1 Miranda D Withers MSN APRN 2 Affiliation to disclose Speaker for Grifols 3 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 ID: 908564
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Slide1
Alpha-1: Demystifying the Mystery
1
Miranda D. Withers, MSN, APRN
Slide22Affiliation to disclose: Speaker for
Grifols
Slide33
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.
Slide4COPD 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
.
Slide5Facts 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
.
Slide6What 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
Slide77
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.
Slide88
Slide9Alleles 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
Slide1010
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
Slide1111
What does an “Alpha”
look like?
Slide1212
Slide1313
Photo taken from Boston University Website;
http
://www.bumc.bu.edu/supportingbusm/research/alpha-1
/
. Accessed February 21, 2015
Slide14Have 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
Slide1515
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
Slide16Pay 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
Slide1717
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
Slide18Diagnosis 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
Slide1919
Importance of Finding Carriers
Slide20Management 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.
Slide21Benefits 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..
Slide2222
How can I make time for Alpha-1 testing in my busy practice?
Slide23Testing 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
Slide24Resources 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
Slide2525
Case Studies
Slide26Would 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
Slide2727
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
Slide2828
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
Slide2929
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?
Slide3030
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
Slide3131
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
Slide3232
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
Slide33Ethnicity
, 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?
Slide34Family
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.
Slide35Intervention/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.
Slide36Would 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.
Slide37Would 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.
Slide38Would 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.
Slide39Would 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
Slide40Would
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.
Slide41Would 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.
Slide42CT, computed tomography.
Courtesy
of Kyle Hogarth, MD, University of Chicago Medical Center.
Bronchiectasis: Confirmed by CT Scan
Slide43Would 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.
Slide4482 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.
Slide45Intervention/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
Slide46Would 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.
Slide47Family
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
Slide48Would 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.
Slide49Family
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
Slide50Would 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.
Slide51Family
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
Slide5252
When in doubt, refer to the G
uidelines…
Slide5353
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
Slide5454Questions?