What is the management approach for a patient with alpha1 antitrypsin deficiency?

Management of Alpha-1 Antitrypsin Deficiency

Diagnostic Confirmation

All adults with symptomatic COPD, asthma with persistent airflow obstruction, or unexplained bronchiectasis should be tested for alpha-1 antitrypsin deficiency. 1

Initial Testing Approach

• Measure serum alpha-1 antitrypsin level with severe deficiency defined as <11 μmol/L (<0.57 g/L) 2, 3
• Perform SERPINA1 gene sequencing to confirm the specific genetic variant, as over 300 variants exist and some produce normal levels but dysfunctional protein 2, 4
• Obtain baseline post-bronchodilator spirometry to document FEV1 2, 4
• High-resolution CT chest to document presence or absence of emphysema 2, 4
• Baseline liver function tests (AST, ALT, bilirubin, alkaline phosphatase), particularly in patients over 50 years old 2, 3

Clinical Features Prompting Suspicion

• Early-onset emphysema (age ≤45 years) 1
• Emphysema with prominent basilar hyperlucency 1
• Unexplained liver disease or necrotizing panniculitis 1
• C-ANCA-positive vasculitis 1
• Family history of emphysema, bronchiectasis, liver disease, or panniculitis 1

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Management Algorithm Based on Clinical Status

For Asymptomatic Patients (No Emphysema, FEV1 ≥80%)

Asymptomatic patients should NOT receive augmentation therapy. 2

Preventive Measures (Critical)

• Smoking cessation is the single most important intervention, as smokers with AATD have FEV1 decline of 70 ml/year versus 47 ml/year in non-smokers 2
• Avoid occupational exposures to respiratory irritants, dust, gases, and fumes 2, 3
• Vaccinations: influenza (annual), pneumococcal, hepatitis A and B 2, 3, 4

Surveillance Protocol

• Annual spirometry to monitor FEV1 decline 2
• Repeat HRCT chest if symptoms develop or FEV1 declines abnormally 2
• Liver surveillance with ultrasound, especially for patients >50 years old, as 30-40% develop cirrhosis or hepatocellular carcinoma 3
• Refer to hepatology if persistent abnormal liver function tests or age >50 years 2

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For Symptomatic Patients (Emphysema Present, FEV1 <80%)

All patients require standard COPD management regardless of augmentation therapy eligibility. 3, 4

Standard COPD Therapy (Required for All)

• Bronchodilators for symptomatic relief 3, 4
• Inhaled corticosteroids for those with bronchial hyperreactivity 4
• Early antibiotic therapy for all purulent exacerbations due to increased elastolytic burden risk 3
• Brief courses of systemic corticosteroids during acute exacerbations 3
• Pulmonary rehabilitation for functional impairment 4
• Supplemental oxygen when standard criteria are met 4

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Augmentation Therapy Decision Algorithm

Augmentation therapy is indicated ONLY when ALL of the following criteria are met: 3, 4

Mandatory Eligibility Criteria

1. Severe AAT deficiency: serum level <11 μmol/L (<0.57 g/L) 3, 4
2. Documented SERPINA1 deficiency genotype (typically PI*ZZ) 3, 4
3. CT-documented emphysema 3, 4
4. FEV1 <80% predicted on post-bronchodilator spirometry 3, 4
5. Nonsmoker for ≥6 months (absolute requirement) 4
6. On optimal COPD therapy as outlined above 4

Strongest Evidence for Benefit

• Patients with FEV1 31-65% predicted (moderate emphysema) show the most robust benefit, with yearly FEV1 decline of -53 ml in treated versus -75 ml in untreated groups 4
• Mortality benefit demonstrated specifically in subgroup with FEV1 35-49% predicted 4
• Evidence is weaker for severe airflow obstruction (FEV1 <30%) 4

Dosing

• 60 mg/kg intravenously weekly is the standard on-label dose 4

Absolute Contraindications

• Active smoking (negates protective benefits entirely) 4, 5
• IgA deficiency with anti-IgA antibodies 4
• Lack of documented emphysema on imaging 4

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Critical Pitfalls to Avoid

• Never initiate augmentation therapy based on AATD diagnosis alone—emphysema must be documented and FEV1 must be <80% predicted 2, 4
• Never overlook liver surveillance, as cirrhosis-related complications are a major cause of death, particularly in non-smoking older individuals 2, 3
• Never assume augmentation therapy replaces standard COPD management—it is adjunctive therapy only 4
• Never approve augmentation therapy without genetic confirmation, as some variants produce normal levels but dysfunctional protein 2, 4
• Smoking cessation must be verified and maintained—even post-lung transplant patients who resume smoking can redevelop emphysema 5

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Family Screening

• Test all first-degree relatives of individuals with confirmed AATD, as family testing is currently the most efficient detection technique 6