Alpha-1: Demystifying the Mystery 1 Miranda D. Withers, MSN, APRN

2 Includes chronic bronchitis and emphysema 1 More than 3 million people died of COPD in 2012, which is equal to 6% of all deaths globally that year 2 Third leading cause of death in the US 3 What is COPD? 1. American Thoracic Society website; Accessed February 21, 2015http:// 2. WHO website Accessed February 21, 2015http:// 3. Miniño AM, et al. Natl Vital Stat Rep. 2010;59(2): Mannino DM. Chest. 2002;121(5 suppl):121S-126S.

COPD Risk Factors  Smoking 1 − At least 25% of long-term smokers develop COPD 2  Other inhaled agents 1  Genetic factors 1  Lung growth and development 1  Asthma/bronchial hyperreactivity 1  Age 1  Respiratory infections 1  Socioeconomic status 1 3 COPD, chronic obstructive pulmonary disease. 1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease—Updated Available at: Accessed February 21, Løkke A, et al. Thorax. 2006;61(11):

Facts About Alpha-1 4  Up to 25 million Americans have an abnormal allele (S or Z) 2  An estimated 100,000 Americans have alpha-1 3  90% remain undiagnosed 4,5  Early diagnosis and treatment is associated with health benefits 6  Most common inherited risk factor for COPD (1 in 10 COPD patients) 6 COPD, chronic obstructive pulmonary disease. 1. de Serres FJ. Environ Health Perspect. 2003;111(16): de Serres FJ, et al. Clin Genet. 2003;64(5): Campos MA, et al. Chest. 2005;128(3): Silverman EK, Sandhaus RA. N Engl J Med. 2009;360(26): About AAT deficiency. professionals/about-aat-deficiency/. Accessed February 21, Brantly M. Clin Chem. 2006;52(12):

What is Alpha-1 Antitrypsin and What does it do? 5 Protein produced in the liver Purpose is to protect the lungs from neutrophil elastase, which is an enzyme that digests damaged or aging cells and bacteria Neutrophil elastase can also affect good, healthy tissue if left unchecked Alpha-1 Foundation Website

6 Sharp, R, Serres, F, Newman, L, Sandhaus, R, Walsh, J, Hood, E and Harry, G 2003, ‘Environmental, occupational, and genetic risk factors for alpha-1 antitrypsin deficiency,’ Environmental Health Perspectives, vol. 111, no. 14, November, pp

Alleles of Alpha-1 7 AAT Deficiency is a genetic mutation of SERPINA1 Most common allele is M and is considered normal Most common variations are S and Z Z produces the least alpha-1 and can cause the most problems Individuals who have two copies of the deficient alleles are considered to have Alpha-1 NIH Website; Accessed February 21, 2015http://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency

8 All COPD (especially emphysema) is caused by smoking 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 complete diagnosis of alpha-1 can be made on serum levels alone I know an alpha-1 patient when I see one Myths surrounding COPD

9 What does an “Alpha” look like?

Have you seen this patient? 10  Dyspnea  Decreased exercise tolerance  Wheezing, Cough  Excess sputum production  Frequent lower respiratory tract infections  History of suspected allergies and/or asthma

11 Test all adults with symptomatic COPD, regardless of smoking history Test all adults with symptomatic emphysema, regardless of smoking history Test all adults with symptomatic asthma whose airflow obstruction is incompletely reversible after bronchodilator therapy Test asymptomatic patients with persistent obstruction on pulmonary function tests with identifiable risk factors (eg, smoking, occupational exposure) Test siblings of individuals with alpha-1 ATS Testing Guidelines Am J Respir Crit Care Med Vol 168. pp 818–900, 2003 DOI: /rccm Internet address:

Pay special attention to these: 12 Family history of lung or liver disease Early onset emphysema or emphysema in the absence of a known risk factor Frequent, severe respiratory infections Significant decline in lung function following severe respiratory infection Lung function decline that seems greater than a patient’s smoking history would predict American Thoracic Society/European Respiratory Society. Am J Respir Crit Care Med. 2003;168(7):

13 Lab testing including Alpha-1 phenotype and level and possibly LFT Levels alone cannot diagnose Alpha-1 (acute phase reactant) Free Testing is available from companies that provide Augmentation therapy Making the Diagnosis

Diagnosis is important 14  Promotes smoking prevention and cessation and other healthy lifestyle modifications  Increases potential for family testing and genetic counseling  Raises awareness to avoid hazards of occupational respiratory pollutants

15 Importance of Finding Carriers

Management of Alpha-1  Family testing and counseling  Lifestyle changes – Smoking cessation – Exercise – Avoidance of environmental pollutants – Limit alcohol consumption  Vaccinations – Influenza/pneumococcal – Hepatitis A/B  Drug therapy for lung disorders – Bronchodilators – Inhaled steroids – Antibiotics – Oxygen  Pulmonary rehabilitation  Surgical procedures – Lung transplantation in end-stage lung disease – Lung volume reduction surgery  Augmentation therapy 16 SaO 2, oxygen saturation in arterial blood; VO 2 max, maximal oxygen uptake. 1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease—Updated Available at: Accessed July 7, British Thoracic Society. Thorax. 2001;56(11): Ortega F, et al. Am J Respir Crit Care Med. 2002;166(5): Ries AL, et al. Am J Respir Crit Care Med. 2003;167(6):

Benefits of Pulmonary Rehab 17 Reduces dyspnea 1-3 Improves endurance 2 Reduces number of hospitalizations 2,3 Improves exercise capacity 1,3 Improves HRQOL 3 Improves survival 3 Reduces anxiety and depression associated with COPD 3 COPD, chronic obstructive pulmonary disease; HRQOL, health-related quality of life. 1. British Thoracic Society. Thorax. 2001;56(11): American Thoracic Society, European Respiratory Society. Am J Respir Crit Care Med. 2003;168(7): Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease—Updated Available at: Accessed February 21,

18 How can I make time for Alpha-1 testing in my busy practice?

Testing Strategies 19 Establish a formal practice protocol 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 (alpha- 1foundation.org/clinical-resource-centers) or from published literature 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 Place test kits near COPD medication samples

Resources for Providers & Patients  AlphaNet  Alpha-1 Foundation foundation.org  Alpha-1 Association Genetic Counseling Center genetic-counseling-program  Clinical Resource Centers alpha-1foundation.org/ clinical-resource-centers 20