Alpha1-antitrypsin (AAT) deficiency, sometimes known simply as “alpha-1”, is a genetic disease primarily affecting the lungs and liver that is characterised by a decrease in circulating levels of a protein called alpha1 antitrypsin (AAT).1
- AAT deficiency is the major known genetic risk factor for chronic obstructive pulmonary disease (COPD)2
- Over 90% of people with AAT deficiency are believed to be undiagnosed3,4
- Up to 3% of all COPD cases may be due to an underlying AAT deficiency3
AAT counteracts the effects of an enzyme called neutrophil elastase, which is released by immune cells during infection. AAT helps to protect lung tissue from destruction caused by neutrophil elastase.5
- AAT is a protein encoded by a gene in which there are many genetic variants and some are associated with AAT deficiency5,6
- Certain genetic variants are also associated with liver disease5
All COPD patients should be screened for AAT deficiency according to the following international professional organisations:
The World Health Organization (WHO)2
The American Thoracic Society (ATS)6
The COPD Foundation Clinical Guidelines8
The European Respiratory Society (ERS)6
The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD)9
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Once diagnosed, patients can be counselled to adopt healthier lifestyles. Since AAT deficiency is a genetic disease, early detection may also help affected relatives.3
Once someone is diagnosed, next steps may include:
- Familial genetic screening3,6,10
- Genetic counselling3,6,10
- Smoking prevention or cessation3,11
- Avoidance of occupational respiratory pollutants3,11
- Optimisation of COPD treatment3,6,10
- Intravenous infusion of AAT, also known as augmentation therapy — the only specific treatment for AAT deficiency10
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Augmentation therapy has been demonstrated to raise levels of AAT in the blood and lungs above the threshold needed to protect lung tissue.6,12
- The goal of augmentation therapy is to correct the deficiency state and keep neutrophil elastase in check12,13
Professional guidelines recommend general management strategies that include pharmacologic and non-pharmacologic treatments.6,9
- Health management programs include patient support and education14,15
- Stoller JK, Lacbawan FL, Aboussouan LS. Alpha-1 antitrypsin deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al. editors. GeneReviews(R). Seattle (WA)2006 (updated 2014).
- World Health Organization. Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ. 1997;75(5):397-415.
- Campos MA, Wanner A, Zhang G, et al. Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003. Chest. 2005;128(3):1179-86.
- Orphanet Report Series. Prevalence and incidence of rare diseases: January 2019 - Number 1. 2019 [Updated]. Available at: http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf.
- Köhnlein T, Welte T. Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment. Am J Med. 2008;121(1):3-9.
- ATS, ERS. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900.
- Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult (Clinical Practice Guidelines). Chronic Obstr Pulm Dis (Miami). 2016;3(3):668-82.
- Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2020 [Updated]. Available at: http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/.
- Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. European Respiratory Journal. 2017;50(5).
- Bals R, Kohnlein T. Alpha-1 Antitrypsin Deficiency. Pathophysiology, Diagnosis, and Treatment. 2009.
- Wewers MD, Casolaro MA, Sellers SE, et al. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med. 1987;316(17):1055-62.
- Stoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet. 2005;365(9478):2225-36.
- Campos MA, Alazemi S, Zhang G, et al. Effects of a disease management program in individuals with alpha-1 antitrypsin deficiency. COPD. 2009;6(1):31-40.
- Campos MA, Runken MC, Davis AM, et al. Impact of a Health Management Program on Healthcare Outcomes among Patients on Augmentation Therapy for Alpha 1-Antitrypsin Deficiency: An Insurance Claims Analysis. Adv Ther. 2018;35(4):467-81.
AAT: alpha1 antitrypsin; COPD: chronic obstructive pulmonary disease.