Bronchoalveolar lavage, serum angiotensin-converting enzyme, and gallium-67 scanning in extrathoracic sarcoidosis

Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis.     

The relationship between disease duration and noninvasive pulmonary explorations in sarcoidosis with erythema nodosum

In order to investigate the initial course of pulmonary sarcoidosis, the following investigations were carried out in 14 nonsmoking patients with Logfren 's syndrome 3 to 12 wk after the onset of erythema nodosum (EN): bronchoalveolar lavage (BAL) (cellular and protein components), serum assays of lgG and of the activity of angiotensin-converting enzyme (SACE), and pulmonary function tests. These results were related to the disease duration, estimated by the time lapse separating the onset of EN from the investigations. All patients but one showed a large increase in the percentage of lymphocytes (%-L) in BAL fluid (more than 30%). Although each patient was evaluated only once, and thus this work was not an actual longitudinal study, a linear relationship between lymphocyte count per milliliter of recovered fluid during BAL (L-count) and disease duration was found during the first 8 wk (r = 0.78, p less than 0.01), suggesting a fast-developing alveolitis. The delayed rise in SACE level may indicate a secondary activation of macrophages; SACE and L-count were well related, either up to 8 wk (SACE versus L-count: r = 0.84, p less than 0.01) or up to 12 wk (SACE versus L-count: r = 0.61, p less than 0.01). Serum lgG levels were found to follow the L-count (serum lgG versus L-count: r = 0.79, p less than 0.01) and appeared to be a reliable index of disease activity. Respiratory function showed a univocal pattern, with a marked decrease in all of the patients in carbon monoxide diffusing capacity (DLCO), contrasting with normal lung volumes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum angiotensin-converting enzyme is elevated in association with underground coal mining.

Serum angiotensin-converting enzyme activity (SACE) and lysozyme activity were measured in a group of 40 underground coal miners and two control groups, 20 subjects with sarcoidosis and 15 normal non-dust-exposed volunteers. The miners were grouped first according to whether they had recent exposure (still actively mining or retired three years or less prior to measurement) or temporally more distant exposure (retired more than three years prior to measurement). Secondly, they were grouped as to whether or not they had coal workers' pneumoconiosis (CWP). The subjects with sarcoidosis were grouped according to disease activity. As expected, the subjects with active sarcoidosis had elevated SACE activity compared with normal subjects. The coal miners as a group did not have elevation of their SACE activity. However, the coal miners with recent exposure had elevated SACE activity (57.1 +/- 3.9 U/ml) compared with normal controls (43.8 +/- 1.5 U/ml, p = 0.007). The SACE activity in miners without recent exposure was not elevated (39.8 +/- 1.3 U/ml) compared with the normal controls. No increase in SACE activity was found when the miners were grouped according to the presence or absence of CWP. In contrast, the miners' serum lysozyme activity was not elevated. Since alveolar macrophages are a potential source of SACE, elevation of SACE activity in underground coal miners may reflect alveolar macrophage activation caused by increased pulmonary mixed coal mine dust burden. Furthermore, since both SACE and serum lysozyme are elevated in association with silicosis, these findings may confirm that the macrophage responses to inhaled silica and coal dust differ.     

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.     

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.     

Urinary neopterin in pulmonary sarcoidosis. Relationship to clinical and biologic assessment of the disease

Neopterin is a metabolite of guanosine-triphosphate, released in vitro by macrophages under the control of gamma-interferon and described as a marker of T cell activation in vivo. We have compared the urinary neopterin/creatinine ratio (mumol/mol) in patients with pulmonary sarcoidosis (n = 66), interstitial lung diseases other than sarcoidosis (nonsarcoid ILD, n = 35), and 45 normal control subjects. For the sarcoid population as a whole, urinary neopterin was higher (496 +/- 52 mumol/mol [mean +/- SEM]) than in control subjects (126 +/- 5 mumol/mol) (p less than 0.001). In patients with nonsarcoid ILD, urinary neopterin was frequently higher in granulomatous and/or lymphoproliferative diseases (hypersensitivity pneumonitis, tuberculosis, primitive Sj?gren's syndrome, and malignant lymphomas) (781 +/- 193 mumol/mol, n = 10) but remained normal in other types of nonsarcoid ILD [( 163 +/- 14 mumol/mol, n = 25]: histiocytosis X, idiopathic pulmonary fibrosis, lung collagen-vascular diseases, diffuse neoplasms, pneumoconiosis; p less than 0.001 compared with sarcoidosis). We have also evaluated the relationship between urinary neopterin and the clinical or biologic markers currently used to assess sarcoidosis: alveolar lymphocytosis in lavage fluid (ALY), 67-gallium scan semiquantitative index (67Ga), or serum angiotensin-converting enzyme (SACE). Sarcoid patients with the highest urinary neopterin were those in whom mean values of these markers were the highest (p less than 0.05, all comparisons). Patients with positive markers (i.e., either clinical expression of sarcoidosis-ALY greater than 30%-67Ga greater than 20-SACE greater than 60 U/ml) had significantly higher urinary neopterin levels than did other sarcoid patients (p less than 0.05, all comparisons).     

Asymptomatic gastrocnemius muscle biopsy: an extremely sensitive and specific test in the pathologic confirmation of sarcoidosis presenting with hilar adenopathy

OBJECTIVE: To evaluate asymptomatic gastrocnemius muscle biopsy as a tool in the histologic confirmation of the diagnosis of sarcoidosis. METHODS: Twenty-two patients admitted over a 2-year period to our department with bilateral hilar adenopathy and a variety of symptoms compatible with sarcoidosis were studied prospectively. Besides a complete history and physical, serum angiotensin converting enzyme (SACE) determination, pulmonary function, slit lamp eye examination, PPD skin test, gallium 67 scan and gastrocnemius muscle biopsy were performed. RESULTS: The biopsy revealed non-caseating granuloma in all patients, confirming the diagnosis of sarcoidosis. No other patient in our department received this diagnosis over the 2-year period of the study. The procedure was well tolerated by all patients and almost zero morbidity was noted. Erythema nodosum was present in 68.2% of the patients, PPD was negative in all of them, SACE was elevated in 59.1% and pulmonary function was normal in the majority. CONCLUSION: The impressive sensitivity of asymptomatic gastrocnemius muscle biopsy, its safety and ease of performance, along with the extreme rarity of muscle involvement by other granulomatous diseases included in the differential diagnosis, may render it the procedure of choice for the histologic confirmation of sarcoidosis presenting with hilar adenopathy.     

Pulmonary cavitary sarcoidosis: clinico-radiologic characteristics and natural history of a rare form of sarcoidosis

Pulmonary cavitary lesions in the absence of concomitant comorbidities are an uncommon and often confusing manifestation of sarcoidosis. We retrospectively reviewed the clinical and high-resolution computed tomography (HRCT) characteristics and the natural history of a series of 23 patients with pulmonary cavitary lesions found on HRCT extracted from a large cohort of patients with pulmonary sarcoidosis. The estimated prevalence of cavitary sarcoidosis was 2.2%. Cavitary lesions developed in patients with severe and active sarcoidosis (serum angiotensin-converting enzyme [SACE] > or =2 times the upper limit of normal range: 63.6%). Twelve (52.2%) patients had evidence of radiographic stage IV, 9 of whom (75%) had persistently increased SACE. As found on HRCT, cavitary lesions were multiple in 21 patients (91.3%), including 5 patients with 10 or more cavities. The size of cavitary lesions was variable, with a median diameter of 20 mm (range, 11-100 mm). Follow-up was available for 20 patients with a median follow-up of 6.25 years (range, 6 months to 15 years). Seven patients (35%) experienced some type of complication related to cavitary lesions, including 6 episodes of hemoptysis in 5 patients and aspergilloma occurrence in 3 patients. As seen on HRCT, the evolution of the number and size of cavitary lesions was variable, with a complete resolution of the largest cavitary lesion in only 5 patients (25%). During follow-up, wall thickening was always associated with a further infectious complication. In summary, cavitary lesions are rare in pulmonary sarcoidosis and usually occur in active and severe sarcoidosis. Their evolution is unpredictable, and complications are frequent.     

Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to 99mTc-DTPA

Respiratory epithelial clearance of 99mTc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of 113mIn-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stable during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.     

Serum angiotensin-converting enzyme and blood monocytes in splenectomized individuals

In 45 splenectomized individuals without malignancies, residual splenic tissue was detected by 99mTc-scanning using reinjection of labelled heat-damaged and autologous erythrocytes. The angiotensin-converting enzyme in serum (SACE) and the blood monocyte count were measured in order to demonstrate an eventual association between these parameters as well as the influence of residual splenic tissue. In 20 patients with detectable spleen tissue SACE was normal (26.2 +/- 4.4 U/ml), but in 25 patients without residual spleen tissue SACE was slightly elevated (28.7 +/- 6.4 U/ml; p less than 0.02) as compared with healthy controls (24.4 +/- 6.2 U/ml). In both groups of patients blood monocytes were markedly increased. However, no correlation could be demonstrated between SACE and the monocyte count in any group. In 2 patients SACE was above the upper limit of the normal range (greater than 36.8 U/ml) as found in sarcoidosis but no signs of this disease could be demonstrated. It is concluded that splenectomy must be taken into account when the significance of raised SACE is evaluated. It may be suggested that the spleen exerts an effect on the metabolism of SACE or on the ACE-producing cells in the organism.     

Acid phosphatase (EC 3.1.3.2) activity in alveolar macrophages from patients with active sarcoidosis.

Five main acid phosphatase (AcP) zones have been recognized and studied by polyacrylamide-gel electrophoresis. Band 5 represents the only tartrate-resistant form and is present in bone osteoclasts and in human alveolar macrophages (AMs). This study was carried out to quantify the presence of total and tartrate-resistant AcP (TrAcP) in AMs from bronchoalveolar lavage (BAL) of 11 patients with first stage sarcoidosis and in 13 nonsmokers and 16 smokers serving as control healthy subjects. The AMs from smokers showed an increase in total AcP activity (115.9 +/- 77.8 mU/10(6)); on the contrary, macrophages of patients with sarcoidosis revealed a consistent decrease in total AcP (27.8 +/- 7.0 mU/10(6)) and particularly the TrAcP subtype (14.8 +/- 3.7 mU/10(6)) in comparison with control nonsmokers (AcP = 42.2 +/- 18.9 mU/10(6) [p = NS]; TrAcP = 35.1 +/- 15.1 mU/10(6) [p less than 0.005]). The decrease in TrAcP activity was inversely correlated with the lymphocyte number (r = -0.75; p less than 0.01), lymphocyte percentage (r = -0.62; p less than 0.05), and CD4/CD8 ratio (r = -0.61; p less than 0.05). After six months of follow-up, the cytologic BAL picture returned completely to normal in five patients with full spontaneous regression of sarcoidosis; and also at the same time, normal values of TrAcP activity were restored. Since TrAcP activity can be easily detected, its possible use, along with the lymphocyte count and CD4/CD8 ratio, as a prognostic indicator of the clinical course of sarcoidosis deserves further investigation.     

Prognostic value of chest radiograph, serum-angiotensin-converting enzyme and T helper cell count in blood and in bronchoalveolar lavage of patients with pulmonary sarcoidosis

We studied the prognostic value of the initial radiologic stage, the serum-angiotensin-converting enzyme (SACE) and T helper cells in blood (OKT-4-Bl) and in bronchoalveolar lavage (OKT-4-BAL) for patients with biopsy-proven pulmonary sarcoidosis. Thirty-seven patients without prior treatment were followed up for a period of 2 years. A BAL was performed in 22 of them as part of the diagnostic workup. Clinical examination, chest radiographs, vital capacity, diffusion capacity for CO, airway resistance and PaO2 at rest and during exercise were determined initially and after 6, 12 and 24 months. According to these results, patients were classified as having progressive or nonprogressive disease. The radiologic stage and the initial SACE (38.3 +/- 10.2 vs. 43.7 +/- 13.0 nmol/ml/min) could not discriminate between the two groups. Patients with progressive disease had significantly fewer OKT-4-Bl cells (403.3/microliter +/- 146.7/microliter vs. 842.0/microliter +/- 430.1/microliter) and more OKT-4-BAL cells (24.5 +/- 15.4% vs. 7.0 +/- 2.6%) than patients with stable disease (p less than 0.01). A negative correlation between OKT-4-Bl and OKT-4-BAL cells was shown (Rs = -0.79; p less than 0.001). We conclude that the number of OKT-4-Bl and OKT-4-BAL cells can be used as prognostic parameter for patients with sarcoidosis.     

Angiotensin-converting enzyme. Investigation of diurnal variation, the effect of a large dose of prednisolone, and prednisolone pharmacokinetics in patients with sarcoidosis

Serial assay of serum angiotensin-converting enzyme concentrations (SACE) is advocated for monitoring disease progress in sarcoidosis. Because little is known of nondisease factors affecting SACE, 10 patients with histologically proved sarcoidosis were assessed for diurnal fluctuation in SACE and as to whether a large dose of corticosteroid had an immediate effect on SACE independent of disease. The pharmacokinetics of prednisolone in 8 of these patients was also evaluated. On Day 1, serum samples were obtained for 24 h after placebo, and the next day at the same times after 75 mg of orally administered prednisolone. There was no obvious diurnal pattern on either day, and there was no significant difference in SACE after prednisolone. The mean maximal difference obtained within or between days was 8.8%. Prednisolone pharmacokinetics were comparable to normal volunteers. SACE concentrations can be confidently determined at any time of day, and changes of greater than 9% are probably significant. The use of prednisolone in patients with sarcoidosis can be safely based upon pharmacokinetic data obtained from normal volunteers.     

Chemiluminescence of lung macrophages and blood leukocytes in sarcoidosis

A luminol-enhanced chemiluminescence assay was used to measure light elaborated by peripheral blood polymorphonuclear leukocytes (PMNs) and by pulmonary alveolar macrophages (PAMs) from 14 healthy, normal subjects and 16 patients with sarcoidosis. Resting peripheral blood PMNs (incubated only in medium) from patients with sarcoidosis generated substantially more chemiluminescence than PMNs from normal control subjects (p = 0.002). With zymosan stimulation, greater chemiluminescence was produced by PMNs from untreated patients with sarcoidosis than from normal subjects (p less than 0.05), whereas no differences were noted with latex stimulation. Chemiluminescence for resting PAMs was not different between normal subjects and patients with sarcoidosis. However, PAMs from untreated patients with sarcoidosis had higher chemiluminescence with latex particle ingestion than PAMs from normal subjects (p less than 0.05), but no differences in PAM chemiluminescence were found when zymosan was the phagocytic particle. Increased chemiluminescence by PMNs and PAMs from patients with sarcoidosis may reflect phagocyte activation in the disease process.     

Diagnostic, prognostic and developmental value of serum angiotensin converting enzyme in sarcoidosis

Two hundred ninety three patients with mediastinal and pulmonary sarcoidosis were assayed one or more than one time for seric angiotensin converting enzyme (SACE) using the method of Cushman and Cheung (substrate hippuryl-histidyl-leucin). Seventy one normal subjects and 163 patients with various broncho-pulmonary diseases excluding sarcoidosis were used as control. SACE is elevated in 67.2 p. 100 of the patients with sarcoidosis and reflects the intra and extrathoracic extend of the granuloma. Elevated levels of SACE in pneumoconiosis diminishes the diagnostic value of this test (as well as the presence of a normal SACE level in some sarcoid patients). There is no correlation between SACE and the percentage of lymphocytes in bronchoalveolar lavage fluid. SACE returns to normal in cases with spontaneous radiological improvement, and reaches more elevated levels in cases with worsening. An initial low level of SACE is usually a sign of a future good evolution. An initial high level is an argument for starting on steroid treatment. Repeated dosages of SACE are useful for monitoring the steroid posology at the end of the treatment and for deciding to stop it. Persistence of low levels allows to stop the treatment. Re-elevation of SACE may correspond to a radiological and clinical relapse or to an isolated and resolvent rebound.     

Airway obstruction in bronchial sarcoidosis: outcome with treatment

STUDY OBJECTIVE: Airway obstruction (AO) in sarcoidosis is reported to be associated with respiratory symptoms, increased morbidity, and an increased mortality risk. Because AO in sarcoidosis may result from several causes, the therapeutic benefit of corticosteroids is difficult to determine. The aim of this study was to evaluate the therapeutic response of AO attributable to sarcoid granulomas in the bronchial wall. PATIENTS: We selected 11 patients who had sarcoidosis with AO (defined as FEV(1)/vital capacity [VC] < 70%) associated with sarcoid granulomas on an endobronchial biopsy. Exclusion criteria were history of asthma, smoker or ex-smoker, stage 4 disease, evidence of extrinsic compression by enlarged lymph nodes, and localized endobronchial stenosis seen during fiberoptic bronchoscopy. INTERVENTIONS: We compared the results of pulmonary function tests and clinical, radiologic, and biological findings at baseline with those obtained at the time of the last pulmonary function tests available, between the sixth and 12th months of treatment. Eight patients took oral corticosteroids (20 to 60 mg/d initially), one received IV methylprednisolone pulses, another took oral hydroxychloroquine, and the last one received IM methotrexate. Measurements and results: With treatment, FEV(1) and FEV(1)/VC significantly improved in eight patients (72%), normalized in four patients, and was unchanged in the remaining three patients. The mean FEV(1) increased from 60.8 +/- 10.8% to 76 +/- 13.7% of the predicted value (p < 0.02). VC did not change significantly. FEV(1)/VC increased from 76.1 +/- 6.4% to 87.6 +/- 10.7% of the predicted value (p < 0.01). Dyspnea on exertion and other clinical findings were attenuated in 10 patients; the chest radiograph improved in 9 patients, and normalized in 5 patients. The mean serum angiotensin-converting enzyme level decreased from 112 +/- 48 to 58 +/- 40 IU/mL (p < 0.05), and normalized in four patients. CONCLUSION: The present study indicates that AO caused by sarcoid granulomas in the bronchial wall can be either partially or completely reversed by treatment with a concomitant attenuation of pulmonary symptoms.     

肺结节病27例临床分析

目的对27例肺结节病进行临床分析,为早期诊断和治疗提供思路。方法对27例病理证实为非特异性肉芽肿的肺结节病患者进行回顾性分析,仔细观察这些患者的临床特征表现、影像特征变化、以及血钙、血管紧张素转化酶（SACE）等,并进行分析归纳。结果肺结节病患者临床表现多样,无特异性,有较典型的影像学表现,血某些生化指标升高,纵隔镜或支气管镜肺活检等检查能确诊。结论详细的病史与比较特征性影像,早期进行活检是确诊的依据,其他血钙、SACE等升高对诊断肺结节病有一定参考作用,糖皮质激素可以改善肺结节病患者的临床症状与影像表现。     

Increased levels of oxidized methionine residues in bronchoalveolar lavage fluid proteins from patients with idiopathic pulmonary fibrosis

Phagocytic cells are believed to play a crucial role in the development of inflammatory lung diseases. We assumed that the oxidation of methionine (met) to methionine sulfoxide [met(O)] by oxygen-derived free radicals released from phagocytes is one parameter to identify the oxidative mechanisms of lung injury. To test this hypothesis we determined the molar ratio of met(O)/met in the soluble protein fraction of bronchoalveolar lavage (BAL) fluids from healthy nonsmokers and from nonsmoking patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. The met(O)/met ratio of the healthy nonsmoker group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). In contrast, the met(O)/met ratio of the nonsmoking IPF group (n = 11) was significantly increased to 0.223 +/- 0.053 (p less than 0.0002). The BAL fluids of this group showed strongly increased numbers of neutrophils but normal numbers of alveolar macrophages (AM). In the sarcoidosis group (n = 10) the met(O)/met ratio (0.048 +/- 0.010) was not significantly different from control values. A close relationship was found between the met(O)/met ratios and the relative as well as the absolute neutrophil counts (r = 0.86; p less than 0.0002; n = 22). In contrast, no significant correlation was found between the met(O)/met ratios and the absolute AM counts (r = 0.22; p = 0.32; n = 22). We conclude that mechanisms of oxidative lung injury in IPF can be characterized by oxidation of met and that this oxidation may be mediated by neutrophils.     

IL-1 and IL-1 inhibitory activity in the culture supernatants of alveolar macrophages from patients with interstitial lung diseases

Under normal conditions, the release of interleukin 1 (IL-1) and IL-1 inhibitors play a role in tissue homeostasis. We have already reported an increase in IL-1 activity and a decrease in IL-1 inhibitory activity (IHA) in the supernatants of alveolar macrophages from healthy long-term smokers as compared with healthy nonsmokers. In this study, we report an alteration in the release of IL-1 and IL-1 IHA from alveolar macrophages in patients with interstitial lung diseases (sarcoidosis and idiopathic pulmonary fibrosis [IPF]). IL-1 activity released from alveolar macrophages stimulated by lipopolysaccharide was increased in patients with active sarcoidosis (mean +/- SD, 2.52 +/- 1.33 U/ml [n = 6] vs 1.38 +/- 0.62 U/ml [n = 15] for healthy non-current smokers [HNS]; p less than 0.05). IL-1 IHA released from alveolar macrophages was significantly different among the groups examined: a decrease of IL-1 IHA occurred in patients with active sarcoidosis (61.4 +/- 19.2 [n = 6] vs 85.9 +/- 13.9 percent:HNS; p less than 0.05) and IPF (64.7 +/- 18.5 [n = 9]; p less than 0.05). Prednisolone in the culture medium at physiologic concentrations suppressed the release of IL-1 and enhanced the release of IL-1 IHA. IL-1 IHA inhibited not only mouse thymocyte proliferation but also human fibroblast proliferation in the presence of IL-1.     

Pulmonary tuberculosis in Kigali, Rwanda. Impact of human immunodeficiency virus infection on clinical and radiographic presentation.

The aim of the present study was to compare the clinical and radiographic presentation as well as the therapeutic outcome of pulmonary tuberculosis (PT) in adult patients with and without human immunodeficiency virus type 1 (HIV-1) infection in Kigali, Rwanda. Over a 17-month period 59 consecutive patients with bacteriologically and/or histopathologically documented PT were enrolled. Of these, 48 (81%) patients were HIV seropositive. Among these, 35 fit the WHO clinical criteria for AIDS (WHOCCA) at the time of admission. Significant differences were found between the HIV-seropositive and HIV-seronegative groups of patients: fever (85 versus 36%; p less than 0.001), tuberculin skin test anergy (69 versus 0%; p less than 0.01), mediastinal and/or hilar adenopathies (31 versus 0%; p = 0.05), and pleural effusion (43 versus 9%; p less than 0.05) were more frequently encountered in the HIV-seropositive group, and upper lobe infiltrates (55 versus 16%; p less than 0.02) and cavitation (91 versus 39%; p less than 0.003) were more often seen in the HIV-seronegative group. However, HIV-seropositive patients not meeting WHOCCA were less frequently anergic (0 versus 100%; p less than 0.001) and feverish (53 versus 97%; p less than 0.01) and more often had cavitation (69 versus 28%; p less than 0.02) and less often mediastinal and/or hilar adenopathies (7 versus 40%; p less than 0.04) compared with HIV-seropositive patients meeting WHOCCA. Under antituberculosis treatment, clearance of fever was slower in HIV-seropositive compared with HIV-seronegative patients, and among the HIV-seropositive group it was slower in those fitting WHOCCA.(ABSTRACT TRUNCATED AT 250 WORDS)