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U Costabel

Publications and source records attributed to U Costabel.

At least 55 records · Page 3Linked to original sources
PubMed2001

Calprotectin expression and mononuclear phagocyte subpopulations in peripheral blood and bronchoalveolar lavage.

BACKGROUND AND AIM OF THE WORK: The phenotype of human alveolar macrophages (AM) can be affected by the process of maturation/differentiation and by multiple factors from the local environment. The aim of our study was to assess the expression of selected phenotypic markers characteristic for subsets of mononuclear phagocytes in bronchoalveolar lavage fluid (BAL) and peripheral blood with special attention to calprotectin (27E10), a marker of acute inflammatory macrophages. METHODS: The expression of calprotectin and 13 other phenotypic markers was evaluated by an immunoperoxidase slide assay and computer image analysis. RESULTS: We consider calprotectin (27E10 antigen) to be a marker of freshly recruited, monocyte-like, mononuclear phagocytes, being expressed in 84 +/- 13% PBM and only 10 +/- 11% of AM, p < 0.001. Computer image analysis confirmed that calprotectin-positive mononuclear cells in peripheral blood and BAL are morphologically very similar in contrast to the much larger calprotectin-negative AM. On the other hand, 25F9 antigen, the transferrin receptor (CD71), KiM8 (CD68), RFD1 (marker of dendritic cells), RFD7 (marker of mature macrophages), RFD9 (marker of epithelioid cells and macrophages of germinal centers), and RM3/1 (macrophages of late phase inflammation) were restricted preferentially to mature AM. CONCLUSIONS: Our study demonstrates phenotypic differences between mononuclear phagocytes derived from BAL and their peripheral blood precursors, and indicates markers useful for assessing the stages of maturation/differentiation of these cells. The percentage of calprotectin (27E10) positive AM might represent a parameter for assessing mononuclear phagocyte influx from peripheral blood to the lung in the very early stage of inflammatory reactions.

Adult↗
PubMed2001

Interstitial lung diseases: an epidemiological overview.

Epidemiological studies on interstitial lung diseases (ILDs) may be schematically subdivided into the following major types: 1) quantifications of disease, broken down into incidence, prevalence and mortality data; 2) identification of aetiological factors; and 3) clinical epidemiological studies. Epidemiological data may be obtained from different sources or population groups, using different study designs such as systematic national statistics, population-based data and registries, and large case series of specific diseases. Differences in results between epidemiological studies may be due to real differences in incidence, but may also be due to changes in disease definitions and classifications, differences in the epidemiological design of the studies, or even registration bias. Comparative epidemiological data of different ILDs are almost limited to the general population study in Bernalillo County and to national mortality statistics, which should be interpreted with great caution. Also, some, mostly national registries of the different ILDs have been carried out by specific medical profession groups (especially pulmonologists), which clearly underestimate the real incidence of ILDs, but in which the comparison of the relative frequencies is probably accurate. Based on all these comparative studies, sarcoidosis and idiopathic pulmonary fibrosis appear to be the most frequent ILDs, followed by hypersensitivity pneumonitis and ILD in collagen vascular disease, when classical pneumoconioses are not included. There is also a relatively large group of nonspecific fibrosis. Much more data have been published on the epidemiology of specific forms of interstitial lung disease. Most information is available on the epidemiology of sarcoidosis, and those data are probably the most accurate. Data on idiopathic pulmonary fibrosis have the disadvantage of the recent changes in definition and classification of this disease. Hypersensitivity pneumonitis has been studied epidemiologically, especially in some exposure groups such as farmers and pigeon breeders, and in some regions in North America, UK, France and Scandinavia. Estimates of frequencies of interstitial lung disease in collagen vascular disease or of drug-induced interstitial lung disease are less accurate and more variable, depending on diagnostic criteria. Notwithstanding the aforementioned problems, this report tries to provide a balanced overview of the epidemiology of different interstitial lung diseases.

Humans↗
PubMed2001

Sarcoidosis: clinical update.

Many advances have been made regarding sarcoidosis in the past 2 decades. As a result, sarcoidosis is now defined as a multisystem disorder with a heightened cellular immune response at sites of disease activity in patients with a predisposition for sarcoidosis and a presumed exposure to as yet unknown transmissible environmental agents. Recent International Consensus Statement recommendations regarding diagnosis and therapy have been published. The diagnosis of sarcoidosis is based on a compatible clinical and/or radiological picture, histological evidence of noncaseating granulomas and exclusion of other diseases capable of producing a similar histological or clinical picture. Therapy is based on corticosteroids, although there are indications of valuable alternatives. Except for life- and sight-threatening organ involvement, it should be carefully considered whether the patient might benefit from treatment. For asymptomatic pulmonary sarcoidosis, a watch and wait approach is appropriate; treatment should mainly be considered if symptoms develop or lung function deteriorates.

Europe↗
PubMed1999

[Hepatopulmonary syndrome].

ANAMNESIS: We report about a 60-year-old woman with hepatopulmonary syndrome. The patient suffered from progressive dyspnea and liver cirrhosis following viral hepatitis C, acquired through blood transfusion 30 years ago. EXAMINATION RESULTS: Remarkable were clinical signs of chronic liver disease (cutaneous spider naevi, palmar erythema) and signs of chronic respiratory failure (clubbing) with platypnea. Arterial pO2 was 33 mm Hg under 41 O2/min nasal oxygen supplement and improved to 74 mm Hg under 81 O2/min. Arterial pO2 deteriorated in upright position (orthodeoxia). Contrast enhanced two-dimensional transthoracic echocardiography showed a delayed microbubble opacification in the left heart chambers (without atrial or ventricular septal defect), suggesting pulmonary vascular dilatations. Perfusion scan with macroaggregated albumin labelled with technetium-99m showed uptake over thyroid, kidneys, liver, and spleen suggesting an abnormal passage through the pulmonary vascular bed. The radiological examination with chest radiography and high resolution computer tomography revealed no signs of interstitial lung disease. The pulmonary artery angiography showed neither anatomical shunts nor malformations. DIAGNOSIS: The final diagnosis was hepatopulmonary syndrome Type 1. TREATMENT/FOLLOW-UP: The patient underwent liver transplantation with following good function of the liver graft. After 6 months the patient presented in a much better general condition, but with persisting severe hypoxemia whereas the spider naevi disappeared completely. One year after the liver transplantation in the perfusion scan the uptake over thyroid, kidneys, liver, and spleen was absent. The orthodeoxia and hypoxemia improved evidently. From that we conclude that the pulmonary vascular dilatations diminished after liver transplantation.

Diagnosis, Differential↗
PubMed1999

[Diffuse panbronchiolitis. A rare differential diagnosis of chronic obstructive lung disease].

HISTORY AND ADMISSION FINDINGS: A 36-year-old Korean had since childhood suffered from a chronic progressive lung disease, marked by dyspnoea, productive cough and recurrent sinusitis. He was in a reduced general condition on admission. There were hyperresonant sounds on palpation over both lungs, a low diaphragm and slight vesicular breath sound as well as occasional rales and sibilant rhonchi. INVESTIGATIONS: Laboratory tests showed increased blood cell sedimentation of 52 mm at 1 h, leukocytosis of 24.3/nl, and a raised cold-agglutinin titre. Haemophilus influenza and Pseudomonas aerogenes were cultured from the bronchial secretion. Lung function tests revealed severe obstruction with hyperinflation and partial respiratory failure with a much reduced 1-sec forced expiratory volume (FEV1) of 0.71, 19% of normal; residual volume (RV) 6.61, 550% of normal; arterial oxygen partial pressure 61 mm Hg; arterial CO2 partial pressure 36 mm Hg. Chest X-ray showed emphysematous changes with diffuse small nodular shadows. Bronchoalveolar lavage revealed 96% neutrophils, indicating marked granulocytic inflammation. A video-assisted thoracoscopic biopsy was performed which showed diffuse panbronchiolitis. TREATMENT AND COURSE: The symptoms, radiological changes and lung functions clearly improved under long-term treatment with 500 mg erythromycin daily. CONCLUSION: Diffuse bronchiolitis is rarely seen outside of Asia, but it should be included in the differential diagnosis because, in contrast to other forms of chronic obstructive lung disease, it responds to long-term erythromycin medication.

Adult↗
PubMed1999

Elevated levels of soluble TNF receptors in bronchoalveolar lavage fluid in extrinsic allergic alveolitis.

BACKGROUND: Soluble TNF receptors (sTNFR1 and sTNFR2) are inhibitors of TNF and can block TNF bioactivity. TNF plays an important role in the development of extrinsic allergic alveolitis (EAA). OBJECTIVE: To evaluate whether sTNFR1 and sTNFR2 are locally increased in EAA. METHODS: We measured sTNFR1 and sTNFR2 in bronchoalveolar lavage fluid (BALF) and serum from nine EAA patients and 11 control subjects using an ELISA method. RESULTS: BALF sTNFR1 and sTNFR2 levels were 0.24+/- 0.04 ng/mL and 0.59+/-0.16 ng/mL in EAA patients, and thus significantly elevated in comparison with the controls (0.13+/-0.02 ng/mL and 0.08+/-0.04 ng/mL, both P<0.05). Serum sTNFR levels were not significantly different between the two groups. Both sTNFR1 and sTNFR2 concentrations in BALF correlated significantly with the lymphocyte percentage of BALF (r = 0.57 and 0.81, respectively). CONCLUSION: The two alveolar sTNFRs, particularly sTNFR2, may be involved in the pathogenesis of EAA as counter-regulators of TNF.

Aged↗
PubMed1999

Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages.

Tumor necrosis factor-alpha (TNF-alpha) is an important proinflammatory cytokine. Recently, pentoxifylline (POF) has been shown to suppress the synthesis of TNF-alpha from lipopolysaccharide (LPS)-stimulated human monocytes in cell cultures and in vivo. The aim of this study was to investigate whether POF-induced suppression of TNF-alpha secretion affects peripheral blood monocytes (PBM) and alveolar macrophages (AM) equally, and whether POF is able to suppress the spontaneous TNF-alpha production from AM in pulmonary sarcoidosis in vitro. In seven patients without interstitial lung disease we studied the effect of POF on LPS-stimulated PBM and AM cultured for 24 h. In six patients with sarcoidosis we investigated the effect of POF on the enhanced spontaneous TNF-alpha production by AM in vitro. POF induced a dose-dependent suppression of the LPS-stimulated TNF-alpha production which was not different for PBM and AM, respectively. In sarcoidosis, POF inhibited the spontaneous TNF-alpha production of AM at 0.1 mM by 91% and at 1 mM by 98%. In conclusion, POF inhibits LPS-induced TNF-alpha production from PBM and AM to a similar extent and can also inhibit the exaggerated spontaneous TNF-alpha production from AM in sarcoidosis in vitro. This may be the basis for further clinical trials to evaluate POF as an immunotherapeutic agent in sarcoidosis.

Adult↗
PubMed1999

Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis.

The Fas receptor (FasR) and the tumour necrosis factor (TNF) receptor 55/60 kDa (TNFR1) are recognized as apoptosis signalling receptors. They are known to be expressed by lymphocytes in association with immune regulation and immunological disorders. This study aimed to investigate the expression of FasR and TNFR1 by alveolar macrophages (AM) in patients with sarcoidosis. Bronchoalveolar lavage (BAL) was performed in 12 patients with active sarcoidosis and 11 control subjects. BAL cells were characterized by monoclonal antibodies using a peroxidase-antiperoxidase method. Both FasR and TNFR1 were expressed on a higher percentage of AM in sarcoidosis with respect to control subjects (mean +/-sem 40.8+/-3.1% versus 14.9+/-1.7%, p<0.001 and 61.9+/-3.3% versus 23.1+/-4.1%, p<0.001, respectively). There was a close relationship between the expression of FasR and TNFR1 on AM (r = 0.86, p<0.001). The percentages of FasR+ AM and TNFR1+ AM were in direct proportion to the percentage of BAL lymphocytes (r = 0.75 and 0.84), the CD4/CD8 ratio (r = 0.78 and 0.78), and the percentage of the CD14+ AM subset (r = 0.77 and 0.87), p<0.001 for all correlations. This study indicates that alveolar macrophages expressing apoptotic receptors are increased in patients with active sarcoidosis. Further studies are required to determine whether these alveolar macrophages from patients with sarcoidosis undergo apoptosis more readily than those from control subjects.

Adult↗
PubMed1999

Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen.

In a few patients with chronic sarcoidosis, prolonged, unacceptably high doses of corticosteroids are required to achieve symptomatic relief. In these cases, a corticosteroid-sparing drug might be administered to allow long-term treatment without the adverse effects of corticosteroids. This study examines azathioprine as a prednisolone-sparing treatment. In an open study, the course of 11 patients with chronic sarcoidosis was analysed. In an induction phase, 2 mg azathioprine x kg body weight (BW)(-1) x day(-1) in combination with 0.6-0.8 mg prednisolone x kg BW(-1) x day(-1) were administered with prednisolone being reduced to 0.1 mg x kg BW(-1) x day(-1) within 2-3 months. This was followed by a 21-22-month maintenance phase with 2 mg azathioprine x kg BW(-1) x day(-1) and 0.1 mg prednisolone x kg BW(-1) day(-1). Clinical parameters and immunological findings of bronchoalveolar lavage (BAL) were analysed. All patients had significant symptomatic relief and improvements or resolutions of physiological, serological and radiographic findings without suffering from serious adverse effects. Nine of 11 patients completed therapy after 19-26 months, and 2/11 patients terminated therapy after 8 and 12 months, respectively. Eight patients had remissions lasting 4-73 months. Three relapses occurred after 8, 18, and 22 months. During the induction phase, BAL cell composition changed and their activity in terms of cytokine release was suppressed. This preliminary study suggests that azathioprine may be effective as a corticosteroid-sparing agent in long-term therapy of sarcoidosis, but a much larger study is necessary to give the definitive answer.

Adult↗
PubMed1998

[Bronchoalveolar lavage in the diagnosis of diffuse interstitial lung disease].

Since the introduction of bronchoalveolar lavage (BAL), this technique is used both clinically and for research. Use of BAL as a diagnostic aid was introduced fairly recently. For the different steps of the procedure a standardized approach has been proposed. Analysis of BAL fluid includes determination of the total number of cells, of the differentiation and of non-cellular components, as well as various staining and culturing methods. The analysis may be useful in the diagnosis of interstitial pulmonary diseases and opportunistic infections. Smoking and pharmacotherapy affect the results of the analysis. BAL is a safe procedure with hardly any side effects. This method may in some diseases replace more invasive diagnostic procedures such as biopsy by demonstrating characteristic cells or micro-organisms.

Bronchoalveolar Lavage↗
PubMed1998

Sarcoidosis news: immunologic frontiers for new immunosuppressive strategies.

Although the etiology of sarcoidosis is still unknown, it is now clear that the formation of the sarcoid granuloma is keenly regulated by a cascade of cytokines. Furthermore, several experimental data indicate a direct association between the release of cytokines and the development of lung fibrosis. In a recent meeting over 300 investigators convened to assess current knowledge in the field of sarcoidosis, vasculitis, and diffuse lung diseases. The meeting provided an overview on the complex networks between immunocompetent cells, cytokines, and mesenchymal cells setting the stage for the pathogenesis of granulomatous and vasculitic disorders. However, emphasis was given to the possibility of using innovative immunotherapies to target relevant cytokines or molecules involved in granuloma formation and the remodelling of lung tissue.

Adjuvants, Immunologic↗
PubMed1998

Alveolo-capillary protein permeability and lung function in patients with late pulmonary complications after allogeneic bone marrow transplantation.

A prospective study was performed to identify markers predictive for the development of pulmonary complications in the early (<50 days) and late (>50 days) phase after bone marrow transplantation (BMT). The characterization of BMT patients with early or late pulmonary complications revealed clear-cut differences. Early and long term increase of alveolo-capillary protein permeability was associated with smoking and was found in 20 patients developing pulmonary complications within 50 days after BMT (group 1). The 22 patients who developed such complications thereafter (group 2) had more acute graft vs host disease than 66 patients who remained free of these complications for a minimum of 1 year. Concentrations of bronchoalveolar lavage (BAL) fluid albumin (alb) and serum beta2-microglobulin (S-beta2m) were determined 10 days before BMT, on days 1, 30, and 40 after BMT, whereas lung function tests were performed before BMT, after discharge from the hospital, and 6 months as well 1 year after BMT. Using cut-off values for BAL fluid alb (>2.3 mg/dl) and S-beta2m (>0.8 mg/liter) we could significantly discriminate 12 patients out of 19 group 1 patients (early pulmonary complications) as well as 9 out of 21 group 2 patients (late pulmonary complications) from 12 out of 64 group 3 patients (without such complications) 1 day after BMT. Our results demonstrate that early increased alveolo-capillary protein permeability defines a patient population at risk to develop pulmonary complications later than 50 days after BMT with up to 1 year significantly decreased lung volumes (FEV1, 73% predicted, VC, 85% predicted).

Adolescent↗