Augmentation Therapy Reduces Lung Infections In Patients with a Common Genetic Disease

For Immediate Release

AUGMENTATION THERAPY REDUCES LUNG INFECTIONS IN PATIENTS WITH A COMMON GENETIC DISEASE

Antiprotease augmentation therapy reduces lung infection in patients with Alpha 1-Antitrypsin (AAT) deficiency, the most prevalent, potentially lethal hereditary disorder among the white adult population in the United States, according to a new study.

The study was reported in the November issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians (ACCP).

AAT is protein primarily manufactured by the liver and is ordinarily abundant in the blood. The normal function of AAT is to protect the tissues of the body by neutralizing the action of neutrophil elastase, an enzyme found in white blood cells. When a deficiency of AAT occurs in the blood, neutrophil elastase is allowed to attack various tissues of the body, especially lung tissue.

An estimated 80-100,000 Americans have the severe form of AAT deficiency, but only about 4,000 individuals have been diagnosed with the deficiency. In people with AAT deficiency, serious changes in the lungs may develop between the ages of 30 and 40. It is a chronic, slowly progressive illness characterized by a breakdown of the lung tissue resulting in chronic shortness of breath. A genetic disorder, AAT deficiency is not curable, but there are some treatments and lifestyle modifications that can help slow the progression of the disease.

Antiprotease augmentation therapy was developed in the 1980s. It increases the circulating levels of AAT in the blood. Human "1 -proteinase ( Prolastin) is the primary augmentation therapy now being used. In AAT-deficient patients, once-weekly intravenous infusions of this inhibitor maintain circulating levels of AAT that are thought to be adequate for protection of the lung tissue. Although there have been reports of substantial benefit from augmentation therapy, there has not been any long-term controlled clinical trials to show that it alters the course of lung disease.

Aware of these reports and aware of other studies that showed that trypsin inhibitors had an antibiotic action and that antiproteases were effective in the treatment of HIV infections, Jack Lieberman, M.D, FCCP, of the UCLA School of Medicine, postulated that a rise in antiprotease levels in the blood may play an important role in resistance to infection in AAT-deficient patients. He developed a survey to determine the following: the percent of AAT-deficient patients who feel that they have benefitted from augmentation therapy; the impressions of these patients as to how they benefitted; and, the frequency of respiratory infections per year before starting augmentation therapy as compared with the rate following therapy. He also recruited a second group of AAT- deficient patients who were not receiving augmentation therapy to compare their rate of infections.

Of 89 patients who were receiving augmentation therapy, 74 (83.1%) believed that they had definitely benefitted from the therapy. More than two thirds of these cited the reduction of lung infections as evidence of benefit. Since starting therapy, the number having zero to one infection per year increased from 27% to 73%. The number having two or more infections dropped from 64.6 % to 18 %. In the group of 49 patients not receiving therapy, 43% had zero to one infection per year, and 32% had two or more infections.

"The results of this study," Dr. Lieberman said, "support the hypothesis that augmentation therapy reduces the incidence of lung infections in patients with AAT-related emphysema." He added that the association is so striking that it should be noted so that future, more rigid, prospective studies in this field will look for a reduction of infection rate as a potential benefit of augmentation therapy.

Commenting on the possible pathophysiological connection between augmentation therapy and lung infection, Dr. Lieberman said: "The mechanism whereby AAT protects the patient against recurrent lung infections may involve both a direct antibacterial action of AAT and an anti-inflammatory, anti-immune response action of AAT. A deficiency of AAT also may thereby promote excessive inflammatory responses to minimal insults and a predisposition to autoimmune diseases as has been reported for rheumatoid arthritis, anterior uveitis, systemic lupus erythematosus, and asthma."

CHEST is published by the American College of Chest Physicians, which represents 15,000 members who provide clinical, respiratory, and cardiothoracic care in the U.S. and throughout the world.

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Reporters may wish to contact Kimberly Lynch of the ACCP at (847) 498-8341. She can be reached by email at [email protected] for a copy of the article. Dr. Lieberman can be reached by phone at (818) 349-7490 or by email at [email protected].