What is the management and treatment for alpha 1 antitrypsin deficiency?

Management and Treatment of Alpha-1 Antitrypsin Deficiency

The management of alpha-1 antitrypsin deficiency (AATD) requires a comprehensive approach including smoking cessation, standard COPD therapies, and augmentation therapy for eligible patients with documented emphysema and FEV1 <80% predicted.

Diagnosis and Initial Assessment

• SERPINA1 gene sequencing is recommended before initiating augmentation therapy to confirm the diagnosis 1
• Testing is strongly recommended for:
  • Patients with early-onset emphysema
  • Emphysema without recognized risk factors
  • Unexplained liver disease 2
• Regular monitoring includes:
  • Pulmonary function testing every 6-12 months
  • CT scan to document presence and progression of emphysema
  • Liver function monitoring 2

General Management of Lung Disease

Non-pharmacological Interventions

• Smoking cessation is the single most important intervention to prevent accelerated lung function decline 2
• Minimize exposure to respiratory irritants, dust, and fumes 2
• Pulmonary rehabilitation for individuals with functional impairment 1
• Annual influenza and pneumococcal vaccinations 1, 2

Pharmacological Management

• Standard COPD therapies:
  • Inhaled bronchodilators (even without objective bronchodilator responsiveness) 1, 2
  • Inhaled corticosteroids for those with bronchial hyperreactivity 2
  • Aggressive antibiotic treatment for respiratory infections (early intervention for purulent exacerbations) 1, 2
  • Supplemental oxygen when indicated by conventional criteria 1

Augmentation Therapy

Indications

Augmentation therapy is indicated for patients with:

• Documented SERPINA1 genotypes associated with AATD
• Severely reduced functional AAT level
• FEV1 <80% predicted
• Documented emphysema on CT scan
• Non-smoking status 2

Administration and Dosing

• Standard dosing: 60 mg/kg body weight administered intravenously weekly 2, 3
• Goal: Maintain serum AAT levels above the protective threshold (>11 μM) 3
• Treatment should be initiated as early as possible once criteria are met 2

Clinical Benefits

• Reduces FEV1 decline (53 ml/year in treated vs. 75 ml/year in untreated patients) 2
• Preserves CT scan lung density and significantly slows lung density decline over 2 years 2
• Most beneficial in patients with moderate emphysema (FEV1 31-65% predicted) 2

Management of Advanced Disease

• Consider lung transplantation for selected individuals with severe functional impairment 1
• Limited evidence for lung volume reduction surgery in AATD patients, with shorter benefit duration than in non-AATD COPD 1

Liver Disease Management

• Regular monitoring of liver function tests 2
• Testing for hepatitis serology and considering vaccination 2
• Hepatology referral for patients with evidence of liver involvement 2

Common Pitfalls to Avoid

• Failing to recognize the importance of smoking cessation 2
• Misdiagnosing asthma symptoms, which can be early manifestations of COPD in AATD 2
• Overlooking the need for aggressive infection management 2
• Assuming all heterozygotes need augmentation therapy (evidence does not support routine use in MZ individuals without significant emphysema) 2
• Neglecting liver monitoring, as AATD can affect the liver, especially in older patients 2

Special Considerations

• Smoking cessation is mandatory before initiating augmentation therapy, as it is significantly less effective in current smokers 2
• The clinical efficacy of augmentation therapy in influencing the course of pulmonary emphysema has not been definitively demonstrated in randomized, controlled clinical trials 3
• Augmentation therapy should be part of a comprehensive management plan that includes standard COPD treatments 2