Pulmonary function in middle-aged women with heterozygous deficiency of the serine protease inhibitor alpha 1-antichymotrypsin.

Heterozygous alpha 1-antichymotrypsin (ACT) deficiency is inherited in an autosomal dominant mode independently of alpha 1-antitrypsin with a gene frequency (q) of 0.003. In a previous study, a high prevalence of enlarged residual volumes in subjects with the trait were noted. Neutrophil cathepsin G, the target proteinase of ACT, enhances the elastolytic action of elastase. Thus, hypothetically, subjects with the trait may have increased risk for developing pulmonary emphysema. To test whether heterozygous ACT deficiency predisposes to lung disease, plasma ACT concentrations were determined in a cohort of 1,872 middle-aged women. Women with subnormal levels were studied with respect to heredity, airway symptoms, and lung function. Twelve women (0.64% of the cohort) were classified as heterozygotes after family studies and were compared with control subjects, matched for age, weight, sex, and smoking status. There were no significant differences in airway symptoms between heterozygotes and control subjects. However, the prevalence of ex-smokers was significantly higher among heterozygotes than among the screened population as a whole (prevalence ratio, 2.18; 95% confidence interval, 1.004-4.72). There were no differences between the heterozygotes and the control subjects in the basal spirometry. However, after bronchodilation, five of the 12 heterozygotes manifested residual volumes greater than 2.5 standard deviations above normal mean compared with one of 24 control subjects (p = 0.012). The present investigation thus confirms our previous findings of an increased prevalence of enlarged residual volumes in heterozygous ACT deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Serine proteinase inhibitors as acute phase reactants in liver disease.

alpha 1-Antitrypsin, alpha 1-antichymotrypsin and angiotensinogen are three genetically homologous acute phase reactants which belong to the super family of serine proteinase inhibitors (serpins). In this report the dissociate expression of these respective genes in various liver diseases or after exposure to estrogen is emphasized. In addition, the influence of abnormal genetic variants on plasma levels of these proteins and on liver cell function is discussed.

Plasma alpha 1-antichymotrypsin in liver disease.

We studied 229 patients with biopsy verified liver disease and compared the plasma levels of alpha 1-antichymotrypsin and alpha 1-antitrypsin. We found a significant overall correlation between alpha 1-antichymotrypsin and alpha 1-antitrypsin levels (r = 0.50, p less than 0.001). The strongest correlations were found in patients with chronic active hepatitis (r = 0.76, p less than 0.0001) and alcohol hepatitis (r = 0.60, p less than 0.001). Several clinical subgroups lacked correlation. Unexpectedly high alpha 1-antichymotrypsin values were found in patients with venous congestion. We also used the alpha 1-antichymotrypsin/alpha 1-antitrypsin ratio as a tool to identify PiZ carriers (intermediate alpha 1-antitrypsin-deficiency, PiZ). The sensitivity and predictive values were low and did not exceed that obtained by the simple use of an isolated alpha 1-antitrypsin determination. A small subgroup with low alpha 1-antichymotrypsin/alpha 1-antitrypsin ratio included patients with chronic active hepatitis of unknown etiology. Hypo-alpha 1-antichymotrypsinemia may be secondary to the liver disease per se or be an expression of an abnormal genetic trait.