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Biomedical subjects

U Costabel

Publications and source records attributed to U Costabel.

At least 73 records · Page 4Linked to original sources

Different expression of integrins by mononuclear phagocytes in peripheral blood and bronchoalveolar lavage fluid.

Alveolar macrophages (AM) originate from blood monocytes and, during the maturation process, undergo functional and morphological changes which are also reflected in their phenotypic pattern. Among the macrophage membrane antigens, adhesion molecules of the integrin family are particularly important for effector functions and cell-cell interactions. The aim of this study was to analyse the membrane expression of selected integrins by AM recovered from bronchoalveolar lavage (BAL) as compared to their precursors, peripheral blood monocytes (PBM). The cells were stained using a sensitive immunoperoxidase assay with 10 different monoclonal antibodies. The data showed a higher expression by AM than PBM of all but one of the studied adhesion molecules. The only exception was CD11b (Mac-1, CR3) which showed a higher expression in PBM than in AM. Several molecules, for example, CD49d (VLA-4), CD51 (vitronectin receptor), and CD54 (intercellular adhesion molecule-1, ICAM-1) were found to be upregulated by AM in patients with a lymphocytic pattern of BAL. In contrast, the phenotype of PBM does not show any changes in these patients. In conclusion, we have demonstrated differences in the expression of integrins between AM and PBM which can be partially responsible for some of their functional differences.

Adult↗

Acute allergic reaction and demonstration of specific IgE antibodies against alpha-1-protease inhibitor.

A 44 yr-old female with severe pulmonary emphysema and reduced alpha-1-protease inhibitor (alpha1-PI) serum levels developed an acute anaphylactic reaction following the third intravenous infusion of human alpha1-PI which was administered to prevent the progression of pulmonary emphysema. Specific immunoglobulin E-antibodies against human alpha1-PI could be demonstrated in the patient's serum using an enzyme allergosorbent test. Because of the risk of further severe anaphylactic reaction, the replacement therapy with alpha1-PI was discontinued. Physicians should be aware of this rare complication.

Adult↗

Clinical findings in 715 patients with newly detected pulmonary sarcoidosis--results of a cooperative study in former West Germany and Switzerland. WATL Study Group. Wissenschaftliche Arbeitsgemeinschaft für die Therapie von Lungenkrankheitan.

BACKGROUND AND AIM OF WORK: Clinical appearance of sarcoidosis depends on the methods of case finding and geographical factors. In a further effort to clarify clinical characteristics of pulmonary sarcoidosis, we examined a larger population of consecutive pulmonary sarcoidosis cases throughout former West Germany and Switzerland. METHODS: In a prospective multicenter study from January 1982 to December 1984, 715 patients with newly-diagnosed pulmonary sarcoidosis were studied for their clinical appearance, roentgenological and laboratory findings and pulmonary function. RESULTS: The group consisted of 366 male and 349 female patients with a median age of 33 years (range 14 to 76). 35% presented with roentgenological stage I disease, 51% with stage II and 14% with stage III. Extrapulmonary manifestations were found in 16%. Angiotensin converting enzyme was elevated in 62% of the cases. Lung function tests revealed a restrictive pattern in 19% and airway obstruction in 4%; 2% showed a combined ventilation disturbance. 66% of our patients were symptomatic in contrast to reports from former East Germany, a country with mass X-ray screening where only 18 to 35% of the patients presented with symptoms and 51 to 74% were in stage I. CONCLUSIONS: Differences between our findings and data from East Germany underline the importance of case finding methods for the patterns of clinical appearance of sarcoidosis.

Adolescent↗

Biochemical changes in sarcoidosis.

Biochemical markers in sarcoidosis are closely related to the immunological events and the activity of inflammatory effector cells at sites of granuloma formation. The markers can be measured in serum, then reflecting whole body concentration, or in BAL fluid, then indicating activity in the lung. Only calcium and ACE serum levels have gained a proven value in the clinical field.

Biomarkers↗

Smoker's lung transplanted to a nonsmoker. Long-term detection of smoker's macrophages.

Alveolar macrophages (AM) from smokers contain characteristic smoker's inclusion bodies within the cytoplasm as a result of ingestion of substances in the inhaled smoke. How long these smoking-related changes in the AM population can be seen after smoking cessation is largely unknown. We had the unique opportunity to investigate a 51-yr-old never-smoker after single lung transplantation (TX) for alpha 1-antitrypsin deficiency emphysema who received a donor's lung from a heavy cigarette smoker. Serial bronchoalveolar lavage (BAL) was performed in the donor's lung for transplant surveillance at defined time intervals, and the percentage of AM with characteristic smoker's inclusions was counted on slides stained with May-Grünwald-Giemsa stain. The patient had an uneventful course after TX with no major infectious complications or episodes of rejection. One month after TX the percentage of smoker's AM was 98%. BAL after 2, 5, 7, and 12 mo showed a similar high percentage. After 18 mo a first a decrease was seen, down to 78%, and after 2 yr a decrease to 59% was seen. After 3 yr, the smoker's AM had mostly disappeared, only 3% were still present. In conclusion, smoker's inclusions in AM may be detected for at least 2 yr after smoking has ceased, which is considerably longer than the estimated life span of the AM.

Bronchoalveolar Lavage Fluid↗

[Bronchoalveolar lavage in childhood: technical aspects and reference values].

(BAL) has been increasingly used in recent years also in children. In paediatric pulmonary diseases, however, interpretation has proved difficult in the absence of standard reference values for BAL in childhood. It is the purpose of the present publication to discuss the methodological aspects of BAL in childhood and to proviced criteria by means of standard reference values for the assessment of BAL in paediatric patients. In a group of 50 children aged 3 to 15 years with healthy lungs, who were subjected to BAL during an elective surgical intervention, we examined both cellular and non-cellular components of the BAL. Whereas the percentage of macrophages and lymphocytes in the total population did not differ significantly from the standard values in adults, the absolute and relative granulocyte count was found to be elevated in children under 8 years of age. The CD4/CD8 quotient of BAL was 0.7 on the average, and hence clearly below the standard reference values defined for adults. In the non-cellular components we found an increase in the level of all proteins from plasma, whereas locally produced proteins did not differ from the findings in healthy adults. The total phospholipid content of BAL was markedly enhanced in children below 8 years of age and decreased with increasing age. These differences between children and adults should be taken into account when interpreting pathological findings. They are the basis for better defining the ranking of BAL in paediatric pulmonary diseases.

Adolescent↗

[Functional results of surgical lung volume reduction in severe pulmonary edema].

BASIC PROBLEM AND OBJECTIVE OF THE STUDY: Lung volume reduction (LVR) is a new surgical approach designed to relieve shortness of breath and improve exercise tolerance in patients with severe lung emphysema. The aim of this study was to analyse changes of lung function, gas exchange, exercise tolerance and degree of dyspnoea one and 3 months after LVR. PATIENTS AND METHODS: Seventeen patients (15 men and two women; mean age 53 [38-68] years) with severe emphysema (six with alpha 1-PI deficiency) underwent unilateral (n = 14) or bilateral (n = 3) LVR surgery. One week before and one and 3 months after surgery pulmonary function tests, arterial blood gas analysis at rest breathing room air, 6-minute walking distance and dyspnoea score (Medical Research Council Scale) were determined. RESULTS: There was a significant increase in forced expiratory vital capacity after one second (FEV1, P < 0.001), and a significant decrease in total lung capacity (TLC, P < 0.0001) and residual volume (RV, P < 0.0001). The mean increase in FEV1 was 39% and in PaO2 9%. The mean decrease in TLC was 20%, in RV 26% (P < 0.001; both comparisons), and in paCO2 4% (not significant). The mean 6-minute walking distance increased by 96% from 229 to 405 meters (P < 0.0001). The mean dyspnoea score on a five point scale (0-4 points) decreased by 52% from 3.4 to 1.6. With the exception of the improved inspiratory vital capacity the postoperative results at one and 3 months after LVR did not differ significantly. All patients were alive 3 months postoperatively. CONCLUSIONS: In patients with severe emphysema surgical LVR shows significantly improved pulmonary function, gas exchange, dyspnoea and walking distance as assessed one and three months postoperatively. The early mortality seems to be low.

Acute Disease↗

Differential cytology of bronchoalveolar lavage fluid in immunosuppressed children with pulmonary infiltrates.

OBJECTIVE: Bronchoalveolar lavage (BAL) is a well established technique for the detection of pathogens in immunosuppressed children, but its diagnostic yield is variable. The aim of this study was to investigate whether BAL differential cell counts are helpful in the evaluation of pulmonary infiltrates in immunocompromised children. STUDY DESIGN: BAL was performed 28 times in 27 febrile immunocompromised children with pulmonary infiltrates. All patients were pretreated with broad spectrum antibiotics; 11 children also received amphotericin B. BAL was conducted with a flexible bronchoscope wedged in the area of maximal pathology as suggested by the chest radiograph or in the middle lobe in patients with diffuse interstitial radiographic changes. Differential cell counts were performed from cell smears obtained after centrifugation of BAL fluid. RESULTS: Bacterial or fungal organisms were detected in BAL fluid of 12 patients. Patients with bacterial or fungal infections (group 1) had a significantly higher percentage of granulocytes in BAL fluid both compared with patients with sterile BAL cultures (group 2) and with a control group of children without pulmonary disease (p < 0.001, Wilcoxon test). The proportion of lymphocytes was not different from the control group in group 1 but significantly increased in group 2 (p < 0.001, Wilcoxon test). Blood differential cell counts were not different in the two patient groups. Lymphocyte subsets of BAL fluid obtained in a subgroup of patients were not significantly different from controls. CONCLUSION: These data suggest that BAL differential cell counts may be a useful adjunct in the differential diagnosis of pulmonary infection in immunocompromised children.

Adolescent↗

Oxidized BAL fluid proteins in patients with interstitial lung diseases.

Oxygen-derived free radicals, released by phagocytic cells, have been postulated to contribute to lung tissue damage. We therefore investigated oxidative damage to proteins from bronchoalveolar lavage fluid (BALF) as an indicator of oxidative stress and to assess antioxidant defences in the lungs. We examined BAL fluids from patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF, nonsmokers (NS) and smokers (S)), sarcoidosis (SARC, nonsmokers), and asbestosis (ASB, ex-smokers (EXS)). The oxidation of BALF proteins is accompanied by the introduction of carbonyl groups into their amino acid side-chains and can be quantitated by labeling these groups with tritiated borohydride. The total lung content of oxidized proteins recovered by bronchoalveolar lavage (BAL) was 0.3 +/- 0.07 nmol carbonyl.mL-1 BALF (mean +/- SEM) in the NS control group (n = 9) and tended to be increased, in the asymptomatic S group (n = 8; 0.59 +/- 0.14 nmol.mL-1). This parameter was significantly elevated both in IPF-NS (n = 14; 0.84 +/- 0.2 nmol carbonyl.mL-1 BALF) and SARC-NS (n = 15; 0.73 +/- 0.16 nmol.mL-1) as compared with the NS control. On the contrary, in smoking patients with IPF (n = 6; 0.41 +/- 0.1 nmol carbonyl.mL-1 BALF) and also in ASB-EXS (n = 6; 0.37 +/- 0.06 nmol.mL-1) it was not different from NS controls. The total amount of oxidized proteins correlated positively with the absolute number of eosinophils (EOS) in IPF-NS, IPF-S and SARC, and also with absolute polymorphonuclear neutrophil (PMN) numbers in IPF-NS and IPF-S. In conclusion, oxidative damage of BALF proteins occurred in nonsmoking patients with IPF and SARC. The amount of oxidized bronchoalveolar lavage fluid protein may provide a quantitative assessment of oxygen burden, a balance between oxidant stress and antioxidant defences.

Adult↗

Age-dependency of surfactant phospholipids and surfactant protein A in bronchoalveolar lavage fluid of children without bronchopulmonary disease.

Whilst alterations in surfactant components of bronchoalveolar lavage fluid (BALF) have been described in a variety of pulmonary diseases in adults, no information is available on the surfactant composition in children beyond the neonatal period. In order to obtain reference values for the paediatric age group, we have studied phospholipid profiles of BALF in children without pulmonary disease. The study population consisted of 38 children aged 3-15 yrs (mean +/- SD 8 +/- 4 yrs) undergoing elective surgery for nonpulmonary illnesses. Surfactant composition was analysed by high pressure liquid chromatography using both an ultraviolet and a light-scattering detector. Total phospholipid concentration was higher in children under 8 yrs of age and decreased with age. In contrast, the total protein concentration remained constant throughout the age range. No age-related changes in the relative composition of phospholipid fractions could be observed. Surfactant protein A concentrations were highly variable in all age groups. This study provides the first data on surfactant components in bronchoalveolar lavage fluid of healthy children and will be the basis for future studies of children with pulmonary diseases.

Adolescent↗

Preparation of bronchoalveolar lavage fluid with microscope slide smears.

The method of preparation of bronchoalveolar lavage fluid (BALF) for cytological examination can significantly affect the results of cellular quantitation. Investigations have shown that cytocentrifugation leads to an underestimation of the number of lymphocytes and membrane filter preparation to an underestimation of the number of neutrophils. As a simple alternative to these two techniques, BALF cells could be prepared by the microscope slide smear technique, which is familiar as the means for preparing peripheral blood for differential counts. In order to compare cell differentials determined by microscope slide technique with differentials resulting from cytocentrifugation, cells were isolated from 35 BALF samples using standard methods, and counted using a haematocytometer. Forty thousand cells in 200 microL were prepared by cytocentrifugation (3 min, 57 x g; Cytospin 2) and 5 x 10(5) cells in 5 microL by microscope slide smear. Both samples were air-dried, stained using May-Grünwald Giemsa stain, and 600 cells were counted to obtain differentials. To test the adequacy of sampling by the microscope slide smear technique, known quantities of lymphocytes or neutrophils were added to fixed numbers of BALF cells, microscope slide smears prepared, and differentials determined on 600 cells. The resulting differentials were compared to the calculated differentials. Preparation of BALF cells with the microscope slide smear technique yielded well-preserved cell morphology. Compared to cytocentrifugation, microscope slide smear preparations had significantly higher percentages of lymphocytes. The microscope slide smears for the samples with predetermined numbers of cells yielded lymphocyte and neutrophil percentages which did not differ from the calculated differentials (59.6 +/- 1.5 vs 59.6 +/- 5.2% and 54.6 +/- 6.0 vs 53.1 +/- 6.0%, respectively). Varying the number of cells counted from 100 to 800 confirmed the reproducibility of the counts for counting 600 cells. Using 5 x 10(5), 2.5 x 10(5), or 1 x 10(5) cells per preparation demonstrated that adequate specimens could be obtained from as few as 1 x 10(5) cells. Thus, microscope slide smear preparation is a simple and accurate method for the quantitation of bronchoalveolar lavage fluid cytology.

Analysis of Variance↗

Relevance of asbestos bodies in sputum.

The presence of asbestos bodies (ABs) in sputum specimens of individuals with occupational asbestos exposure has been well-documented. The aim of this study was to determine their clinical relevance in comparison to the concentration of AB in bronchoalveolar lavage (BAL) and lung tissue. Subjects were included following a well-documented exposure of asbestos history (n = 93) or BAL fluid analysis positive for ABs (n = 42). The subjects with a well documented history of AB exposure were divided into three groups: heavy (Group 1, n = 29); moderate (Group 2, n = 31); or occasional exposure (Group 3, n = 33). BAL fluid was available from all subjects, and lung tissue from 21 subjects. To assess the variability, 10 sputum positive subjects collected subsequent sputum on days 2, 7, 14, 30 and 90. ABs were determined by light microscopy after membrane filtration of specimen digests. The mean sputum AB content was highest in Group 1 (2.4 +/- 5.5 AB.mL-1), lower in Group 2 (0.2 +/- 0.3 AB.mL-1) and lowest in Group 3 (0.1 +/- 0.1 AB.mL-1) suggesting a correlation with cumulative exposure. However, many negative sputum samples were noted, when BAL specimens were positive. The AB content of sputum and BAL specimens did not correlate. ABs were found in sputum of all subjects with a tissue content of > 1,000 AB-cm-3, but in none with contents of < 1,000 AB-cm-3. Substantial variability of ABs was found in the five sequentially collected sputa of 10 initially positive patients (coefficient of variation 28-93%), but only two false negatives were found in these 50 samples. Thus, sputum analysis for asbestos bodies is an insensitive method for assessing the lung asbestos burden, much less sensitive than bronchoalveolar lavage fluid analysis. However, a sputum sample positive for asbestos bodies is suggestive of a high lung asbestos burden.

Aged↗

Feather wreath lung: chasing a dead bird.

We report the case of a 50 year old clerk with chronic extrinsic allergic alveolitis due to a wreath of feathers from his dead budgerigar hanging in his living-room. Diagnosis was confirmed by serum precipitins, bronchoalveolar lavage and open lung biopsy. It is important to recognize unusual sources of exposure in this disease.

Alveolitis, Extrinsic Allergic↗

Effect of surgical lung volume reduction on respiratory muscle function in pulmonary emphysema.

Lung volume reduction surgery (LVRS) in patients with severe lung emphysema restores the thoracic configuration to a more normal functional capacity. The aim of this study was to investigate whether reduction in intrathoracic volume by LVRS improves the inspiratory muscle force generation of the respiratory pump. Pulmonary function tests, maximal inspiratory mouth pressure (MIP), sniff nasal inspiratory pressure (SNIP), sniff transdiaphragmatic pressure (Pdi), and inspiratory mouth occlusion pressure (P0.1) were measured in 17 emphysematous patients (mean (+/- SEM) age 53 +/- 2 yrs) before and 1 month after LVRS. The mean value of forced expiratory volume in one second (FEV1) increased (0.82 +/- 0.07 vs 1.12 +/- 0.08 L; p < 0.0001), whilst there was a decrease (p < 0.0001) in residual volume (RV) (337 +/- 31 vs 250 +/- 21 % of predicted), functional residual capacity (FRC) (210 +/- 9 vs 159 +/- 9% pred), and total lung capacity (TLC) (138 +/- 6 vs 110 +/- 5% pred). The mean value of MIP increased by 52% from 4.8 +/- 0.4 to 7.3 +/- 0.6 kPa (p < 0.001), the mean value of SNIP increased by 66% from 3.9 +/- 0.4 to 6.5 +/- 0.5 kPa (p < 0.001), and the mean value of Pdi increased by 28% from 6.0 +/- 0.6 to 7.7 +/- 0.8 kPa (p < 0.05) after LVRS. P0.1 decreased on average by 24% from 0.46 +/- 0.03 to 0.35 +/- 0.02 kPa after LVRS. No significant correlations were found between inspiratory muscle (MIP, SNIP, Pdi) and respiratory drive (P0.1) indices, lung function data, 6 min walk distance, or dyspnoea score. In conclusion, the observed clinical improvement of patients with severe emphysema after lung volume reduction surgery results, in part, from an increased ability of the inspiratory muscles to generate force, which is paralleled by a significant decrease in central respiratory drive.

Adult↗