From the Guidelines
Patients with Alpha-1 Antitrypsin Deficiency (AATD) should undergo regular monitoring every 6-12 months, including pulmonary function tests (PFTs), liver function tests, and serum AAT levels, as recommended by the most recent guidelines 1.
Monitoring Components
The monitoring approach should include:
- Pulmonary function tests (PFTs) with spirometry, lung volumes, and diffusion capacity to track lung function decline
- Liver function tests, including AST, ALT, alkaline phosphatase, bilirubin, albumin, and prothrombin time
- Serum AAT levels to assess the severity of deficiency
- Chest imaging with CT scans every 1-2 years to assess for emphysema progression
- Abdominal ultrasound annually to screen for liver complications
Augmentation Therapy Monitoring
For patients on augmentation therapy, trough AAT levels should be measured periodically to ensure they remain above the protective threshold of 11 μM (57 mg/dL), as recommended by the Canadian Thoracic Society 1. This is crucial to ensure the effectiveness of the therapy and to adjust the treatment plan as needed.
Frequency of Monitoring
The frequency of monitoring may need to be adjusted based on the severity of the disease and the presence of complications. More frequent monitoring may be necessary for patients with advanced disease or during exacerbations, as recommended by the guidelines 1. This approach allows for early detection of complications and timely intervention to improve outcomes.
Clinical Recognition
Clinical recognition of AAT deficiency is crucial, and physicians should suspect AAT deficiency in patients with early-onset emphysema, emphysema without a recognized risk factor, or otherwise unexplained liver disease, as recommended by the American Thoracic Society/European Respiratory Society statement 1. This includes patients with a family history of emphysema, bronchiectasis, liver disease, or panniculitis.
From the FDA Drug Label
Because emphysema affects many, but not all individuals with the more severe genetic variants of Alpha1-PI deficiency (AAT deficiency), augmentation therapy with Alpha1-Proteinase Inhibitor (Human) is indicated only in patients with severe Alpha1-PI deficiency who have clinically evident emphysema Individuals with the lack of, or low, endogenous serum levels of Alpha1-PI, i. e., below 11 μM, manifest a significantly increased risk for development of emphysema above the general population background risk Although the maintenance of blood serum levels of Alpha1-PI (antigenically measured) above 11 μM has been historically postulated to provide therapeutically relevant anti-neutrophil elastase protection, this has not been proven The clinical efficacy of GLASSIA in influencing the course of pulmonary emphysema or the frequency, duration, or severity of pulmonary exacerbations has not been demonstrated in randomized, controlled clinical trials
The monitoring of Alpha-1 Antitrypsin Deficiency involves tracking serum Alpha1-PI levels, with a target level of above 11 μM. However, it is essential to note that the clinical benefit of achieving this level has not been established.
- Key points:
- Serum Alpha1-PI levels should be monitored
- Target level: above 11 μM
- Clinical benefit of achieving this level: not established
- Augmentation therapy is indicated for patients with severe Alpha1-PI deficiency and clinically evident emphysema
- Efficacy in influencing pulmonary emphysema: not demonstrated in randomized, controlled clinical trials 2 2
From the Research
Alpha-1 Antitrypsin Deficiency Monitoring
- Monitoring lung function, especially through spirometry, is essential in alpha-1 antitrypsin deficiency (AATD) as it provides information on the progression of the disease 3.
- Pulmonary densitometry appears to be the most sensitive measure of emphysema progression, but it should not be used in routine clinical practice to monitor patients 3.
- Lung function tests or computed tomography (CT) densitometry may allow physicians to identify progressive disease during follow-up of patients, with a view to decision-making about AATD-specific therapy 4.
- Different types of biological markers have been suggested for disease monitoring and therapy selection, although most need further investigation 4.
Diagnosis and Monitoring Pathways
- Vibration-controlled transient elastography (VCTE) is the preferred non-invasive test for the initial assessment of AATD-associated liver disease owing to its accessibility and reliability 5.
- Magnetic resonance elastography and enhanced liver fibrosis tests are also considered valuable for diagnosis and monitoring 5.
- A strong consensus was achieved around the use and evaluation of non-invasive tests for risk stratification and monitoring in AATD-associated liver disease 5.
Treatment and Management
- Exogenous administration of purified human serum-derived AAT is the only specific treatment approved for AATD in non-smoking patients with severe deficiency 3.
- Augmentation therapy reduces the progression of emphysema in PiZZ patients and is available in many European countries, but its effect in milder deficiency is less certain 4.
- Treatment is similar to that indicated for patients with COPD not caused by AATD, and ongoing research is focusing on the development of specifically targeted, new medications 3, 6.