Management of Alpha-1 Antitrypsin Deficiency

Diagnostic Approach

The American Thoracic Society recommends that all patients with COPD, adult-onset asthma with persistent airflow obstruction, or unexplained bronchiectasis should be evaluated for alpha-1 antitrypsin deficiency (A1AT) 1, 2
The European Respiratory Society suggests that simultaneous collection of two blood tubes, one for serum A1AT level and one for DNA analysis of the SERPINA1 gene, is required for diagnostic testing 1
The American College of Chest Physicians states that DNA sequencing of the SERPINA1 gene is the gold standard for definitive diagnosis, surpassing isoelectrofocusing (IEF) because it detects rare variants and provides invariant results 1, 2

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends that smoking cessation is the most important intervention and should be the primary focus at each patient visit, as smoking dramatically accelerates the progression of emphysema 3, 2
The American College of Cardiology suggests that vaccination against influenza and pneumococcus is mandatory 2
The European Respiratory Society recommends that reduction of occupational exposure to dust, smoke, gases, and air pollutants is essential 3

The American Thoracic Society states that augmentation therapy is specifically indicated for severe hereditary alpha-1 antitrypsin deficiency with clinically evident emphysema 2
The European Respiratory Society suggests that the dosage is 60 mg/kg of body weight once a week by intravenous infusion, which increases lung levels of alpha-1 antitrypsin to 60-70% of normal 3
The American College of Chest Physicians recommends that absolute contraindications include active smoking, IgA deficiency with anti-IgA antibodies, and absence of documented emphysema on imaging 2

The American Association for the Study of Liver Diseases (AASLD) recommends that for suspected liver disease associated with A1AT deficiency, phenotyping plus abdominal ultrasound establishes the diagnosis—the liver biopsy is not necessary 1
The European Association for the Study of the Liver (EASL) suggests that simple liver function tests and regular ultrasound are necessary for follow-up of asymptomatic individuals with A1AT deficiency 4, 5

The Society of Thoracic Surgeons recommends that lung volume reduction surgery (LVRS) improves survival in patients with COPD and upper lobe emphysema and low exercise capacity post-rehabilitation compared to medical therapy 3
The International Society for Heart and Lung Transplantation states that lung transplantation is the only treatment option when patients develop terminal lung disease and can improve lung physiology and patient health status 3

The American Thoracic Society recommends that nutritional support is essential, as weight loss and malnutrition are common problems due to increased metabolic rate from increased respiratory work 3
The European Respiratory Society suggests that early signs of depression, such as loss of appetite, should be recognized and treated aggressively 3

The American College of Medical Genetics recommends that family screening should be discussed, recognizing that it can reasonably be accepted or declined, as if an individual is heterozygous for an A1AT deficiency allele, their sibling has a 25% chance of being heterozygous 8
The European Society of Human Genetics suggests that descendant screening should be discussed, as the offspring of a heterozygous parent has a 25% chance of being heterozygous 8