Finding the Needle in the Haystack: Diagnosing and Managing Alpha-1 Antitrypsin Deficiency in Patients with COPD.

Finding the Needle in the Haystack: Diagnosing and Managing Alpha-1 Antitrypsin Deficiency in Patients with COPD

Faculty Franck Rahaghi, MD, MHS, FCCP Director of Advanced Lung Disease Clinic Director, Pulmonary Hypertension Clinic Chairman, Dept. of Pulmonary and Critical Care Cleveland Clinic Florida Weston, FL Robert A. Sandhaus, MD, PhD, FCCP Professor of Medicine Director, Alpha-1 Program National Jewish Health Clinical Director, Alpha-1 Foundation Executive VP and Medical Director, AlphaNet Medical Director, AlphaNet Canada Coral Gables, FL

Disclosures Idiopathic Pulmonary Fibrosis: Ensuring an Accurate Diagnosis and Personalizing a Therapeutic Plan Franck Rahaghi, MD, MHS, FCCP serves as a speaker/consultant and researcher for Shire. Dr. Rahaghi also serves as a speaker and consultant for Grifols. Robert A. Sandhaus, MD, PhD, FCCP serves as principal Investigator for NIH/NHLBI and MatRx. NACE - Emerging Challenges in Primary Care: 2014

Learning Objectives Discuss the pathophysiology of Alpha-1 antitrypsin deficiency (AATD) and its impact on chronic obstructive pulmonary disease (COPD) risk. Interpret the clinical significance of laboratory test results for AATD. Discuss treatment options for AATD and latest GOLD guideline recommendations. Discuss strategies to enhance detection and treatment of AATD in clinical practice.

PRE-TEST QUESTIONS

Pre-test ARS Question 1 Pre-A1: Please rate your confidence in your ability to integrate the assessment and management of AATD into the care of patients with COPD: Not at all confident Slightly confident Moderately confident Pretty much confident Very confident LO #1, 2, 3, 4 ** confidence

Pre-test ARS Question 2 Pre-A2: How often do you consider screening patients with COPD for AATD? Never Rarely Sometimes Frequently Always LO #1, 2, 3, 4 ** practice

Pre-test ARS Question 3 Pre-A3: Which of the following statements about alpha-1 antitrypsin is correct? Protease inhibitor synthesized in kidney Proteolytic enzyme released by white blood cells Inactivates neutrophil elastase and other enzymes Inhibits urokinase plasminogen activator in lung tissue LO 1 Answer 3 ** knowledge

Pre-test ARS Question 4 Pre-A4: A 42-year-old man with no smoking history is diagnosed with COPD. Testing for AATD identifies serum AAT 90 mg/dL. Which of the following statements is correct? He has normal AAT levels, which rules out a carrier state He has AAT levels <100mg/dL and therefore is a candidate for replacement therapy Monitor AAT levels every 6 months; if levels remain <100 mg/dL, refer for replacement therapy Initial testing should have included BOTH phenotype/genotype and AAT levels to better advise the patient Competence LO 2,3 Answer 4

Alpha-1 Antitrypsin Deficiency (AAT): 50 Years of Progress
Pre-test ARS Question 5 Pre-A5: Methods for identifying the majority of patients with AATD include all the following, EXCEPT: Using spirometry to identify patients Performing point-of-care testing using kits Test only young patients with emphysema for AATD Using reminders from PFTs or Electronic Medical Records to elicit testing Knowledge LO 4 Answer 3 NACE - Emerging Challenges in Primary Care: 2014

Pre-test ARS Question 6 Pre-A6: All of the following benefits of AATD replacement therapy have been demonstrated (Registry or RCT), EXCEPT: Reduced decline in CT densitometry Improved survival in patients with lower FEV1 Reduced decline in FEV1 for patients with FEV1 < 30% Reduced decline in FEV1 for patients with FEV 35%-65% Knowledge LO 3 Answer 3 NACE - Emerging Challenges in Primary Care: 2014

Malmö Pictures of Laurell and Eriksson, Malmo hospital in Sweden and a missing Alpha-1 band NACE - Emerging Challenges in Primary Care: 2014

What is Alpha-1 Antitrypsin (AAT)?
Protease inhibitor primarily synthesized by hepatocytes Some contribution from lung epithelial cells and macrophages Protects normal body tissue from proteolytic enzyme damage Especially neutrophil elastase (NE) released by white blood cells Theoretical protective threshold = 11 µM/L Mahadeva R. Am J Pathol. 2005;166: Ranes J. Semin Respir Crit Care Med. 2005;26:

Normal AAT Inactivation of Neutrophil Elastase
“Mousetrap -like” Closure of AAT on NE AAT with Reactive Loop Neutrophil Elastase (NE) Inactivated NE ©2004 by BMJ Publishing Group Ltd and British Thoracic Society Lomas D. Thorax 2004;59:

AAT and Neutrophil Elastase Balance
Healthy AAT-deficient Elastase burden Elastase protection Elastase burden Elastase protection Elastase AAT AAT Elastase Breakdown of lung tissue Janoff A. Am Rev Respir Dis. 1985;132: Hunninghake G. Am Rev Respir Dis. 1983; 128:

AAT Deficiency Prevalence (US)
COPD prevalence: ~13 million 1%-3% of all emphysema patients have severe AATD Emphysema prevalence due to AATD: ~80, ,000 AATD diagnosed: ~7,000 diagnosed with AATD Estimated <10% diagnosed Emphysema Organization. Accessed March AATD update 2006;1:1-11.

Alpha-1 is More Common than Previously Thought
Prevalence of Alpha-1 in the US Idiopathic Pulmonary Fibrosis1 Alpha-12* Sickle Cell3 Cystic Fibrosis4 Huntington’s Disease5 Genetic COPD is more common than previously thought. Alpha-1 is not a rare disease but instead a disease that has been rarely diagnosed.1 In the United States, the estimated prevalence of alpha-1 is 80,000 to 100,000 individuals.2 Other genetic diseases, such as cystic fibrosis and Huntington’s disease, occur less often in the US population.3,4 Sickle cell disease has approximately the same prevalence as alpha-1.5 Approximately 128,000 patients in the US have idiopathic pulmonary fibrosis.6 20 40 60 80 100 120 140 Number of Patients (x103) *Homozygote Pi ZZ only Over 25 million Americans (1/13) are carriers 1. Accessed February 21, Campos MA, et al. Chest. 2005;128(3): Accessed February 16, Accessed February 16, Accessed February 10, 2017. References: 1. de Serres FJ. Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed. Environ Health Perspect. 2003;111(16): 2. Campos MA, Wanner A, Zhang G, Sandhaus RA. Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and Chest. 2005;128(3): 3. Accessed November 20, 2015. 4. Accessed February 16, 2017. 5. Accessed February 16, 2017. 6. Accessed February 16, 2017.

Genetic Aspects Heterozygous Homozygous 2 different alleles
Two alleles that genetically code for AAT = “phenotype” Alleles M allele - Normal variant ~95% of US population Z allele Found in 95% with clinically recognized AATD Ineffective AAT release from hepatocytes (hepatic accumulation, polymerization) S allele (slightly more common than Z) Variant causing mildly decreased AAT levels Null allele Interrupted AAT synthesis due to transcriptional or translational errors No liver accumulation Heterozygous 2 different alleles Expressed as “Pi*MZ” Homozygous 2 same alleles Expressed as “Pi*ZZ” ATS/ERS Statement: Am J Respir Crit Care Med ; 168:

Inheritance of AATD and Allele
AATD is inherited in an autosomal co-dominant pattern The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of AAT. Most people carry two copies of the M allele (MM) in each cell. Other versions of the SERPINA1 gene, as the S or Z allele, can cause low to no production of AAT.

AAT Clinical Tests Available Qualitative (Genetic Profile)
Quantitative (Level) Serum level tests (CPT 82103) Rocket immunoelectrophoresis Radial immunodiffusion Nephelometry Immunoassay/double antibody assay Qualitative (Genetic Profile) Phenotyping (CPT 82104) Identification of AAT variants (phenotypes) by isoelectric focusing (IEF) Serum or plasma, some use “dried blot spot” samples Genotyping (CPT 83894) Molecular level Dx of genomic DNA Whole blood or buccal swab samples “Dried blot spot” samples

Serum Levels Differ Depending on Test Method
AAT is an acute phase reactant; inflammatory conditions may falsely elevate levels Radial immunodiffusion >>> Rarely Done Now! Normal range: 150/200–350/400 mg/dl* Protective threshold: 80 mg/dl* Nephelometry Normal range: 83/120–200/220 mg/dl* Protective threshold: 57 mg/dl*; 11 µM† Methodologies and Reporting Create Confusion Read the Reports Carefully * Varies by lab performing test. † Value obtained by the NHLBI standard. ATS/ERS Standards. Am J Respir Crit Care Med. 2003; 168:

Free, easy, and confidential testing kits are available
Testing All COPD Patients Can Help Detect Those at Increased Risk for Lung Disease This slide represents the range of serum AAT levels by phenotype (serum AAT levels in a µM concentration and in mg/dL). Free, easy, and confidential testing kits are available AAT, alpha1-antitrypsin. Data on file, Grifols.

AATD Clinical Manifestations
Lung disease Emphysema Chronic Bronchitis Bronchiectasis Childhood and adult liver disease Hepatitis, cirrhosis, hepatocellular carcinoma Fulminant liver failure Occasional systemic manifestations Necrotizing panniculitis Vasculitis Ranes J. Semin Respir Crit Care Med. 2005;26:

Clinical Presentation of AATD: Lung Disease
No unique presenting features Dyspnea (84%) Decreased exercise tolerance Wheezing (76%) Cough (42%) Excess sputum production (46%) Frequent lower respiratory tract infections History of suspected allergies and/or asthma In NHLBI Registry, 61% had FEV1 reversibility when tested with 3 serial spirometries Alpha-1 Association Website. Accessed January McElvaney NG. Chest. 1997;111(2): The Alpha-1-Antitrypsin Deficiency Registry Study Group. Am J Resp Crit Care Med. 1998;158:49-59.

Age, Smoking History, or Severity of FEV1 Decline Should NOT Define Which COPD Patients to Test FEV1 percentage predicted by age for 378 Pi ZZ patients stratified by smoking status1,2 100 120 80 60 40 20 FEV1 Predicted (%) 30 35 50 45 70 65 140 55 75 Severe COPD* Age *Stage III severe COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Nonsmokers Smokers As demonstrated above, severely deficient alpha patients (Pi ZZ) have varying profiles. Although smoking and age are risk factors for alpha-1, they do not always identify patients with severe alpha-1 FEV1 levels alone can be misleading when considering who to test Some nonsmokers have low FEV1 levels; some smokers have high FEV1 levels Consider how many alphas are overlooked if testing only those at a severe stage of COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines Remember that only a laboratory test can confirm the presence of alpha-1 DeMeo DL, et al. Thorax. 2007;62(9): Image reproduced with permission from BMJ Publishing Group Ltd. Global Initiative for Chronic Obstructive Lung Disease. Pocket guide to COPD diagnosis, management, and prevention. 2010:1-28. NACE - Emerging Challenges in Primary Care: 2014

Self-reported Diagnoses in Severe AATD
(N=1851 Patients with Severe AATD) n=61 Asthma Obstructive Lung Disease n=69 Emphysema Chronic Bronchitis Liver Disease No Lung or Liver Related Symptoms n =287 n = 95 n=110 n = 314 n =199 n=159 n=315 n=122 n = 197 Strange C. Respiration 2006;73(2):185.

Clinical Presentation of AATD—Lung Disease
AATD may present in several ways on chest X-rays In advanced disease, AATD produces panacinar, basilar emphysema AAT-Deficient Regular Chest X-ray American Thoracic Society. Am J Respir Crit Care Med. 2003;168:

Inconsistent Imaging in AATD
Chest X-rays from 165 ZZ Alpha-1 patients:1 15% were normal Only 20% showed “classic” emphysema at bases CTs from 102 ZZ Alpha-1 patients:2 64% showed basal predominance 36% had predominant apical disease 1. Gishen. Clin Radiol 1982; 33: Parr D. Am J Respir Crit Care Med 2004; 170:

Clinical Presentation of AATD: Liver Disease
Infancy – prolonged jaundice1 Leading genetic cause of liver disease in children2 2nd most common indication for liver transplantation3 in children Older children and adults1 Elevated liver function tests, abnormal clotting, enlarged liver or spleen, portal hypertension, esophageal varices, ascites, chronic active hepatitis, “cryptogenic” cirrhosis 1. Alpha-1 Association Website. Accessed Sept 2008. 2. Morrison ED, Kowdley KV. Postgrad Med. 2000;107: 3. Primhak RA, Tanner MS. Arch Dis Child. 2001;85:2-5.

AAT Z Variant Retained in Hepatocytes
Intracellular Inclusions Intracellular Inclusions Lomas DA. Thorax 2004;59:

Clinical Presentation of AATD: Necrotizing Panniculitis

Natural History of Emphysema in AATD
Risk of developing emphysema with AATD not completely understood Some with AATD never develop the disease Estimated annual rate of FEV1 decline PI*ZZ non-smokers = mL/yr PI*ZZ smokers = 113 mL/yr1 Predictors of greater FEV1 decline: Smokers, males, age years, FEV % predicted value, decreased serum AAT levels, bronchodilator response2 1. Piitulainen, E. Eur Respir J. 1999;13: Stoller JK. Lancet. 2005;365:

Questions to Consider

AATD is “frequently underdiagnosed or misdiagnosed by clinicians.”
From a Joint Statement of American Thoracic Society and European Respiratory Society... AATD is “frequently underdiagnosed or misdiagnosed by clinicians.” ATS/ERS Standards. Am J Respir Crit Care Med. 2003; 168:

Diagnosis of AATD Delays and Missed Opportunities
Mean delay of 7.2 years between first symptom and initial AATD diagnosis1 Survey of 300 AATD patients 44% reported seeing at least 3 physicians before initial AATD diagnosis1 No improvement in early disease diagnosis between 1968 and 20032 1. Stoller JK. Lancet. 2005;365: Campos MA. Chest. 2005;128:1179–1186.

ATS Diagnostic Testing Guidelines*
Type A – Recommend Symptomatic adults with: -Emphysema -COPD Incompletely reversible asthma Asymptomatic individuals with: -Persistent obstruction on PFT and identifiable risk factors (patients with FEV1< 80% predicted and FEV1/FVC less than 0.70) All individuals with unexplained liver disease Adults with necrotizing panniculitis Type B – Consider Adults with bronchiectasis of unknown source Adolescents with persistent airflow obstruction Asymptomatic individuals with persistent airflow obstruction and no identifiable risk factors Adult C-ANCA-positive vasculitis *Recommendations, graded from type A to type D, made based on supportive and weighing for and against all issues.

GOLD Guidelines on AATD
The World Health Organization recommends that all patients with a diagnosis of COPD should be screened once especially in areas with high AATD prevalence. A low concentration (< 20% normal) is highly suggestive of homozygous deficiency. Family members should also be screened. WHO meeting participants. Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ 1997; 75(5):

Common AATD Testing Barriers
Lack of AATD awareness and knowledge Lack of adherence to guidelines Problem with guidelines Physician adherence to any guidelines Unfamiliarity/Nihilism with treatment options Office workflow may not be conducive Testing fatigue

Approaches to Increasing Testing
Campaigns to enhance awareness of AATD among primary care physicians and respiratory therapists using a variety of media, including targeted publications Presentations at grand rounds and at national meetings, and in web-based instructional programs Distributing free test kits for AATD and providing free, conﬁdential home-based testing for AATD Evolving interest in developing a rapid point-of-care test for AATD Family testing Stoller and Brantly COPD, 10(S1):26–34, 2013

Approaches to Increasing Testing, cont’d
Issuing written recommendations to physicians to test for AATD in the written results of pulmonary tests. Clinical decision support within an electronic medical record to prompt physicians to test for AATD in appropriate clinical settings. Testing for AATD and recognition of affected individuals by RTs and by the physicians with whom they practice will increase. Renewing consideration of wide-spread, mandatory newborn screening for AATD. Stoller and Brantly COPD, 10(S1):26–34, 2013

In-Office Strategies to Rule Out Alpha-1
Establish a formal practice protocol or standard orders for ruling out alpha-1 in COPD patients ATS guidelines recommend testing all COPD patients Seek out protocols/guidance from the Alpha-1 Foundation’s Clinical Resource Centers (alpha1.org/Newly- Diagnosed/Living-with- alpha-1/Find-an-alpha-1-Specialist) or from published literature1,2 and choose what’s right for your practice Identify 1 to 2 in-office “champions” Include alpha-1 testing in your practice EMR for current and newly diagnosed COPD patients All newly diagnosed COPD patients should get an alpha-1 test ATS, American Thoracic Society; COPD, chronic obstructive pulmonary disease; EMR, electronic medical records. 1. Rahaghi FF, et al. COPD. 2012;9(4): Stoller JK. Respir Care. 2010;55(6): 41

Testing Protocols Help Identify People With Alpha-1
To ensure universal testing, many practices find it helpful to establish a formal protocol for alpha-1 testing A 2012 study found that a standardized testing protocol is effective for identifying AAT deficiency 3,152 adults with COPD GOLD II-IV diagnosis Tested at US PFT labs by RTs or pulmonary function technicians Despite ATS (American Thoracic Society) guidelines recommending broad testing, fewer than 10% of alpha-1 individuals have been identified. In an effort to address under-diagnosis of alpha-1, this study tested implementation of a formal testing protocol using respiratory therapists and pulmonary function technicians. The aim was to estimate frequency rates of abnormal alpha-1 genotypes among patients with fixed airflow obstruction, and assess feasibility of having pulmonary function laboratory personnel administer the study. Consecutive eligible patients were offered testing for alpha-1 by the PFT lab personnel at the time of their PFT testing. Eligible patients were defined as adults (age >18 years) with no prior knowledge of their alpha-1 status and who were found to have COPD GOLD II-IV (FEV1/FVC ratio <0.7, with post-bronchodilator FEV1 <80% predicted). The RTs and pulmonary function technicians approached eligible patients, obtained consent, and evaluated subjects based on inclusion and exclusion criteria. Subjects who consented to participate underwent genotyping for AATD and were administered a brief survey (to assess demographic features, family history, and baseline smoking history). These assessments were administered by the RTs or pulmonary function technicians. Genotyping was conducted using dried blood spot card test kits in which the eluted blood underwent polymerase chain testing for the S and Z AAT alleles at a central laboratory (Alpha-1 Genetics Laboratory at the University of Florida, Gainesville, FL). A total of 3,457 subjects were recruited from 19 US academic centers (range of 9 to 766 subjects per center). Of 3152 eligible subjects: 0.63% (n=20) were found to have severe AATD and 10.88% (n=352) were identified as being MZ or MS heterozygotes. This study supports the value of a formal testing protocol for widespread alpha-1 testing and identification, and reinforces the value of complying with ATS guidelines by testing broadly among adults with fixed airflow obstruction. Results also support the feasibility and effectiveness of RTs or PFT technicians as study coordinators capable of conducting a multicenter PFT laboratory-based alpha-1 detection effort. AAT, alpha1-antitrypsin; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; PFT, pulmonary function test; RT, respiratory therapist. Rahaghi FF, et al. COPD. 2012;9(4): Reference: Rahaghi FF, et al. The prevalence of alpha-1 antitrypsin deficiency among patients found to have airflow obstruction. COPD. 2012;9:

Why Test? Because alpha-1 antitrypsin (AAT) deﬁciency is inherited as an autosomal co-dominant condition, family members of probands are at risk of having AATD and of developing associated disease Diagnosis of AATD can favorably affects smoking behaviors Because occupational dust exposure is associated with worsened clinical status in individuals with AATD, detection could affect occupational choice Specific therapy for AATD is available and has been recommended for individuals with emphysema due to AATD Official society guidelines endorse testing for AATD, establishing a standard of care that warrants compliance Stoller and Brantly COPD, 10(S1):26–34, 2013

Augmentation Therapy The emphysema link to PiMZ individuals (levels >50 to 60 % of normal) is relatively weak Prevalence appears to increase with PI*SZ individuals (whose levels are approximately 25%–35% of normal) A level of 11 µmol/L has been set as the protective threshold based on the lowest level of PI*SS patients, who do not typically develop COPD

Augmentation Therapy Increases serum and lung epithelial lining fluid (ELF) levels of AAT Indicated for adult patients with AATD and evidence of emphysema/COPD 60mg/kg/week IV Chronic Obstr Pulm Dis. 2016; 3:

Benefits of Early Intervention
May slow decline of pulmonary function Early identification of at-risk or carrier family members Aggressive smoking cessation efforts to reduce risk of related emphysema Reassessment and change of occupational/environmental risk factors Chronic Obstr Pulm Dis. 2016; 3:

Why Augmentation Therapy?
Alpha-1 Antitrypsin Deficiency (AAT): 50 Years of Progress Wewers in NEJM 1987;316:1055 NACE - Emerging Challenges in Primary Care: 2014

FEV1 Decline NHLBI Registry Study Stratification by FEV1 % Predicted
FEV1 Decline (mL/yr) -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 <35% 35%-49% 50%-79% ≥80% No Augmentation Augmentation Baseline FEV1 % Predicted * * P=0.03 Adapted from The Alpha-1-Antitrypsin Deficiency Registry Study Group. Am J Respir Crit Care Med. 1998;158:49-59.

Chapman Meta-Analysis
Chapman KR. J Chronic Obstructive Pulmonary Disease. 2009;6:

Lung Densitometry

The RAPID Trial Placebo controlled, 2-year CT densitometry follow-up
Alpha-1 Proteinase Inhibitor (60 mg/Kg) Placebo group crossed over to Rx – followed + 2 years Pre-specified (in 2003) primary endpoint of combined CT densitometry score at TLC and FRC was not significantly different (p=0.027)* between treated and placebo CT densitometry at TLC was significantly different (p=0.007) None of the other secondary endpoints were different between groups (FEV1, exacerbations, quality of life) Placebo patients crossed over to treatment and followed for an additional 2 years showed slowing of decline in CT densitometry at TLC *NB: significance is p of or better because this was analyzed as a one-sided test Am J Respir Crit Care Med 187;2013:A6069

The RAPID Trial Am J Respir Crit Care Med 187;2013:A6069

Rate of Lung Infections in AATD Patients
Lieberman J. Chest 2000; 118:

Survival in Individuals with Severe Alpha-1 Antitrypsin Deficiency
The Alpha-1-Antitrypsin Deficiency Registry Study Group. Am J Resp Crit Care Med. 1998;158:49-59.

Alpha-1 Antitrypsin Augmentation Improves Survival in Individuals with
Low Lung Function and Severe Alpha-1 Antitrypsin Deficiency (AATD) Staring with FEV1 of 60% Down to 10% No Augmentation Augmentation Rahaghi et al. ATS 2014

Testing and Replacement
Therapy are Indicated in Advanced COPD Patients

Future Interventions in AATD
Decrease Inflammatory/ NE Burden Smoking cessation Environmental Intervention Vaccination Early/ aggressive treatment of inflammation and infection Treatment IV augmentation In the Future Gene Therapy Gene Correction Therapy Anti-polymer drugs Molecular chaperone iPS cells Oral Elastase Inhibtors Aerosolized rAAT Human Transgenic Yeast Plant

Summary AATD is difficult to identify based on clinical symptoms alone
AATD is a lab diagnosis Testing/screening important to identify patients One test once in a lifetime will identify AATD Optimal therapy for AATD includes lifestyle changes, symptom management and augmentation therapy

POST-TEST QUESTIONS

Post-test ARS Question 1
Post-A1: After completing this activity, please rate your confidence now in your ability to integrate the assessment and management of AATD into the care of patients with COPD: Not at all confident Slightly confident Moderately confident Pretty much confident Very confident LO #1, 2, 3, 4 ** confidence

Post-A2: After completing this activity, how often do you intend to consider screening patients with COPD for AATD? Never Rarely Sometimes Frequently Always LO #1, 2, 3, 4 ** practice

Post-A3: Which of the following statements about alpha-1 antitrypsin is correct? Protease inhibitor synthesized in kidney Proteolytic enzyme released by white blood cells Inactivates neutrophil elastase and other enzymes Inhibits urokinase plasminogen activator in lung tissue LO 1 Answer 3 ** knowledge

Post-A4: A 42-year-old man with no smoking history is diagnosed with COPD. Testing for AATD identifies serum AAT 80 mg/dL. Which of the following statements is correct? He has normal AAT levels, which rules out a carrier state He has AAT levels <100mg/dL and therefore is a candidate for replacement therapy Monitor AAT levels every 6 months; if levels remain <100 mg/dL, refer for replacement therapy Initial testing should have included BOTH genotype and AAT levels to inform treatment decisions Competence LO 2,3 Answer 4

Alpha-1 Antitrypsin Deficiency (AAT): 50 Years of Progress Post-test ARS Question 5 Post-A5: Methods for identifying the majority of patients with AATD include all the following, EXCEPT: Using spirometry to identify patients Performing point-of-care testing using kits Testing all young patients with emphysema for AATD Using reminders from PFTs or Electronic Medical Records to elicit testing Knowledge LO 4 Answer 3 NACE - Emerging Challenges in Primary Care: 2014

Alpha-1 Antitrypsin Deficiency (AAT): 50 Years of Progress Post-test ARS Question 6 Post-A6: All of the following benefits of AATD replacement therapy have been demonstrated (Registry or RCT), EXCEPT: Reduced decline in CT densitometry Improved survival in patients with lower FEV1 Reduced decline in FEV1 for patients with FEV1 < 30% Reduced decline in FEV1 for patients with FEV 35%-65% Knowledge LO 3 Answer 3 NACE - Emerging Challenges in Primary Care: 2014

Questions

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Finding the Needle in the Haystack: Diagnosing and Managing Alpha-1 Antitrypsin Deficiency in Patients with COPD.

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Finding the Needle in the Haystack: Diagnosing and Managing Alpha-1 Antitrypsin Deficiency in Patients with COPD.

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