What is alpha1-antitrypsin (AAT) deficiency (Alpha-1)?
Alpha-1, the major known genetic risk factor for chronic obstructive pulmonary disease (COPD), is one of the world's most prevalent, potentially fatal hereditary diseases.1,2
Alpha-1, the major known genetic risk factor for chronic obstructive pulmonary disease (COPD), is one of the world's most prevalent, potentially fatal hereditary diseases.1,2
AAT deficiency is an inherited condition that is caused by mutations in the SERPINA1 gene, which is responsible for producing the AAT protein. The AAT protein, which is produced in the liver and then released in the blood, is responsible for protecting the body from the neutrophil elastase enzyme.3
When mutations occur in the SERPINA1 gene, the result is the production of an abnormal protein that gets trapped in the liver, resulting in low serum levels of AAT. Low serum levels of AAT can predispose to lung breakdown by neutrophil elastase and other enzymes that break down proteins.3
To date, more than 150 different mutations have been identified in the SERPINA1 gene.
The most common mutations are the S and Z alleles, which cause AAT deficiency3:
The M allele is the most common and produces normal levels of the AAT protein.3,4
AAT deficiency is a codominant genetic condition. Codominant genetic conditions occur when each inherited allele expresses some effect, such as lowering serum levels of AAT. Generally, in a codominant condition, an individual who inherits 2 copies of a mutated gene (ZZ) has a higher risk of developing emphysema than someone inheriting 1 abnormal allele (MZ; low risk of developing disease, only in the absence of smoking).3
In the case of an individual inheriting an S allele and a Z allele (SZ), the risk of developing chronic obstructive pulmonary disease is increased if he or she smokes.
Because AAT is an autosomal condition, the risk of inheriting a defective gene is the same for both males and females because the gene is not on the sex chromosome (X or Y).
The chance that 2 carrier parents will pass on the mutated gene and have an affected (ZZ) child
The chance that a child of 2 carrier parents will become a carrier
The chance that a child of 2 carrier parents will receive normal genes
For patients with alpha-1, the most common symptoms of lung disease include:
Early diagnosis and treatment of alpha-1 is very important. However, alpha-1 can't be diagnosed by symptoms or by a medical examination alone; patients need to be screened to know for sure.6
COPD describes multiple lung diseases, including emphysema and chronic bronchitis. Alpha-1 often goes undiagnosed because its symptoms are similar to COPD.1,4
It's critical to remember that a patient with alpha-1 cannot be identified by symptoms or medical examination alone. The only way to truly know if a patient has alpha-1 is through a laboratory test.6
While the symptoms of alpha-1 usually appear between the ages of 20 and 50 years of age, data obtained over a 3-year period (2004–2007) from the renowned Alpha-1 Genetics Laboratory in Florida showed that the majority of newly diagnosed patients were 50 years of age or older.6,7
Smoking accelerates lung function decline in patients with alpha-1. In a national registry study of 1129 patients with alpha-1, approximately 80% were either current smokers (8%) or ex-smokers (71%).8,9
Given the disparity in patient diagnoses, ALL patients with COPD should be screened for alpha-1, regardless of smoking history.10
These readings can be misleading because some nonsmokers have low FEV1 levels and some smokers have high FEV1 levels.8
FEV1=forced expiratory volume in 1 second.
AAT is a protein with potent protease inhibitor activity. Its main function is to protect normal lung tissue from proteolytic attack during inflammation, such as that caused by infection and inhaled irritants like tobacco smoke. When low levels of AAT occur, the lungs are at risk for serious lung disease.11-14
Low levels of circulating AAT allow potentially harmful enzymes, like neutrophil elastase, to remain in the lungs unchecked. This combination of low levels of AAT and the consequent proliferation of neutrophil elastase leave lung tissue vulnerable to destruction, resulting in a decline in lung function. Alpha-1 may be a contributing cause of up to 3% of all COPD cases in the United States.1,11,12
Lungs with normal AAT levels keep neutrophil elastase in check so that lung structure is preserved11
In AAT-deficient individuals, excess neutrophil elastase cannot be neutralized, lung elastin is destroyed, and lung function is compromised11
To help your practice and your patients learn more about alpha-1, access such resources as videos, peer testimonials, and downloadable PDFs.
Important Safety Information
PROLASTIN®-C LIQUID is an alpha1-proteinase inhibitor (human) (alpha1-PI) indicated for chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary deficiency of alpha1-PI (alpha1-antitrypsin deficiency).
Limitations of Use
PROLASTIN-C LIQUID is contraindicated in immunoglobulin A (IgA)-deficient patients with antibodies against IgA or patients with a history of anaphylaxis or other severe systemic reaction to alpha1-PI products.
Hypersensitivity reactions, including anaphylaxis, may occur. Monitor vital signs and observe the patient carefully throughout the infusion. If hypersensitivity symptoms occur, promptly stop PROLASTIN-C LIQUID infusion and begin appropriate therapy.
Because PROLASTIN-C LIQUID is made from human plasma, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens.
The most common adverse reactions during PROLASTIN-C LIQUID clinical trials in >5% of subjects were diarrhea and fatigue, each of which occurred in 2 subjects (6%).
Please see full Prescribing Information for PROLASTIN-C LIQUID.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
References