Lung Transplantation Biology Robert Padera, M.D., Ph.D. HBTM 235 September 23, 2015 rpadera@partners.org

Goal To teach you everything something about the many facets of lung transplantation

Outline Introduction The recipient The donor The transplant The complications Outcomes

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. Therefore, these numbers should not be interpreted as the rate of change in lung procedures performed worldwide. 2010 ISHLT J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141 NOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as representing changes in the number of lung transplants performed worldwide.

AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS (1/1985-6/2009) 2010 ISHLT J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

Outline Introduction The recipient The donor The transplant The complications Outcomes

The Recipient Respiratory failure of lung origin Idiopathic pulmonary fibrosis/UIP COPD/Emphysema Cystic fibrosis Primary pulmonary hypertension Alpha-1 antitrypsin deficiency Others All other options exhausted

ADULT LUNG TRANSPLANTATION Major Indications By Year (Number) 2010 ISHLT J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

Usual Interstitial Pneumonia Also known as idiopathic pulmonary fibrosis UIP adds cells and fibrous tissue (scar) to the lung, thickening and stiffening it and restricting the elastic stretching, making inspiration harder Manifestations include: Decreased compliance – stiff lung Decreased lung volumes – spirometry measurements Impaired diffusion - DLCO measurement Abnormal small airway function Pulmonary hypertension

UIP - Gross Honeycombing, most severe/earliest in lower zones, subpleural areas

UIP - Microscopic End-stage lung Normal lung Fibroblastic foci

Emphysema

Cystic Fibrosis

Evaluation of Candidacy Blood tests Nicotine/cotine (6 months) Blood type (ABO) Tissue typing (HLA – major histocompatibility complex) Infection/immunity General hematology/chemistry Imaging tests Chest X-ray, chest computed tomography (CT) Pulmonary function tests Spirometry, 6 minute walk Cardiac tests EKG, coronary angiography, echocardiography

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Outline Introduction The recipient The donor The transplant The complications Outcomes

Donor Characteristics Brain death Medical history Transmissible entities: infections, malignancy Willingness to be organ donor Imaging Pneumonia, hemorrhage, underlying lung disease, pulmonary emboli, etc. Function?

Ex Vivo Lung Perfusion Preservation during transport Evaluation Treatment https://www.youtube.com/watch?v=emP9vrsdPwo

Outline Introduction The recipient The donor The transplant The complications Outcomes

Procedure Multiorgan harvest Removed from donor Transport to recipient Implantation and anastomosis Bronchus Pulmonary artery Pulmonary veins

Lung Anatomy Vasculature 21

Outline Introduction The recipient The donor The transplant The complications Outcomes

Rejection Hyperacute ABO mismatch Acute cellular HLA mismatch Antibody mediated Developed Chronic

Acute Rejection Vascular Airway

Chronic Rejection Vascular Airway

Post-transplant Medications 30-40 pills/day Immunosuppressants Cyclosporine Mycophenolate Prednisone Antibiotics PCP, CMV Vitamins/minerals

Infection Increased risk from Immunosuppression Cytomegalovirus Increased risk from Immunosuppression Cough reflex diminished Mucociliary clearance impaired Opportunistic infections common Pneumocystis jiroveci Aspergillus

Outline Introduction The recipient The donor The transplant The complications Outcomes

ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Era (Transplants: January 1988 – June 2008) Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period. Survival rates were compared using the log-rank test statistic. 2010 ISHLT J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

ADULT LUNG RECIPIENTS Employment Status of Surviving Recipients (Follow-ups: April 1994 – June 2009) 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 2009 were included, the bars do not include the same patients. 2010 ISHLT J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

ADULT LUNG TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death (Deaths: January 1992 - June 2009) Only known causes of death are included in the tabulation. 2010 ISHLT J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141