Key Point

Simple testing criteria are necessary to facilitate the detection of patients with lung disease associated with α1-antitrypsin deficiency, because this disorder often is overlooked.

CHICAGO—Current clinical application of the guidelines for the diagnosis of α₁-antitrypsin (AAT) deficiency in patients with obstructive lung disease may be too restrictive, as doctors have tested for the deficiency mainly in patients with obvious and more severe lung obstruction. However, that approach has caused
the vast majority of patients with the genetic disorder to be overlooked, pointed out D. Kyle Hogarth, MD, at the American College of Chest Physicians’ 2007 Annual International Scientific Assembly.

A COMMON RARITY

Although AAT deficiency is relatively rare, it is one of the most common genetic disorders worldwide, noted Dr. Hogarth, Assistant Professor of Pulmonary and Critical Care at the University of Chicago. The deficiency occurs mainly in those of Northern European and Iberian descent. “It is estimated that there are probably about a hundred thousand Americans with deficient α₁,” Dr. Hogarth related.
Other estimates place that number substantially lower, at perhaps 40,000 to 60,000 Americans. “We have only found 7,000, so clearly we are missing a lot of folks,” said Dr. Hogarth. In fact, patients with AAT deficiency have respiratory symptoms for an average of about seven years before a clinician thinks to order a simple blood test for the deficiency, he pointed out.

Recognition can be difficult, though, because the presentation of patients with the deficiency may not conform to what is emphasized in current practice guidelines and medical school—frank emphysema. Rather, these patients may appear to have asthma, a condition that clinicians do not usually associate with AAT deficiency.

UNUSUAL PHENOTYPES

To help raise awareness and improve detection of the deficiency, Dr. Hogarth and colleagues conducted a study in which 40 office-based pulmonologists were asked to increase serum testing during a one-month period by offering the test to patients with persistent asthma and/or COPD and loss of lung function. Loss of lung function was defined as either an FEV₁ or an FEV₁/FVC ratio of less than 70%.

Among 454 adult patients tested, the mean age was 63, and the average smoking history was 20 pack-years. “We found that 3.3% had test values that were below the normal range,” reported Dr. Hogarth. An additional 2.9% of the patients had borderline low AAT values.
AAT deficiency was associated with several abnormal phenotypes—
asthma, COPD, or a combination of the two diseases.

“There was no distinguishing feature among this cohort of patients to help identify patients with an abnormal α₁-antitrypsin level or phenotype,” Dr. Hogarth observed. “FEV₁, FEV₁/FVC, and number of bronchial infections in the past 12 months were similar between these patients and normal controls.”

Since patients with and without AAT deficiency were not easily differentiated clinically, Dr. Hogarth suggested simple criteria to raise suspicion for the disorder in patients with persistent asthma and/or COPD.

“Any adult patient with respiratory symptomatology and a minor degree of obstruction should be offered an α₁-
antitrypsin test,” he advised.           

—Timothy Begany

Return to table of contents