Update in Lung Transplant
Kapil Patel, MD
Clinical Assistant Professor of Medicine
Center for Advanced Lung Disease
Stanford University Medical Center
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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 TRANSPLANTS
Kaplan-Meier Survival by Diagnosis
(Transplants: January 1990 - June 2010)
100
Alpha-1 (N=2,490)
CF (N=5,608)
COPD (N=11,948)
IPF (N=7,540)
IPAH (N=1,308)
Sarcoidosis (N=849)
80
Survival (% )
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
60
40
20
0
0
1
2
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4
5
6
7
Years
ISHLT
8
9
10
11
12
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14
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 posttransplant 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
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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 posttransplant 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)
CF Transplanted
• 26 observed vs
9.6 expected
(SIR 2.7)
Digestive Tract Cancers
• 45 observed vs
12.8 expected
(SIR 3.5)
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