Alpha-1 Antitrypsin Deficiency or Inherited Emphysema

What is inherited emphysema?
What does the alpha-1 antitrypsin protein do in the body?
How is the diagnosis made?
How is inherited emphysema managed?
What does the future hold?

What is inherited emphysema?

Most cases of emphysema are caused by smoking or other environmental factors. There is growing evidence that genetics can also increase the risk of developing emphysema. In about one out of every 50 cases of emphysema, there is a specific hereditary basis for the disease called Alpha-1 Antitrypsin Deficiency or, more simply, Alpha-1.

People with Alpha-1 don't have enough of a major protein in the blood. This protein is alpha-1 antitrypsin. Although there are many different genetic variations of this protein, only some will cause lung disease. The most common variant of the protein is often seen in people of northern European descent, especially Scandinavians. Recent evidence shows that Alpha-1 can be found in all populations and all ethnic groups.

Return to Top

What does the alpha-1 antitrypsin protein do in the body?

Alpha-1 antitrypsin is a major protein in the blood. It is produced mainly in liver cells. It protects the lung by blocking the effects of a powerful enzyme called elastase. Elastase is normally carried in the body's white blood cells and is used by these cells when they kill invading bacteria and neutralize tiny particles inhaled into the lung. Alpha-1 antitrypsin inactivates excess elastase left over after the white blood cell has finished its job. Without alpha-1 antitrypsin, this white blood cell elastase can destroy the normal air sacs of the lung.

Did you know that Alpha-1 Antitrypsin Deficiency can also cause liver disease and is also known as "inherited liver disease "? 

Return to Top

How is the diagnosis made?

The COPD caused by Alpha-1 is essentially the same as any other form of COPD so the diagnosis is made by the same methods - except for two special blood tests. Your doctor may have you do a number of tests to evaluate your breathing.

Tests to diagnose COPD may include:

• Detailed medical history including family history of lung disease
• Physical exam
• Breathing tests and X-rays
• Oxygen levels

Two special blood tests determine the diagnosis of inherited emphysema. The first test measures the concentration of alpha-1 antitrypsin in the blood. A second blood test determines the actual gene product in the person with the disease. Healthy people have an MM genetic pattern. This leads to normal levels of alpha-1 antitrypsin in the blood. The most common abnormal genetic pattern seen with inherited emphysema is ZZ. Some people may inherit only a single gene for inherited emphysema, such as MZ. Individuals carrying a single abnormal gene for Alpha-1 have only a slightly increased risk of emphysema.

Return to Top

How is inherited emphysema managed?

Medication Therapy

Specific therapy has been available for inherited emphysema since 1987: a class of medicine called augmentation therapy. This medicine replaces the alpha-1 antitrypsin protein in the blood with normal alpha-1 antitrypsin from healthy plasma donors. It is given in a vein (IV). The dose is adjusted based on body weight. This treatment is often given once a week. There are three brands of augmentation therapy. They include:

• Prolastin®
• Aralast™
• Zemaira™

Behavior Modification

In addition to medicines, the management of inherited emphysema includes:

• Exercise and a healthy lifestyle
• Avoidance of infection
• Techniques to bring up mucus
• Oxygen therapy
• Pulmonary rehabilitation.

Giving Up Smoking

Giving up smoking and avoiding secondhand smoke is very important. Smoking can accelerate or speed the development of the Alpha-1 related emphysema and shorten the lifespan.

Genetic Counseling

Genetic counseling is important for family members of the person diagnosed with inherited emphysema. Family planning issues and early interventions, such as giving up smoking can be addressed. Screening of family members for Alpha-1 is highly recommended.

Surgery

Lung transplants or lung reduction surgery may be an option for people severely affected by the disorder.

It is important to appreciate that people with Alpha-1 may never develop emphysema. That is why Alpha-1 is referred to as a disorder or condition, rather than a disease. People with Alpha-1 are also at risk of developing liver disease and certain skin conditions. There may also be an association between Alpha-1 and atypical TB infections in the lung, also called non-tuberculous mycobacteria.

Return to Top

What does the future hold?

Inherited emphysema is fairly common among inherited disorders. Research is constantly being done to develop new therapies. One promising therapy is replacement of the abnormal gene. Doctors at National Jewish follow one of the largest groups of Alpha-1 patients in the country. Virtually every new drug evaluated for this condition has been tested here. Doctors and researchers at National Jewish are always looking for new ways to manage and treat Alpha-1 and other chronic lung diseases.

Return to Top

This information has been approved by Robert Sandhaus MD and Janis Berend RN, MSN, C-ANP (January 2007)