Alpha-1

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General Information

Alpha-1 Week

Alpha-1 is the most common known genetic form of chronic obstructive pulmonary disease (COPD). More than 100,000 people in America have Alpha-1. However, fewer than 10 percent have been properly diagnosed. Laurell and Eriksson performed the pioneering work and discovered the absence of the Alpha-1 band in serum electrophoresis gels. The normal alpha-1 antitrypsin phenotype is M and 95 percent is made in the liver. The main function of the alpha-1 antitrypsin protein is to neutralize/control neutrophil elastase, a potent proteolytic enzyme that can damage the elastin matrix of the lung.

The PiZ protein results from a point mutation that encodes a single amino acid substitution. The Z protein misfolds, polymerizes, and accumulates in the liver, where it can damage the liver, leading to cirrhosis and hepatoma.  Secretion of the alpha-1 protein from the liver is impaired, and low serum levels can lead to lung disease. COPD is a common chronic lung disease in which Alpha-1 is not rare: in 965 emphysema patients 1.9 percent was Pi*ZZ and 8 percent were Pi*MZ, or carriers of the defective alpha-1 gene.

The clinical presentation of Alpha-1 from two outpatient registries reveals the following: 54 percent had emphysema, 72 percent had respiratory symptoms, 45 percent had chronic bronchitis, and 35 percent had a diagnosis of asthma. Also, the presence of bronchiectasis in the Alpha-1 population is very common.

In clinical presentations, Alpha-1 patients often are short of breath and have hyperinflation of the lungs. A review of 102 cat scans showed 64 percent have basal disease. But it is essential to remember that clinical findings, CT scans and chest x-rays do not identify Alpha-1. The diagnosis is made by testing the serum, and this is provided free of charge by the Alpha-1 Foundation at testing centers at the University of Florida and Medical University of South Carolina, the site of the registry for Alpha-1.

It is also important to note that patients have various therapeutic options. The Alpha-1 Foundation has designated more than 80 clinical resource centers across the country to serve patients with this condition. While there are no specific treatments to prevent Alpha-1 disease at present, augmentation therapy has been shown to be effective on the lung disease at least retrospectively in the NIH Registry. Similarly, liver disease is undergoing intense investigation at the present time. Patients with Alpha-1 must assume liver protective lifestyle guidelines for clinical care of patients with either lung and liver diseases or both are available.

Who should be tested? All subjects with COPD, regardless of smoking history, all adults with asthma characterized by incompletely reversible airflow, patients with bronchiectasis, chronic liver disease and panniculitis. The lab testing involves a finger stick, and phenotyping or Pi-typing of the protein is done. This can determine whether the patient is a carrier or homozygous (ZZ) for the deficiency. Genotyping is DNA testing that determines the Pi genes from extracted DNA.

Augmentation therapy is now available, and there are four approved drugs: Aralast, Glassia, Prolastin and Zemaira. These agents given intravenously each week were approved based on pharmacokinetic and biochemical data under the FDA orphan disease regulatory process. Many studies such as the NIH Registry support the use of augmentation therapy, but intense research continues into new products using different routes of administration.

Both the ATS and Alpha-1 Foundation recognize the critical importance of targeted research, comprehensive education, unrelenting advocacy and excellence in clinical care of patients with Alpha-1.


Four Facts About Alpha-1

  1. Alpha-1 Antitrypsin Deficiency (Alpha-1) is a genetic condition – passed on from parents to their children through genes.

  2. Alpha-1 may result in serious lung disease in adults and/or liver disease at any age.

  3. Alpha-1 has been identified in virtually all populations. About 1 in every 2,500 Americans has Alpha-1.

  4. Alpha-1 is the most common known genetic risk factor for emphysema, and a leading cause of liver transplants in children.