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Update in Lung Transplant

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

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Update in Lung Transplant

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  1. Update in Lung Transplant Kapil Patel, MD Clinical Assistant Professor of Medicine Center for Advanced Lung Disease Stanford University Medical Center

  2. Introduction • Referral and Evaluation • Lung Allocation Score • Infections • Diabetes • Gastroenterology related diseases • Sinus Disease • Malignancy • Conclusion

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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. ThoracCardiovasc Surg. 2000 Bartz et al. Pre-transplant Mechanical Ventilation and Outcome in Patients With Cystic Fibrosis. J Heart Lung Transpl. 2004

  8. 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)

  9. Factors used to calculateLung Allocation Score Factors used to predict waiting list survival… 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 • FVC (% predicted) • PA systolic pressure • Oxygen required at rest (L) • Age • BMI • NYHA functional status • Diagnosis • Six-minute walk distance • Continuous mechanical ventilation • Diabetes

  10. 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 RespirCrit Care Med. 2013

  11. Infections • Pseudomonas aeruginosa • Mucoid and non-mucoid organisms • Multi-drug resistant • Aspergillus species (20%) • Increased risk for developing bronchiolitis obliterans syndromeand airway complications (e.g. bronchial anastomotic infection) Hadjiliadis et al. Survival of Lung Transplant Patients With Cystic Fibrosis Harboring Panresistant Bacteria Other Than Burkholderiacepacia, Compared With Patients Harboring Sensitive Bacteria. J Heart Lung Transplant. 2007

  12. Infections • Burkholderiacepacia 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 Burkholderiacepaciain Cystic Fibrosis. Outcome Following Lung Transplantation. Am J RespirCrit Care Med. 2001.

  13. 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

  14. GI • Gastro-esophageal Reflux Disease • Malnutrition • Pancreatic Insufficiency • Liver Disease (e.g. Cholelithiasis, biliary cirrhosis, cirrhosis) • Distal Intestinal Obstruction Syndrome

  15. GERD • Prevalence of 75-90% in post-transplant CF • Increased risk for developing Chronic Rejection • NissenFundoplication (laparoscopic antireflux surgery) superior medical therapy (PPI) Mendez et al. Gastroesophageal reflux disease in lung transplant patients with cystic fibrosis. Am J Surg 2012

  16. 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 RespirCrit 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

  17. 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)

  18. 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).

  19. Malignancy CF Non-transplanted CF Transplanted 26 observed vs 9.6 expected (SIR 2.7) Digestive Tract Cancers 19 observed vs 1.1 expected (SIR 17.3) • 172 observed vs 153.5 expected (SIR 1.1) Digestive Tract Cancers • 45 observed vs 12.8 expected (SIR 3.5) Maisonneuve et al. Cancer Risk in Cystic Fibrosis: A 20-Year Nationwide Study From the United States. JNCI (2013)

  20. 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

  21. Conclusion • Possible areas for future research to improve transplant outcomes include: • Surgical technique • Organ procurement and preservation • Post-operative management in the ICU

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