Serum angiotensin converting enzyme in sarcoidosis--its value in present clinical practice.

Angiotensin converting enzyme (ACE) has a central role in blood pressure homeostasis. It is present in low and fairly constant concentration in the serum and in high concentration in the pulmonary capillary bed. Unusually high serum angiotensin converting enzyme (SACE) activity is present in active sarcoidosis, an observation now confirmed by many investigators. In spite of its lack of specificity as a test for sarcoidosis, SACE provides a good monitor of disease activity which clinicians find useful in the management of patients with sarcoidosis. There continues to be considerable interest in SACE in sarcoidosis and with the recent development of simpler assays, more centres may be expected to offer SACE measurements as a service. In this paper we discuss the indications for estimating SACE in sarcoidosis and its relevance to current clinical practice.

Bronchoalveolar lavage in the diagnosis of diffuse pulmonary shadowing.

Bronchoalveolar lavage (BAL) was performed during fibreoptic bronchoscopy in 79 patients with undiagnosed diffuse radiographic pulmonary shadowing and in 20 control subjects undergoing investigation for respiratory symptoms not associated with diffuse radiographic shadowing. The highest percentages of cells other than macrophages found in BAL fluid from the controls were 11% for lymphocytes and a total of 10% for neutrophils and eosinophils. 72 (91%) of the patients with diffuse shadowing had higher percentages of one or more of these inflammatory cell types than were found in any of the controls. Patients with increased lymphocytes differed in their eventual diagnosis from those without increase lymphocytes but with increases in other inflammatory cells (P less than 0.001). The use of BAL cell profiles as an aid to diagnosis in certain situations is illustrated by calculation of predictive values using Bayes' theorem. BAL has diagnostic value in the investigation of diffuse pulmonary shadowing if the cell profile is considered in conjunction with other information.

Angiotensin-converting enzyme and its clinical significance--a review.

There have been considerable advances in understanding the metabolic role of the endothelial lining cells of the blood vessels. Angiotensin-converting enzyme activity is concentrated in these cells, especially those lining the pulmonary circulation. The enzyme exerts control over systemic vascular tone indirectly through the powerful pressor effect of angiotensin II. A number of therapeutic agents are now available which directly inhibit converting enzyme activity and thereby effect a reduction in blood pressure. Macrophages are the source of increased angiotensin-converting enzyme activity commonly found in association with active sarcoidosis. A better understanding of this phenomenon may give fresh insight into this puzzling condition. Pulmonary endothelial metabolism is affected by lung injury and it is likely that in this situation changing activities of serum angiotensin converting enzyme may indicate the extent of damage and the response to therapy. The full clinical significance of serum ACE measurements has yet to be established. However, raised activities have been reported in a number of other conditions and diabetes mellitus and hyperthyroidism are of particular current interest. The numerous methods and reference ranges described in the literature for the measurement of serum ACE activity require further assessment, and there is a clear need for an accepted reference method.

Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests.

Five patients with respiratory disorders associated with hard metal exposure are described. In four patients electron microprobe analysis of bronchoalveolar lavage cells or lung tissue was used to show tungsten and other hard-metal components. Three patients had interstitial pneumonia and fibrosis with unusual multinucleate giant cells. Electron microscopy showed that the giant cells comprised both type II alveolar epithelial cells and alveolar macrophages. The multinucleate macrophages formed a distinctive feature of the bronchoalveolar lavage material but the multinucleate alveolar epithelial lining cells were evident only in lung tissue. The other two patients both suffered from work-related asthma, one of whom also had pulmonary opacities. Bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible.

Inhibition of exercise-induced asthma by an orally absorbed mast cell stabilizer (M & B 22,948).

M&B 22,948 (2-o-propoxyphenyl-8-azapurin-6-one) is an orally absorbed mast cell stabilizer which is 30 times as potent as disodium cromoglycate in laboratory and animal studies. In a double-blind placebo-controlled cross-over trial we studied the protection afforded by a single oral dose of 10 mg of M&B 22,948 against asthma induced by histamine and exercise, each in 12 patients. Compared with placebo the drug had no significant effect on the response to inhaled histamine but significantly inhibited the fall in FEV1 induced by exercise on treadmill (P less than 0.005). The exercise-induced fall in FEV1 was less following M&B 22,948 than placebo in all patients and the fall was inhibited by more than 50% in five (42%) of 12 patients. The degree of inhibition was significantly correlated with the plasma drug concentration (r = 0.65, P less than 0.025). M&B 22,948 merits evaluation in the treatment of asthma.

Bronchoscopic and percutaneous aspiration biopsy in the diagnosis of bronchial carcinoma cell type.

The cell type of bronchial carcinoma predicted from the results of bronchial biopsy at fibreoptic or rigid bronchoscopy or of percutaneous aspiration lung biopsy was compared with the type determined by histological examination of specimens obtained by thoracotomy, biopsy of an extrapulmonary metastasis, or necropsy in 180 cases. The rates of agreement with the final diagnosis were 95.7% for bronchial biopsy through the fibreoptic bronchoscope and 86.5% through the rigid bronchoscope. For percutaneous biopsy, which was usually carried out on tumours inaccessible to the bronchoscope, the rate of agreement was 61%, significantly lower than by the other methods (p less than 0.001). The diagnosis of oat-cell carcinoma by any technique was very reliable. Bronchial biopsy was more reliable than was percutaneous biopsy in diagnosing squamous-cell carcinoma. With any technique the commonest error was the incorrect diagnosis of squamous-cell carcinoma or adenocarcinoma as large-cell undifferentiated carcinoma.

Complications of intrapleural BCG in the treatment of operable non-small-cell bronchial carcinoma.

Seventy-eight patients entered a randomized study of postoperative intrapleural BCG in the treatment of bronchial carcinoma. 39 patients received BCG (Tice strain), of whom 17 took isoniazid, and there were 39 controls. There was a high rate of complications related to the use of intrapleural BCG, in both isoniazid and non-isoniazid treated groups. Postoperative infections occurred in eight BCG treated patients and one control; seven BCG treated patients but only one control developed prolonged postoperative chest pain. Empyema developed six months postoperatively in three of the BCG treated group. Furthermore BCG conferred no survival advantage at one year. We considered the complications to be of sufficient severity and incidence to discontinue the study.

Biochemical findings in sarcoidosis.

The majority of patients with sarcoidosis in this large series have had a number of biochemical investigations performed. Abnormal calcium metabolism was demonstrated in 40% of the patients but permanent renal damage due to nephrocalcinosis as a result of persistent derangement of calcium metabolism was rare. Raised immunoglobulin levels were seen. Half the white and two-thirds of the West Indian patients had elevated IgG levels. Abnormal immunoglobulin levels carried no obvious diagnostic or prognostic significance. Raised alkaline phosphatase levels reflected space-occupying hepatic granulomas and occurred in 23% of patients. Serum angiotensin converting enzyme (SACE) was elevated in half the patients. The highest SACE activity was found in patients with severe parenchymal lung infiltration due to sarcoidosis, and the lowest levels in those with inactive disease or after successful management with steroid drugs. SACE levels were not significantly elevated in four other granulomatous conditions: Crohn's disease, primary biliary cirrhosis, Hodgkin's disease, and active tuberculosis.