Biomedical subjects
Publications and source records attributed to U Costabel.
This is the report on a lethal course of idiopathic pulmonary fibrosis in two monozygotic twins. The specific aspects of familial idiopathic pulmonary fibrosis and the pattern of inheritance are discussed. The pattern is probably autosomal dominant with variable penetrance.
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CD14 is a myeloid differentiation antigen which exists in a membrane-bound (55 kD) and a soluble (48 kD) form. This antigen is a receptor for lipopolysaccharide (LPS) structures and triggers the production of various cytokines. The aim of this study was to evaluate whether in active sarcoidosis, a disease with increased proportions of alveolar macrophages (AM) with CD14 expression in BAL fluid, the soluble form of CD14 (sCD14) is also increased. The sCD14 levels were measured in BAL fluid with an ELISA, and membrane-bound CD14 was determined by an immunoperoxidase assay, in active sarcoidosis (n = 13), inactive sarcoidosis (n = 9), idiopathic pulmonary fibrosis (IPF) (n = 6), and control subjects (n = 8). Higher concentrations of sCD14 were present in BAL fluid of patients with active sarcoidosis (58 +/- 34 ng/ml) than in those with inactive disease (13 +/- 10 ng/ml), patients with IPF (5 +/- 5 ng/ml), or control subjects (10 +/- 8% ng/ml) (p < 0.01). Similarly, the proportions of AM expressing membrane-bound CD14 were increased in active sarcoidosis (91 +/- 6%) compared with inactive sarcoidosis (82 +/- 6%), patients with IPF (76 +/- 13%), and control subjects (79 +/- 9%) (p < .05). In sarcoidosis, a significant correlation was found between the sCD14 concentration in BAL fluid and AM membrane expression of CD14 (r = 0.57, p < 0.01). We conclude that sCD14 is increased in BAL of active sarcoidosis suggesting a potential role for this substance as marker of activity and in the pathogenesis of pulmonary sarcoidosis.
Bronchoalveolar lavage (BAL) is increasingly used in the pediatric age group. However, normal values for BAL fluid (BALF) constituents are lacking. As part of an investigation to define reference values in children, we studied lymphocyte surface markers of BALF in 28 children 3 to 16 yr of age without bronchopulmonary disease. All of them were undergoing elective surgery for nonpulmonary illnesses. BAL was performed under general anaesthesia with tracheal intubation. A flexible bronchoscope (Pentax 3.5 or 4.9 mm) was wedged into the middle lobe or into one of its segments, and 3 x 1 ml/kg body weight normal saline warmed to body temperature were instilled and immediately withdrawn. The first sample was studied separately; subsequent samples were pooled for analysis. Studies on lymphocyte surface markers were performed on the pooled sample only. The distribution of B-cells, pan T-cells, and CD57 positive cells was within the range reported for adult subjects. However, CD4/CD8 ratios were lower than in adults (0.7 +/- 0.4, mean +/- SD). This decrease in the CD4/CD8 ratio was caused by an increase in CD8 cells. Comparative analysis of blood and BALF lymphocytes in a subgroup of children showed that CD4/CD8 ratios in blood were within the normal range reported for this age group and significantly higher when compared with BALF. The lower CD4/CD8 ratios in normal children have to be considered in the interpretation of BALF in children with pulmonary diseases.
The aim of this study was to investigate the relationship between release of tumor necrosis factor-alpha (TNF-alpha) by alveolar macrophages (AM) and the phenotypic characteristics of bronchoalveolar lavage (BAL) cells in sarcoidosis. We studied the spontaneous release of TNF-alpha by AM in vitro and the phenotypic characteristics of freshly recovered BAL T-cells and AM in 31 individuals (13 with active sarcoidosis, nine with inactive sarcoidosis, and nine normal controls). TNF-alpha was measured by enzyme-linked immunosorbent assay (ELISA) in supernatants from unstimulated AM after 24 h culture. Phenotypic markers of BAL cells were determined by an immunocytochemical assay. AM of patients with active sarcoidosis released more TNF-alpha (1,355 +/- 133 pg/ml/ 10(6) AM/24 h) than those of the inactive group (651 +/- 142 pg/ml/10(6) AM/24 h) or the normal controls (425 +/- 121 pg/ml/10(6) AM/24 h), with p < 0.001 for both comparisons. The amount of TNF-alpha released correlated positively with the percentage expression of CD4 (r = 0.72) and CD25 (r = 0.70) by lymphocytes, and of CD14 (r = 0.63), VLA-4 (r = 0.59), FRD1 (r = 0.67) and 27E10 (r = 0.67) by AM, with p < 0.001 for all correlations. In conclusion, this relationship suggests that these antigens may be considered as cellular activation markers, and that some of these AM antigens may indirectly characterize the AM phenotype that is capable of producing TNF-alpha.
INTRODUCTION: CD14 is a cell surface glycoprotein expressed mainly on mature monocytes and macrophages. Soluble CD14 (sCD14) is present in normal plasma and is found increased in serum of patients with septicemia, polytrauma, and sarcoidosis. In active sarcoidosis, increased levels of sCD14 in BAL supernatant have been demonstrated. STUDY OBJECTIVE: To investigate sCD14 levels in BAL of pulmonary tuberculosis (PTB), another inflammatory disease characterized by granuloma formation. METHODS: BAL was performed in 12 patients with active but untreated PTB and 12 healthy persons. Cytologic and immunocytologic characteristics were determined. sCD14 was measured by a sandwich enzyme-linked immunosorbent assay. RESULTS: The level of sCD14 in patients with PTB was increased compared with controls (mean +/- SEM: 34.4 +/- 9.6 ng/mL vs 11.5 +/- 2.2 ng/mL; p = 0.02). No correlation was found between sCD14 levels and BAL cell differentials or lymphocyte surface markers. CONCLUSION: Similar to sarcoidosis, increased levels of sCD14 are found in BAL supernatant of PTB patients.
The aim of this prospective study was to identify markers in bronchoalveolar lavage fluid (BAL fluid) and serum predictive for the development of pulmonary complications in the early phase (< 50 days) post-BMT. Concentrations of BAL fluid albumin (alb) and serum beta 2-microglobulin (S-beta 2m,) were determined 10 days before BMT (BAL-B, baseline) and on day 1 post-BMT (BAL-1) in 20 patients who subsequently developed pulmonary complications (group 1) and in 66 patients who remained free of complications for a minimum of 12 months (group 2). Median BAL fluid alb concentrations were significantly (P < 0.05) higher in group 1 patients as compared to group 2 patients at BAL-B (40 vs 28 mg/l) and at BAL-1 (30 vs 15 mg/l). S-beta 2m at BAL-1 was also significantly elevated in group 1 patients (median 1.3 mg/l) compared to group 2 patients (median 1.15 mg/l). Using cut-off values for BAL fluid alb (> 23 mg/l) and S-beta 2m (> 0.8 mg/l) we identified 12 patients out of 19 who developed subsequent pulmonary complications from 12 out of 62 patients without such complications, 1 day post-BMT.
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BACKGROUND: Endobronchial tuberculosis (EBTB) is not seen often in the adult population. In most cases it is associated with pulmonary tuberculosis. During its course significant tracheobronchial stenosis may develop. In this study we report our experience with patients with EBTB. METHODS: The records of 38 patients in whom EBTB had been proved by fibre optic bronchoscopy, microbiology and histology studies were evaluated. RESULTS: Symptoms were non-specific and represented mainly the co-existing pulmonary tuberculosis. Signs characteristic of airway obstruction were rare (localized wheezing in 6%). Indications for bronchoscopy were radiographic features (87%), microscopy smear negatives (8%), wheezing (3%), and blood stained sputum (3%). The lesions were more likely to be seen in the main and upper bronchi. In 5% of patients the lower trachea was involved. Most lesions looked inflamed (51%), followed by caseous (19%), granulomatous (17%), ulcerative (12%), and fibrotic appearance (1%). The degree of stenosis was nil (22%), minor (45%), significant (13%), subtotal (13%), or total (7%). The patients were treated with a combination of antituberculosis drugs. Four patients underwent surgical procedures. Dilatation techniques were used in two patients for a right and left main bronchus stenosis respectively, with significant improvement in one. Dilatation in combination with laser therapy of a right intermediate bronchus stenosis did not result in re-expansion of the dependent part of the lung due to pleural adhesions. Left pneumonectomy was performed in one patient for destroyed lung. Twenty-two patients agreed to follow up bronchoscopy. The macroscopic appearance of the mucosa had improved in most cases but the degree of stenoses was unchanged in a considerable proportion (58%). Bronchial stenosis in one patient subsided during therapy but developed again at a later stage. CONCLUSIONS: Patients with pulmonary tuberculosis and radiographic evidence of volume loss are recommended to undergo bronchoscopy to rule out EBTB. Specific symptoms for EBTB are rare. Biopsy of inflamed areas of bronchial mucosa seems to be indicated. Despite adequate antituberculosis therapy tracheobronchial stenosis may develop. Long term follow up including bronchoscopy seems therefore advocated. Dilatational intervention may be indicated in selected cases.
Limited data on the cellular and immunocytologic characteristics of bronchoalveolar lavage (BAL) fluid in pulmonary tuberculosis have been reported. We therefore studied 40 patients with active disease. BAL fluid differential cell counts and lymphocyte subsets were determined. The findings were compared with data from 47 patients with active sarcoidosis and 30 healthy control subjects. The proportion of lymphocytes was increased in both diseases (p < 0.001 versus control subjects) but with no difference compared to one another. The CD4/CD8 ratio was normal in 33 of 40 patients with pulmonary tuberculosis in contrast to sarcoidosis, with an increased ratio in 33 of 47 patients. HLA-DR+ T lymphocytes were significantly increased in both pulmonary tuberculosis and sarcoidosis (p < 0.05 versus control group). The proportion of CD57+ lymphocytes was normal in all study groups. We conclude that pulmonary tuberculosis and sarcoidosis are characterized by an increased percentage of lymphocytes in BAL fluid with a similar proportion of activated T cells. In contrast to active sarcoidosis, in which an elevated CD4/CD8 ratio is characteristic, in the majority of pulmonary tuberculosis patients the CD4/CD8 ratio is within the normal range.
Bronchoalveolar lavage (BAL) provides a simple method of sampling inhaled particles deposited in the lower respiratory tract. We hypothesized that BAL could be used to measure the quantity and quality of lung asbestos burden. This would be true if BAL fluid asbestos fiber content reflected the total content as well as the size distribution of both uncoated and coated asbestos fibers in lung parenchyma. Therefore, we analyzed the asbestos fiber counts of 23 individual sample pairs in both BAL fluid and lung tissue samples obtained from 20 patients with occupational asbestos exposure using transmission electron microscopy (TEM). In addition, fiber type, fiber size, and aspect ratio were compared. Coated asbestos fibers were found in 10 of 23 BAL samples and 16 of 23 biopsies. The mean concentrations of coated asbestos fibers (i.e., asbestos bodies) in BAL and lung parenchyma showed a positive correlation (r = 0.75, p < 0.001). Likewise, the mean amphibole fiber concentrations correlated positively (r = 0.55, p < 0.01). However, there was no relationship between the mean chrysotile fiber counts in BAL and lung parenchyma (r = 0.18, p = 0.40). Asbestos fibers in lung tissue were significantly longer (8.2 +/- 0.5 versus 4.8 +/- 0.6 microns; p < 0.001) but had the same width (0.12 +/- 0.27 versus 0.11 +/- 0.15 microns; p = 0.24) when compared with those retrieved by BAL from the airspace compartment. The aspect ratio (dividing fiber length by width) was much higher in lung tissue than in BAL fluid (66.4 +/- 0.4 versus 42.9 +/- 0.5; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adhesion molecules are involved in the recruitment of leucocytes to sites of inflammation. In this study, we determined the expression of several adhesion molecules on isolated human alveolar type II pneumonocytes. Type II pneumocytes were isolated from 10 normal lung specimens, by enzymatic digestion with dispase, followed by metrizamide gradient centrifugation and panning on immunoglobulin G (IgG)-coated plastic dishes. With the freshly isolated type II cells, immunostaining was performed using a sensitive immunoperoxidase slide technique. In all cases, 60-90% of type II cells were positive for intercellular adhesion molecule-1 (ICAM-1) (CD54). A minor portion of type II cells expressed the alpha 4 (CD49d) subunit of the beta 1-integrins, and the alpha-v (CD51) subunit of the vitronectin receptor. CD11a, CD11b, CD11c, CD18, CD49b, and CD49f failed to demonstrate any immunostaining with type II cells. In conclusion, the observation of the expression of ICAM-1 and, to a lesser degree, of some integrin subunits, may indicate that alveolar type II cells participate in local immune and inflammatory responses.
Bronchoalveolar lavage (BAL) is increasingly used in the assessment of pulmonary diseases in children. However, reference values for cellular and non-cellular constituents of BAL fluid in children are lacking. We have studied the differential cytology of BAL fluid in 48 children aged 3-16 years (mean age +/- SD 7.9 +/- 3.5 yrs) undergoing elective surgery for nonpulmonary illnesses. A flexible bronchoscope (Pentax 3.5 or 4.9 mm) was wedged in the middle lobe or one of its segments. BAL was performed with 3x1 ml-kg-1 body weight of normal saline warmed to body temperature. The first sample was studied separately; subsequent samples were pooled for analysis. The mean recovery was 58 +/- 15%. Significantly more granulocytes and less lymphocytes were found in the first, as compared to the pooled, sample. Total cell counts were highly variable and ranged from 0.5-57.1 x 10(4) ml-1. Macrophages were the predominant cell type, with a mean percentage of 81.2 +/- 12.7%. The relative proportion of lymphocytes was higher than that reported in most studies of adult volunteers (16.1 +/- 2.4%). No age dependency was observed for either cell type. The mean percentage of granulocytes was 2.5 +/- 3.3%. Absolute granulocyte counts were significantly higher in children under 8 yrs of age. This study provides the first reference data on BAL differential cytology in children without pulmonary disease and will be the basis for future investigations of BAL in paediatric lung diseases.
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