Respiratory

Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency (Alpha-1) is a genetic (inherited) condition – it is passed from parents to their children through their genes. Alpha-1 may result in serious lung disease in adults and/or liver disease at any age. Earlier screening helps to accurately diagnose Alpha-1, allowing for a treatment plan to be established.

Alpha-1 antitrypsin (A₁AT) is a protein produced primarily by hepatocytes and released into circulation by the liver. A₁AT functions in the lungs to inactivate neutrophil elastase, a powerful protease that contributes to the innate immune response.

A₁AT keeps neutrophil elastase levels in check, thereby protecting the lung against alveolar wall destruction. A₁AT provides > 90% of the anti-neutrophil elastase protection in the lungs.

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AATD Information

A₁AT deficiency (AATD) results in uninhibited neutrophil elastase activity, and this imbalance can lead to lung damage, including emphysema.

Caused by low levels of alpha₁ antitrypsin (A₁AT), a protein synthesized and secreted by the liver
A₁AT protects the lungs from infection and lung diseases such as emphysema and COPD
More than 20 million individuals in the United States possess the genetically deficient alleles that cause Alpha-1 antitrypsin deficiency
Affects up to 5% of the approximately 12 million patients with COPD in the United States
An estimated 100,000 individuals are affected in the United States
An estimated 90% have not been diagnosed, and fewer are being treated
Lung-related symptoms usually develop between the ages of 20 and 40

Earlier screening helps to accurately diagnose Alpha-1, allowing for a treatment plan to be established that may lead to improved outcomes.
Lifestyle changes such as smoking cessation, healthy eating habits, and regular exercise can improve overall health.
A₁AT augmentation therapy has been shown to raise and maintain serum levels of A₁AT protein.

The Journal of the COPD Foundation states intravenous augmentation therapy in those with AATD is recommended for:

Individuals with an FEV₁ less than or equal to 65% predicted.
For those with lung disease related to AATD and an FEV₁ greater than 65%, we recommend discussion of potential benefits of reducing lung function decline with consideration of the cost of therapy and lack of evidence for such benefit.
Individuals with necrotizing panniculitis.

1.National Human Genome Research Institute. About Alpha-1 Antitrypsin Deficiency. https://www.genome.gov/Genetic-Disorders/Alpha-1-Antitrypsin-Deficiency. Accessed June 5, 2019. 2.de Serres FJ, Blanco I. Prevalence of a1-antitrypsin deficiency alleles PI*S and PI*Z worldwide and effective screening for each of the five phenotypic classes PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ: a comprehensive review. Ther Adv Respir Dis. 2012;6(5):277-295. 3.Brode SK, Ling SC, Chapman KR. Alpha-1 antitrypsin deficiency: a commonly overlooked cause of lung disease. CMAJ. 2012;184(12):1365-1371.4.Alpha-1 Foundation. Questions and Answers About Alpha-1 Antitrypsin Deficiency (Alpha-1). https://www.alpha1.org/Alpha1/wp-content/uploads/2019/11/Questions-and-Answers-About-Alpha-1.pdf. Accessed June 5, 2019. 5.Siri D, Farah H, Hogarth DK. Distinguishing alpha1-antitrypsin deficiency from asthma. Ann Allergy Asthma Immunol. 2013;111:458-464 6. Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis. 2016;3(3):668-682. 7. Alpha-1 Antitrypsin Deficiency: A Guide for the Recently Diagnosed Individual. Alpha-1 Foundation. Version 1.7, December 2015.