What is the management for alpha 1 antitrypsin (A1AT) deficiency?

Management of Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) requires augmentation therapy with intravenous alpha-1 antitrypsin for patients with documented emphysema and FEV1 <80% predicted, along with comprehensive COPD management. 1

Diagnosis and Testing

Alpha-1 antitrypsin deficiency is frequently underrecognized, with less than 10% of cases identified 2. Testing should be performed in the following populations:

• Type A recommendation (strongly recommended) 3:

  • Early-onset emphysema (age ≤45 years)
  • Emphysema without recognized risk factors
  • Emphysema with prominent basilar hyperlucency
  • Otherwise unexplained liver disease
  • Necrotizing panniculitis
  • Anti-proteinase 3-positive vasculitis
  • Family history of emphysema, bronchiectasis, liver disease, or panniculitis

• Type B recommendation (should be discussed) 3:

  • Bronchiectasis without evident etiology
  • Adolescents with persistent obstructive defects on pulmonary function testing
  • Asymptomatic individuals with persistent obstructive defects and smoking exposure

Initial screening should include serum AAT level, and if level is <23 μmol/L, proceed to genetic testing with DNA sequencing of the SERPINA1 gene 1.

Non-Specific Medical Treatment

All patients with AATD-related lung disease should receive:

1. Smoking cessation - most critical intervention as smoking accelerates lung function decline 3
2. Vaccinations - influenza and pneumococcal vaccines 3
3. Bronchodilators - even if objective bronchodilator responsiveness is lacking 3
4. Inhaled steroids - for those with bronchial hyperreactivity 3
5. Antibiotics - for respiratory infections, with macrolides potentially reducing neutrophil inflammation 3
6. Oxygen therapy - for those with desaturation during exercise or severe hypoxemia 3
7. Pulmonary rehabilitation - improves endurance, reduces dyspnea, and reduces hospitalizations 3
8. Management of depression and anxiety - common in patients with chronic lung disease 3

Augmentation Therapy

Augmentation therapy is indicated for patients with:

1. Documented SERPINA1 genotypes associated with AATD
2. Severely reduced functional AAT level (<11 μmol/L or <0.57 g/L)
3. FEV1 <80% predicted
4. Documented emphysema on CT scan
5. Non-smoking status (for at least 6 months)
6. Receiving optimal pharmacological and non-pharmacological therapies for COPD 1

Standard dosing: 60 mg/kg body weight administered intravenously weekly, with the goal of maintaining serum AAT levels above the protective threshold (>15 μmol/L) 1, 4.

Benefits of Augmentation Therapy:

• Preservation of CT scan lung density and significant slowing of lung density decline over 2 years 1
• Reduced FEV1 decline (53 ml/year in treated vs. 75 ml/year in untreated patients) 1
• Most beneficial in patients with moderate emphysema (FEV1 31-65% predicted) 1, 5
• Reduced mortality (NHLBI Registry showing lower mortality rates in those receiving augmentation therapy) 1

Monitoring:

• Pulmonary function tests every 6-12 months
• CT scans to assess emphysema progression
• Monitor for adverse reactions to augmentation therapy (fever, chills, dyspnea in ~5% of patients)
• Regular liver function tests for patients with evidence of liver involvement 1

Special Considerations

Liver Disease

Cirrhosis and its complications can be the main cause of death, especially in elderly never-smokers 3. Regular monitoring of liver function and hepatology referral for patients with evidence of liver involvement is recommended.

Necrotizing Panniculitis

A rare complication of PI*ZZ AATD that presents with inflammatory necrotic lesions in the subcutis and dermis 3. Augmentation therapy may ameliorate signs of vasculitis 3.

Bronchiectasis

Saccular and cylindrical bronchiectasis has been associated with AATD, either with or without concomitant emphysema 3. Treatment follows standard bronchiectasis management with more prolonged antibiotic courses.

Algorithm for Management

1. Confirm diagnosis with serum AAT level and genetic testing if level <23 μmol/L
2. Assess lung function with pulmonary function tests and CT scan
3. Implement non-specific medical treatment (smoking cessation, vaccinations, bronchodilators, etc.)
4. Evaluate for augmentation therapy if:
   • Confirmed AATD (serum level <11 μmol/L)
   • FEV1 <80% predicted
   • Documented emphysema on CT scan
   • Non-smoking status
5. Administer augmentation therapy at 60 mg/kg IV weekly if criteria met
6. Monitor response with regular pulmonary function tests and CT scans
7. Manage complications including liver disease, necrotizing panniculitis, and bronchiectasis

The management of AATD requires a comprehensive approach focusing on both preventing further lung damage and treating existing symptoms. Augmentation therapy remains the cornerstone of treatment for those with documented emphysema and reduced lung function.