Alpha-1 Antitrypsin Deficiency

By: Sandra Tindle, RRT,Koumail

CardioPulmonary
Yassine Rehabilitation
Coordinator
6th year Doz 1
What is Alpha-1 Antitrypsin
Deficiency?
 What is Alpha-1 Antitrypsin
Deficiency?
 It is a genetic condition, passed from the
parents to the children.
 People with Alpha-1 have received 2 abnormal
Alpha-1 Antitrypsin genes, 1 from their
mother and 1 from their father.
 It can result in serious lung disease in adults.
 It can result in liver disease at any age.
The Abnormal Alpha-1 Genes
 The Abnormal Alpha-1 Genes
 There are many types of abnormal Alpha-1 genes.
 The most common abnormal genes are called S
and Z.
 Most people with Alpha-1 usually have two Z
genes.
 Another deficient combination is SZ although
people with this gene combination are less likely
to have lung or liver problems than those with
two Z genes.
The Abnormal Alpha-1 Genes
What Happens in Alpha-1 Lung
Disease?
 What happens in Alpha-1 Lung
Disease?
 Alpha-1 Antitrypsin is a protein that is made
mainly in the liver.
 The Alpha-1 Antitrypsin isn’t made properly and
gets trapped in the liver, which leads to liver
disease.
 This leads to a lack of Alpha-1 in the blood, which
leads to lung disease
 The main function of Alpha-1 is to protect the
lungs from inflammation caused by irritants and
infection.
 What Happens in Alpha-1 Lung
Disease?
 WBCs in the lung make an enzyme called
neutrophil elastase that destroys invading germs
and digests damaged or aging cells. In most
people, the Alpha-1 protein neutralizes the
enzyme after a short time.
 In Alphas there isn’t enough of the Alpha-1
protein in the lungs, so the enzyme keeps
working, attacking and destroying normal lung
tissue and lung disease develops.
 Alphas who smoke are at a much greater risk of
COPD than most people.
 What Happens in Alpha-1 Lung
Disease?
 Alphas often develop COPD in their 30s or 40s,
while people who don’t have Alpha-1 usually
don’t develop COPD symptoms until they are
in their 60s or 70s.
 Alphas often develop COPD primarily in the
lower part of their lungs, whereas most non-
Alphas, especially smokers, show the worst
COPD damage in the top part of their lungs.
 What Happens in Alpha-1 Lung
Disease?
 Alpha-1 lung problems don’t usually occur in
children, but it is very important for children
with Alpha-1 to avoid all exposure to cigarette
smoke or heavy air pollution to protect their
lungs.
 Sometimes children with Alpha-1 can have
severe asthma
 The Most Common Signs and
Symptoms of Alpha-1 Lung Disease
 The Most Common Signs and
Symptoms of Alpha-1 Lung Disease
 Shortness of Breath
 Wheezing
 Chronic Bronchitis
 Recurring Chest Colds
 Less Exercise Tolerance
 Asthma that can’t be completely reversed with
aggressive medical treatment
 Year round allergies
 Bronchiectasis
Alpha-1 Facts
 Alpha-1 Facts
 Alpha-1 has been diagnosed in almost all
ethnic groups.
 Alphas may remain healthy throughout their
lives, but early diagnosis and avoiding risk
factors can help prevent Alpha-1 from causing
disease.
 Alpha-1 Facts
 Many Alphas with ZZ or SZ genes are healthy
 Alpha-1 is the most common genetic risk factor for
emphysema.
 Up to 3% of all people diagnosed with COPD may have
undiagnosed Alpha-1.
 Alpha-1 can also lead to liver disease. The most serious
liver diseases are cirrhosis and liver CA.
 There is a wide variation in how sick people get from
Alpha-1. Some patients have severe disease, while
some have little to none.
Diagnosing Alpha-1
 Diagnosing Alpha-1
 Alpha-1 can only be diagnosed by a blood test.
 The World Health Organization, American
Thoracic Society, and COPD foundation
recommend that everyone with COPD be
tested for Alpha-1.
 Alpha-1 is often first diagnosed as asthma or
smoking related COPD.
 Treatment for Alpha-1 Lung Disease
 There is no cure for Alpha-1
 Alphas with lung diseases such as asthma or
COPD can be helped by the same drugs that
are used by non-Alphas for these conditions.
 These include bronchodilators and
corticosteroids
 Infections are usually treated aggressively
with antibiotics
Augmentation Therapy
 Augmentation Therapy
 Weekly IV infusions of the Alpha-1 protein from
purified healthy plasma donors to increase the
level of the Alpha-1 protein in the blood and
lungs to slow or stop the progression of Alpha-1
lung disease.
 There are currently 4 medications available for
use in augmentation therapy: Prolastin-C, Aralast
NP, Zemaira, and Glassia.
 Has been shown to increase blood and lung levels
of Alpha-1 and reduce the rate of progression of
Alpha-1 lung disease and improved survival.
 Augmentation Therapy
 Cannot restore lost function and is not a cure,
but is currently standard therapy for Alphas
with COPD.
 Augmentation therapy is also effective for the
Alpha-1 related skin disease Necrotizing
Panniculitis.
 Augmentation therapy does not work for
Alpha-1 liver disease.
Augmentation Therapy
Children and Alpha-1 Liver Disease
 1/20 babies born with Alpha-1 will have liver
disease, sometimes sever, in the first year of life.
 1/14 will have blood tests showing that the liver
is being injured, but the infants look and feel fine.
 In most children with abnormal blood tests, the
liver disease improves by itself by the time these
children reach their teens and they remain
healthy.
Children and Alpha-1 Liver Disease
 Alphas have a 30-40% chance of developing
liver problems during their lifetime.
 Avoiding alcohol, maintaining a healthy
weight, getting vaccinated against infections
that damage the liver, and eating a healthy
diet are important.
 Treatment for Alpha-1 Liver Disease
 When treating Alpha-1 liver disease, the focus
is on treating the symptoms and keeping the
patient as healthy as they can be and
preventing health problems.
 Treatments are available for intestinal
bleeding, fluid in the abdomen, nutrition and
other problems from scarring of the liver.
 The Liver in Alpha-1
 Alpha-1 can cause liver problems at any age.
 Large amounts of the Alpha-1 Antitrypsin protein
are made in the liver; nearly 85% of the protein
get stuck in the liver.
 The liver gradually gets damaged and scarred
 There is no way to prevent the abnormal AAT
from getting stuck in the liver.
 The lack of AAT in the blood allows the lungs to
get damaged by smoke and air pollution and can
show up as lung disease with Alpha-1.
 The Most Common Signs and
Symptoms of Alpha-1 Liver Disease
 The Most Common Signs and
Symptoms of Alpha-1 Liver Disease
 Unexplained liver disease or elevated liver
enzymes
 Eyes and skin turning yellow (jaundice)
 Swelling of the abdomen or legs
 Vomiting blood (enlarged veins in the
esophagus or stomach)
 In babies: jaundice, swelling of the abdomen,
and poor growth, diarrhea
 The Most Common Signs and
Symptoms of Alpha-1 Liver Disease
 Feeling weak and tired
 Most Alphas have no symptoms of liver
disease
 Testing for Alpha-1
 The Alpha-1 Foundation encourages testing
for Alpha-1 for those who are at a high risk for
the genetic disorder.
 It is recommended that anyone diagnosed
with the following diseases be tested for
Alpha-1: COPD, asthma that is incompletely
irreversible after aggressive treatment,
chronic liver disease, unexplained liver disease
in infants and children.
 Testing for Alpha-1
 Anyone can ask their doctor to test them for
Alpha-1, or choose to be tested confidentially
through the Foundation’s Alpha-1 coded
testing study.
 Resources
 The Alpha-1 Foundation: www.alpha1.org
 The National Human Genome Research
Institute: www.genome.gov
 Boston University: www.bu.edu
 Cleveland Clinic:
www.clevelandclinicmeded.com