Alpha-1 : Demystifying the Mystery - PowerPoint Presentation

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Alpha-1: Demystifying the Mystery

1

Miranda D. Withers, MSN, APRN

Slide2

2Affiliation to disclose: Speaker for

Grifols

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3

Includes chronic bronchitis and emphysema

1More 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 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.

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COPD Risk FactorsSmoking1

At least 25% of long-term

smokers develop COPD

2

Other inhaled agents

1

Genetic factors

1Lung growth and development1

Asthma/bronchial hyperreactivity

1

Age

1

Respiratory infections1Socioeconomic status1

4

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

.

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Facts About Alpha-15

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):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

.

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What is Alpha-1 Antitrypsin and What does it do?

6

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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7

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.

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8

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Alleles of Alpha-19

AAT Deficiency is a genetic mutation of SERPINA1

Most common allele is

M

and is considered normal

Most common variations are

S

and ZZ 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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10

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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11

What does an “Alpha”

look like?

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12

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13

Photo taken from Boston University Website;

http

://www.bumc.bu.edu/supportingbusm/research/alpha-1

/

. Accessed February 21, 2015

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Have you seen this patient?14

Dyspnea

Decreased

exercise

tolerance

Wheezing, Cough

Excess

sputum production

Frequent lower respiratory tract

infections

History of suspected allergies and/or

asthma

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15

Test all adults with symptomatic COPD,

regardless of smoking historyTest 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

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Pay special attention to these:16

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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17

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

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Diagnosis is important18

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

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19

Importance of Finding Carriers

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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

20

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 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.

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Benefits of Pulmonary Rehab21

Reduces dyspnea

1-3

Improves endurance

2

Reduces number of hospitalizations

2,3

Improves exercise capacity

1,3Improves HRQOL3

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):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?

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Testing Strategies23

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

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Resources for Providers & Patients

AlphaNet

1-800-577-2638

www.alphanet.org

Alpha-1 Foundation

1-877-228-7321

www.alpha-1foundation.org

Alpha-1 Association Genetic Counseling Center

1-800-785-3177www.alpha1.org/support/genetic-counseling-programClinical Resource Centersalpha-1foundation.org/

clinical-resource-centers

24

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25

Case Studies

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Would you test?26

Ethnicity, age, and sex:

76-year-old white female

Profession:

Retired administrative assistant

Personal history:

40 pack-year smoker

Medical

history:

Diagnosed with advanced COPD 20 years ago; stable lung function

Current COPD medicationsLAMASABA

ICS/LABA

Family medical history:

2 brothers diagnosed with COPD

Pulmonary function testing results:

FEV

1

45% of predicted

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27

Diagnosis:

COPD confirmed

Heterozygote for alpha-1 with MZ genotype (“carrier”)

Actions

taken:

Maintain current COPD medications

Maximize bronchodilators

Treat lung infections aggressively

Avoid all tobacco and environmental hazards

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28

Actions taken for her family:

Family testing/genetic counseling offered

Family testing results:

1 MZ (patient) yielded 3 ZZ

Son (50 years old): ZZ with normal

lung function

Granddaughter (26 years old): ZZ;

new diagnosis of COPD

Great-granddaughter (14 years old):

ZZ with normal lung function

Daughter (53 years old): MZ;

Daughter’s husband: MZ

All counseled to avoid tobacco and

environmental hazards

Routine follow-up for all to monitor PFTs

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29

Ethnicity, age, and sex:

62-year-old white male

Profession:

Plumbing contractor

Personal history:

30 pack-year smoker; quit 5 years ago

Routinely consumes up to 4 beers/day

Medical history:

Diagnosed with COPD 5 years ago

Current COPD medications

LAMA

SABA

Lab results from recent yearly physical showed elevated LFTs (negative hepatitis virus panel)

Would you test?

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30

Family medical history:

Father died of emphysema

Sister diagnosed with COPD and heterozygous alpha-1 MZ genotype

7 brothers in the family

Pulmonary function testing results:

FEV

1

70% of predicted

FEV

1

/FVC ratio 62% of predicted

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31

Intervention/Testing:

Tested for alpha-1 based on COPD diagnosis and elevated LFTs

AAT serum levels confirmed at 5

µM

(normal level for ZZ 3-7)

ZZ allele combination identified through genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

COPD confirmed

Alpha-1

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32

Actions taken:

Genetic counseling and family

testing recommended

Lifestyle changes

Limit alcohol intake

Continue liver function monitoring

Influenza, hepatitis A, hepatitis B,

pneumococcal vaccinations

Treat lung infections aggressively

Maximize bronchodilators

Follow up with pulmonologist in 6 months

to review PFTs and determine need for

augmentation therapy

Slide33

Ethnicity

, age, and sex:

55-year-old white male

Profession:

Welder/forklift driver in a gate shop

Personal history:

81 pack-year smoker (3 ppd x 27 years); quit 4 years ago

Lives with smoker of 1 ppd

Medical history:

HTN; mild Diagnosed with COPD 4 years ago; moderate obstructionCurrent COPD medicationsLAMA

SABAICS/LABA

COPD, chronic obstructive pulmonary disease; HTN, hypertension; ICS, inhaled corticosteroid; LABA, long-acting beta

2

-agonist; LAMA, long-acting muscarinic antagonist; ppd, pack per day; SABA, short-acting beta

2

-agonist.

Would you test?

Slide34

Family

medical history:

Father died from MI at age 62Mother had moderate asthma

Pulmonary function testing results:

FEV

1

43% of predicted

FEV1/FVC ratio 62% of predicted

FEV

1

, forced expiratory volume in 1 second; FVC, forced vital capacity; MI, myocardial infarction.

Slide35

Intervention/Testing

:

Symptoms were more severe than expected based on PFT results; sent for cardiac

work-up (negative)

Tested for alpha-1 by practitioner after

attending medical conference

AAT serum levels confirmed at 5 µM

ZZ allele combination identified through

genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

Emphysema

Severe alpha-1AAT, alpha

1

-antitrypsin; COPD, chronic obstructive pulmonary disease; PFT, pulmonary function test.

Slide36

Would you test a heavy smoker?

Ethnicity

, age, and sex:

60-year-old white male

Profession:

Owner of family retail hardware store

Personal history:

30 pack-year smoker

Works in a retail hardware store and is exposed to dust and some pollutants

Medical history:

Diagnosed with asthma 30 years ago

Current asthma medicationsSABA

ICS/LABADiagnosed with sleep apnea 4 years ago

ICS, inhaled corticosteroid; LABA, long-acting beta

2

-agonist; SABA, short-acting beta

2

-agonist.

Slide37

Would You Test a Heavy Smoker? (cont.)

Family

medical history:

Father had COPD and died of emphysema

Brother has been diagnosed with COPD and liver disease

Pulmonary function testing results:

FEV

1

45% of predicted prebronchodilator; 70% of predicted postbronchodilator

FVC 70% of predicted prebronchodilator;

100% postbronchodilator

RV 200% of predicted

Dlco 67% of predictedCOPD, chronic obstructive pulmonary disease; D

lco

, diffusing capacity; FEV

1

, forced expiratory volume in 1 second; FVC, forced vital capacity; RV, residual volume.

Slide38

Would You Test a Heavy Smoker? (cont.)

Intervention/Testing

:

Symptoms continued to worsen; referred

to pulmonary specialist, who performed alpha-1 testing

AAT serum levels confirmed at 15

µM

(normal MZ 15-42)

MZ allele combination identified through genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

Asthma with reversibility

Heterozygote for alpha-1 with MZ genotype (“carrier”)

AAT, alpha

1

-antitrypsin.

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Would You Test If No COPD Family History?

E

thnicity

, age, and sex:

45-year-old white male

Profession:

Marketing consultant

Personal history:

20 pack-year smoker; still smokes half a pack per day

Works in an office setting

Medical history:

Daily sputum production over past 6 years with blood tingeingDiagnosed with chronic bronchitis 3 years ago with episodes 3-4 times per year and multiple regimens of oral antibioticsSymptoms improve then return

Slide40

Would

You Test

If

No COPD Family History?

Family

medical history:

No known history of lung disease

Father had cirrhosis of the liver

Pulmonary function testing:

FEV

1

45% of predicted prebronchodilator;

no significant change postbronchodilator

FVC 85% of predicted prebronchodilator;

no significant change postbronchodilator

RV 300% of predicted

D

lco

65% of predicted

D

lco

, diffusing capacity; FEV

1

, forced expiratory volume in 1 second; FVC, forced vital capacity; RV, residual volume.

Slide41

Would You Test If No COPD Family History?

(cont.)

Intervention/Testing

:

CT scan revealed bronchiectasis and evidence of mild emphysema

Alpha-1 testing performed

AAT serum levels confirmed at 6 µM

ZZ allele combination identified through genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

Emphysema

Severe alpha-1

AAT, alpha

1

-antitrypsin; CT, computed tomography.

Slide42

CT, computed tomography.

Courtesy

of Kyle Hogarth, MD, University of Chicago Medical Center.

Bronchiectasis: Confirmed by CT Scan

Slide43

Would You Test an 82-Year-Old?

43

Ethnicity, age, and sex:

82-year-old white female

Profession:

Retired

Personal history:

20 pack-year smoker; quit in her late 40s before COPD diagnosis at age 52

Widowed 10 years ago with 3 daughters (aged 47, 53, and 55), 8 grandchildren, and 2 grandnieces

Medical history:

Diagnosed with COPD at age 52; on COPD medications for more than 30 years

LAMA

ICS/LABA

Symptoms worsening despite COPD treatment and occasional use of oxygen

ICS, inhaled corticosteroid; LABA, long-acting beta

2

-agonist; LAMA, long-acting muscarinic antagonist.

Slide44

82 Year-old

Family

medical history:

Both father and mother were smokers

Mother died of lung disease

Father died of cardiovascular and liver disease

Pulmonary function testing results:

FEV

1

35% of predicted prebronchodilator;

no significant change postbronchodilator

FVC 80% of predicted prebronchodilator;

no significant change postbronchodilatorRV 350% of predictedD

lco 45% of predicted

D

lco

, diffusing capacity; FEV

1

, forced expiratory volume in 1 second; FVC, forced vital capacity; RV, residual volume.

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Intervention/Testing

:

Changed to new primary care physician who routinely tests all COPD patients based on newly implemented alpha-1

in-office testing protocol

Alpha-1 testing performed

AAT serum levels confirmed at 7 µM

ZZ allele combination identified through genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

Emphysema

Severe alpha-1

AAT, alpha

1-antitrypsin; COPD, chronic obstructive pulmonary disease.

82 Year-old

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Would You Test a Nonsmoker?

Ethnicity

, age, and sex:

62-year-old Hispanic female

Profession:

Mathematics professor

Personal history:

Nonsmoker

Medical history:

Diagnosed with COPD

5 years ago at age 57Frequent bouts of bronchitis—2-3 times per yearDyspnea and cough present over the past 5-6 years, worsening at last visit

Significant drop in lung function over last 5 years despite COPD medications

LAMA, SABA, ICS/LABA

COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting beta

2

-agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting beta

2

-agonist.

Slide47

Family

medical history:

No other lung diseases in first-degree

relatives

Recalls that her father had frequent bouts of bronchitis but was not a smoker

Intervention/Testing:

Tested for alpha-1 based on emphysema diagnosis

AAT serum levels confirmed at 6 µM

ZZ allele combination identified through genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

EmphysemaSevere alpha-1

AAT, alpha

1

-antitrypsin.

Nonsmoker

Slide48

Would You Test in Presence of Worsening COPD?

Ethnicity

, age, and sex:

60-year-old white male

Profession:

Delicatessen owner/operator

Personal history:

20 pack-year smoking history

Quit smoking at age 40

Occasional exposure to environmental pollutants

Medical history:

COPD diagnosed 4 years agoDyspnea and cough present for 10 years, worsening at last visitSignificant drop in lung function over last 3 years

Patient frustrated due to minimal response to COPD medications

LAMA, SABA, ICS/LABA

COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting beta

2

-agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting beta

2

-agonist.

Slide49

Family

medical history:

Mother died of COPD complications at age 69

No other lung diseases in first-degree relatives

Intervention/Testing:

Performed alpha-1 testing

AAT serum levels confirmed at 4.7 µM

ZZ allele combination identified through

genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

EmphysemaSevere alpha-1

COPD, chronic obstructive pulmonary disease.

Worsening COPD

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Would You Test Based on Exposure to Pollutants?

Ethnicity

, age, and sex:

53-year-old white male

Profession:

Construction contractor

Personal history:

NonsmokerExposure to environmental pollutants, primarily carbon monoxide fumes and particulates from construction demolitions

Medical history:

COPD diagnosed 5 years ago

Current medications

LAMASABAICS/LABAFrequent bronchitis attacks (2-3 per year)

COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting beta

2

-agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting beta

2

-agonist.

Slide51

Family

medical history:

Unknown

Intervention/Testing:

Performed alpha-1 testing

AAT serum levels confirmed at 6.7 µM

ZZ allele combination identified through genotype testing

Confirmed through Pi testing (phenotyping)

Diagnosis:

Emphysema

Severe alpha-

1

AAT, alpha1

-antitrypsin.

Exposure to Pollutants

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52

When in doubt, refer to the G

uidelines…

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53

Test all adults with symptomatic COPD,

regardless of smoking historyTest 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

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54Questions?