Comparison of gallium-67 scanning, bronchoalveolar lavage, and serum angiotensin-converting enzyme levels in pulmonary sarcoidosis. Predicting response to therapy

Patients with active pulmonary sarcoidosis underwent bronchoalveolar lavage, gallium scan, and serum angiotensin-converting enzyme (ACE) level determination prior to treatment with corticosteroids. Pulmonary function was tested before and after therapy. Increase in vital capacity after treatment ranged from 40 to 1,030 ml; 12 of the 16 patients studied had an increase of more than 200 ml. There was a close correlation between the percentage uptake of gallium scan and the increase of the vital capacity after therapy (r = 0.95, p less than 0.01). There was no relationship between the percentage of lymphocytes obtained on lavage and the changes in vital capacity with therapy (r = 0.05). There was a positive correlation between the changes in vital capacity and the ratio of T4(+):T8(+)lymphocytes (r = 0.62, p less than 0.05) and number of T4 (+) lymphocytes (r = 0.92, p less than 0.01) in the bronchoalveolar fluid. There was a low correlation between the pretreatment ACE level and the change in vital capacity (r = 0.368, p greater than 0.05).     

Prediction of therapeutic response in steroid-treated pulmonary sarcoidosis. Evaluation of clinical parameters, bronchoalveolar lavage, gallium-67 lung scanning, and serum angiotensin-converting enzyme levels

To find a pretreatment predictor of steroid responsiveness in pulmonary sarcoidosis we studied 21 patients before and after steroid treatment by clinical evaluation, pulmonary function tests, bronchoalveolar lavage (BAL), gallium-67 lung scan, and serum angiotensin-converting enzyme (SACE) level. Although clinical score, forced vital capacity (FVC), BAL percent lymphocytes (% lymphs), quantitated gallium-67 lung uptake, and SACE levels all improved with therapy, only the pretreatment BAL % lymphs correlated with the improvement in FVC (r = 0.47, p less than 0.05). Pretreatment BAL % lymphs of greater than or equal to 35% predicted improvement in FVC of 10/11 patients, whereas among 10 patients with BAL % lymphs less than 35%, 5 patients improved and 5 deteriorated. Clinical score, pulmonary function parameters, quantitated gallium-67 lung uptake, and SACE level used alone, in combination with BAL % lymphs or in combination with each other, did not improve this predictive value. We conclude that steroid therapy improves a number of clinical and laboratory parameters in sarcoidosis, but only the pretreatment BAL % lymphs are useful in predicting therapeutic responsiveness.     

Bronchoalveolar lavage fluid angiotensin-converting enzyme in interstitial lung diseases

In this study we evaluated the disease specificity of bronchoalveolar lavage fluid angiotensin-converting enzyme (BALF-ACE), its correlation with cellular constituents of bronchoalveolar lavage fluid (BALF), and for sarcoidosis, with other proposed markers of disease activity. Furthermore, the question of the clinical value of BALF-ACE determinations in in interstitial lung diseases or any of its subgroups was addressed. The study population consisted of 222 patients, 69 with biopsy proven sarcoidosis, 3 with hypersensitivity pneumonitis, 4 with acute histoplasmosis, 27 with idiopathic pulmonary fibrosis (IPF), 4 with rheumatoid arthritis-related interstitial fibrosis, 9 with pulmonary drug toxicity, 16 with pulmonary malignancies, 26 with other parenchymal lung disease entities, and 30 in whom the final diagnosis remained indeterminate. Elevated BALF-ACE concentrations were seen in all diagnostic categories. In sarcoidosis BALF-ACE levels correlated well with lavage lymphocyte counts (r = 0.49; p less than 0.0001), in contrast to IPF where they correlated well with lavage neutrophil counts (r = 0.51; p less than 0.007). The correlation of BALF-ACE and serum-ACE was significant. In sarcoidosis the mean BALF-ACE level was lower for patients with Stage-I chest roentgenographic patterns (0.664 U/L), compared to those with Stage II (1.112 U/L) and Stage III (1.083 U/L). It was concluded that elevated BALF-ACE levels are not specific for sarcoidosis. The correlations of BALF-ACE levels with different cellular constituents of BALF suggest a different cellular origin of BALF-ACE. In sarcoidosis BALF-ACE levels correlate well with other proposed markers of disease activity and seem to reflect pulmonary activity better than serum ACE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchoalveolar lavage in sarcoidosis

There is no single cell type present in bronchoalveolar lavage (BAL) fluid that appears to be predictive for sarcoidosis. However, BAL fluid analysis can be very helpful in the differential diagnosis. A grouping of features, an elevated total cell count, predominantly lymphocytes, together with a nearly normal percentage of eosinophils and polymorphonuclear neutrophils and the absence of plasma cells, distinguish the most likely diagnosis of sarcoidosis from the most common interstitial lung diseases, extrinsic allergic alveolitis (EAA), nonspecific interstitial pneumonia (NSIP), and idiopathic pulmonary fibrosis (IPF). In sarcoidosis the majority of cases have an increased number of lymphocytes and a normal amount of eosinophils and neutrophils. Disease presentation or activity at the time the BAL is performed as well as the smoking status is crucial for interpretation of individual BAL fluid analysis results. In severe cases the number of neutrophils can be increased as well. For an individual case the CD4:CD8 ratio is of less importance because it can be increased, normal, and even decreased. In the follow-up depicting prognosis and response to treatment, BAL fluid analysis has less clinical relevance.     

Bronchoalveolar lavage in sarcoidosis

Bronchoalveolar lavage (BAL) was performed in 1,188 patients suffering from sarcoidosis. After technical considerations, the authors analyze the results of BAL from a practical point of view concerning its value for the diagnosis of sarcoidosis and its prognostic value and its value for the selection of therapy, particularly for the decision as to steroid treatment. BAL helps in the diagnosis of sarcoidosis, but is not specific enough to provide this diagnosis on its own. The persistence of high alveolar lymphocytosis within the first year of evolution is strongly correlated with nonrecovery from pulmonary sarcoidosis at 2 years and thus with the evolution towards a chronic phase of the disease. On the other hand, BAL can provide basic information for a better understanding of the disease and permits immunocompetent cells and soluble factors to be recovered from the lung, which is useful for immunological studies.     

Bronchoalveolar lavage fluid and serum complement activity in pulmonary sarcoidosis

In this work, using bronchoalveolar lavage fluids (BALF), we demonstrated the presence of complement within airways by assaying hemolytic activity of the whole classical pathway (CH50) and by measuring the complement component C2 (C2H50). Patients with sarcoidosis, patients with idiopathic pulmonary fibrosis (IPF), and healthy control subjects were compared. No CH50 activity was found in BALF from healthy control subjects (n = 9), but some activity (mean, 20 CH50) was associated with IPF (n = 7). Complement activities ranged from 40 to 554 CH50 in patients with sarcoidosis (n = 27). During the treatment, complement activity decreased in BALF from the few patients in our series who received corticotherapy. C2 hemolytic activity was detected in BALF from the normal control group (in the absence of CH50 activity). In the sarcoidosis and IPF groups when CH50 was present, the variations in the C2/CH50 ratio were studied. The high ratio observed in BALF from patients with sarcoidosis and a chronic derangement of alveolar structure suggests either an increased C2 production or an alternative complement pathway (C2-independent) activation within their lungs.     

Bronchoalveolar lavage in extrapulmonary sarcoidosis

Twenty-one patients presenting with extrapulmonary sarcoidosis, 20 patients with pulmonary sarcoidosis, and 12 healthy volunteers were investigated. They were evaluated for roentgenographic findings, as well as for immunologic marker expression of cells in bronchoalveolar lavage (BAL) fluid. The patients presenting with extrapulmonary sarcoidosis could be divided in two groups: nine of 21 (43 percent) presented with a stage 1 or stage 2 chest x-ray film, while 12 of 21 (57 percent) had no chest x-ray film abnormalities (stage 0). In all three groups of sarcoidosis patients, a significant increase of CD3+ T lymphocytes in the BAL fluid was found as compared to the healthy volunteers. However, the percentages of T lymphocytes in BAL fluid of patients with extrapulmonary sarcoid lesions and a normal (stage 0) chest x-ray film was significantly lower as compared to patients with extrapulmonary sarcoidosis and an abnormal (stage 1, 2) chest x-ray film, while the latter patient group did not differ from the patients with pulmonary sarcoidosis. This suggests that in patients with extrapulmonary sarcoidosis, a gradual progression of the T cell alveolitis may occur. Furthermore, these data indicate that a marked discrepancy between chest x-ray film abnormalities and the presence of an alveolitis as determined by immunologic marker analysis exists in more than 50 percent of the patients with extrapulmonary sarcoidosis.     

Angiotensin-converting enzyme in serum and in bronchoalveolar lavage in sarcoidosis

Angiotensin-converting enzyme (ACE) determinations were made in serum and in bronchoalveolar lavage fluid in 20 controls and in 28 patients with sarcoidosis. Serum ACE was significantly higher in patients with active sarcoidosis (54.3 +/- 19.0 SD nmol/ml/ min; n = 24) compared to controls (25.7 +/- 8.2; n = 20) or to patients with inactive sarcoidosis (23.6 +/- 7.3; n = 4). In contrast, ACE in bronchoalveolar lavage fluid was similar in nonsmoking controls (16.4 +/- 7.3 nmol/ml/min/macrophage; n = 8), smoking controls (10.4 +/- 11.9; n = 7); nonsmoking active sarcoidosis patients (16.7 +/- 14.6; n = 10), smoking sarcoidosis patients (17.9 +/- 8.4; n = 6) and inactive sarcoidosis patients (14.5 +/- 8.2; n = 3). Since ACE has been demonstrated by immunofluorescence in mononuclear phagocytes in granulomas, the authors speculate that macrophages recovered by alveolar lavage are not activated and do not reflect sarcoid alveolitis at the tissue level.     

Follow-up on angiotensin-converting enzyme in serum of patients with sarcoidosis

Fluorimetrically measured serum angiotensin-converting enzyme (ACE) activity was found to be significantly elevated (p less than 0.001) in 31 untreated patients with sarcoidosis in comparison to 38 healthy controls, 20 corticosteroid-treated patients with sarcoidosis, 15 subjects with resolved sarcoidosis and 100 patients with other lung diseases. ACE values more than 2 SD above the control mean value were seen in 68% of untreated patients with sarcoidosis, but only in 5% of healthy controls, 7% of patients with tuberculosis, 0% of patients with lung tumors, 9% of patients with bronchial asthma or chronic obstructive pulmonary disease and in 17% of patients with pulmonary fibrosis due to hypersensitivity pneumonitis or diffuse idiopathic fibrosis. Resolution of sarcoidosis, spontaneously or induced by corticosteroid therapy, was accompanied by normalization of serum ACE activity in 18 out of 19 cases. In 7 out of 9 patients without clear-cut clinical improvement, changes of serum activity of ACE were not substantiated. Relapse of sarcoidosis seen in 1 case qas associated with a significant increase in ACE levels. Our results suggest that longitudinal studies of serum ACE activity are valuable in assessing the current activity and the course of sarcoidosis. Furthermore, they may contribute to restriction of necessary operative diagnostic procedures.     

Predictive value of gallium scan,angiotensin-converting enzyme level,and bronchoalveolar lavage in two-year follow-up of pulmonary sarcoidosis

Evaluation of patients with pulmonary sarcoidosis with serum angiotensin-converting enzyme (ACE), gallium scan, and bronchoalveolar lavage (BAL) has proved useful in demonstrating active disease, especially in the lungs. Long-term prognosis based on the results of pretreatment ACE, gallium scan, and BAL has not been previously clarified. We studied 44 patients with initially symptomatic pulmonary sarcoidosis who were begun on steroid therapy after initial evaluation. At 2 years, 21 of 44 (48%) patients still had worsening disease. Of 31 patients who had positive gallium scan pretreatment, 21 (68%) still had worsening disease at 2 years. None of the 13 patients with a negative gallium scan had worsening disease at 2 years (Chi square =14.2,P <0.01). Similar analysis of the pretreatment serum ACE level, percentage of lymphocytes in the BAL fluid, and ratio of T-helper/inducer to T-suppressor/cytotoxic (T4/T8) in the BAL fluid also had some predictive value for worsening disease at 2 years; however, these tests were less sensitive than the gallium scan. In patients with pulmonary sarcoidosis, the finding of a negative gallium scan suggests a small likelihood that disease activity will worsen after 2 years. Presented in part to the national meeting of the american Thoracic Society, May 1986.     

Predictive value of gallium scan, angiotensin-converting enzyme level, and bronchoalveolar lavage in two-year follow-up of pulmonary sarcoidosis

Evaluation of patients with pulmonary sarcoidosis with serum angiotensin-converting enzyme (ACE), gallium scan, and bronchoalveolar lavage (BAL) has proved useful in demonstrating active disease, especially in the lungs. Long-term prognosis based on the results of pretreatment ACE, gallium scan, and BAL has not been previously clarified. We studied 44 patients with initially symptomatic pulmonary sarcoidosis who were begun on steroid therapy after initial evaluation. At 2 years, 21 of 44 (48%) patients still had worsening disease. Of 31 patients who had positive gallium scan pretreatment, 21 (68%) still had worsening disease at 2 years. None of the 13 patients with a negative gallium scan had worsening disease at 2 years (Chi square = 14.2, P less than 0.01). Similar analysis of the pretreatment serum ACE level, percentage of lymphocytes in the BAL fluid, and ratio of T-helper/inducer to T-suppressor/cytotoxic (T4/T8) in the BAL fluid also had some predictive value for worsening disease at 2 years; however, these tests were less sensitive than the gallium scan. In patients with pulmonary sarcoidosis, the finding of a negative gallium scan suggests a small likelihood that disease activity will worsen after 2 years.     

Longitudinal observations of serum angiotensin-converting enzyme activity in sarcoidosis with and without treatment

Serial measurements of serum angiotensin-converting enzyme activity were made to estimate its usefulness in following the course of 17 patients with sarcoidosis. In nine cases with spontaneous remissions, the enzyme levels decreased gradually, accompanied by improvements in chest radiologic findings. In eight patients given corticosteroids, the enzyme levels decreased rapidly preceding improvements in the chest roentgenograms. The levels returned to pretreatment values when there was radiologic relapse of disease. Reelevation of the enzyme level was also observed without determination of the chest radiologic findings in four of five patients who responded to therapy, but the elevated enzyme level remained lower than the pretreatment level. These observations suggest that the serum angiotensin-converting enzyme level reflects the activity of disease in untreated and corticosteroid-treated patients with sarcoidosis. However, a partial reelevation of the decreased enzyme activity in corticosteroid-treated patients does not necessarily indicate a relapse of the disease.     

The value of gallium-67 scanning in pulmonary tuberculosis

We studied 59 patients presumed to have pulmonary tuberculosis to determine whether gallium-67 citrate scintigraphy could improve diagnostic accuracy and help clinical decision making for empiric treatment pending culture results. The sensitivity of 67Ga scintigraphy was 95% and the specificity 27%. Our positive predictive value of 69% does not contribute substantially to increase the prior probability of diagnosis in settings similar to ours. The existence of a false negative rate essentially precludes the use of the scan to rule out active disease. The use of the scan for clinical decisions in pulmonary tuberculosis is not recommended.     

Bronchoalveolar lavage fluid granulomas in a case of severe sarcoidosis.

A case of pulmonary sarcoidosis is presented in which cytologic analysis of bronchoalveolar (BAL) fluid showed intact granulomas. The patient had severe alveolar inflammation and probable endobronchial sarcoidosis. Thus the granulomas in the BAL fluid probably reflect a high burden of alveolar wall granulomas and/or the removal of granulomas from proximal inflamed airways. This is the first reported case of granulomas in BAL fluid in sarcoidosis. Although an unusual finding, the recovery of BAL granulomas is not diagnostic for sarcoidosis and cannot substitute for the demonstration of granulomatous inflammation in lung tissue.     

Bronchoalveolar lavage quality influences the T4/T8 ratio in sarcoidosis

BACKGROUND: Sarcoidosis is characterised by a T-lymphocytic alveolitis with a typically increased T4/T8 ratio. The diagnostic value of this ratio is under debate. AIM OF THE WORK: We prospectively evaluated the influence of BAL pre-lavage and the impact of bronchial contamination on BAL differential cell count in 108 BAL specimens obtained from patients with histologically confirmed sarcoidosis. METHODS: BAL was performed by instilling 150-300 ml normal saline either in the middle lobe or the lingula. Fifty-one patients (47%) underwent additional pre-lavage with 50 ml normal saline. Bronchial contamination was assessed by semi-quantitative analysis of mucus, ciliated and squamous cells in the untreated BAL recovery. RESULTS: Pre-lavage did neither influence the lavage cellularity nor extend of contamination of the BAL. Content of mucus and ciliated cells, indicating bronchial contamination, showed a high correlation (Kendal's tau=0.61). Presence of either mucus or ciliated cells in the BAL recovery was associated with a significant lower T4/T8 ratio (mucus: 4.9 vs. 8.0, p=0.009; ciliated cells: 4.1 vs. 7.4, p=0.001). Squamous cells in the BAL recovery representing oropharyngeal contamination did not significantly influence the T4/T8 ratio (7.7 vs. 5.6, p=0.10). CONCLUSION: Bronchial contamination of BAL as determined by the presence of mucus and ciliated cells in the recovery decreases the T4/T8 ratio of BAL in sarcoidosis.