Alpha-1: Demystifying the Mystery

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Miranda D. Withers, MSN, APRN

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• Includes chronic bronchitis and emphysema1

• More than 3 million people died of COPD in 2012, which is equal to 6% of all deaths globally that year2

• Third leading cause of death in the US3

What is COPD?

1. American Thoracic Society website; http://www.thoracic.org/clinical/copd-guidelines/resources/copddoc.pdf Accessed February 21, 2015 2. WHO website http://www.who.int/mediacentre/factsheets/fs315/en/. Accessed February 21, 2015 3. Miniño AM, et al. Natl Vital Stat Rep. 2010;59(2):1-52. 4. Mannino DM. Chest. 2002;121(5 suppl):121S-126S.

3COPD Risk Factors

Smoking1

− At least 25% of long-term smokers develop COPD2

Other inhaled agents1

Genetic factors1

Lung growth and development1

Asthma/bronchial hyperreactivity1

Age1

Respiratory infections1

Socioeconomic status1

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 2014. Available at: www.goldcopd.org. Accessed February 21, 2015. 2. Løkke A, et al. Thorax. 2006;61(11):935-939.

4Facts About Alpha-1

Up to 25 million Americans have an abnormal allele (S or Z)2

An estimated 100,000 Americans have alpha-13

90% remain undiagnosed4,5

Early diagnosis and treatment is associated with health benefits6

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):1851-1854. 2. de Serres FJ, et al. Clin Genet. 2003;64(5):382-397. 3. Campos MA, et al. Chest. 2005;128(3):1179-1186. 4. Silverman EK, Sandhaus RA. N Engl J Med. 2009;360(26):2749-2757. 5. About AAT deficiency. http://www.alpha1health.com/healthcare-professionals/about-aat-deficiency/. Accessed February 21, 2015. 6. Brantly M. Clin Chem. 2006;52(12):2180-2181.

5What is Alpha-1 Antitrypsin and

What does it do?

• 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 www.alpha1.org

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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. 1749-1752.

7Alleles of Alpha-1

• 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; http://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency; Accessed February 21, 2015

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• 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

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What does an “Alpha”

look like?

10Have you seen this patient?

Dyspnea Decreased exercise toleranceWheezing, Cough Excess sputum production Frequent lower respiratory tract infectionsHistory of suspected allergies and/or asthma

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• 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, 2003DOI: 10.1164/rccm.168.7.818Internet address: www.atsjournals.org

12Pay special attention to these:

• 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):818-900

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• 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

14Diagnosis is important

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

15Importance of Finding Carriers

16Management 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 therapySaO2, oxygen saturation in arterial blood; VO2 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 2014. Available at: www.goldcopd.org. Accessed July 7, 2014. 2. British Thoracic Society. Thorax. 2001;56(11):827-834. 3. Ortega F, et al. Am J Respir Crit Care Med. 2002;166(5):669-674. 4. Ries AL, et al. Am J Respir Crit Care Med. 2003;167(6):880-888.

17Benefits of Pulmonary Rehab

• Reduces dyspnea1-3

• Improves endurance2

• Reduces number of hospitalizations2,3

• Improves exercise capacity1,3

• Improves HRQOL3

• Improves survival3

• Reduces anxiety and depression associated with COPD3

COPD, chronic obstructive pulmonary disease; HRQOL, health-related quality of life.1. British Thoracic Society. Thorax. 2001;56(11):827-834. 2. American Thoracic Society, European Respiratory Society. Am J Respir Crit Care Med. 2003;168(7):818-900. 3. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease—Updated 2014. Available at: www.goldcopd.org. Accessed February 21, 2015..

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How can I make time for Alpha-1

testing in my busy practice?

19Testing Strategies

• 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

20Resources for Providers & Patients

AlphaNet1-800-577-2638www.alphanet.org

Alpha-1 Foundation1-877-228-7321 www.alpha-1foundation.org

Alpha-1 Association Genetic Counseling Center1-800-785-3177www.alpha1.org/support/genetic-counseling-program

Clinical Resource Centersalpha-1foundation.org/clinical-resource-centers