From the Guidelines
Low alpha-1 antitrypsin (AAT) levels are significant because they indicate a genetic disorder that increases risk for lung and liver disease, and management includes complete smoking cessation, avoiding secondhand smoke and environmental pollutants, annual influenza and pneumococcal vaccinations, and prompt treatment of respiratory infections, as well as augmentation therapy with weekly or monthly intravenous AAT (60 mg/kg) for those with emphysema. AAT is a protein that protects the lungs from damage by neutrophil elastase, an enzyme that can destroy lung tissue. When AAT levels are low, typically below 11 μmol/L (57 mg/dL), the lungs become vulnerable to progressive damage, particularly in smokers, leading to early-onset emphysema, often before age 40 1. The condition can also cause liver disease, including cirrhosis and hepatocellular carcinoma, due to abnormal AAT protein accumulation in liver cells.
Some key points to consider in the management of AAT deficiency include:
- Genetic counseling is recommended for family members since AAT deficiency follows an autosomal codominant inheritance pattern 1
- The most severe deficiency occurs in individuals with the ZZ genotype, while MZ carriers have intermediate levels and may have increased risk with environmental exposures 1
- Augmentation therapy with AAT can reduce mortality and slow disease progress in individuals with emphysema due to severe AAT deficiency 1
- Adverse reactions to AAT concentrate are rare, but can include fever, chills, dyspnea, and anaphylactic reactions 1
Overall, the management of AAT deficiency requires a comprehensive approach that includes lifestyle modifications, medical therapy, and genetic counseling to reduce the risk of lung and liver disease. The use of augmentation therapy with AAT is a key component of this approach, and can help to slow lung deterioration and improve quality of life for individuals with emphysema due to AAT deficiency.
From the FDA Drug Label
Individuals with these low serum Alpha1-PI levels, i.e., less than 11 microM, have an increased risk of developing emphysema over their lifetimes. Individuals with the PiZZ variant typically have serum Alpha1-PI levels less than 35% of the average normal level. Individuals with the Pi(null)(null) variant have undetectable Alpha1-PI protein in their serum.
A low Alpha-1 Antitrypsin (A1AT) level is significant because it increases the risk of developing emphysema. Individuals with A1AT levels less than 11 microM are at a higher risk of developing emphysema over their lifetimes. Specifically, those with the PiZZ variant (A1AT levels < 35% of average normal) and the Pi(null)(null) variant (undetectable A1AT protein) are at increased risk 2.
From the Research
Significance of Low Alpha-1 Antitrypsin (A1AT) Levels
- A low Alpha-1 Antitrypsin (A1AT) level is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD) and other lung diseases, such as emphysema and bronchiectasis 3, 4.
- Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that results in decreased circulating levels of A1AT, leading to a disruption of the protease-antiprotease balance in the lungs 5, 4.
- Individuals with severe A1AT deficiency are at risk of developing lung disease, including emphysema, and may experience a faster decline in lung function compared to those with usual COPD 3, 6.
- A low A1AT level can also increase the risk of liver disease, such as liver cirrhosis, and other conditions like necrotizing panniculitis 7, 4.
Diagnosis and Treatment
- Diagnosis of AATD can be attained through qualitative or quantitative laboratory testing, including measurement of serum A1AT levels and genetic testing for allelic variants 3, 7, 4.
- Treatment for AATD typically involves augmentation therapy with exogenous administration of purified human serum-derived A1AT, which is the only FDA-approved treatment for the condition 3, 7, 4.
- Patients with AATD may also receive treatment for symptoms similar to those of COPD, including pharmacological and non-pharmacological therapies 3, 7.
Clinical Implications
- Early diagnosis and treatment of AATD are crucial to prevent further deterioration of lung function and to reduce the risk of developing lung disease 5, 3, 7.
- Clinicians should be aware of the importance of testing for AATD in individuals with COPD, adult-onset asthma, and unexplained bronchiectasis, as well as in those with a family history of the condition 3, 7.
- Monitoring lung function, particularly through spirometry, is essential to track the progression of the disease and to adjust treatment accordingly 7, 4.