An International Case Study of Lung Transplantation Selim M. Arcasoy, M.D. Professor of Medicine Medical Director, Lung Transplantation Program Director, Interstitial Lung Disease Program New York-Presbyterian Hospital Columbia University Medical Center

The Impact of Lung Disease Chronic, progressive and disabling symptoms Breathlessness, cough, sputum production Decline in functional status and quality of life Greater than 35 million Americans have lung disease Financial cost to society (>$150 billion per year) Decreased work days and productivity, disability, costs of medical care Premature mortality Number 3 killer in the U.S. behind heart disease & cancer 400,000 Americans die of lung disease every year Responsible for one in six deaths

Four Major Lung Diseases Treatable with Lung Transplantation Chronic obstructive pulmonary disease (COPD) Emphysema/chronic bronchitis due to tobacco smoking or alpha1-antitrypsin deficiency (genetic) 12 million have COPD, 12 million are under-diagnosed Pulmonary fibrosis (scarring of the lungs) End result of more than 200 diseases Affects >500,000 Americans Cystic fibrosis (CF): A genetic disease ~30,000 Americans have CF with 1,000 new cases/yr Pulmonary hypertension

Cystic Fibrosis Patient 1 9-year old girl Diagnosed with CF at age 4 months Recurrent respiratory infections and low body weight Developed pulmonary MRSA infection 2 years prior Nine hospitalizations for intravenous antibiotics Lung function at 30% of predicted for her age and needs to use 3 LPM of supplemental oxygen Family makes contact with our Lung Txp Program Required tests ordered and performed in Turkey Tests reviewed and family moves to U.S. for evaluation

Cystic Fibrosis Patient 1 First visit on April 6, 2007 Further testing and consultations Multidisciplinary team discussion Placed on the active lung transplant list Recurrent infections while awaiting transplant Lung transplantation on November 25, 2009

Cystic Fibrosis Patient 2. A Case of Good Fortune Older sister of our first patient Diagnosed at age 7 years Much healthier than her younger sister Attending school in the U.S. as her family moved for her sister’s transplant Becomes sicker in 2010 Lung function drops from 51% to 22% Hospitalized with fever and respiratory failure Urgent lung transplant evaluation and listing Lung transplantation performed on Sep 17, 2010

End-stage Lung

And, here they are….

Stages of Respiratory Disease and Failure

History of Lung Transplantation JD Hardy, MD June 11, 1963 36 patients underwent lung transplantation between 1963 and 1975 with no long-term survivors Introduction of cyclosporine in 1978 First successful heart-lung Tx performed in 1981, single lung Tx in 1983 and double lung Tx in 1986 1954 - First successful kidney transplant 1967 - First successful liver transplant 1968 - First successful heart transplant

Number of Lung Transplants in the Last 3 Decades JHLT. 2013 Oct; 32(10): 965-978 2013

Who is a Candidate for Lung Transplant? General Guidelines YES Advanced lung disease with limited lifespan and severe functional limitation Lack of alternative therapies Demonstrated compliance with therapy and follow-up Strong family support NO Active or recent cancer Advanced dysfunction of a major organ system Untreatable infection Substance addiction Documented noncompliance and lack of family support A complex decision that requires extensive evaluation and multidisciplinary team discussion

Lung Transplantation on a Scale Risk-Benefit Balance Benefits Survival Function Quality of Life Risks Mortality Morbidity Complexity Patient Expectations Patient characteristics Type of lung disease Other medical illnesses Prognosis without transplant

Steps From Initial Evaluation to Transplantation First visit to meet the transplant team Focus on initial patient screening, assessment of patient/family motivation, and education Extensive testing and consultations Multidisciplinary team meeting for a decision Potential outcomes: Immediate active listing Accepted as a potential future candidate, but needs to meet certain goals or get sicker Denial because of contraindications

Transplant Listing and The Call Patients are placed on the active national list All listed patients are assigned a Lung Allocation Score (LAS) based on their clinical characteristics Age, disease, lung, heart and kidney function, labs Score ranging from 0 (less ill) to 100 (gravely ill) Waiting period with significant regional variation Donor and recipient matched by blood type and size Transplant has to occur within 6 to 8 hours after removal of lungs from the donor

Ex Vivo Lung Perfusion “Lung In A Box”

Extracorporeal Membrane Oxygenation (ECMO)

Case 3

Before And After

NewYork-Presbyterian Hospital Lung Transplant Volume Per Year 1996-2012 New Program 28

New York-Presbyterian Hospital Lung Transplant Survival 7/01/2001 - 12/31/2012 (n = 559) NYPH vs UNOS 1-year: 91% vs 84% 5-year: 68% vs 53% 10-year: 47% vs 28%

Functional Status Before and After Lung Transplantation This figure shows the functional status reported on the 1-year, 3-year, 5-year and 10-year annual follow-ups. Because all follow-ups between April 1994 and June 2006 were included, the bars do not include the same patients.

Employment Status Before and After Lung Transplantation This figure shows the employment status reported on the 1-year, 3-year, 5-year and 10-year annual follow-ups. Because all follow-ups between April 1994 and June 2006 were included, the bars do not include the same patients.