Genetic disorder linked to rapid lung function decline in some World Trade Center rescue workers
Finger-stick test in development for alpha-1 antitrypsin deficiency could provide immediate screening results
A rare genetic disorder known as alpha-1 antitrypsin (A1AT) deficiency may predispose patients to developing lung conditions, but a new rapid-response test could help identify patients with the deficiency before significant lung damage has occurred.
New research presented at CHEST 2006, the 72nd annual international scientific assembly of the American College of Chest Physicians (ACCP), shows that World Trade Center rescue workers deficient in the A1AT protein who were exposed to environmental irritants had more rapid decline in lung function compared with exposed workers with normal levels of protein. A1AT deficiency alters the ability of the lungs and liver to control the naturally-occurring healing process, thereby leading to unchecked inflammation in these areas. Individuals with low levels of A1AT are at an increased risk for chronic lung and liver disorders.
"A1AT deficiency is a genetic defect with variable penetrance," said the study's lead researcher Gisela Banauch, MD, Montefiore Medical Center, New York, NY. "Some with the defect will develop emphysema early, even without cigarette smoking. Others, with less penetrance, may need to be exposed to additional environmental irritants in order to develop emphysema and other forms of obstructive airway disease."
Dr. Banauch and colleagues followed 90 World Trade Center (WTC) rescue workers from October 2001 through 2005. Patients underwent annual lung function testing and, in September 2005, all patients were offered A1AT testing. Of the patients, 11 were categorized as either severely or moderately A1AT deficient, while the remaining patients showed normal A1AT levels. Results showed that severely deficient patients had significantly faster post-WTC lung function declines than all other subjects, while moderately deficient patients experienced faster lung function declines than normal patients. Prior to the WTC disaster, A1AT-deficient patients showed no accelerated lung function decline.
If further research in larger numbers of patients confirms these preliminary findings, then early screening in patients may help minimize lung damage in patients with this condition.
"A1AT deficiency is underrecognized and underdiagnosed," said the study's coauthor David J. Prezant, MD, FCCP, Montefiore Medical Center. "But we can overcome this challenge by a simple blood test that should be performed in all persons with family members having A1AT deficiency and in all persons who have no risk factors for early onset of COPD but are showing symptoms of disease."
An estimated 150,000 people in North America have A1AT deficiency, but only about 5 percent of these people have been diagnosed, reinforcing the need for effective awareness and screening programs that lead to diagnosis and treatment.
Current guidelines recommend screening all symptomatic individuals with lung disease with no known risk factors or who have a family history of the deficiency. However, some experts believe screening programs have not been completely effective because of slow data analysis, cost, and other logistical problems. A new test for A1AT deficiency, currently in development in Great Britain, may make screening for the deficiency easier and more accessible.
In a separate study presented at CHEST 2006, researchers from the United States and Great Britain introduced preliminary data on a point-of-care test for A1AT deficiency that uses as little as one drop of blood from a finger-stick test to deliver rapid results. Using plasma samples, the test demonstrated specificity by delivering a negative result with normal samples and a positive result with samples that were abnormally low in A1AT. Although the test is still in development, researchers are hopeful that the new screening tool will enable physicians to screen patients for A1AT deficiency in their offices and obtain accurate test results within minutes.
"Early and proper diagnosis of A1AT deficiency is vital to managing and treating this chronic lung and liver disorder. However, the most important issue associated with timely screening for A1AT is increased awareness among primary care physicians and pulmonologists," said the study's lead author Jim Carney, PhD, British Biocell International (BBI), Cardiff, UK. "An inexpensive, sensitive, and specific screening tool applied at the point of care, combined with effective A1AT deficiency awareness programs, will move us closer to the goal of quickly recognizing and confirming symptoms of A1AT deficiency." The test is being developed by Talecris Biotherapeutics, Research Triangle Park, NC, in partnership with BBI.
"A1AT deficiency can greatly affect the health and well being of patients, particularly in those who remain undiagnosed," said Mark J. Rosen, MD, FCCP, President of the American College of Chest Physicians. "It is important for pulmonologists and other clinicians to understand screening guidelines for A1AT deficiency and recommend appropriate testing for patients accordingly."
CHEST 2006 is the 72nd annual international scientific assembly of the American College of Chest Physicians, held October 21-26 in Salt Lake City, UT. ACCP represents 16,500 members who provide clinical respiratory, critical care, sleep, and cardiothoracic patient care in the United States and throughout the world. The ACCP's mission is to promote the prevention and treatment of diseases of the chest through leadership, education, research, and communication. For more information about the ACCP, please visit the ACCP Web site at www.chestnet.org.
Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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