Emphysema is a type of chronic obstructive pulmonary disease (COPD) that affects approximately 3 million people in the United States. While smoking is considered the most common cause, some people may also develop this lung disease if they have an alpha-1 antitrypsin (AAT) deficiency (AATD).

In this article, we take a closer look at this often underdiagnosed disorder, including how it may lead to emphysema in some adults and what doctors can do to help diagnose and treat it.

AATD is a clinically under-recognized, inherited disorder affecting the lungs, the liver, and, rarely, the skin. In the lungs, AATD causes COPD, specifically emphysema and bronchiectasis (which are dilated and thickened airways).

AATD is one of the three most common and potentially lethal genetic diseases among white individuals. The condition affects 1 in 1,500 to 3,500 individuals with European ancestry. Severe AATD affects an estimated 100,000 individuals in the United States.

AATD is inherited by autosomal codominant transmission, meaning that affected individuals have inherited an abnormal AAT gene from each parent.

The SERPINA1 gene helps make AAT, which is responsible for protecting your body from neutrophil elastase enzymes.

Emphysema in AATD is thought to result from an imbalance between neutrophil elastase in the lung. This imbalance destroys elastin, and the elastase inhibitor AAT, which is synthesized in the liver and protects against the degradation of elastin.

While the exact symptoms and incidence may vary depending on the level of AAT and the genotype, it’s important to know that having AATD may increase your risk of developing emphysema. This type of COPD is caused by damage within the small air sacs (alveoli) in your lungs.

It’s also important to note that certain environmental triggers that may independently increase your risk of emphysema, such as air pollutants and smoking, can also worsen cases of AATD.

Other issues associated with an alpha-1 antitrypsin deficiency (AATD)

AATD may also cause problems with your liver. AAT protein usually travels from your liver through your blood to protect your lungs and other organs. But if the proteins aren’t the right shape, they can get stuck in your liver.

According to Medline Plus, 10% of infants with the genetic disorder may develop liver problems that may present as jaundice.

Additionally, 15% of adults may develop cirrhosis, a severe scar tissue in the liver that results in permanent damage. Some may even go on to develop hepatocellular carcinoma, a type of liver cancer.

An even rarer complication of AATD is panniculitis. This is a type of skin condition characterized by hardened patches or lumps, which may be painful and severe. Panniculitis from AATD may also develop at any age.

Emphysema develops gradually. Over time, the alveoli and tissue in your lungs slowly become damaged, eventually creating one larger air space instead of many small ones. This reduces the surface area available for gas exchange, hindering the movement of oxygen between your lungs and bloodstream.

In addition, when emphysema develops, the alveoli can’t support the bronchial tubes. The tubes collapse and cause an “obstruction,” which traps air inside the lungs.

People with AATD may develop lung disease between the ages of 25 and 50, depending on the level of AAT and the genotype. This may occur on the earlier end of this age range if you smoke or are regularly exposed to tobacco smoke.

Early symptoms of AATD-related lung problems may include:

  • shortness of breath, especially during rest or light activities
  • wheezing
  • fatigue
  • recurring lung infections
  • decreased ability to exercise
  • unintentional weight loss

As emphysema progresses, you may experience worsening respiratory symptoms, including a hacking cough and breathing difficulties. It’s also possible to develop a barrel-shaped chest due to the trapping of air.

Other symptoms of emphysema include tightness in your chest and coughing up mucus, especially if you develop bronchiectasis (thickened and dilated airways).

For some people, symptoms of emphysema may be among the first signs of AATD.

AATD is considered underdiagnosed because it may go undetected for years until symptoms of COPD show up. Even then, AATD may never officially be diagnosed.

A doctor may recommend running diagnostic tests if you’re experiencing any symptoms of lung disease. Examples of diagnostic tests for emphysema include the following:

In general, imaging of the chest with X-rays and CT scans for traditional emphysema typically reveals damage mostly in the upper lungs. AATD-related emphysema primarily causes lower lung damage.

However, if you have a known family history of AATD and/or COPD, it may be worth asking a doctor for help with getting tested for AATD yourself. This is done via a blood test that measures AAT in the body.

Treatment options for emphysema caused by AATD are the same as those used for regular emphysema.

Treatments for emphysema may include a combination of:

  • inhaled bronchodilators to help you breathe better by opening your airways
  • oral corticosteroid medications to reduce lung inflammation, which are usually given during an acute flare and aren’t intended for maintenance therapy
  • inhaled corticosteroids for severe emphysema with frequent exacerbations
  • antibiotics, usually for acute attacks, especially if a bacterial infection is suspected

Additionally, a doctor will likely recommend vaccinations for:

Supportive therapy for people with emphysema due to AATD follows the usual guidelines for COPD, which include pulmonary rehabilitation, nutritional support, and supplemental oxygen if needed.

The specific therapy for the treatment of AATD-related lung disease is augmentation therapy, also called replacement therapy.

Augmentation therapy is the use of AAT protein to increase the AAT levels circulating in the blood and lungs. The therapy is usually administered by a weekly intravenous infusion, and, until other therapies become available, is considered ongoing and lifelong.

In the case of end-stage lung disease caused by AATD, a doctor may recommend a lung transplant. Both single and double lung transplantation have been successful in qualifying candidates with AATD.

There’s no cure for emphysema induced by AATD. However, the outlook for people with AATD is positive when diagnosis and treatment for emphysema and AATD are received early.

Avoiding smoking and other inhaled irritants can also help improve the outcome of emphysema caused by AATD.

To make sure that your medications are working as they should, a doctor may recommend follow-up testing every 6 to 12 months if not more frequently, depending upon the severity of the disease and response to treatment.

What’s the difference between inherited emphysema and traditional emphysema?

Emphysema is a lung condition that causes shortness of breath. In people with emphysema, the air sacs in the lungs (alveoli) are damaged.

The main cause of traditional emphysema is long-term exposure to airborne irritants, including tobacco smoke, air pollution, chemical fumes, and dust.

Inherited emphysema is caused by a genetic deficiency of a protein called AAT that protects the elastic structures in the lungs.

Is there a test that can confirm an alpha-1 antitrypsin deficiency?

Yes. A doctor may order an AATD test, which measures the AAT level in your blood, and the associated genetic testing.

There are many types of abnormal AAT gene variations. The most common abnormal variations are called S and Z alleles. Normal AAT alleles are called M alleles. Individuals who don’t have AATD will have two M alleles (MM). People with identified AATD most commonly have two Z alleles (ZZ).

Another deficiency-related combination is the SZ allele combination, although people with this combination are less likely to get lung or liver problems than those with two Z alleles.

Low levels of AAT could indicate that you have AATD and that you’re at a higher risk of developing lung and/or liver disease. However, it’s important to realize that you can have normal levels of AAT and still have the condition based on genetic studies.

Is there anything you can do to prevent an alpha-1 antitrypsin deficiency from progressing into emphysema?

Having a diagnosis of AATD doesn’t mean you’ll automatically develop emphysema. You can still reduce your risk of developing this lung disease by not smoking, eating a balanced diet, and getting regular exercise. You can also reduce your risk by taking your medications as prescribed.

Are there lifestyle choices to avoid if you have an alpha-1 antitrypsin deficiency?

Smoking is still considered the number one cause of emphysema, even without AATD. Smoking and secondhand exposure to cigarette smoke can also worsen the outcome of AATD-related lung diseases.

A doctor may also recommend avoiding alcohol if you have liver involvement, as well as exposure to environmental pollutants, such as chemicals and dust that can irritate your lungs.

AATD is a genetic (inherited) condition. It’s passed from parents to their children through their genes. AATD may result in serious lung disease in adults and/or liver disease at any age.

Low levels of AAT in the blood occur because the AAT is abnormal and can’t be released from the liver. This leads to a buildup of abnormal AAT in the liver that can cause liver disease and a decrease of AAT in the blood that can lead to lung disease.

If you have a known family history of AATD, or have suspicious respiratory symptoms that aren’t improving, it’s important to see a doctor for an accurate and timely diagnosis.