Sensitivity of alpha-1 antitrypsin level for inherited deficiency detection in COPD patients

ArticleinPneumologia 61(1):34-6 · January 2012with6 Reads
Source: PubMed
Abstract
Alpha-1 antitrypsin deficiency is an underdiagnosed condition in patients with chronic obstructive pulmonary disease. Diagnosis of this genetic condition is confirmed by genetic verification of pathology, but for screening purposes quantitative methods can be useful. The aim of our study was to evaluate sensitivity and specificity of quantitative methods for alpha-1 antitrypsin deficiency detection. Serum alpha-1 antitrypsin concentrations from patients (n = 1167) with chronic obstructive pulmonary disease, defined according to the GOLD criteria, were analysed by nephelometry, alpha-1 antitrypsin genotype was determined by means of isoelectric-focusing. Eight severe alpha-1 antitrypsin deficiency genotypes in homozygous type (ZZ) and 40 in heterozygous genotype (-Z) were identified. Calculated sensitivity of quantitative alpha-1 antitrypsin measurement by nephelometry for heterozygous PI*Z allele is 45% and for homozygous ZZ genotype is 88%. Specificity of quantitative alpha-1 antitrypsin deficiency determining analysis is 99%. A case detection program of alpha-1 antitrypsin deficiency in patients with chronic obstructive pulmonary disease using quantitative methods is specific, but due to limited sensitivity should be used only in screening programs.
  • [Show abstract] [Hide abstract] 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.
    Full-text · Article · Sep 2006
  • Article · Jan 2005
  • [Show abstract] [Hide abstract] ABSTRACT: α1-antitrypsin (AAT) deficiency is an inherited condition characterized by low serum levels of AAT and an increased risk of developing pulmonary emphysema. The disease occurs mainly in Caucasians, but Southern Europe, including Italy, is considered a low prevalence area. We developed a national program in Italy in order to improve our knowledge of the epidemiology of AAT deficiency and to establish a registry of the AAT-deficient individuals. The program had two phases: the first lasted 36 months, during which blood from coupons mailed by respiratory physicians from throughout the country, was isoelectrofocused by the Central Laboratory in Rome. The second phase started in February 1996, and the Registry was established. Up to August 1998, 151 subjects with AAT deficiency have been identified and 64 have been enrolled in the Registry. We believe that such a program plays a crucial role in identifying AAT deficiency in a country such as Italy, with low prevalence and low awareness of this rare condition.
    Full-text · Article · Mar 1999
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