How do you treat alpha 1 antitrypsin deficiency affecting the lungs in older adults?

Treatment of Alpha-1 Antitrypsin Deficiency Lung Disease in Older Adults

Intravenous augmentation therapy with alpha-1 antitrypsin (60 mg/kg weekly) is recommended for older adults with confirmed severe AAT deficiency who have established emphysema on CT scan and moderate airflow obstruction (FEV1 30-65% predicted), as this population demonstrates the strongest evidence for slowed disease progression and reduced mortality. 1

Augmentation Therapy: Specific Indications

The decision to initiate augmentation therapy requires meeting ALL of the following criteria:

• Confirmed severe AAT deficiency: Serum AAT level <11 µM 1
• Documented emphysema: High-resolution CT chest showing emphysematous changes 2
• Moderate airflow obstruction: Post-bronchodilator FEV1 between 30-65% predicted 1
• Smoking status: Must be a never-smoker or former smoker (smoke-free for ≥6 months) 2

Evidence Strength by Disease Severity

The benefit of augmentation therapy varies significantly by baseline lung function:

• Strongest evidence (FEV1 31-65% predicted): The German-Danish study showed yearly FEV1 decline of -53 ml in treated versus -75 ml in untreated patients (p<0.02) 1. The NHLBI Registry demonstrated slower FEV1 decline (p<0.03) and reduced mortality (OR 0.79, p<0.02) specifically in patients with FEV1 35-49% predicted 1

• Unclear benefit (FEV1 <30% or >65% predicted): Evidence for augmentation therapy efficacy is less clear in patients with severe or mild airflow obstruction 1

• Exception for rapid decliners: Patients with near-normal lung function may be treated if experiencing rapid FEV1 decline (>120 ml/year) 1

Standard Dosing Protocol

• Dose: 60 mg/kg body weight 2
• Frequency: Weekly intravenous infusion 1
• Target trough level: Serum AAT should exceed 15 µM (35% predicted threshold) on Day 7 immediately before next infusion 1

Safety Profile

Augmentation therapy has a favorable safety profile with rare adverse reactions. In a series of 58,000 infusions, only 124 mild reactions (fever, chills, dyspnea) occurred in 65 patients, with 4 anaphylactic reactions (all with complete recovery) 1

Comprehensive COPD Management (Essential for All Patients)

Beyond augmentation therapy, older adults require standard COPD management:

• Inhaled bronchodilators for symptomatic relief 1
• Influenza and pneumococcal vaccinations 1
• Supplemental oxygen when indicated by conventional criteria (including during air travel) 1
• Pulmonary rehabilitation for those with functional impairment 1, 2
• Early antibiotic therapy for all purulent exacerbations (given increased elastolytic burden risk in AAT deficiency) 1

Advanced Disease Considerations

For older adults with severe functional impairment:

• Lung transplantation: Consider for selected individuals with severe airflow obstruction and functional impairment 1
• Lung volume reduction surgery: Possible improvement in dyspnea and lung function, though benefit duration appears shorter than in AAT-replete COPD 1
• Continue augmentation if already receiving: Patients with very poor lung function already on treatment should be kept on therapy 1

Critical Pitfalls to Avoid

Do not initiate augmentation therapy based solely on AAT deficiency diagnosis. The presence of emphysema on CT scan is mandatory, as augmentation is not recommended for individuals without emphysema 1, 2

Do not assume benefit in patients with FEV1 >65% predicted. The 2025 Canadian Thoracic Society guideline explicitly states "it is not known whether augmentation therapy is beneficial for patients without impaired FEV1" 2

Do not use augmentation for liver disease. Intravenous augmentation therapy does not confer benefits for AAT deficiency-related liver disease 1

Age-specific consideration: Cirrhosis in PI*ZZ AAT-deficient individuals peaks in elderly never-smokers who survived without developing severe emphysema, requiring regular liver function monitoring 1

Emerging Evidence

The RAPID trial demonstrated significant slowing of CT lung density decline over 2 years with augmentation therapy, with modeling suggesting 6 years longer survival before death or transplantation if continued beyond the trial period 1. However, CT lung density measurements are not yet validated for real-world clinical decision-making 1