photo of three generations of women
In This Article

Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), but it's not the only cause. Nearly 1 in 3 people with this lung disease have never smoked. Some were exposed to pollution and other irritants in the air. And about 2% inherited a rare condition called alpha-1 antitrypsin (AAT) deficiency. 

Most people with AAT deficiency have never been diagnosed and don't know they have it. Learning your risks and getting treatment early is important to prevent the disease from damaging your lungs and liver.

What Is AAT Deficiency?

AAT is a protein your liver makes. Its main job is to protect your lungs from inflammation caused by infections and irritants like smoke or dust in the air. In AAT deficiency, a genetic change makes the AAT protein abnormal. 

"If you are deficient in AAT, then your lungs have no protection from cigarette smoke, dust, and fumes that otherwise might cause COPD," says Charlie Strange, MD, a professor of pulmonary and critical care medicine at the Medical University of South Carolina.

In healthy people, AAT travels from the liver to the lungs and other organs that it protects. But when you have AAT deficiency, this protein has an abnormal shape. So it gets stuck in your liver and builds up there. Eventually, so much AAT collects that it damages and scars the liver. 


How Do You Get Inherited COPD?

Changes , or mutations, to the SERPINA1 gene cause AAT deficiency. You inherit one copy of this gene from your mother and another from your father. Each contributes to your AAT level. 

If you inherit just one abnormal gene, you'll be a carrier and you may avoid lung problems. But if you inherit two abnormal genes, your alpha-1 level could be severely deficient. "That's a situation where you can develop COPD without smoking," Strange says.

Your environment matters, too. Exposure to dust, dirt, chemical fumes, and tobacco smoke speeds lung damage.

"If you smoke cigarettes and you have a severe deficiency, you might have severe emphysema at age 35," Strange says. "Or if you live a really clean life, you can live to age 90 and not have any disease at all."

Is It Different From Smoking-Related COPD?

In your lungs, AAT deficiency doesn't look much different from COPD caused by other things. In both cases, COPD involves a group of diseases like emphysema that block the flow of air into your lungs and make it hard to breathe.

One slight difference is that AAT deficiency often appears at a younger age than typical COPD, but that's not a hard and fast rule, Strange says. Also, AAT deficiency can affect your liver, too. 

How Do You Know You Have AAT Deficiency?

You might not know you have this deficiency. Symptoms sometimes don't appear until middle age. And when symptoms like coughing, shortness of breath, and wheezing do show up, they look a lot like other lung diseases – including asthma and bronchitis.

AAT deficiency in your liver can cause symptoms like:

  • Yellow eyes and skin, called jaundice
  • Swelling of your belly or legs
  • Throwing up blood

Your doctor might suspect AAT deficiency if you have emphysema and you:

  • Don't smoke
  • Have a family history of COPD
  • Have liver disease or a family history of liver disease

The FDA recently approved a home testing kit you can use to see whether you're genetically at risk for AAT deficiency. It's sold over the counter as AlphaID At Home. To test yourself, you collect a saliva sample, then send it to a lab for processing. But this kit can't diagnose either AAT deficiency or COPD. So you'll need to see your doctor for further testing. 

Your doctor can determine whether you have COPD with a spirometry test that measures the force of your breathing. A blood test to check your alpha-1 antitrypsin level can confirm the diagnosis. 

The Alpha-1 Foundation, American Thoracic Society, and other health organizations recommend that everyone with COPD get the blood test, but "it just isn't happening," Strange says. Experts think only about 10% of people with AAT deficiency in the United States are diagnosed. 

If you test positive for the abnormal alpha-1 gene, your parents, siblings, children, and other family members should get tested, too.

What's the Treatment?

If your alpha-1 antitrypsin level is low, you'll see a specialist for more tests and treatment. You can find a specialist through the Alpha-1 Foundation's website. 

Your doctor will do imaging tests and lung function tests to look for emphysema. Mild emphysema might not need treatment. If you have a more serious case, you'll need replacement therapy. That involves getting weekly IVs of the AAT protein from healthy donors to boost your levels.

This treatment is expensive – it can cost more than $100,000 per year, before insurance. And you'll need to take it for the rest of your life to prevent emphysema from damaging your lungs. You may not need treatment if your lung function is normal and you don't have emphysema, Strange says.

A few lifestyle changes are important, too. If you smoke, quitting will help slow the disease and prevent it from further damaging your lungs. Though it can be hard to quit, knowing that it could extend your life is a strong incentive. Losing weight if you're overweight helps protect your liver.

COPD treatments also help with symptoms of AAT deficiency. Treatments include:

  • Inhaled bronchodilators and other medicines that relax the muscles of your airways and reduce swelling in your lungs
  • Antibiotics to treat infections 
  • Pulmonary rehabilitation, a program that teaches you how to live better with COPD

The Future of AAT Deficiency

The search is on for alternatives to once-a-week IVs, and for gene therapies that might one day cure the disease, says Strange. In the meantime, you'll have the best possible outlook if you see a specialist, take any medication your doctor prescribes, and avoid smoke and other lung irritants. 

"We have plenty of people in the community who were diagnosed by genetic testing companies when they were in their early 20s. They still have another 70 years in front of them if they live a healthy lifestyle," Strange says.

Show Sources

Photo Credit: Halfpoint / Thinkstock


Alpha-1 Foundation: "Alpha-1 Antitrypsin Deficiency: Healthcare Provider's Guide," "Diagnosing Alpha-1," "Liver Disease," "Treatment," "What is Alpha-1?"

American Lung Association: "Alpha-1 Antitrypsin Deficiency Symptoms and Diagnosis," "COPD Causes and Risk Factors," "Spirometry."

BMC Research Notes: "Alpha 1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease: is systematic screening necessary?"

Charlie Strange, MD, professor of pulmonary and critical care medicine, Medical University of South Carolina, Charleston.

Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation: "Costs of Medical Care Among Augmentation Therapy Users and Non-Users with Alpha-1 Antitrypsin Deficiency in the United States."

COPD: Journal of Chronic Obstructive Pulmonary Disease: "Alpha-1 Antitrypsin Deficiency and Tobacco Smoking: Exploring Risk Factors and Smoking Cessation in a Registry Population."

Journal of Nucleic Acids: "SERPINA1 mRNA as a Treatment for Alpha-1 Antitrypsin Deficiency."

Mayo Clinic: "COPD."

News release, National Institutes of Health, June 9, 2020.

National Organization for Rare Diseases: "Alpha-1 Antitrypsin Deficiency."

UpToDate: "Treatment of alpha-1 antitrypsin deficiency." 

Cedars-Sinai: "Alpha-1 Antitrypsin Deficiency (AATD)."

FDA: "FDA allows marketing of first direct-to-consumer tests that provide genetic risk information for certain conditions."

News release, Grifols.