Naming it matters

Alpha-1 antitrypsin deficiency, also known as Alpha-1, is a genetic condition that can damage the lungs and is the most well-known genetic risk factor for the development of chronic obstructive pulmonary disease (COPD). Some people can also develop liver disease. More than 250,000 people worldwide are estimated to have severe Alpha-1,1 yet most don't know they have it.

It’s difficult to differentiate it from non-genetically caused COPD because its symptoms are the same, which is why many people do not immediately receive an accurate diagnosis when they seek medical advice. On average, five to eight years can pass between the first symptoms and an Alpha-1 diagnosis,2 and along the way it is common to see several doctors.
 

What is alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency is an inherited genetic disorder in which the body produces insufficient amounts of the alpha-1 antitrypsin (AAT) protein, a defective form of it, or, in rare cases, does not produce it at all.

AAT is produced mainly in the liver and plays a key role in protecting the lungs from inflammatory enzymes that can damage lung tissue. When there is a deficiency of this protein, the lungs become more vulnerable to damage, increasing the risk of developing respiratory diseases.
 

 

Worldwide, approximately 90% of people with Alpha-1 remain undiagnosed.3

What happens in a healthy lung4

Air enters the lungs

Every time we breathe, air enters through the nose and mouth, travels down the windpipe (trachea) and branches out through the bronchi until it reaches the alveoli, the tiny air sacs where oxygen passes into the blood.

The immune system's response

Bacteria, dust and other particles also come in with the air. To defend itself, the body sends immune cells called neutrophils to the alveoli. These cells release a substance called neutrophil elastase, which breaks down foreign particles so they can be cleared away.

Alpha-1 antitrypsin acts as a protective brake

Once its work is done, the elastase has to be stopped. That is the job of alpha-1 antitrypsin: it acts as a brake that keeps elastase from attacking the tissue of the alveoli themselves.

In people with Alpha-1, air follows the same path, but the brake fails. Elastase keeps working and begins to damage the tissue that supports the lungs, especially the walls between the alveoli.

The alveoli lose their elasticity, become enlarged and break down. This is how emphysema develops: when you breathe out, air cannot fully escape and becomes trapped in the lungs. Breathing gets harder, especially during physical activity.

In some forms of the deficiency, the protein is made in an abnormal shape and gets stuck inside liver cells, where it can build up and cause damage. 
 

Alpha-1 antitrypsin: A rare genetic condition

250,000+

people worldwide have severe Alpha-1.1

Only about 10%

of people with Alpha-1 know they have it.3

5-8 years

on average between the first symptoms and diagnosis.2

What are the symptoms of Alpha-1?*

In the lungs, the symptoms can be:

  • shortness of breath, especially during physical activity
  • a persistent cough with mucus (phlegm)
  • wheezing
  • frequent respiratory infections
  • a reduced ability to be physically active

In the liver, if detected:

  • prolonged jaundice in newborns
  • inflammation of the liver (hepatitis)
  • or, over time, chronic liver disease that can lead to cirrhosis. 

Less often, in other parts of the body, when there is:  

  • inflammation of the fatty tissue under the skin (panniculitis) 
  • or of the blood vessels (vasculitis)

Alpha-1 is not contagious, and it does not develop with age: it is an inherited genetic condition. It is caused by changes in the SERPINA1 gene, which carries the instructions for making alpha-1 antitrypsin.5

Diagnosis

Naming it is easier than you might think

Alpha-1 cannot be diagnosed from symptoms or a physical exam alone. Diagnosis requires specific testing ordered by a medical doctor, either a blood test or genetic testing.**

Who should be tested?

The American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines6-7 recommend testing for Alpha-1 in people with:

  • Family history of alpha-1 antitrypsin deficiency
  • Early-onset pulmonary emphysema
  • COPD
  • Unexplained liver disease
  • Asthma in which lung function fails to return to normal with therapy
  • Adults with bronchiectasis without evident cause
  • Shortness of breath and cough in multiple family members

Preventing Alpha-1-related lung deterioration8

The following measures can help reduce the risk of lung deterioration:

  • Don't smoke and avoid secondhand smoke. 
  • Reduce exposure to dust, fumes and vapors.
  • Stay up to date with influenza and pneumonia vaccines.
  • Maintain a healthy weight.
  • Avoid extreme temperatures.

“Before my diagnosis, I lived with uncertainty and frequent breathing problems.”

Meritxell Alpha-1 patient

“I went from running regularly to being unable to climb stairs. After numerous tests and a great deal of uncertainty, I was finally tested for Alpha-1 a year later, following a bout of pneumonia.”

Tanya Alpha-1 patient

“My husband was diagnosed with Alpha-1 at the age of 39, after experiencing two or three severe episodes of pneumonia.”

Cristina Caregiver of an Alpha-1 patient

References

1 Blanco I, et al. Int J Chron Obstruct Pulmon Dis. 2017;12:561–569.
2 Stoller JK. Cleve Clin J Med. 2026;93(3):153–157.
3 Brantly M, Campos M, Davis AM, et al. Orphanet J Rare Dis. 2020;15(1):96.
4 Fazleen A, Wilkinson T. ERJ Open Res. 2021;7(4):00494-2021.
5 Turner A, et al. Ther Adv Respir Dis. 2025;19:1–17.
6 American Thoracic Society; European Respiratory Society. Am J Respir Crit Care Med. 2003;168(7):818–900.
7 Miravitlles M, et al. Eur Respir J. 2017;50:1700610.
8 Fahy B, Lareau S, Meek P, Strange C. Am J Respir Crit Care Med. 2018;198(12):P23–P24.
9 Bull World Health Organ. 1997;75:397–415.
10 World Health Organization (WHO). Chronic obstructive pulmonary disease (COPD). 2016. WHO: Chronic obstructive pulmonary disease (COPD)
*In case of doubt, please consult your doctor. Only medical doctors are qualified to diagnose alpha-1 antitrypsin deficiency.
**In the U.S., patients can order genetic testing directly.
 

 

Frequently Asked Questions About Alpha-1

It is an inherited genetic disease that reduces the amount, or changes the function, of a protein that helps protect the lungs. It can also affect the liver.

It can cause shortness of breath, a persistent cough, wheezing, frequent respiratory infections and a reduced exercise tolerance.

Alpha-1 is a genetic risk factor for the development of COPD. Based only on symptoms, a person cannot be diagnosed with alpha-1 antitrypsin deficiency. They need specific testing for Alpha-1.

COPD is a chronic lung disease that narrows the airways and makes it hard to breathe out. In most cases it is caused by smoking, but not always. Alpha-1 is its best-known genetic risk factor and may contribute to up to 3% of all COPD cases in the U.S.3 However, alpha-1 antitrypsin deficiency can be overlooked as a cause of COPD, particularly because it is a rare condition that is frequently undiagnosed. On average, patients are estimated to wait between five and eight years for a diagnosis.2

  COPD COPD associated with Alpha-1

Main cause

Long-term exposure to tobacco smoke and other harmful substances.

An inherited genetic change. Smoking does not cause it, but it speeds up lung damage.

Age of onset

Usually after age 40 or 50.

Can appear earlier, as early as in the thirties, especially in people who smoke.

People who have never smoked

Less common.

Can also occur in nonsmokers.

Family

No single gene is responsible.

Inherited: close family members may have it or be carriers.

Organs affected

Mainly the lungs.

The lungs and, in some people, the liver.

Global prevalence

250+ million people10

250,000+ people with severe Alpha-11

How it is identified

By its clinical symptoms and a spirometry test.

Same as COPD, but also with specific testing for Alpha-1 (blood test or a simple genetic test).

It can be diagnosed in several ways, with a blood test that demonstrates a low alpha-1 level or with genetic testing that shows abnormal genes. 

Yes. Alpha-1 is not contagious, and it does not develop with age: it is an inherited genetic condition. It is caused by changes in the SERPINA1 gene, which carries the instructions for making alpha-1 antitrypsin.5

More than 500 variants of this gene have been identified. The most important are:

  • M variant: the normal variant. It produces enough alpha-1 antitrypsin and does not increase the risk of lung or liver disease.
  • S and Z variants: produce less protein than the body needs. Z is the most common of the variants associated with the deficiency and the one linked to the most severe forms.
  • Null variants: very rare; they produce no protein at all.

Everyone has two copies of the gene: one inherited from their mother and one from their father. Severe deficiency usually develops when a person inherits two altered copies, for example, one Z from each parent.

A person with one normal copy and one altered copy is a carrier. Carriers do not usually develop severe deficiency, but they can pass the variant on to their children.

When both parents are carriers, each pregnancy carries a 25% chance that the baby will inherit two altered copies and have the deficiency, a 50% chance that the baby will be a carrier, and a 25% chance that the baby will inherit neither.
 

Genetics explain why the protein is missing, but some external factors speed up the damage:

  • Tobacco smoke, whether from smoking or from breathing in other people's smoke.
  • Breathing in harmful substances, such as dust, fumes, gases, or vapors at work or at home.

Both increase the release of elastase in the lungs and can inactivate what little alpha-1 antitrypsin is available. The result is faster damage and symptoms that appear earlier and worsen more easily. That is why, in people with Alpha-1, smoking is the factor that most accelerates lung disease.
 

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