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Pharmacological treatment of alpha 1 antitrypsin deficiency.

Alpha 1 proteinase inhibitor is intended for therapy of congenital alpha 1 antitrypsin deficiency, which leads to emphysema. The product is prepared from pooled human plasma from normal donors, with purification and treatment to remove potentially infectious agents. This article with briefly describe alpha 1 lung disease and pharmacological treatment with porteinase inhibitors.


Alpha 1-Antitrypsin Deficiency

Alpha 1 -Antitrypsin deficiency is a genetic defect that can lead to the development of severe panacinar emphysema. This autosomal recessive disorder is characterized by serum API levels below 35% of normal and presents as panacinar emphysema at age 30 to 50 years. It is estimated that API deficiency accounts for approximately 2% of all emphysema in the United States. It is estimated that there are 60,000 to 100,000 Americans with severe alpha 1 antitrypsin deficiency. Studies done in the United States vary in their estimates of the prevalence among newborns of alpha 1 antitrypsin deficiency, ranging from 1 in 2857 to 1 in 5097. Among white individuals, alpha 1 deficiency is as common a genetic disorder as cystic fibrosis. In about 50% of emphysema that results from alpha 1 deficiency, there is accompanying chronic bronchitis with mucus hypersecretion, perhaps as a result of secretory cells changing from normal to abnormal cells caused by unchecked proteases in the epithelial lining fluid. Emphysema caused by alpha 1 deficiency is worse in the lower lung zones and can be markedly accelerated by cigarette smoking. Therefore, all patients diagnosed with alpha 1 deficiency should stop smoking immediately.

The basic pathology of emphysema resulting from alpha 1 deficiency is an imbalance between proteases, especially neutrophil elastase and antiproteases, especially alpha 1-proteinase inhibitor. The main substrate for alpha 1 is neutrophil elastase. The pathogenesis of emphysema is described as a process of alveolar wall destruction caused by insufficient protection from the protease neutrophil elastase, an enzyme that can cleave all forms of connective tissue and degrade elastic fiber in the lungs by turning the elastin in to a soluble form. With inadequate alpha 1 proteinase inhibitor (also known alpha 1-antitrypsin) levels in the lung to balance the protease activity, emphysema results at a significantly earlier age than is normally seen. A presentation of severe emphysema at an unexpectedly young age, as early as 30 years old, leads to a high suspicion of a genetic defect causing inadequate alpha 1 proteinase inhibitor levels in the blood and subsequently in the lungs. The main role of another protease inhibitor, secretory leukocyte protease inhibitor, which is secreted by bronchial glands and goblet cells, is to protect the airway epithelium against proteolytic injury. However, evidence that alpha 1 proteinase inhibitor is the predominant antiprotease protecting against neutrophil elastase.

Indication for Pharmacological Treatment

Alpha 1 proteinase inhibitor therapy is indicated for chronic replacement therapy in individuals with congenital deficiency of alpha 1 antitrypsin, with clinically demonstrable emphysema. At present there are three agents available: Aralast, Prolastin, and Zemaira. Aralast and Zemaira are indicated only for patients who have established alpha 1 proteinase deficiency. Prolastin is not indicated for use in patients other than those with the a specific genetic phenotype. Results from controlled, long-term trials are not available to show that chronic therapy halts the progression of emphysema because of inherent difficulties in such trials, including the need for large numbers of patients. Alpha 1 proteinase inhibitor therapy has been provided only to adult subjects. Given the nature of the disease and the action of the drugs, the drugs cannot reverse damage or improve lung function. The drugs are extremely expensive, costing in the range of $25,000 to $40,000 per year for therapy. A cost-effectiveness analysis of Prolastin concluded that alpha 1 antitrypsin replacement therapy is cost effective in individuals who have severe alpha 1 deficiency and severe chronic obstructive pulmonary disease. The American Thoracic Society states that alpha 1 augmentation therapy should be used for patients with a serum concentration of alpha 1 proteinase less than 80 mg/dl. It is not indicated for patients with cigarette smoking related emphysema who have normal or heterozygous phenotypes. It is not indicated for individuals with liver disease associated with alpha 1 deficiency, unless they also have lung disease. The ATS guidelines suggest using augmentation therapy if lung function studies become abnormal and if serial studies show deterioration.

Dosage and Administration

The recommended dosage of alpha 1 augmentation therapy is 60 mg/kg of body weight, given once weekly. The dose is given intravenously at a rate of 0.08 ml/kg/min or greater, depending on patient comfort, and usually takes about 15-30 minutes for total infusion.

Warnings and Adverse Reactions

Alpha 1 proteinase inhibitor agents are derived from human plasma there is a risk of disease transmission and allergic reaction. Although there was some variation in reactions to each agent, fever, exacerbation, and flulike symptoms were most common.

Respiratory Therapy Assessment and Treatment

Respiratory therapists may not be directly involved in the application of these agents. However, it is very important that respiratory therapists are involved in the care of patients with alpha 1 deficiency. The respiratory therapist should be involved in working with patients to stop smoking, providing education and information for cessation. Measurement and monitoring of lung function is critical in the detection and treatment of these patients. To find more information or to get involved visit the Alpha 1 Association at

Douglas Gardenhire is a veteran therapist, author, educator and the Director of Clinical Education in the RC Program at CA State University.

By Doug Gardenhire MS, RRT-NPS
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Author:Gardenhire, Doug
Publication:FOCUS: Journal for Respiratory Care & Sleep Medicine
Date:Jan 1, 2010
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