Alpha-1 antitrypsin deficiency, usually shortened to AATD, is an inherited condition in which the body makes too little of a protein that protects the lungs, and in which an abnormal form of the same protein can build up in the liver, so it can lead to lung disease, liver disease, or neither [1,2].
This page provides general information. It does not replace advice from a doctor or another qualified healthcare professional.
Alpha-1 antitrypsin is a protein made in the liver that travels in the blood to the lungs [5,10]. Deficiency means the body makes too little of it, or makes a form that does not work [2].
What the protein does. White blood cells release a substance called neutrophil elastase to fight infection, and it damages tissue if nothing holds it back. Alpha-1 antitrypsin holds it back, providing more than 90% of that protection in the lower airways [1]. With too little, the substance slowly destroys the walls of the tiny air sacs where oxygen enters the blood [2].
Why the liver is involved too. In the lungs the problem is too little protection. In the liver it is the opposite: the abnormal protein cannot fold correctly, so much of it never leaves the cells that made it, and what stays behind can damage the liver over years [14].
AATD is also called AAT deficiency, alpha-1 or inherited emphysema [1,2]. It is one inherited cause of COPD rather than COPD itself: see our guide to COPD. It is often mistaken for asthma [2,12].
AATD is usually called rare. It is more accurate to call it common and rarely identified. It affects about 1 in 1,500 to 3,500 people with European ancestry and is uncommon in people of Asian descent [1,2]. Estimates vary widely across Europe, from about 1 in 1,368 people in Denmark to 1 in 58,319 in Poland [6]. Around 1 in 3,000 people in the United Kingdom are affected [4], and roughly 10% of people in Europe carry a single altered copy [3].
Set against those figures, only about 5,000 to 10,000 people in the United States have been identified with a gene change that causes AATD [1]. That gap is the central fact about this condition.
A gene is a set of instructions inside cells, inherited means passed from parent to child, and a gene variant is a change in those instructions. AATD is caused by variants in a gene called SERPINA1 [3,12].
The letters people meet. Gene versions are labeled with letters, and “Pi” stands for protease inhibitor, an older name for the protein. M makes normal amounts, S a moderately reduced amount, and Z very little [1,3]. Everyone has two copies, so a result names both [2]:
Two words for the same inheritance. AATD is often called autosomal recessive, meaning two altered copies are usually needed for the severe form. Genetics guidance prefers codominant: both copies are active and both contribute [1,2,3]. One altered copy does not simply switch off, so carriers sit at a level in between, which is why a single Z copy is not always harmless alongside smoking [1,3].
AATD itself causes no symptoms; the damage it allows does [4].
Lungs. First signs usually appear between ages 25 and 50: breathlessness after mild activity, wheezing, cough, phlegm, repeated chest infections and tiredness [2,5]. Emphysema or chronic bronchitis develops in 60% to 80% of people identified with AATD [1]. In about two thirds, damage is worse at the bottom of the lungs than the top, the reverse of the usual pattern [1].
Liver in babies and children. In a Swedish study of 200,000 newborns, 12% of babies with the ZZ combination had prolonged jaundice, meaning yellowing of the skin and eyes lasting longer than usual, 8% developed severe liver disease and 2% to 3% needed a transplant [14]. Most reach adulthood without major liver problems [10].
Liver in adults. Scarring of the liver, called cirrhosis, can appear with no history of childhood liver trouble, and is more common in men [1,3]. Reported rates range from 12% to 40%, and the risk of liver cancer is raised [1,2].
Skin. Rarely, a condition called panniculitis causes tender lumps that can ulcerate [1].
When to seek urgent help. Call emergency services, 999 in the United Kingdom or 911 in the United States, if breathing suddenly becomes very hard and you cannot speak, if you vomit blood or pass blood in your stools, if your skin or eyes turn yellow, or if you become confused [4,10]. For a chest infection or worsening breathlessness, contact your team the same day [4].
A blood test finds it. The level of alpha-1 antitrypsin is measured first: normal is roughly 100 to 220 mg/dL, and levels below 57 mg/dL are typical where AATD has caused lung disease [1]. If the level is low, a second test identifies which versions of the gene a person has, and one test in a lifetime settles it [1,3,5]. Breathing tests, a chest CT scan and liver tests then show how much damage has happened [9,10].
Who should be tested. Everyone diagnosed with COPD, at any age, plus anyone with unexplained bronchiectasis, unexplained long-term liver disease or panniculitis [1,8]. The World Health Organization recommends testing everyone with COPD or adult-onset asthma [6].
Why diagnosis is often late. Symptoms overlap with far more common conditions, so lung problems are put down to asthma or ordinary COPD, and liver problems to fatty liver disease or alcohol [2,12]. The average gap between first symptoms and diagnosis is five to seven years [1]. A blood level alone cannot identify carriers, whose levels overlap the normal range [1].
There is no cure. Treatment protects the lungs, treats the disease that develops, and in some countries replaces the missing protein [4,5].
Not smoking comes first, as a matter of fact rather than blame. Smoking speeds up lung damage more in AATD than in people without it, and it is the main reason lung disease can start in the forties [1,2]. Stopping brings the rate of decline back toward that of a never-smoker with AATD, and it is never too late [4,6]. Avoiding secondhand smoke, vaping, dust and fumes at work and heavy alcohol helps too [3,5].
Lung treatment follows COPD care: inhalers, pulmonary rehabilitation, prompt treatment of flare-ups, home oxygen where needed, and vaccination against flu, pneumococcus, COVID-19 and hepatitis A and B [4,12].
Augmentation therapy, and what the evidence shows. Alpha-1 antitrypsin purified from donated plasma is given into a vein, usually weekly, for life [5,7]. No trial has been large enough to test the outcomes usually measured in COPD [7]. The largest, in 180 people, showed slower loss of lung tissue on CT scanning, without improving symptoms, breathlessness, quality of life or flare-ups [7]. Global guidance suggests it for people who have stopped or never smoked, with a discussion about cost and the evidence [8].
Availability differs enormously between countries, with very high cost and simple unavailability the main limits [8]. It is fully funded in Germany, Italy, Spain, Portugal and France among others, and not funded in most Eastern European countries or in the United Kingdom, Ireland, Denmark and Sweden [6]. The European Medicines Agency has approved none of the nine substances it has granted orphan status for AATD [13].
Liver and transplantation. Nothing yet clears the clumps from the liver, so care means monitoring, avoiding alcohol and treating complications [1,10]. A liver transplant restores normal production of the protein, and a lung transplant is considered for very severe lung disease [1,6,10].
Care is best organized through a center that sees the condition regularly [6]. Breathing tests are usually repeated every six to twelve months, alongside liver blood tests and scans [1]. Telling relatives matters, so anyone affected can avoid smoking and dusty work early rather than late [1,9]. Keeping alcohol low, staying active and having a plan for chest infections all help [4,10]. Low mood and anxiety are common, and support groups help [11].
Clinical trials test whether a treatment works and is safe. AATD research is unusually active at present, in both the lung and the liver. Deciding whether to look into a study is personal, and it helps to take it in steps.
Worth being clear on what a study involves:
Every trial has rules about who can take part, called eligibility criteria. For an AATD study they might include a confirmed genetic result such as PiZZ, a blood level of alpha-1 antitrypsin below a set figure, a breathing measurement inside a set range, emphysema on a CT scan, a set amount of liver scarring, not smoking for a defined period, or already being on or off augmentation therapy.
trialport’s medifit helps people consider information related to possible medical suitability. It does not diagnose a condition, confirm eligibility or replace formal screening by the study team.
Explore alpha-1 antitrypsin deficiency clinical trials through trialport
A study can look right on paper and still be hard in practice:
trialport’s readifit helps people reflect on their understanding, motivation, time, routines, support, emotions and practical arrangements.
Useful questions to put to a research team:
Taking part is voluntary. A person can ask questions, speak with people they trust and choose not to participate.
Search for clinical trials at app.trialport.com.
Study status checked: 3 August 2026. Research moves quickly, so this list will date. For current information, search at app.trialport.com.
John W. Walsh was diagnosed with AATD alongside his twin brother Fred when the condition was little known. He left his business, co-founded the Alpha-1 Foundation and AlphaNet, and in 2004 founded the COPD Foundation. He described himself publicly as the “impatient patient”, and he died in 2017 [15].
Is AATD the same as COPD?
No. AATD is an inherited condition that raises the risk of COPD. Most people with COPD do not have it, and some people with AATD never develop lung disease [1,4].
My result says PiMZ. Should I worry?
A single Z copy usually leaves enough protein to protect the lungs, and non-smokers with this result are not considered to be at increased risk of lung disease. Smoking or dusty work changes that [1,2,3].
Should my family be tested?
Yes. Testing should be offered to parents, brothers, sisters and children of someone with severe AATD. Where both parents carry one Z copy, each child has a 25% chance of inheriting two [1,9].
Can children have it?
Yes. Lung disease in childhood is extremely rare, while liver problems in babies and children do happen. Prolonged jaundice in a newborn is the usual sign [3,14].
Can it be cured?
No, though not smoking and treating the lung and liver disease both help [4,5].
If I have never smoked, am I safe?
Not guaranteed, though the outlook is much better. Around half of people with the severe form who have never smoked keep breathing tests in the normal range into later life [6].
Written by: trialport editorial team
Reviewed by: Keith Berelowitz, Founder and CEO, trialport
Reviewed on: 3 August 2026
Next review due: 3 August 2027
References last checked: 3 August 2026