Serum prealbumin levels in alpha1-antitrypsin deficiency (PiZ)

The relationship between low serum prealbumin levels and alpha₁-antitrypsin deficiency (PiZ) was investigated. Pi typing was done by acid starch gel electrophoresis followed by crossed antigen-antibody electrophoresis and/or immunofixation. Serum prealbumin levels were determined by radial immunodiffusion. While the serum concentration of prealbumin was low in nine of the fifteen PiZ children, this could be explained by the presence of liver disease in eight of those patients; one patient was asymptomatic. In contrast, only one of the twelve adult PiZ patients exhibited a low prealbumin level, also due to liver disease. We conclude that there is no direct association between PiZ alpha₁-antitrypsin deficiency and low serum prealbumin levels in children or adults.     

Serum angiotensin converting enzyme levels in patients with alpha 1-antitrypsin variants

Serum angiotensin converting enzyme levels were measured in 184 subjects having either MM, MZ, ZZ, or MS Pi-types of alpha 1-antitrypsin. Elevated angiotensin converting enzyme levels were detected in 31 percent of the patients with the MZ Pi-type, 20 percent of the patients with the ZZ Pi-type, and 20 percent of the patients with the MS Pi-type compared with 1.33 percent of those with normal MM Pi-type. The mean serum angiotensin converting enzyme levels were also significantly higher in those with the MZ, ZZ, and MS Pi-types. Multiple family members of two families were found to have both the Z variant and angiotensin converting enzyme elevations, suggesting the possibility of a genetic linkage. Alpha 1-antitrypsin deficiency must be added to the list of disease states potentially associated with elevated serum angiotensin converting enzyme levels.     

Serum trypsin inhibitory capacity and alpha 1-antitrypsin levels in liver cirrhosis and hepatoma.

alpha 1-Antitrypsin levels were measured in sera of 134 patients with cirrhosis and in 64 with cirrhosis and hepatoma. S-TIC was determined in 105 patients with cirrhosis and in 54 with cirrhosis and hepatoma. The mean alpha 1-at and S-TIC values in patients with cirrhosis were 369.59 +/- 14.072 mg% and 1,808 +/- 0.05 mg/ml respectively. In patients with cirrhosis and hepatoma the mean alpha 1-at level was 406.595 +/- 17.834 mg% and the S-TIC mean values was 2.064 +/- 0.82 mg/ml. Although these values are higher than those found in the healthy controls, the differences are not statistically significant.     

Exacerbations in {alpha}1-antitrypsin deficiency.

This study aimed to investigate the nature and effect of exacerbations in patients with alpha(1)-antitrypsin deficiency and to assess the impact of exacerbations on health status. Furthermore, the relationship of exacerbations to changes in lung function and health status was investigated. In total, 265 patients with severe deficiency (PiZ phenotype) were assessed over 12 months and a subgroup of 87 patients was studied for 3 yrs. Exacerbations were recorded and patients underwent full lung function testing and health status measurement. Exacerbations occurred in 142 patients (54%) over 12 months, with a median duration of 14 days (interquartile range 7-21). Health status was significantly worse in patients with exacerbations, especially those with frequent exacerbations. Neither the presence nor the frequency of exacerbations showed a relationship to decline in forced expiratory volume in one second, but the number of exacerbations was weakly associated with decline in gas transfer of the lung for carbon monoxide. Despite lung function decline, health status did not change significantly over 3 yrs. In conclusion, exacerbations occur commonly in patients with alpha(1)-antitrypsin deficiency and are associated with worse health status. Exacerbations were associated with a decline in the gas transfer of the lung for carbon monoxide over time, but show no relationship to changes in forced expiratory volume in one second. Despite lung function decline, patients do not show a progressive loss in health status.     

Severe alpha1-antitrypsin deficiency and pregnancy.

This case study describes a successful pregnancy in a 27-yr-old patient with severe emphysema, secondary to alpha1-antitrypsin deficiency, genotype PiZZ. Despite significant respiratory compromise, more severe than previously reported, no complications ensued. Maternal pulmonary function did not deteriorate significantly until the 32nd week of pregnancy, with an elective Caesarean section being performed during the 37th week. This experience suggests that even severe maternal airflow obstruction is, in itself, not an absolute contra-indication to pregnancy. Pre-pregnancy multidisciplinary counselling is likely to be helpful in these patients, including frank discussion on the risks of pregnancy, the prospects of successful completion and the mother's future prognosis in relation to caring for the child.     

Circulating immune complexes, free antigen and alpha 1-antitrypsin in levels in sarcoidosis patients.

Consecutive serum samples from 26 sarcoidosis patients were examined for circulating immune complex (IC) activity. Fifteen (58%) gave IC-positive reactions in a complement consumption (CC) test and a significant difference as regards anticomplementary was observed when comparing patients in clinical stages 2 and 1 respectively (P less than 0.01) The serum alpha 1-antitrypsin levels were not correlated (r=0.36) to the results of the CC-assay. The duration of IC-occurrence was studied, by two IC-assays, over 1 1/2 to 2 years. The majority of the positive reactions were registered in patients in clinical stage 2. Isolated IC was used for immunization of rabbits. Absorbed immune sera produced a single precipitate of postalbumin mobility with seven out of 36 sarcoidosis sera. In two cases a tailing of the recipitate suggested that the antigen was in complex formation. Immunoelectrophoresis indicated identity between the antigen detected in different sarcoidosis sera. No precipitates were observed using 130 sera from other patients, and screening of 100 blood donors revealed one positive reaction. The antigen, which eluted in the first protein peak on Sephadex G-200, has not been identified serologically.     

Liver injury in alpha 1-antitrypsin deficiency

Alpha 1-antitrypsin deficiency is the most common genetic cause of liver disease in children. It is also associated with chronic liver disease, hepatocellular carcinoma, and pulmonary emphysema in adults. Liver injury is caused by hepatotoxic effects of retention of the mutant alpha 1-antitrypsin molecule within the endoplasmic reticulum of liver cells, and emphysema is caused by uninhibited proteolytic damage to elastic tissue in the lung parenchyma. Recent studies of the biochemistry and cell biology of the mutant alpha 1-antitrypsin molecule have led to advances in understanding susceptibility to liver injury and in developing new strategies for prevention of both liver and lung disease.     

Effect of age and asthma duration upon elastase and alpha1-antitrypsin levels in adult asthmatics.

In asthmatic subjects an imbalance between elastase and alpha1-antitrypsin (alpha1-PI) exists. This study aims to evaluate whether ageing per se affects the levels of elastase. Both young and elderly asthmatics with comparable severity and duration of disease, as well as young and elderly healthy subjects, underwent an induced sputum procedure to measure levels of elastase and alpha1-PI. The percentage of sputum neutrophils and eosinophils was higher in young and elderly asthmatics than in young and elderly controls. The levels of both total and active elastase were significantly higher in young and elderly asthmatics than in young and elderly controls, and directly correlated with the percentage of neutrophils. In addition, in both young and elderly asthmatics the levels of total and active elastase were negatively correlated with forced expiratory volume in one second values, but positively correlated with the duration of the disease. This study indicates that ageing per se does not necessarily lead to a progressive elastase/alpha1-antitrypsin imbalance in asthma, and suggests that an important variable in the development of airway remodelling in both young and elderly asthmatics is represented by the duration of the disease.