Disclosures Transplanting Interstitial Lung Disease I have nothing - PowerPoint PPT Presentation

11/5/2016 � Disclosures Transplanting Interstitial Lung Disease I have nothing to disclose Steven Hays, MD Associate Professor Medical Director, Lung Transplantation UCSF Medical Center Lung Transplantation Adult Lung Transplants Number of Transplants by Year and Procedure Type Indications • A consensus document for the selection of lung transplant candidates 2014. J Heart Lung Transplant • Chronic advanced lung disease • Failed medical management • For most patients the ultimate “ treatment ” • Primary goal is improved duration of life but improved quality of life is also a consideration rather than cure • Trading one medical condition for another � JHLT. 2015 Oct; 34(10): 1264-1277 1 �

11/5/2016 � Lung Transplant Lung Transplantation Major Indications By Year Disease Indications Pulmonary Vascular • Disease Restrictive Lung • Disease PAH • PH secondary to systemic IPF • • disease NSIP • Eisenmenger’s syndrome Sarcoidosis • • Obstructive Lung Disease Eosinophilic granuloma • • Smoking related LAM • • A1ATd Occupational lung • • disease Suppurative Lung Disease • Hypersensitivity Cystic Fibrosis • • pneumonitis Bronchiectasis • Bronchiolitis obliterans • 2015 � For some retransplants, a diagnosis other than retransplant was reported, so the total � JHLT. 2015 Oct; 34(10): 1264-1277 � JHLT. 2014 Oct; 33(10): 1009-1024 percentage of retransplants may be greater. UCSF Transplant Recipient Characteristics Lung Allocation Score Implemented May 2005 UCSF • Region US Way to determine who receives donor • lungs based on medical urgency and PAH 0 4.0 3.6 probability of success Based on medical testing completed during CF 11.1 14.2 12.3 • evaluation IPF 77.8 Also based on diagnosis, favoring ILD and 61.0 53.8 • CF (have highest risk on waiting list) Electronic listing COPD 11.1 18.5 27.5 • Repeat specified tests every 6 months • Other 0 2.3 2.8 2 �

11/5/2016 � Lung Allocation Score LAS Calculation Waiting List Urgency Post Tx Survival Parameters Age • Age Mechanical Ventilation • • O2 requirement at rest Functional Status • • BMI Dx • • DM PCWP • • Dx FVC • • 6 MWD < 150 ft PaCO2 • • Functional Status • Mechanical ventilation • FVC • PaCO2 • PAP • http://optn.transplant.hrsa.gov/resources/allocationcalculators.asp?index=88 Lung Allocation Score Predicts Pulmonary Fibrosis Survival in Lung Transplantation Patients With Pulmonary Fibrosis Pre-LAS The Annals of Thoracic Surgery Thabut. J Thorac Cardiovasc Surg Volume 88, Issue 6, December 2009, Pages 1757– 1764 2003;126:469 3 �

11/5/2016 � Pulmonary Fibrosis Timing of Referral Disease Specific Guidelines General Recommendations Referral Guidelines • UIP • Fibrotic NSIP Early referral is highly desirable • • Oxygen requirement Consider when patient is symptomatic during daily • • DLCO < 40% activities (NYHA III or IV) When expected survival is 2-3 years • Listing Guidelines Aids in the psychology of accepting and confronting life- • • 10% drop in FVC over 6 threatening illness months Aids in actively managing end-stage illness • • 15% drop in DLCO over 6 months • Desaturation with 6MWT or drop in 6MWT distance • Pulmonary hypertension or hospitalization J Heart Lung Transplant 2014 Pulmonary Fibrosis and Pulmonary Fibrosis Pancytopenia Disease Specific Guidelines 56 y/o female presents to UCSF in 2/2009 with � complaints progressive non-productive cough If IPF, Cough progressive over the course of 3-4 years � REFER EARLY Notes mild dyspnea on exertion, though is able to � exercise for 30 minutes on an elliptical machine No other systemic symptoms such as arthralgias, � myalgias, rashes or photosensitivity 4 �

11/5/2016 � Pulmonary Fibrosis and Pancytopenia � PMHx: � Lyme Disease in 2004. She was noted to have a mild pancytopenia at that time – thought to be related � FHx: � Mother was diagnosed with pulmonary fibrosis at the age of 55 and died at 60. She had possible lupus. � Sister has asthma � SHx: no exposures 18 Pulmonary Fibrosis and Pulmonary Fibrosis and Pancytopenia Pancytopenia DATA Started on Perfenidone through a trip to Europe • By 2011 dyspnea became the prominent problem PFTs: • � She was now hypoxic and using oxygen with both rest � TLC 4.11 (76%) • and exertion � FVC 2.83 (76%) PFTs show a progression • � FEV1 2.31 (80%) • TLC 2.85 (52%) � DLCO 15.33 (55%) • FVC 1.68 (46%) CBC: � • DLCO 10.49 (38%) � WBC 3,200 FHx – sister previously thought to have asthma now • � HCT 32.0 diagnosed with Hypersensitivity Pneumonitis � PLT 73,000 5 �

11/5/2016 � Pulmonary Fibrosis and Pancytopenia Referred for Lung Transplant Evaluation Hematology Evaluation: BM Biopsy 5/27/2011 • • Hypocellular marrow for age with mixed hematopoesis and blasts less than 5% • Borderline/minimal normochromic and normocytic anemia and thrombocytopenia Diagnosis: Mild aplastic anemia • FHx: Sister now has undergone lung transplant. She developed significant hematologic problems post transplant including thrombocytopenia 21 • Telomerase mutation genetic What test would help explain the analysis was performed cause of this patients progressive pulmonary fibrosis and • This revealed a sequence variant in pancytopenia? the TERC gene 6 �

11/5/2016 � Pulmonary Fibrosis and Familial Fibrosis and Lung Pancytopenia Transplantation Retrospective case series of 14 lung transplant • • Patient underwent double lung recipients with telomerase complex mutations All had fibrotic lung disease but only 43% had UIP transplant • pattern on CT imaging • Post-operative course complicated by High incidence of cytopenias, particularly leukopenia, • thrombocytopenia into the 20,000s post transplantation (83%) Of these, 5 could not tolerate anti-proliferative agents • Platelets gradually recovered to her • – but not associated with acute rejection or CLAD baseline of 80-90,000 CLAD occurred in 33% of recipients at median 3.1 • • Her sister, transplanted at another years center is also doing well Hypersensitivity Pneumonitis Hypersensitivity Pneumonitis Rare, progressive ILD triggered by inhaled antigens • Retrospective cohort study of 31 patients • Primary treatment is removal of antigen from transplanted for HP between 2001-2013 • environment • 12 of 31 had known inciting exposure (39%) Offending agent only ID’d in 40% of cases • • 5 of the 31 had diagnosis of IPF prior to A subset of patients develop progressive fibrosis • transplant Can Lung Transplantation help this group? • What is the outcome including survival? • Does it recur? • 7 �

11/5/2016 � Hypersensitivity Pneumonitis Hypersensitivity Pneumonitis • 2 of the 31 patients developed recurrent HP • Both cases were associated with: • Exposure to presumed antigen • Granulomas on biopsy • Drop in lung function • No infectious cause • Improvement/stabilization with treatment with steroids Hypersensitivity Pneumonitis CTD related ILD 8 �

11/5/2016 � Adult Lung Transplantation: Indications (1/1995- Pulmonary Fibrosis 6/2010) DIAGNOSIS SLT (N = 12,339) BLT (N = 18,334) TOTAL (N = 30,673) Collagen Vascular Diseases COPD/Emphysema 5,769 ( 46.8% ) 4,839 ( 26.4% ) 10,608 ( 34.6% ) Idiopathic Pulmonary Fibrosis 3,995 ( 32.4% ) 2,938 ( 16.0% ) 6,933 ( 22.6% ) Cystic Fibrosis 214 ( 1.7% ) 4,941 ( 26.9% ) 5,155 ( 16.8% ) Alpha-1 728 ( 5.9% ) 1,225 ( 6.7% ) 1,953 ( 6.4% ) Idiopathic Pulmonary Arterial 78 ( 0.6% ) 894 ( 4.9% ) 972 ( 3.2% ) Associated with: Scleroderma, Rheumatoid Hypertension • Pulmonary Fibrosis, Other 424 ( 3.4% ) 537 ( 2.9% ) 961 ( 3.1% ) arthritis, Mixed connective tissue disease, Bronchiectasis 50 ( 0.4% ) 815 ( 4.4% ) 865 ( 2.8% ) Dermatomyositis Sarcoidosis 236 ( 1.9% ) 547 ( 3.0% ) 783 ( 2.6% ) Re-Transplant: Obliterative Bronchiolitis 253 ( 2.1% ) 219 ( 1.2% ) 472 ( 1.5% ) Each patient should have individual Connective Tissue Disease 127 ( 1.0% ) 232 ( 1.3% ) 359 ( 1.2% ) • Obliterative Bronchiolitis (Not Re- 80 ( 0.6% ) 237 ( 1.3% ) 317 ( 1.0% ) consideration Transplant) LAM 101 ( 0.8% ) 207 ( 1.1% ) 308 ( 1.0% ) • Evidence of quiescent systemic disease is Re-Transplant: Not Obliterative 127 ( 1.0% ) 162 ( 0.9% ) 289 ( 0.9% ) Bronchiolitis desired Congenital Heart Disease 43 ( 0.3% ) 224 ( 1.2% ) 267 ( 0.9% ) Cancer 6 ( 0.0% ) 26 ( 0.1% ) 32 ( 0.1% ) • Active vasculitis is a contraindication Other 108 ( 0.9% ) 291 ( 1.6% ) 399 ( 1.3% ) J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 � Freedom from BOS Lung Transplant Survival Scleroderma vs. IPF Scleroderma vs IPF 9 �

11/5/2016 � Scleroderma and Aspiration Risk Scleroderma and Aspiration Risk Scleroderma Evaluation Severe pulmonary fibrosis (FVC and DLCO <40%), • unresponsive to medical treatment What about patients who are referred Creatinine clearance above 60 mL/min • late or who have acute illness? Absence of severe skin involvement (severe cutaneous • thickening) Absence of severe esophageal dysmotility and • aspiration Absence of significant conduction abnormalities • Absence of severe small intestine, gastroparesis, • colorectal and rectum involvement such as pseudo- obstruction, diverticulitis, and perforation � 39 10 �