to improve survival

Referral for Transplant

• Guideline recommendations: – FEV₁ < 30% of predicted

or

– Rapidly progressive respiratory deterioration with FEV₁ > 30% • Increasing frequency of exacerbation requiring IV antibiotic

• Recurrent hemoptysis

• Refractory/recurrent pneumothorax

Evaluation

• Pulmonary – CXR/CT chest

– Pulmonary Function Test

– Six-minute walk

• Cardiac – Echocardiogram

– RHC (± LHC)

• Renal – Cr Cl (> 50 mL/min)

• Infection – HIV, Hepatitis, EBV, CMV

– Colonized Organisms

• GI – CT Abd/Pelvis

• Liver

– GERD evaluation

– Esophagram

• Psychosocial evaluation

Transplant Listing

• Oxygen-dependent

• Hypercapnia (chronic)

• Pulmonary hypertension

• Mechanically ventilated CF patients

Venuta et al. Pulmonary hemodynamics contribute to indicate priority for lung transplantation in patients with cystic fibrosis. J. Thorac Cardiovasc Surg. 2000 Bartz et al. Pre-transplant Mechanical Ventilation and Outcome in Patients With Cystic Fibrosis. J Heart Lung Transpl. 2004

Lung Allocation Score

• In 2005, the Lung Allocation Score was implemented by the Organ Procurement and Transplantation Network

• Derived from a prediction of benefit (expected 1-year post-transplant survival days and expected 1-year waiting list time survival days)

Factors used to calculate Lung Allocation Score

Factors used to predict waiting list survival…

• FVC (% predicted)

• PA systolic pressure

• Oxygen required at rest (L)

• Age

• BMI

• NYHA functional status

• Diagnosis

• Six-minute walk distance

• Continuous mechanical ventilation

• Diabetes

Factors used to predict post-transplant survival…

• FVC (% predicted)

• PCW mean pressure

(≥ 20 mmHg)

• Continuous mechanical ventilation

• Age

• Serum creatinine (mg/dL)

• NYHA functional status

• Diagnosis

Lung Allocation Score

• UNOS registry identified 704 adult CF patients on waiting list from 2005-2009

• Lung transplant is associated with a 69% reduction in risk of death

Thabut et al. Survival benefit of lung transplant for cystic fibrosis since Lung Allocation Score Implementation. Am J Respir Crit Care Med. 2013

Infections

• Pseudomonas aeruginosa

– Mucoid and non-mucoid organisms

– Multi-drug resistant

• Aspergillus species (20%)

– Increased risk for developing bronchiolitis obliterans syndrome and airway complications (e.g. bronchial anastomotic infection)

Hadjiliadis et al. Survival of Lung Transplant Patients With Cystic Fibrosis Harboring Panresistant Bacteria Other Than Burkholderia cepacia, Compared With Patients Harboring Sensitive Bacteria. J Heart Lung Transplant. 2007

Infections

• Burkholderia cepacia complex (3-5%)

– B.cenocepacia (formly “genomovar III”)

• Associated with increased 1 year post-transplant mortality

• Non-tuberculous mycobacterium (10-15%)

– Mycobacterium Avium Complex (most common)

– Mycobacterium abscessus

Chaparro et al. Infection with Burkholderia cepacia in Cystic Fibrosis. Outcome Following Lung Transplantation. Am J Respir Crit Care Med. 2001.

Diabetes

• CF related diabetes affects approximately 19% of adolescents and 40% of adults (> 40 years) with increased likelihood to develop in females

• Post-transplant: No association with mortality

GI

• Gastro-esophageal Reflux Disease

• Malnutrition

• Pancreatic Insufficiency

• Liver Disease (e.g. Cholelithiasis, biliary cirrhosis, cirrhosis)

• Distal Intestinal Obstruction Syndrome

GERD

• Prevalence of 75-90% in post-transplant CF

– Increased risk for developing Chronic Rejection

• Nissen Fundoplication (laparoscopic antireflux surgery) superior medical therapy (PPI)

Mendez et al. Gastroesophageal reflux disease in lung transplant patients with cystic fibrosis. Am J Surg 2012

Malnutrition

• Underweight < 18.5 kg/m²

• Hypoalbuminemia

• CF and hypoalbuminemia are association with significantly reduced 1 year and overall survival

Lederer et al. Obesity and Underweight Are Associated with an Increased Risk of Death after Lung Transplant. Am J Respir Crit Care Med. 2009 Chamogeorgakis et al. Impact of nutritional state on lung transplant outcomes. J Heart Lung Transplant. 2013 Baldwin et al. Hypoalbuminemia and Early Mortality After Lung Transplantation: A Cohort Study. Am J Transplant. 2012

Liver Disease

• 4 - 10% of CF patients develop cirrhosis and portal hypertension resulting in synthetic dysfunction

• If significant liver disease is evident, patients may be evaluated for combined liver and lung transplant

Nash et al. Outcomes of patients with cystic fibrosis undergoing lung transplant w/ and w/out cystic fibrosis associated liver cirrhosis. (2012) Desai et al. Survival of Cystic Fibrosis Patients Undergoing Liver and Liver-Lung Transplantations. Transplant Proc (2013)

Sinus Disease

• Although, sinuses harbor organisms amongst all CF patients, it does not affect the post-transplant outcomes in CF patients

Leung et al. Effects of sinus surgery on lung transplantation outcomes in cystic fibrosis. Am J Rhinol. (2008).

Malignancy

CF Non-transplanted

• 172 observed vs

153.5 expected

(SIR 1.1)

Digestive Tract Cancers

• 45 observed vs

12.8 expected

(SIR 3.5)

CF Transplanted

• 26 observed vs

9.6 expected

(SIR 2.7)

Digestive Tract Cancers

• 19 observed vs

1.1 expected

(SIR 17.3)

Maisonneuve et al. Cancer Risk in Cystic Fibrosis: A 20-Year Nationwide Study From the United States. JNCI (2013)

Conclusion

• Lung transplant remains to be an option for CF patients with end-stage lung disease

• Long term outcomes remains superior to those for patients with other lung diseases amenable to transplant

Conclusion

• Possible areas for future research to improve transplant outcomes include:

– Surgical technique

– Organ procurement and preservation

– Post-operative management in the ICU