Alpha-1 related emphysema is caused by an inherited lack of a protective protein called alpha-1 antitrypsin (AAT). 

In normal and healthy individuals, AAT protects the lungs from a natural enzyme called neutrophil elastase.  Neutrophil elastase is an enzyme that normally serves a useful purpose in lung tissue — it digests damaged or aging cells and bacteria in order to provide for healing. However, once it is done digesting those proteins, it does not stop, and attacks the lung tissue. Alpha-1-antitrypsin, in sufficient amounts, will trap and destroy the neutrophil elastase before it has a chance to begin damaging the delicate lung tissue.

If allowed to progress, this form of emphysema becomes chronic and lung tissue continues to be destroyed; eventually it is fatal if the progress is not slowed down or halted.


Every person inherits two AAT genes, one from each parent. A person has alpha-1 antitrypsin deficiency only if he or she inherits two abnormal genes.

People who have only one abnormal gene and one normal AAT gene are “carriers.” Their AAT levels may be lower than normal, but not as low as the deficiency state, and their risk of significant health problems is much lower than those with the severe deficiency.

People who have Alpha-1 antitrypsin deficiency will pass on one abnormal gene to their children, but they will be “carriers” and will not have Alpha-1 unless they receive an abnormal gene from their other parent.


It is estimated that there are 100,000 Americans today who were born with Alpha-1 deficiency.1 Alpha-1 related emphysema may afflict a majority of these individuals. However, AAT deficiency is often under diagnosed or misdiagnosed. As many as 3% of individuals with chronic obstructive pulmonary disease (COPD) may have undiagnosed Alpha-1 deficiency. If AAT deficient individuals also smoke, their risk of developing emphysema is greatly increased.

Worldwide, it is estimated that 116 million people (25 million Americans) are carriers of the disease.2 The World Health Organization (WHO) recommends that all individuals with COPD, as well as adults and adolescents with asthma (an estimated 20 million Americans) be tested for Alpha-1.


While there are different causes of emphysema (such as smoking and Alpha-1 deficiency), the physical signs and symptoms in each case are similar.

Emphysema begins with the destruction of alveoli, small sac-like structures (resembling bunches of grapes) in the lungs where oxygen from the air is exchanged for carbon dioxide in the blood. The walls of the alveoli are thin and fragile, and are easily damaged.

The damage is irreversible and results in permanent “holes” in the tissues of the lower lungs. As alveoli are destroyed, the lungs are able to transfer less and less oxygen to the bloodstream, causing shortness of breath during exercise and eventually even at rest.

The lungs also lose their elasticity, so the patient experiences great difficulty exhaling. The bronchial tubes leading to the air sacs may collapse, which traps air in the lungs. This is the condition known as emphysema.


The onset of Alpha-1 related emphysema symptoms often appear between ages 32 and 41 but may appear later. The earliest symptom is usually shortness of breath following activity, as well as decreased exercise capacity and wheezing.3

The early age at which the disease is present and the fact that the disease most frequently appears in the lower rather than the upper lung regions helps distinguish Alpha-1-related emphysema from other types of emphysema.


A simple blood test can determine whether a person has low levels of the protective protein AAT. Also, a DNA-based cheek swab test has been recently developed to aid in diagnosis.

It is very important to detect Alpha-1 deficiency as early as possible because smoking cessation is necessary to slow the progression of emphysema. Treatment may also slow the progression of the disease.

If you are diagnosed with Alpha-1 related emphysema, talk to your doctor about having other family members, including your children, tested for Alpha-1 deficiency. Testing should be considered in those with a family history of the disease, or when signs of emphysema appear at an early age.

Your doctor may recommend genetic counseling for you and other family members. It is important for anyone with Alpha-1 deficiency to quit smoking or never start.

Evidence shows that smoking significantly increases the risk and severity of emphysema in AAT deficient individuals and may decrease their life span by as much as ten years.

In addition, the Alpha-1 Foundation supports a coded testing program (the ACT Trial), which permits testing of individuals for Alpha-1 in a confidential manner. Please call the Alpha-1 Research Registry at the Medical University of South Carolina (1-877-886-2383) for more information.


In December 1987, the first specific treatment for Alpha-1 related emphysema was approved. Replacement therapy (also called augmentation therapy) raises the level of AAT in the blood and provides the lungs with a protective shield against neutrophil elastase, the destructive enzyme.

The replacement therapy is derived from human plasma that has been screened and tested for viral markers. During the manufacturing process the product is heat-treated to minimize the risk of viral transmission.

Therapy must be taken throughout a patient’s life for its protective effect. If a patient chooses to stop therapy, his or her lungs will return to the prior imbalanced state of neutrophil elastase and AAT.

Replacement therapy is intended only for AAT deficient patients who have begun to show symptoms of emphysema. It is not recommended for those without Alpha-1 deficiency who develop emphysema as a result of cigarette smoking or other environmental factors.

While replacement therapy does not cure Alpha-1 related emphysema, it does appear to slow the progression of this disease. 

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