Improving Outcomes in COPD: A Closer Look into Genetics Cynthia L. - PDF document

6/12/2019 Scan with Camera for Pre-Test or Click on Link https://msu.co1.qu altrics.com/jfe/for m/SV_7R7xAW6Es 9I85q5 Improving Outcomes in COPD: A Closer Look into Genetics Cynthia L. McNerlin MSN, ANP-BC, FCCP DNP Project 3 Disclosures: • No Disclosures • No Conflicts of Interest 1

6/12/2019 4 Objectives • Outline the basic concepts of COPD • Understand the genetic cause of COPD • Understand the concepts of Alpha-1 Antitrypsin Deficiency (AATD) – Identify patients at risk – Identify screening methods – Identify ways to aid in screening – Identify resources available 5 Brief Overview of COPD • Definition: air flow limitation that is not fully reversible • Diagnosed with PFT with bronchodilator • Progressive decline in both physiologic features and functional status • Symptoms may include chronic cough, wheeze, dyspnea, excessive phlegm production • ≈ 20% of smokers have COPD (worldwide) • Pulmonary rehab improves functional status • Treatment aim is not cure but slowed progression, improved functional status and QOL 6 COPD Burden • 3rd leading cause of morbidity/mortality • Cost to the annual health care budget: $36B (Projected to be $49B in 2020) • Added to the CMS reimbursement repayment penalty act in 2014. • 251 million cases of COPD globally in 2016. • 3.17 million deaths were caused by the disease in 2015 (5% of all deaths). https://www.cdc.gov/copd/infographics/copd-costs.html 2

6/12/2019 7 Additional Costs • 16.4 million sick days per year – Accounts for $3.9B COPD related illness • Unplanned office visits, frequent calls for poorly controlled symptoms • Poor HRQOL scores • Unmet National Quality Measures for COPD 8 Non-Smoking causes of COPD • Burning of bio-mass fuels • Environmental exposures- pollutants • Occupational exposure • Developmentally impaired lung growth • Exposure to indoor air pollution can affect the unborn child and increase risk for COPD later in life • Genetic factors- Alpha-1 Antitrypsin Deficiency – (3-5% of COPD patients) 9 Brief Review of AAT and Deficiency Alpha-1 Antitrypsin : Deficiency: • Circulating Protein that protects • Inherited autosomal co-dominant; vital tissue from the destructive 1:1500-1:3000 effects of neutrophil elastace • Deficient codes: ‘S’, ‘F’, ‘I’, ‘null’ & • Manufactured and secreted by ‘Z’. the liver. • Abnormal combinations: anything • Normal Gene code “M”. (MM) that’s not ‘MM’ • ‘Z’ allele is the most pathogenic • Deficiency of this protective enzyme is causally-linked to multiple chronic diseases (Lung & Liver disease) https://www.genome.gov/19518992/learning-about-alpha1-antitrypsin-deficiency-aatd/ 3

6/12/2019 10 11 Alpha-1 Myths • All COPD is caused by smoking • AATD can be dx with PFT • Alpha-1 is rare, so I don’t need to test my patients • Alpha-1 results exclusively in emphysema • I don’t need to test for alpha-1 since there are no treatments • If I test, I only have to consider homozygous patients (Pi ZZ) • There is no need to test a smoker for alpha-1 • I do not need to test older patients for alpha-1 • A diagnosis of alpha-1 can be made on serum levels alone • I know an alpha-1 patient when I see one • Alpha’s cannot donate blood 12 Comparison to commonly recognized diseases 4

6/12/2019 13 Prevalence • Same for men and women 14 Historical Timeline 1987: 2016: US 1963: Enzyme 2000: Free 2003: Prevalence Discovery of Replacement Test Kits ATS/ERS AATD Therapy Available Guidelines < 10% Developed 53 yrs. 15 Most Individuals with AATD Escape Detection 10% Diagnosed 90% Undiagnosed Symptoms No Signs or but Symptoms Misdiagnosed Stoller, J. K., & Aboussouan, L. S. (2012). 5

6/12/2019 16 Populations at Risk COPD Emphysema Liver Disease Panniculitis • 3-5% Risk • 3% of all • Hepatocellular • 1 per 1,000 emphysema CA cases • Cirrhosis Spontaneous Cerebral Vasculitis Lung Cancers PTX Aneurysms • Giant Cell • 7.7% risk • 11% risk • Increase in adenocarcinomas Arteritis and squamous • Wegners’ cell carcinomas in • Lupus carrier status • PMR • RA 17 How is AATD Diagnosed? • Dried blood sample using free test kits – Genotype (M,S,Z,F,I,null) – Serum Level • Lab order of serum level AND genotype • Test while in-patient? • Home Genetics tests? – May not be an accurate result – 23&Me limits allele testing to ‘z’ and ‘s’ alleles 18 Punnett Square for AATD Risk M M M MM MM Z MZ MZ 6

6/12/2019 19 Offspring Risk with 2 MZ M Z M MM MZ Child #1 Child #2 Z MZ ZZ Child #4 Child #3 20 Case Review #1 • 22yo never smoker • Spontaneous PTX (x8) since age 9 – s/p Talc and mechanical pleurodesis • Aspiring to be an airline pilot • Bullous emphysema on Chest CT upper lobe predominant 21 7

6/12/2019 22 Case Review #2 • 49 yo never smoker • Hx coiling 5 yrs ago for Cerebral Aneurysm • No evidence of lung disease on PFT • Tested for AATD 23 24 8

6/12/2019 25 Pathology of the ‘S’ • Cerebral Aneurysms • Lung Cancers – Large Cell Types Case Review: Brothers 26 Age 64 Lifelong smoker Age 70 Never smoker 27 9

6/12/2019 28 Pathology of the ‘Z’ • Manifestations of liver disease • Abnormal accumulation of damaged AAT in the hepatocyte • Improper folding of allele impacts transportation into circulation (disease of gain) – Neonatal hepatitis – Adult cirrhosis / NASH – Hepatoma • Manifestations of lung disease – Emphysema (disease of loss) – COPD 29 30 Emphysema Features • Breakdown of the alveolar / capillary interface • CXR – flat diaphragms, hyperlucency 10

6/12/2019 31 32 Education for AATD  Alphas CAN donate blood * 33 Augmentation • Weekly infusion of replacement enzyme – Plasma derivative – Out patient clinic – Home infusion (self infusion/nurse infusion) • Helps maintain therapeutic levels of AAT • Does not improve rates of lung infections • 3 companies offer enzyme replacement – One provides the free test kits to your offices 11

6/12/2019 34 Impact 35 Guidelines Characteristic of Healthcare in west MI • Grand Rapids, Muskegon & Holland: Population 1,321,557 • Heavily weighted on 3 major health systems: Spectrum Health, Mercy Health and U of M (Metro). < 10% are Independent providers. • No specific policy for AATD screening. • AATD is not included in the infant dried blood sampling done at birth (State) • Provider discretion • Left to the patient to do their own homework • Resources include Local Certified Alpha Clinic (Spring Lake), Alpha 1 Foundation Website, state/local health dept 12

6/12/2019 37 Human Genome Project • Completed and Published in 2003 • In 2016- – 63% of providers were already in practice when the HGP was published – Missing academic opportunities for genetics education 38 Methods to Improve Screening • Incorporate these concepts into daily practice • EHR Alerts – ICD 10 – CDSR • Scheduling / Use of Medical Assistants • Use waiting room brochures for patients to help remind providers 39 Case Review #1 • 22yo nonsmoker • Spontaneous PTX (x8) since age 9 – s/p Talc and mechanical pleurodesis • Aspiring to be an airline pilot • Bullous emphysema on Chest CT upper lobe predominant 13

6/12/2019 40 Case Review #1 ZZ • 22yo nonsmoker • Spontaneous PTX (x8) since age 9 – s/p Talc and mechanical pleurodesis • Aspiring to be an airline pilot • Bullous emphysema on Chest CT upper lobe predominant 41 Case Review: Brothers • 64 yo lifelong smoker • 70 yo never smoker • FEV1 53% • FEV1 39% • Alpha MZ • Alpha MM Impossible to determine Alpha status solely based on PFT data 42 Alpha-1 Myths • All COPD is caused by smoking • AATD can be dx with PFT • Alpha-1 is rare, so I don’t need to test my patients • Alpha-1 results exclusively in emphysema • I don’t need to test for alpha-1 since there are no treatments • If I test, I only have to consider homozygous patients (Pi ZZ) • There is no need to test a smoker for alpha-1 • I do not need to test older patients for alpha-1 • A diagnosis of alpha-1 can be made on serum levels alone • I know an alpha-1 patient when I see one • Alpha’s cannot donate blood 14

6/12/2019 43 Take Home Points… • AATD is not a zebra • Keep thinking outside the box • Use guidelines as a ‘guide’ but keep up on current evidence in the literature 44 Post Test Questions/Comments https://msu.co1 .qualtrics.com/jf e/form/SV_1Yo GYthpq9N1drv Contact: cindymcnerlin@gmail.com 15