Estimating the risk for alpha-1 antitrypsin deficiency among COPD patients: evidence supporting targeted screening.

Center for the Evaluation of Risks to Human Reproduction, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA.
COPD Journal of Chronic Obstructive Pulmonary Disease (Impact Factor: 2.62). 09/2006; 3(3):133-9. DOI: 10.1080/15412550600829257
Source: PubMed

ABSTRACT Alpha-1 antitrypsin deficiency is known as a significant genetic risk factor for COPD for carriers of phenotype PIMZ, and for phenotypes PIZZ and PISZ. Genetic epidemiological studies for alpha-1 antitrypsin deficiency conducted by others on both COPD patients and concurrent non-COPD controls were used to estimate the risk factors for all six phenotypic classes (namely, the normal phenotype PIMM, and the 5 deficiency allele phenotypes: PIMS, PIMZ, PISS, PISZ, and PIZZ). Studies on alpha-1 antitrypsin deficiency in white (Caucasian) COPD and non-COPD populations in 6 countries were combined to obtain estimates of the prevalence of the PIS and PIZ deficiency alleles in the combined COPD and non-COPD cohorts. The odds ratios for each of the six phenotypic classes of alpha-1 antitrypsin deficiency were calculated for a hypothetical population of 19.3 million white COPD patients in the United States of America. This approach demonstrated that 1,829,673 alpha-1 antitrypsin deficiency patients would be detected by testing 19.3 million white COPD patients and 536,033 in white non-COPD concurrent controls. The odds ratios for each of the phenotypic classes among white COPD patients demonstrate highly significant decreases in the normal phenotype PIMM, no significant change in the PIMS and PISS deficiency phenotypes, but highly significant increases in the prevalences of the PIMZ, PISZ, and PIZZ deficiency phenotypes. The result of the present study supports the concept of targeted screening for alpha-1 antitrypsin deficiency in countries with large populations of white (Caucasian) COPD patients.

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    ABSTRACT: Alpha-1 antitrypsin (AAT) deficiency is an under-recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis, and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasians individuals, and has its highest prevalence (1:2,000-1:5,000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5,000-10,000. Prevalence is five times lower in Latin American countries, and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counseling and, in selected cases, the application of augmentation therapy. Over the past decade, is has been demonstrated that AAT is a broad spectrum anti-inflammatory, immunomodulatory, anti-infective and tissue-repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications, and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency. This article is protected by copyright. All rights reserved.
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May 26, 2014