Management

Quitting smoking is essential for any patient suspected of having or diagnosed with AAT deficiency. Individuals with severe AAT deficiency, such as those with PI ZZ or null genotypes, should undergo regular monitoring with pulmonary function and 6-minute walk testing, clinical assessments, and evaluations of their quality of life. (1)

Supportive treatments include inhaled bronchodilators and inhaled or oral glucocorticoids, as recommended by the guidelines for managing COPD (2)

Preventive vaccination against respiratory viral infections, such as influenza and pneumococcal pneumonia, should be prioritized. (3) Pulmonary rehabilitation and nutritional support are also important components of comprehensive care for these patients

Intravenous augmentation, which involves the infusion of pooled plasma-purified human alpha-1 antitrypsin (an alpha-1 proteinase inhibitor), is the only licensed disease-specific therapy for AAT deficiency associated with lung disease. (4)

While lung transplantation has been shown to provide both quality of life and survival benefits for selected patients with severe AAT deficiency, other therapies, such as lung volume reduction therapy, are not recommended due to a lack of evidence supporting its use (5).

Liver transplantation for hepatic failure prevents further lung damage but is associated with a 30% early mortality.

To prevent secondary complications related to liver disease, it is important to advise patients to limit alcohol intake or abstain from alcohol altogether.

Additionally, hepatitis A and B vaccinations should be recommended. Genetic counseling and testing are recommended for first-degree relatives of individuals with AAT deficiency due to the increased risk of carrying at-risk alleles associated with AAT deficiency. (6)

Reference

1. Miravitlles M et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α₁-antitrypsin deficiency. Eur Respir J. 2017 Nov;50(5)
2. Tamondong-Lachica DR et al. GOLD 2023 Update: Implications for Clinical Practice. Int J Chron Obstruct Pulmon Dis. 2023;18:745-754
3. Walters JA, Tang JN, Poole P, Wood-Baker R. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Jan 24;1(1):CD001390
4. Campos M, Lascano J. Therapeutics: Alpha-1 Antitrypsin Augmentation Therapy. Methods Mol Biol. 2017;1639:249-262
5. Dummer J et al. AE. Diagnosis and treatment of lung disease associated with alpha one-antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand. Respirology. 2020 Mar;25(3):321-335.
6. Strand P, McElvaney NG, Lomas DA. Alpha₁-Antitrypsin Deficiency. N Engl J Med. 2020 Apr 09;382(15):1443-1455.