Alpha-1-antitrypsin (alpha 1AT) deficiency is a hereditary disorder characterized in adults by a high risk for the development of severe destructive lung disease at an early age. The present study was designed to draw conclusions concerning the characteristics of a referral population of 124 patients with alpha 1AT deficiency and symptomatic emphysema. Typically, the alpha 1AT level was 30 mg/dl, and the alpha 1AT phenotype was almost always PiZZ. The individuals in this population were most often male, caucasian, and ex-smokers, and they had become dyspneic between 25 and 40 yr of age. Most routine blood tests were normal. The chest radiographs and ventilation-perfusion studies typically showed abnormalities with a lower zone distribution, and about one third of the study population had evidence suggestive of pulmonary hypertension. Lung function tests were typical for emphysema; the FEV1 and DLCO were the parameters most dramatically reduced, and the annual rate of decline of those parameters was greater than that of the general population. The cumulative probability of survival of this population indicated a significantly shortened lifespan with a mean survival of 16% at 60 yr of age compared with 85% for normal persons.

The AQ20/30 and the SGRQ scores are comparable in terms of measuring QoL in COPD patients and are equally useful in determining the association between utilization of health-care services and QoL.

Alpha 1-antitrypsin (alAT), a 52,000-mol-wt serum glycoprotein produced by hepatocytes and mononuclear phagocytes, functions as the major inhibitor of neutrophil elastase. The alAT haplotype S is associated with childhood liver disease and/or adult emphysema when inherited with the Z haplotype to give the phenotype SZ. To accurately identify the SZ phenotype at the level of genomic DNA, four 32P-labeled 19-mer synthetic oligonucleotide probes were prepared; two to identify the M and S difference in exon III, and two to identify the M and Z difference in exon V. These probes were hybridized with various cloned DNAs and genomic DNAs cut with the restriction endonucleases BglI and EcoRI; the genomic DNAs represented all six possible phenotype combinations of the M, S, and Z haplotypes (MM, MS, MZ, SS, ZZ, and SZ). Using the four probes to evaluate 42 samples of genomic DNA, the "at risk" SZ and ZZ phenotypes were correctly identified in all cases, as were the "not at risk" phenotypes SS, MS, MM, and MZ, demonstrating that both exon III and exon V directed probes are necessary to properly identify all of the major "at risk" alAT genes. However, when used to evaluate a very rare family carrying a null allele, these four oligonucleotide probes misidentified the "at risk" null-null and S null phenotypes as "not at risk" MM and SM combinations. These observations indicate that oligonucleotide gene probes yielded reliable and accurate assessment of "at risk" alAT genotypes in almost all situations, but in the context of prenatal diagnosis and genetic counseling this approach must be used with caution and in combination with family studies so as not to misidentify rare genotypes that may be associated with a risk for disease.