Jack Lieberman

Elevation of serum angiotension-converting-enzyme (ACE) level in sarcoidosis

The level of serum angiotensin-converting enzyme (ACE) was elevated in 15 of 17 patients with active sarcoidosis. Serum ACE was studied to determine the effect of chronic lung disease upon the blood level of an enzyme believed to originate from the lungs. The assay was performed in approximately 200 control subjects and 200 patients with chronic lung disease using hippuryl-L-histidyl-L-leucine as substrate. Enzyme activity greater in male control subjects than in female subjects of comparable age and greater in children than in adults. Serum ACE was significantly reduced in patients with chronic obstructive lung disease, lung cancer, tuberculosis and cystic fibrosis, as compared to control subjects, and was even lower in those receiving corticosteroids. Of greatest interest, however, was that levels in patients with active sarcoidosis not receiving steroids were greater than 2 standard deviations above the mean for the adult control subjects (greater than 11.6 units) whereas levels in patients with sarcoidosis receiving steroids and in those with resolved disease were normal. A survey of subjects with other granulomatous diseases failed to reveal any other condition that was significantly associated with a similar elevation of serum ACE levels. Elevation of ACE levels in sarcoidosis appears to be associated with the active disease process and does not appear to be a familial inherited enzyme abnormality. An assay of serum ACE is a useful tool for regulating therapy in sarcoidosis and for confirming the diagnosis, since it readily distinguishes these patients from others with tuberculosis, lung cancer or lymphoma.

Heterozygous and Homozygous Alpha1-Antitrypsin Deficiency in Patients with Pulmonary Emphysema

Abstract Homozygous deficiency of alpha1-atitrypsin is known to predispose to pulmonary emphysema. Measurement of the trypsin inhibitory capacity (TIC) of serum specimens from 28 relatives of a hom...

Serial changes in markers of disease activity with corticosteroid treatment in sarcoidosis

Serial changes in various markers of disease activity with corticosteroid therapy were assessed in 12 patients with active sarcoidosis. After six weeks of treatment with 40 mg daily of prednisone, all but one patient demonstrated symptomatic and radiographic improvement. For the entire patient group, there were corresponding improvements in forced vital capacity, from 59.2 +/- 5.5 to 70.5 +/- 5.3 percent of the predicted value (p less than 0.001, Student paired t test), serum angiotensin-converting enzyme levels, from 66.0 +/- 12.1 to 28.2 +/- 4.0 U/ml (p = 0.003), 67gallium lung scanning scores, from 3.6 +/- 0.2 to 0.8 +/- 0.3 (p less than 0.001), serum gamma globulin levels, from 2.40 +/- 0.2 to 1.5 +/- 0.1 g/dl (p less than 0.001), and erythrocyte sedimentation rate, from 26.8 +/- 2.7 to 14.8 +/- 3.0 mm per hour (p less than 0.001). Changes in percent of bronchoalveolar lavage fluid lymphocytes were less impressive (from 28.7 +/- 4.9 to 21.2 +/- 5.1, p = 0.034), but the geometric mean number of bronchoalveolar lavage fluid-IgG-secreting cells decreased from 23,861 to 3,830 (p = 0.013). Serial evaluations in five patients treated with decreasing doses of alternate-day prednisone for an additional 10 1/2 months indicated that changes in 67gallium lung scanning scores corresponded most closely to the clinical course in five of five patients. Determination of serum angiotensin-converting enzyme levels also closely paralleled the clinical course in four of five patients, whereas the other parameters measured were more variable markers of clinical response. However, abnormalities of bronchoalveolar lavage fluid-IgG-secreting cells often persisted in the absence of clinically evident disease, and the percentages of bronchoalveolar lavage fluid lymphocytes were frequently normal in patients who responded subsequently to corticosteroids. Larger prospective studies are warranted to more extensively evaluate various measurements of disease activity, especially bronchoalveolar lavage fluid analysis, in sarcoidosis.

A Deficiency of Pulmonary Fibrinolysis in Hyaline-Membrane Disease

THE absence of fibrinolytic enzyme activity in the A lungs of newborn infants succumbing to hyaline-membrane disease was recently reported.1 This enzyme abnormality was manifested by an inability o...

Serum Angiotensin-Converting Enzyme in Severe Nonthyroidal Illnesses Associated with Low Serum Thyroxine Concentration

We evaluated serum angiotensin-converting enzyme levels as an index of thyroid hormone action in severe systemic illness. Angiotensin-converting enzyme was elevated in hyperthyroid patients (37.3 +/- 3.2 U/mL, p less than 0.01) and depressed in hypothyroid patients (17.9 +/- 1.4 U/mL, p less than 0.05). Compared with normal controls (22.6 +/- 1.6 U/mL), patients in an intensive care unit with free thyroxine index greater than 5.0 had normal angiotensin-converting enzyme levels (19.1 +/- 2.5 U/mL), but patients with a free thyroxine index less than 5.0 had angiotensin-converting enzyme levels significantly lower than the normal and hypothyroid groups (10.7 +/- 1.0 U/mL, p less than 0.05). A group of patients in an intensive care unit with alcoholic liver disease (known to elevate angiotensin-converting enzyme) and a low free thyroxine index had depressed angiotensin-converting enzyme levels (16.9 +/- 1.5 U/mL, p less than 0.01). A strong correlation was seen in the combined groups of all patients studied between levels of angiotensin-converting enzyme and a free thyroxine index (r = 0.70, p less than 0.01) and free T3 index (r = 0.72, p less than 0.01).

Alpha-1 antitrypsin levels and prevalence of Pi variant phenotypes in asthmatic children

A total of 151 children with severe atopic bronchial asthma were screened for AAT levels by the STIC and RID methods. They were also phenotyped by the method of acid starch electrophoresis and crossed immunoelectrophoresis. The results were compared with those in a like control age group of children without known pulmonary problems. Both groups revealed similar incidences of AAT deficiency and 3% phenotype Z variants. The children with steroid-dependent severe asthma had a greater proportion of Z heterozygote variants than the non-steroid-dependent asthmatic and control population.

Antitrypsin Deficiency and Abnormal Protease Inhibitor Phenotypes

Protease inhibitor phenotypes associated with severe and intermediate antitrypsin deficiency were observed more frequently than expected in 164 patients with chronic, obstructive lung disease. The risk associated with any phenotype appears related to the severity of the deficiency. An association between the intermediate deficiency and chronic, obstructive lung disease would have been obscured if only the serum concentration of antitrypsin had been measured. When compared with patients with normal protease inhibitor types, those with the intermediate deficiency generally developed overt disease after relativeiy little exposure to cigarette smoke. It is suggested that antitrypsin deficiency is one inherited abnormality that is predisposing to the development of lung disease by rendering individuals more susceptible to the harmful effects of environmental factors, in this circumstance, lung disease in these individuals is preventable.

Pulmonary function in nonsmoking subjects with alpha1 antitrypsin deficiency (MZ phenotype)

We measured pulmonary functions in 10 nonsmoking asymptomatic subjects, ages 40.5 years +/- 9.2 years, with alpha1 antitrypsin heterozygous deficiency (phenotype MZ). The subjects were longstanding residents of the greater Los Angeles area. The range of physiologic studies and per cent of normal predicted values were forced vital capacity (FVC), 2.8 to 7.0 liters (86 to 124 per cent predicted); ratio of the forced expiratory volume in 1 second to the FVC, 70 to 86 per cent (86 to 104 per cent predicted); the ratio of the residual volume to total lung capacity, 28 to 44 per cent (94 to 119 per cent predicted); total lung capacity, 4.8 to 9.8 liters (80 to 119 per cent predicted); flow at 50 per cent FVC, 3.1 to 7.8 liters per second (69 to 140 per cent); and volume of isoflow, 7.3 to 26 per cent of forced vital capacity (38 to 137 per cent predicted). In eight patients studied, static deflation pressure volume curves were normal, and at respiratory rate of 60 breaths/min the ratio of dynamic compliance to static compliance did not fall below 84 per cent. We have found that these nonsmoking heterozygotes with alpha1 antitrypsin deficiency have normal pulmonary functions (within 1.67 SD of predicted mean).

Serum angiotensin-converting enzyme as a marker for the chronic fatigue-immune dysfunction syndrome: A comparison to serum angiotensin-converting enzyme in sarcoidosis

PURPOSE To study the reliability of a serum angiotensin-converting enzyme (ACE) assay as a marker for the chronic fatigue-immune dysfunction syndrome (CFIDS), and to compare some enzyme characteristics of ACE in CFIDS with that in sarcoidosis. PATIENTS AND METHODS Forty-nine patients with CFIDS and 56 endemic control subjects from Lyndonville, New York, and Charlotte, North Carolina; plus 23 untreated patients with active sarcoidosis, 24 with sarcoidosis receiving corticosteroid therapy, and 32 patient controls without sarcoidosis from California. Serum ACE levels were determined with a spectrophotometric method. The effect of freezing and thawing and the effect of storage at 4 degrees C were compared between CFIDS and sarcoidosis samples. RESULTS Serum ACE levels were elevated in 80% of patients with CFIDS and 30% of endemic control subjects as compared with 9.4% of nonendemic California control subjects. The ACE activity in CFIDS differed from that in sarcoidosis because of its lability with storage at 4 degrees C in CFIDS and its partial activation with freezing and thawing. Thus, ACE activity was elevated in the majority of CFIDS patients either upon initial assay or upon a subsequent assay after refreezing. ACE activity was elevated in 87% of patients with active sarcoidosis and was not affected by storage or freezing and thawing. CONCLUSIONS Serum ACE elevations may be a useful marker for CFIDS, especially if a method can be developed to distinguish ACE in CFIDS from that in sarcoidosis. The sensitivity for CFIDS was 80%, with 68% specificity in an endemic area. The increased prevalence of serum ACE elevations in endemic controls as compared with nonendemic controls suggests that an ACE increase may be an early manifestation of CFIDS and supports the concept that CFIDS is a definite disease state.

α1-Antitrypsin deficiency in twins and parents-of-twins

Serum‐trypsin‐inhibitory‐capacity (STIC) and ai‐antitrypsin (AAT) genotypes were evaluated in 83 twins and 112 paired parents‐of‐twins. An increased prevalence (17.0–21.9%) of intermediate AAT deficiency (STIC < 0.95 units/ml) was detected in both of these groups as compared to a prevalence of 4.1 % in 1,841 healthy controls. PiS and PiZ molecular variants of AAT were also found more frequently in the twin and parent groups, but this was not statistically significant. Low levels of protease inhibition may enhance fertility and a tendency towards twinning, since proteolytic enzymes are involved in fertilization of ova by sperm and in gametogenesis. Increased fertility and twinning may be heterozygous advantages for AAT deficiency.