What is the management of Alpha-1-Antitrypsin (A1AT) deficiency?

From the Guidelines

Management of Alpha-1-Antitrypsin (A1AT) deficiency should prioritize augmentation therapy with intravenous alpha-1 proteinase inhibitor, as well as standard COPD treatments and preventive strategies to minimize lung damage and improve quality of life, as recommended by the most recent Canadian Thoracic Society meta-analysis and clinical practice guideline 1.

Key Components of Management

• Augmentation therapy with intravenous alpha-1 proteinase inhibitor (Prolastin, Aralast, Zemaira, or Glassia) at 60 mg/kg once weekly to maintain protective serum levels
• Standard COPD treatments, including:
  • Bronchodilators
  • Inhaled corticosteroids
  • Pulmonary rehabilitation
  • Supplemental oxygen if needed
  • Smoking cessation, which is critical to prevent accelerated lung damage
• Vaccinations against influenza and pneumococcal pneumonia to prevent respiratory infections
• Liver disease management, including:
  • Avoiding alcohol and hepatotoxic medications
  • Regular monitoring of liver function
  • Consideration of liver transplantation in severe cases
• Genetic counseling for affected individuals and their families

Importance of Early Diagnosis and Treatment

Early diagnosis and treatment are crucial in A1AT deficiency, as lung damage is irreversible and preventive strategies are key to minimizing disease progression, as highlighted in the 2025 Canadian Thoracic Society guideline 1. The use of DNA sequencing for A1AT deficiency testing is proposed as the gold standard, allowing for accurate identification of genetic variants and functional deficiency, as discussed in the same guideline 1.

Additional Considerations

• Targeted testing for A1AT deficiency is recommended for individuals with respiratory conditions, such as COPD, asthma with persistent airflow obstruction, and unexplained bronchiectasis, as well as for relatives of individuals with known A1AT deficiency, as suggested by the American Thoracic Society/European Respiratory Society statement 1.
• A two-step approach for A1AT deficiency testing is proposed, involving measurement of A1AT serum levels and DNA sequencing, to rule out severe A1AT deficiency and identify genetic variants, as outlined in the 2025 Canadian Thoracic Society guideline 1.

From the FDA Drug Label

Alpha1-PI deficiency is a chronic, autosomal, co-dominant hereditary disorder characterized by reduced levels of Alpha1-PI in the blood and lungs. Augmenting the levels of functional protease inhibitor by intravenous infusion is an approach to therapy for patients with Alpha1-PI deficiency. However, the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials

The management of Alpha-1-Antitrypsin (A1AT) deficiency involves augmentation therapy with Alpha1-Proteinase Inhibitor (Human) to increase the levels of the deficient protein. This approach is intended to inhibit serine proteases such as neutrophil elastase, which can degrade protein components of the alveolar walls. However, the clinical benefit of this therapy has not been established, and the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials 2.

Key points:

• Alpha1-PI deficiency is a chronic, hereditary disorder
• Augmentation therapy is an approach to therapy for patients with Alpha1-PI deficiency
• The efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated
• The clinical benefit of increased blood levels of Alpha1-PI at the recommended dose has not been established 2

From the Research

Management of Alpha-1-Antitrypsin (A1AT) Deficiency

The management of A1AT deficiency involves a combination of treatments aimed at slowing the progression of lung and liver disease. Some key aspects of management include:

• Augmentation therapy with purified AAT for patients with deficient AAT levels and significant lung disease, which has been shown to slow the progression of emphysema 3, 4, 5
• Aggressive avoidance of smoking and biomass burning, vaccinations, antibiotics, exercise, and good diet to reduce the risk of lung disease exacerbations 3
• COPD medications and serial assessment to monitor disease progression 3
• Individualized pulmonary rehabilitation, exercise, and educational programs to encourage health-enhancing patient behavior and improve patient quality of life 5
• Lung transplantation as a treatment option for patients with end-stage lung disease, which can improve lung physiology and patient health status 6
• Liver transplantation as a treatment option for patients with end-stage liver disease, which can normalize AAT serum levels and halt further lung and liver disease progression 6

Treatment Options

Treatment options for A1AT deficiency are limited, but augmentation therapy with purified AAT is the only disease-specific therapy available. Other treatments, such as COPD medications and surgical interventions, may also be used to manage symptoms and slow disease progression. However, there is a paucity of data around the efficacy of these treatments in A1AT deficiency, and further studies are needed to determine the best course of treatment for this disease group 7.

Screening and Diagnosis

Screening and diagnostic tests are essential for identifying A1AT deficiency, particularly in high-risk groups such as individuals with COPD, nonresponsive asthma, bronchiectasis of unknown etiology, or unexplained liver disease. Screening guidelines have been established by organizations such as the World Health Organization, European Respiratory Society, and American Thoracic Society 3. Early diagnosis and treatment can help impede loss of lung function and improve patient outcomes 4.

Patient-Centric Care

Patient-centric care is crucial for improving the lives of patients with A1AT deficiency. This includes self-administration of intravenous AAT therapy, pulmonary rehabilitation, and individualized exercise and educational programs 5. By empowering patients to take an active role in their care, healthcare providers can improve patient quality of life, freedom, and mental well-being.