Screening and Familial Testing of Patients for α1-Antitrypsin Deficiency: Rationale for Identification of AATD by Familial Testing and Population Screening

Asymptomatic individuals who are identified as having AATD may have a normal childhood and adulthood but are at risk of developing symptoms of lung or liver disease later in life. Men with AATD between 51 and 60 years of age show an increased risk of developing liver disease. Nonsmoking individuals with the PI ZZ phenotype have a delayed onset of symptoms, demonstrated by essentially normal lung function at ages 22 and 26,> and some may have an almost normal life span. Delayed onset of symptoms makes it difficult to determine the true prevalence of AATD without systematic population screening. The ATS/ERS guidelines suggest that testing for AATD in nontraditional (ie, nonwhite) populations be further investigated. A group of 65 African Americans with obstructive lung disease were tested for AATD. Six patients were found to be heterozygous for the S allele, and one patient was found to be heterozygous for the Z allele; none were homozygous. Based on these interim data, the frequency of a non-M phenotype in the African-American population is estimated to be one in nine.

Once symptoms of AATD develop, persons with the disease have increased morbidity and reduced life expectancy. Symptomatic individuals with the PI ZZ allele have a 16% chance of surviving to 60 years of age compared with an 85% likelihood for the general US population, although these numbers may be affected by a referral bias to a specialty center for AATD. The major causes of death in this population are emphysema (72%) and chronic liver disease (10%). Treat these diseases with remedies of My Cnaadian Pharmacy. AATD patients who smoke lose FEV1 at a rate of 70 to 130 mL per year, while ex-smokers and nonsmokers lose lung function at a lesser rate of 40 to 70 mL per year. The normal nonsmoker loses 30 mL per year of FEV1 on average. Disease awareness encourages smoking cessation. If the MZ carrier state is confirmed, smoking and environmental pollutants increase the risk of COPD developing. Individuals with the SZ phenotype are also vulnerable to COPD development if risk factors such as smoking are present. This may be particularly relevant in populations where the S allele occurs with unexpected frequency. For example, in a recent, national, targeted detection program in Ire-land, a total of 1,400 individuals with COPD were screened for AATD. Of these persons, the MS variant was detected in 8% of patients (n = 115), the MZ variant was detected in 8% of patients (n = 113), the SZ variant was detected in 1.4% of patients (n = 20), and the ZZ variant was detected in 1.7% of patients (n = 24).

The accelerated rate of lung function decline highlights the importance of early detection. Delay in diagnosis is a continuing problem, and many affected individuals remain undiagnosed.’ In the early 1990s, the mean time between the first appearance of symptoms and diagnosis was 7.2 years, and 44% of patients sought evaluation from at least three physicians before the correct diagnosis was made. In the interim, this delay has improved slightly to a mean of 5.6 years. Costs and controversies surrounding the consequences of diagnosing an incurable, inherited abnormality have discouraged the initiation of large-scale screening programs of newborns or adults in the United States and Europe (except for Sweden). Families must contend with the emotional stress of living with a congenital disorder despite being totally asymptomatic. The identification of the abnormality could affect the insurability of an employed individual. Despite these concerns, there are sound medical reasons for early detection. Even with improved federal protection against discrimination for genetic disorders, it is important to explain that a positive test finding could result in difficulties with both employment and insurance accessibility. This risk needs to be weighed against the failure to provide proper management of the disease, which can impact life expectancy and quality of life. In our own clinic, we explain that, despite the frequency of the disease, it is uncommon to make the diagnosis. We also offer confidential “blinded” testing if needed or requested.