1. PFF Teal = 0+160+175 MAIN COLORS PFF Green = 120+162+47 Light Green = 193+216+47 Red = 242+102+73 HIGHLIGHT COLORS Light Grey = 220+220+210 Dark Grey = 100+98+76 Black = 0+0+0 LUNG TRANSPLANTATION: NUTS & BOLTS OR… THIS IS NUTS, I AM GOING TO BOLT! DAVID J. LEDERER, MD, MS CLINICAL CARE: COMPREHENSIVE CARE - BEYOND PHARMACOLOGICAL THERAPIES NOVEMBER 14, 2015

2. Lung Transplantation Background Replacement of one or both lungs with human donor lungs – Bilateral – Single – Heart-Lung – Living donor lobar Potentially life-saving therapy for adults and children with end-stage lung disease – End-stage lung disease patients have a high risk of death without lung transplantation – Non-randomized studies suggest a survival benefit to lung transplantation Resolution of dyspnea and improved gas exchange Hosenpud JD, et al. Lancet 1998;351:24-7. Titman A, et al. Am J Transplant 2009;9:1640-9.

3. Lung Transplant Volume in the United States, 2003-2013 LAS Begins Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

4. Distribution of diagnoses at the time of lung transplantation, 2003-2013 COPD PAH CF ILD Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28. LAS Begins

5. Waiting List = Shortage of Donor Lungs Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

6. Waiting list mortality by diagnosis in the United States, 2002-2013 Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

7. Mortality after Lung Transplantation in the United States, 1991-2013 LAS Begins Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

8. Unadjusted survival after lung transplantation by diagnosis in the United States, 2006-2008 Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

9. Medical Decision Making

10. Equitable Organ Allocation Candidate Other potential candidates

11. Weill et al. J Heart Lung Transplantation 2015;34:1-15.

12. General Indications for Lung Transplantation Lung transplantation should be considered for adults with chronic, end-stage lung disease who meet all the following general criteria: High (>50%) risk of death due to lung disease within 2 years if lung transplantation is not performed. High(>80%) likelihood of surviving at least 90 days after lung transplantation. High (>80%) likelihood of 5-year post-transplant survival from a general medical perspective provided there is adequate graft function Weill et al. J Heart Lung Transplantation 2015;34:1-15.

13. Medical Absolute Contraindications to Lung Transplantation Malignancy (2-5 years free of disease) Major organ dysfunction (heart, kidney, liver disease) Uncorrected atherosclerotic disease with end-organ ischemia/dysfunction Acute medical instability: sepsis, acute MI, liver failure Uncorrectable bleeding diathesis Chronic infection with highly virulent and/or resistant microbes that are poorly controlled pre-transplant Significant chest wall/spinal deformity Body mass index > 35 kg/m 2 Severely limited functional status with poor rehabilitation potential Weill et al. J Heart Lung Transplantation 2015;34:1-15.

14. Psychosocial Absolute Contraindications to Lung Transplantation Current non-adherence to medical therapy History of repeated or prolonged episodes of non-adherence Psychiatric or psychological conditions associated with the inability to cooperate with the medical team and/or adhere with complex medical therapy Absence of an adequate and reliable social support system Substance abuse or dependence Weill et al. J Heart Lung Transplantation 2015;34:1-15.

15. Relative Contraindications to Lung Transplantation Age older than 65 years in association with low physiologic reserve and/or other relative contraindications – Age > 75: unlikely to be candidates in most cases – Age by itself should not be a contraindication Body mass index 30-34.9 kg/m 2 Progressive or severe malnutrition Severe, symptomatic osteoporosis Extensive prior chest surgery with lung resection Mechanical ventilation and/or ECLS Colonization or infection with highly resistant or virulent microbes Atherosclerotic burden that puts the patient at risk for future events Suboptimally managed comorbidities Weill et al. J Heart Lung Transplantation 2015;34:1-15.

16. Selected Criteria for Referral of Patients with ILD for Lung Transplantation Fibrotic idiopathic interstitial pneumonia – Usual interstitial pneumonia – Fibrotic non-specific interstitial pneumonia FVC < 80% predicted DLCO < 40% predicted Any oxygen requirement For inflammatory ILD, failure to improve dyspnea, oxygen requirement, and/or lung function after a clinically indicated trial of medical therapy Weill et al. J Heart Lung Transplantation 2015;34:1-15.

17. Common Questions How old is too old? How sick is too sick? One lung or two?

18. Common Questions How old is too old? How sick is too sick? One lung or two?

19. Age distribution at the time of lung transplantation, 2003-2013 Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

20. Post-transplant survival by age group,2006-2008 Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

21. Common Questions How old is too old? How sick is too sick? One lung or two?

22. Respiratory failure precedes almost 10% of lung transplant procedures in the U.S. Year Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

23. LAS scores at the time of transplant have increased over time Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

24. Higher LAS scores are associated with higher post-transplant mortality Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

25. Common Questions How old is too old? How sick is too sick? One lung or two?

26. Distribution of bilateral transplantation by diagnosis in the United States, 2003-2013 Valapour M, et al. OPTN/SRTR 2013 Annual Data Report: Lung. Am J Transplant. 2015 Jan;15 Suppl 2:1-28.

27. Advantages to both procedures Bilateral Improved physiological outcomes Avoid native lung complications Single Shorter operation Shorter waiting time Native lung function Hadjiliadis & Angel. Semin Respir Crit Care Med 2006;27:561-6.

28. Propensity-matched survival UNOS/OPTN; 3,327 recipients; 1987-2009 Thabut et al. Ann Intern Med 2009;151:767-74.

29. Cause of death by procedure type Thabut et al. Ann Intern Med 2009;151:767-74.

30. Adjusted survival after transplantation for ILD UNOS/OPTN; 11,892 recipients; 2005-2012 Schaffer et al. JAMA 2015;313:936-48.

31. 1-yr waiting list outcomes for 7,341 adults with ILD, UNOS/OPTN, 2005-2012

32. Summary The donor shortage mandates early referral “Candidacy” is multidimensional – Disease severity – Comorbidity – Functional status – Social factors Older & sicker candidates are undergoing lung transplantation…. worse outcomes may be on the horizon