Disclosures Lung transplantation in occupational None and - PDF document

2/28/2017 Disclosures Lung transplantation in occupational • None and environmental lung diseases Jonathan Singer, MD MS Assistant Professor of Medicine UCSF Lung Transplant Program Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine A bit of history • 1963: James Hardy performs first LTx • Patient: Jail inmate; PMH: lung CA, chronic renal insufficiency • Survived 18 days • 1963 ‐ 83: 40 more attempts at LTx • Most survived < 2wks • 1983: FDA approves cyclosporin for renal tx • Joel Cooper performs LTx on a 58yo w/ Idiopathic Pulmonary Fibrosis (lower doses of prednisone) • Survives 8 years; dies of renal failure 2016 JHLT. 2016 Oct; 35(10): 1149-1205 1

2/28/2017 Indications for Lung Transplantation Survival is improving • Pulmonary Vascular Disease • Obstructive Lung Disease • Idiopathic pulmonary • CO COPD arterial hypertension • Alpha ‐ 1 ‐ antitrypsin deficiency Median Me an sur survival (y (years): • Pulmonary hypertension 1990 990 ‐ 1998 998: 4. 4.2; Condit nditiona onal=7.1; • Br Bron onch chio iolitis litis obl obliterans ns secondary to systemic 1999 999 ‐ 2008 008: 6. 6.1; Condit nditiona onal=8.4; disease 2009 009 ‐ 6/20 2014: 14: NA NA; Condit nditiona onal=NA • Restrictive Lung Disease • Eisenmenger’s syndrome • Idiopathic pulmonary fibrosis • Suppurative Disease • Fibrosis secondary to • Cystic Fibrosis connective tissue disorders • Bronchiectasis • Sarcoidosis • Eosinophilic granuloma • Lymphangioleiomyomatosis • Oc Occupa upati tion onal di disea sease • Hyp Hypersensitivit ensitivity pneu pneumonitis itis 2016 JHLT. 2016 Oct; 35(10): 1149-1205 Eligibility Considerations Indications by Year • Severe debilitation due to • Strong psychosocial support pulmonary disease and coping skills • Currently on maximal • No current nicotine or medical management substance abuse • Limited life expectancy • Physical rehabilitation (<2 years) potential • No concurrent severe medical issues/systemic disease 2016 JHLT. 2016 Oct; 35(10): 1149-1205 2

2/28/2017 The “Transplant Window” Listing: The Lung Allocation Score • < 5/05: Seniority based • Rapidly progressive diseases (IPF, PAH) disadvantaged • 5/05: Lung Allocation Score (LAS) CLINICAL STATUS • Urgency based model using clinical variables • Weighted model to predict “transplant benefit” • Waitlist urgency: P(death) within 1 year on waitlist • Post ‐ Tx survival: P(survival) in days during 1 st post ‐ tx yr TOO EARLY TRANSPLANT • 0 ‐ 100 TOO WINDOW LATE • Blood type 2 YEARS • Size TIME “Too late” is a moving target Hoopes CW. J Thorac Cardiovasc Surg. 2013 3

2/28/2017 Single lung transplantation Transplant type based on underlying disease • Initially only offered for ILD and COPD • Single: • now 50/50 single/double • Pulmonary fibrosis • Maximizes donor pool, since one donor may • Emphysema benefit 2 recipients • Double: • Technically easier than double lung • Cystic fibrosis • Bronchiectasis • Contraindicated in CF, and other suppurative • Pulmonary hypertension lung disease • Heart ‐ Lung: CHD with Eisenmenger’s • Use in pulmonary HTN remains controversial • Unique clinical characteristics with pulmonary HTN Case 1. Something stinks… PMH Meds HPI Asthma Albuterol, singulair • 55 yo woman; symptoms begin in 2011 with dry cough SH Works as a floor manager in a local casino; flooding 5 years ago with heavy • 2012: Progressive SOB with periods of sudden worsening. damage to the carpet which covers concrete floors • Diagnosed with pneumonia; multiple rounds of antibiotics ROS did not help None • Diagnosed with asthma  oral steroids steroids provided relief for up to weeks PE: 37.5 110/70 70 16 86% RA • 6/2012 Initiated on oxygen, CT chest showed possible RRR fibrosis Dry inspiratory crackles No rashes, joint swelling 4

2/28/2017 Studies • Autoimmune serologies Spirometry negative FEV1 1.15 (38%) FVC 1.24 (36%) TLC 2.71 (45%) DLCO 5.6 (24%) Expiratory Interstitial Lung Disease Interstitial lung disease • “Interstitium” is a potential Idiopathic Other ILD of known Granulomatous space between the epithelial and Interstitial (eosinophilic etiology (HP, drugs, ILD(Sarcoidosis) endothelial basement membrane Pneumonia pneumonia, LM, collagen ‐ vascular) (IIP) HX etc.) • Interstitial lung disease occurs when there is inflammation or fibrosis in this space Chronic fibrosing Smoking related Acute/subacute IPF NSIP RBILD DIP AIP COP 5

2/28/2017 Return to Case 1. Diagnosis Differential Diagnosis Collagen Vascular Disease/Autoimmune Environmental Antisynthetase syndrome (Jo ‐ 1, PL ‐ 7, PL ‐ 12, EJ, OJ, Hypersensitivity pneumonitis (avian, molds, • • SRP, Mi ‐ 2, Ku), also MDA ‐ 5 isocyonates, other organic dusts) Rheumatoid arthritis (higher proportion of UIP) Pneumoconioses (silicosis, asbestosis, berryliosis, • • coal miner’s lung disease) SLE (greater prevalence of ILD than appreciated in • the literature) Systemic sclerosis (diffuse more associated with Medications • ILD; limited more with PAH) TNF ‐ alpha inhibitors (eternacept, infliximab, • Mixed connective tissue disease adalimumab) • Sjogren’s Chemotherapy drugs: bleomycin, busulfan, etc. • • Vasculitidies: granulomatous polyangiitis Amiodarone • • Idiopathic Methotrexate • IPF Sirolimus/everolimus • • NSIP NSAIDS, antibiotics (eosinophilic) • • COP • AIP (Hamman ‐ Rich Syndrome) Other • RBILD Eosinophilic pneumonia: idiopathic, parasitic • • DIP Sarcoidosis • • LIP Lymphangioleiomyomatosus (LAM) • • PPFE Pulmonary langerhans cell histiocytosis • • Unclassifiable Lymphangitic carcinomatosis • • Pulmonary alveolar proteinosis • Return to Case 1. Diagnosis Hypersensitivity pneumonitis • Allergic reaction to inhaled organic dust, fungus, Hypersensitivity pneumonitis from molds, or chemicals workplace mold exposure • Many names, depending on exposure • Bird fancier’s lung, farmer’s lung, hot tub lung, Woodman’s disease, etc… • Avian antigen most likely to cause fibrosis 6

2/28/2017 Transplant for Group D “Restrictive” 2000 ‐ 2013 Clinical course N = 8692 Scleroderma, Sarcoidosis, 285 • Stopped working, started prednisone and cellcept 121 HP, 147 • Over 6 months 2LPM  10LPM at rest, 15LPM w/ Pulmonary Fibrosis ‐ other, exertion 1090 Other, 1370 • Listed for transplant 3/12/2013 • 4/30/13: underwent bilateral lung transplantation HP on central veno ‐ arterial ECMO support Scleroderma • 22 day recovery period Sarcoidosis • Remains well today with stable allograft function Pulmonary Fibrosis ‐ other IPF, 5679 IPF Other Source: UNOS Hypersensitivity pneumonitis Survival is excellent • Likely under recognized Variable Va HR 95% CI CI P indication Multivariate • National registry: <1% HP Diagnosis 0.25 0.08 ‐ 0.6 0.008 • UCSF: 8% (31 of 222) Age 1.03 0.99 ‐ 1.08 0.091 Bilateral Tx 0.33 0.17 ‐ 0.65 0.001 • 31 cases of HP Male 1.05 0.50 ‐ 2.02 0.987 • 8 (26%) dx made after BMI 1.08 1.01 ‐ 1.16 0.026 transplant Treated for 0.73 0.35 ‐ 1.52 0.404 Rejection Kern RM. CHEST . 2014 Kern RM. CHEST . 2014 7

2/28/2017 PMH Meds Case 2. Between a rock and a hard place • Asthma Albuterol, pulmicort, combivent, singulair HPI SH • 44yo male moved to US from Mexico in late 2012. Lives with his wife and 3 children in Fresno, on disability • 2013: Spontaneous pneumothorax , hospitalized 19 days, TB excluded Life long non ‐ smoker Worked in stone grinding and sculpting work in Mexico (cantera) for 18yrs • 2014: DOE, wheezing  diagnosed with asthma • Inconsistent PPE use • 2014 ‐ 15: multiple ER visits for SOB  prednisone bursts and antibiotics • Stopped working when he moved to the U.S. • Oct 2015: CT chest showed “mild” pleural/paratracheal thickening and mediastinal adenopathy PE: 37.5 105/70 118 36 82% on RA  93% 3LPM • Bronchoscopy negative for cancer/tuberculosis Thin Tachycardi, loud P2 • Jan 2016: second pneumothorax Expiratory wheezes and rhonchi upper lung zones > lower • Feb 2016: started on 2LPM of oxygen, stopped working + clubbing Diagnosis: Progressive massive fibrosis from silica inhalation Spirometry FEV1 0.71 (19%) FVC 2.47 (53%) FEV1/FVC 0.29 DLCO 11.6 (33%) 8