Does alpha 1 antitrypsin augmentation therapy (replacement therapy with protein taken from the blood of healthy donors) help improve the symptoms of respiratory disease in people with alpha 1 antitrypsin deficiency?

Key messages

• In people with alpha 1 antitrypsin deficiency, delivering additional alpha 1 antitrypsin through a drip into a vein (intravenous augmentation therapy) may lead to a slight increase in the number of exacerbations (worsening of lung disease) people experience each year, but may have little or no effect on the number of people who die. We are unsure whether intravenous augmentation therapy has any effect on the number of people who have serious unwanted events like hospitalisation or permanent damage. Delivering additional alpha 1 antitrypsin through a breathing mask (inhaled augmentation therapy) may have little or no effect on the number of people who have serious unwanted events, and we are unsure whether this treatment has any effect on exacerbations.

• Our review included few studies, and we have little confidence in the evidence.

What is alpha 1 antitrypsin deficiency (AATD)?

Alpha 1 antitrypsin (AAT) is a protein that helps protect our organs against damage from our body's own enzymes. AAT deficiency (AATD) is a genetic disease where people do not produce enough AAT. It can lead to lung damage and chronic obstructive pulmonary disease (COPD; a long-term condition that makes it hard to breathe). Symptoms of AATD include shortness of breath, cough, and wheeze. Smokers with AATD have a higher risk of developing severe lung disease. AATD can also lead to liver problems. Some people with AATD can stay healthy throughout their lives.

What is alpha 1 antitrypsin augmentation therapy?

AAT augmentation therapy aims to raise AAT levels in the bloodstream and lungs using AAT protein taken from the blood of healthy donors. AAT augmentation therapy may help protect lung tissue from damage and slow lung disease progression. It can be given through a drip into a vein (intravenous), injected under the skin (subcutaneous), or inhaled through a breathing mask.

What did we want to find out?

We wanted to find out if topping up AAT levels in people with AATD could reduce the number of exacerbations (worsening of the disease), the number of people who die, and the number of people who have serious unwanted events like hospitalisation or permanent damage. Our review focused on the results that were most important to people with the disease.

What did we do?

We searched for studies that compared AAT augmentation therapy given by any route (intravenous, subcutaneous, or inhaled) against AAT augmentation therapy delivered by another route, a dummy treatment (placebo), or no treatment. We compared and summarised the results and rated our confidence in the evidence based on factors such as study methods and sizes.

What did we find?

We found six studies with 524 participants. Four studies looked at intravenous AAT augmentation therapy, and the other two looked at inhaled AAT augmentation therapy. All six compared AAT augmentation therapy with placebo. The studies were conducted in high-income countries across Europe, North America, and Australia. The smallest study had five participants, and the largest had 180 participants.

Main results

Intravenous AAT augmentation therapy versus placebo

• Intravenous AAT augmentation therapy may lead to a slight increase in the number of exacerbations people experience each year. The evidence shows a rate of 1960 yearly exacerbations for every 1000 people receiving intravenous AAT augmentation therapy, compared with 1420 yearly exacerbations for every 1000 people receiving placebo (290 more exacerbations in the AAT group).

• Intravenous AAT augmentation therapy may have little or no effect on the number of people who die compared with placebo.

• We do not know whether people who receive intravenous AAT augmentation therapy are any more likely to have one or more serious unwanted events than those who receive placebo.

Inhaled AAT augmentation therapy versus placebo

• We do not know whether inhaled AAT augmentation therapy has any effect on the number of exacerbations people experience each year compared with placebo.

• No studies reported deaths.

• Inhaled AAT augmentation therapy may make little or no difference to the number of people who have one or more serious unwanted events compared with placebo.

What are the limitations of the evidence?

We have little confidence in the evidence because few studies were available, the studies we found included few participants, and the results only covered some of the people we were interested in.

How up to date is this evidence?

We included evidence published up to August 2025.