Telomerase activity in transthoracic fine needle biopsy aspirates as a marker of peripheral lung cancer.

BACKGROUND: A study was undertaken to evaluate the usefulness of telomerase activity assay in transthoracic fine needle biopsy (TFNB) aspirates collected from peripheral tumours of the lung in predicting the malignant aetiology of lung infiltrations. METHODS: 100 patients with a peripheral infiltration of the lung underwent TFNB of the focal lesion. The aspirates were subjected to standard cytological evaluation. Telomerase activity in the specimens was determined with the PCR-ELISA PLUS method. The sensitivity, specificity, accuracy and predictive value of TFNB were calculated for cytological examination of aspirates alone and cytological examination with additional telomerase activity assessment. RESULTS: Lung cancer was newly diagnosed in 84 subjects and benign peripheral lesions were found in 16. During the first TFNB, lung cancer was identified in 56 cases of cancer (66.7%) while increased telomerase activity was found in 61 cancer aspirates (72.6%). No subject with a benign infiltration had a false positive result from cytological examination, but in one case (6.25%) increased telomerase activity was observed. The diagnostic sensitivity, accuracy and negative predictive value of the combination of cytological examination and telomerase activity assay in TFNB specimens were significantly higher than for cytological examination alone (89.3% vs 66.7%, p = 0.0004; 90% vs 72%, p = 0.001; 62.5% vs 36.4%, p = 0.039), but a combination of the two examinations was associated with a lower specificity of TFNB (96.9% vs 100%, p = 0.002). CONCLUSION: Detection of telomerase activity in aspirates taken during TFNB of a peripheral lung infiltration should be considered as an indication of the risk of malignancy in cases with false negative cytological results.

Influence of age and gender on serum eotaxin concentration in healthy and allergic people.

BACKGROUND: Eotaxin is one of the important chemokines that modulate allergic inflammation. In many studies a correlation between an elevated serum concentration of eotaxin, allergen exposure and allergic symptoms has been confirmed. Influence of other factors on eotaxin concentration is feebly recognized. We made an attempt to assess the influence of age and gender on the serum eotaxin level in healthy people and in patients with intermittent IgE-mediated rhinoconjunctivitis (AR). METHODS: The serum eotaxin level was measured in 245 healthy people and 241 patients with AR before the pollen season with the ELISA technique (KITS, R&D USA, pg/ml). The parametric tests and linear regression analysis were used in statistical calculations. RESULTS: There were no differences between the allergic group and the healthy one in the mean age (accordingly: 31.3 +/- 11.6 yrs. vs. 31.6 +/- 12.5 yrs.; p=0.1) and the mean serum eotaxin content (118.1 +/- 44.9 pg/ml vs. 116.3 +/- 34.8 pg/ml; p=0.3). A significant relationship between the serum eotaxin level, gender and age was revealed in both groups and regression models were derived. A linear correlation between age (semi-partial correlation beta = 0.47, p = 0.0000001) and gender (semi-partial correlation beta = 0.3, p = 0.0000001), on the one side, and the serum eotaxin level, on the other, was found for the allergic people. In the control group a similar relationship between the serum eotaxin level and age (semi-partial correlation coefficient beta = 0.63, p = 0.0000001) and gender (semi-partial correlation factor beta = 0.23, p = 0.000006) was observed. CONCLUSIONS: Age and sex significantly influence the serum eotaxin content in healthy people and patients with IgE-mediated rhinoconjunctivitis.

Monocyte chemotactic and activating factor/monocyte chemoattractant protein (MCAF/MCP-1) in bronchoalveolar lavage fluid from patients with atopic asthma and chronic bronchitis.

Monocyte chemotactic and activating factor/monocyte chemoattractant protein (MCAF/MCP-1) is a member of the beta (C-C) subfamily of chemokines. The biological roles played by MCAF/MCP-1 in a number of inflammatory and noninflammatory diseases states is not well known. Several studies have confirmed that inflammation is present in the airways of subjects with atopic asthma and with chronic bronchitis. Analysis of bronchoalveolar lavage fluid (BALF) is an effective method of sampling lower respiratory tract inflammation. The aim of this study was to examine associations among MCAF/MCP-1, BALF cells and spirometry parameters and bronchial hyperresponsiveness in patients with atopic asthma and chronic bronchitis. Twenty patients with atopic asthma, 10 patients with chronic bronchitis and 10 patients of the control group, took part in this study. An ELISA test was used to assess MCAF/MCP-1 in BALF. The levels of MCAF/ MCP-1 (mean +/- SEM) were 150 +/- 18.6 pg/ml in patients with atopic asthma, 320 +/- 39.7 pg/ml in chronic bronchitis and 74.9 +/- 3.3 pg/ml in the control group (p < 0.05). When all patients with disease were considered, there was negative correlation with FEF50 (Kendall's correlation coefficient = - 0.4; p < 0.01). Regression analysis has shown that a level of MCAF/MCP-1 over 100 pg/ml was correlated with duration of illness (Pearson's correlation coefficient = 0.7; p < 0.02). In conclusion, MCAF/MCP-1 probably possesses proinflammatory properties in atopic asthma and chronic bronchitis. The elevated level of this chemokine may support the clinical suspicion of specific diagnosis.

[Comparison evaluation of cost-effectiveness in bronchial asthma patients]. / Porównawcza ocena skutecznosci i kosztów leczenia chorych na astme oskrzelowa.

A choice of a proper drug and method for clinically successful therapy in patients with bronchial asthma has to be based on results of experimental and clinical studies and cost analysis. Some problems connected with cost-effectiveness analysis are presented in relation to glucocorticosteroids, agonist of beta2-adrenoreceptors and allergen-specific immunotherapy.

[The effect of bronchial inhalation provocation tests on levels of interleukin-8 in material from broncho-alveolar fluid of patients with atopic bronchial asthma]. / Wplyw wziewnych prób prowokacji oskrzeli na stezenie interleukiny-8 w materiale z plukania oskrzelowo-pecherzykowego u chorych na atopowa astme oskrzelowa.

Airway inflammation is a very important feature of asthma and occurs simultaneously with increased hyperreactivity. We have examined whether the local inflammation provoked by histamine and allergen challenge of patients with atopic bronchial asthma is associated with the appearance, in vivo interleukin-B (IL-8) in bronchoalveolar lavage fluid (BAL). Bronchoscopy and BAL for further IL-8 investigation were performed before and 24 h after challenge test with histamine (n = 11), grass pollen antigen (n = 8) and PBS (n = 5). ELISA test was used to measure IL-8 concentration (pg/ml) (kits from R&D, USA). There was observed increased level of IL-8 (p < 0.05) after histamine and allergen challenge test. This increased level of IL-8 was correlated with neutrophils in BAL (Kendall's correlation coefficient = +0.5). We conclude that IL-8 may participate in creation of bronchial hyperreactivity in atopic bronchial asthma.

[Blood serum eotaxin and eosinophil cationic protein in asthmatic patients]. / Stezenia eotaksyny i eozynofilowego bialka kationowego w surowicy chorych na astme oskrzelowa.

Eotaxin belongs to CC class of chemokines and is a potent eosinophil chamoattractant. Activated eosinophils are able to release many cytotoxic proteins, including eosinophil cationic protein (ECP), which has central role in allergic inflammation. The aim of this study was to assess eotaxin and ECP levels in plasma of atopic asthma patients in stable period of the disease. 19 patients with asthma and 10 healthy controls took part in this study. ELISA test was used to measure eotaxin (kits from R&D, pg/ml) and ECP (kits from Pharmacia, mg/l) levels. Plasma eotaxin level (mean +/- SD) was 176.52 +/- 50.3 (range 89-288) in asthma patients and 101.42 +/- 49.4 (range 35-206) in control group (p < 0.001). Plasma ECP concentration was 16.7 +/- 6.4 (6.3-28) and 16.8 +/- 17.1 (3.1-61.6), respectively (n.s). There was correlation between plasma eotaxin and ECP levels (Pearsons correlation co. r = +0.5, p < 0.05) and between eotaxin and FEV1 (Pearsons correlation co r = -0.4, p < 0.05) in asthma patients. We suggest that measurement of eotaxin and ECP levels as well may be useful indicator of disease.

[Expression of adhesion molecules LFA-1 (CD11a and ICAM-1 (CD54) on lymphocytes and chemokines IL-8 and MCP-1 concentrations in bronchoalveolar lavage of patients with asthma or chronic obstructive pulmonary disease]. / Ekspresja czasteczek adhezyjnych LFA-1 (CD11a) i ICAM-1 (CD54) na limfocytach oraz stezenia chemokin IL-8 i MCP-1 w materiale z plukania oskrzelowo-pecherzykowego u chorych na astme oskrzelowa i przewlekla obturacyjna chorobe pluc.

Chemokines and cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues asthma and chronic obstructive pulmonary disease (COPD) are a complex of conditions, which have airflow limitation in common. The aim of this study was to determine the numbers and percentages of lymphocytes expressing adhesion molecules: LFA-1, ICAM-1 together with assessment of chemokines concentrations: IL-8 and MCP-1 in bronchoalveolar lavage fluid (BAL) of patients with asthma or chronic obstructive pulmonary disease (COPD). 12 patients with asthma, 14 patients with COPD, and 6 subjects of control group took part in this study. The expression of LFA-1 and ICAM-1 was assessed on lymphocytes by using immunohistochemistry (streptavidyn-biotin, DAKO, Denmark). ELISA test was used to measure IL-8 and MCP-1 concentrations in BAL (kits from R&D, USA). The percentage of lymphocytes expressing LFA-1 and ICAM-1 were: 33.9 +/- 23.8% and 25.8 +/- 12.2% in COPD patients, 23.9 +/- 12.1% and 15.3 +/- 4.42% in asthma patients, and 14.2 +/- 10% and 5.2 +/- 1.6% in the control group respectively. There was observed significant difference between the percentage of lymphocytes expressing LFA-1 and ICAM-1 of COPD and the control group. The concentrations of IL-8 were: 2306 +/- 1501 pg/ml in COPD, 233 +/- 27.3 pg/ml in asthma and 64 +/- 28.7 in the control group (p < 0.05). The concentrations of MCP-1 were: 768.9 +/- 668.1 pg/ml in COPD, 126.8 +/- 30.8 pg/ml in asthma, and 83.0 +/- 16.4 pg/ml in the control group (p < 0.05). There was observed correlation between lymphocytes expressing LFA-1 and IL-8 concentration (r = +0.5, p < 0.05) and between lymphocytes expressing LFA-1 and MCP-1 concentration (r = +0.5, p < 0.05), and between lymphocytes expressing ICAM-1 and MCP-1 concentration (r = +0.4, p < 0.05) only in COPD patients. Our data suggest that LFA-1 and ICAM-1 are important molecules in the recruitment of leukocytes and together with IL-8 and MCP-1 may have a role in pathomechanism of inflammation in asthma and especially in COPD.

[Tumor necrosis factor-alpha--biological and immunologic properties]. / Czynnik martwicy nowotworów-alpha--wlasciwosci biologiczne i immunologiczne.

The studies investigating antitumor efficacy of bacterial infections, started by Coley, resulted in isolation of tumor necrosis factor (TNF-alpha), released by activated macrophages. It was hoped that direct and indirect cytotoxic, cytostatic and immunomodulatory effects of TNF-alpha would prove helpful in obtaining an effective antitumor drug. In this paper, we describe biologic and immunologic activity of cachectin as well as pre-clinical trials of TNF application in antitumor therapy.

[Tumor necrosis factor-alpha--phase I and phase II clinical trials]. / Czynnik martwicy nowotworów-alpha badania kliniczne I i II fazy.

Not fully successful therapy of carcinomas makes us search for new methods of antitumor treatment. Beside radiotherapy and chemotherapy, immunotherapy is the method we put our hopes on. Since its isolation in mid 70s TNF-alpha has been the subject of careful studies investigating its clinical usefulness. In phase I and II clinical trials dose- and manner of administration-dependent side effects were observed, which considerably limited the use of TNF-alpha in clinical practice. Topical (intratumoral) therapy eliminated most systemic side effects. Synergic antitumor efficacy of TNF-alpha, cytokines, such as interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and cytostatic drugs (etoposide, cyclophosphamide) was proved.

[Pulmonary function tests and bronchial reactiveness with histamine in patients with atopic dermatitis and bronchial asthma]. / Badania czynnosciowe oddychania i reaktywnosc oskrzeli na histamine u chorych na atopowe zapalenie skóry i astme oskrzelowa.

Atopic dermatitis and bronchial asthma are genetically dependent diseases, connected with an over-synthesis of IgE antibodies, in which a chronic inflammation is characteristic for their pathogenesis. The coincidence of bronchial hyperresponsiveness and symptoms of atopic dermatitis suggests to investigate the degree of bronchial reactions in atopic dermatitis or asthma patients. The main goal of this analysis was to compare the pulmonary functional tests and the bronchial histamine induced reactiveness in 71 patients. The investigation included 27 atopic dermatitis patients, 12 asthma-prurigo patients and 32 bronchial asthma patients. All of them were tested with "Pneumoscreen" (Jaeger), in order to define: VC, FEV1, FEF50, and Raw. The bronchial reactiveness with 1% histamine solution, was tested on "Bronchoscreen" (Jaeger). In atopic dermatitis and asthma-prurigo patients, no obstructive ventilation impairment was found. The bronchial hyper-reactiveness to histamine was found in 11.1% of atopic dermatitis patients, 16.7% of asthma-prurigo patients and 78.1% of bronchial asthma patients. The coexistence of bronchial asthma and atopic dermatitis increases the degree of bronchial reactiveness.

[Analysis of measurements: arterial blood pressure, pulse rate and oxygen saturation in arterial blood during broncho-fibroscopy and bronchoalveolar lavage in patients with bronchial asthma and chronic bronchitis]. / Analiza pomiarów: cisnienia tetniczego, czestosci tetna i wysycenia krwi tetniczej tlenem podczas badania bronchofibroskopowego i plukania oskrzelowo-pecherzykowego u chorych na astme oskrzelowa i przewlekle zapalenie oskrzeli.

Bronchial asthma and chronic bronchitis in stable period of disease could be an indication for diagnostic bronchofiberoscopy and broncho-alveolar lavage (BAL). 30 patients with bronchial asthma (aged 27.2 +/- 9.3), 30 patients with chronic bronchitis (aged 55.9 +/- 11.0) and subjects of control group (aged 27.0 +/- 9.7) took part in this study. Selected parameters: heart rate (HR), arterial blood pressure (ABP) and arterial O2 saturation (SaO2) monitored by pulsoximetry were measured during the procedure. It was showed that broncho-fibroscopy and BAL could be performed safe in patients with asthma and chronic bronchitis as well. Bronchospasm was observed only in one subject with asthma. The highest decrease of saturation was observed during BAL in every investigated subject. Because of none of recorded parameters allows identification of the patients at risk of poor tolerance of the procedure, we propose close observation of patient, monitoring parameters: HR, ABP and SaO2, and oxygen supplementation during the investigation.

[The effect of specific immunotherapy on the concentration of some chemokines in BALF in patients with atopic bronchial asthma]. / Wplyw immunoterapii swoistej na stezenia niektórych chemokin w materiale z BAL u chorych na atopowa astme oskrzelow.

The cellular basis the mechanism of specific hyposensitization is still unclear. We studied the effect of immunotherapy on activity of interleukin-8 (IL-8) and monocyte activating and chemoattractant protein (MCAF/MCP1) in bronchoalveolar lavage fluid (BALF). 20 patients with atopic asthma took part in this study. 14 were treated with grass pollen extracts (Allergovit, Allergopharma, Germany) for 7 weeks and 6 of this group were not treated and served as control group. ELISA test (R&D, USA) was used to assess IL-8 and MCAF/MCP1 activity in one ml of BALF recovered before and after immunotherapy. The results indicate that immunotherapy induces the suppression of MCAF/MCP1 production and the increase of IL-8 production in BALF. These chemokines may have reciprocal control on inflammatory cells, which participate in creating of inflammatory changes in asthma.

[The effect of inhaled ambroxol treatment on clinical symptoms and chosen parameters of ventilation in patients with exacerbation of chronic obstructive pulmonary disease patients]. / Wplyw leczenia wziewna postacia ambroksolu na objawy kliniczne i wybrane parametry wentylacji u chorych hospitalizowanych z powodu zaostrzenia przewleklej obturacyjnej choroby pluc.

It was a randomised, double-blind, placebo controlled comparative study of the clinical symptoms and chosen parameters of ventilation of inhaled ambroxol in patients hospitalized with exacerbation of chronic obstructive pulmonary disease (COPD). Eligible patients--30 patients (13 men and 17 women) aged of mean value 70.5 +/- 6.9 years who fulfilled the clinical traits of exacerbation of chronic bronchitis entered the study. 15 patients were treated with inhaled ambroxol and 15 were treated with placebo. Moreover all patients were treated with concomitant medications typical for exacerbation of COPD (systemic steroids, intravenous infusions with euphillin, antibiotics, Berodual nebulizations and oxygen therapy). Spirometry and data related to clinical symptoms were taken at the beginning of the study and after 1 and 3 days and after the end of the treatment. At the end of the treatment period in both groups (inhaled ambroxol therapy vs. placebo) there wasn't found statistically significant difference in the number of cough and dyspnoe attacks. There was found the difference in FEV1 and FEF 50 in both groups, but improvement in patients treated with ambroxol was statistically significantly faster, that can influence the cost of treatment. Moreover there were not found important adverse events in ambroxol group.

[Frequency of complications after transthoracic fine-needle biopsy of lung tumors]. / Analiza czestosci powiklan transtorakalnej biopsji cienkoiglowej guzów pluc.

Transthoracic fine-needle biopsy (TFNB) is a valuable method of recognizing changes in lungs, especially suspected of cancer. Such operations are cheap, don't demand expensive instruments and are possible to perform in each pneumonology ward, especially if they are an ideal supplement for bronchofibroscoping examination. The possibility of quick and effective performance of transthoracic biopsy shortens the diagnostics considerably. From January 1997 to April 1999 there were performed 406 operations of TFNB. There were 334 people operated on (294 men--74.5%; 85 women--25.5%), average age for the whole group of patients--62.8 (+/- 10.4 years). The patients were divided into two groups considering hospitalization places: I--patients from (not transported for operation)--135 (40.4%), II--patients transported for operation from another hospitals--199 (59.6%) The examination was performed under control of rtg apparatus (7600 OEC Medical System with mobile x-ray tube on a C-arm and laser localizer). The usual complication was an pneumothorax--52 cases (12.8%); drained--16 cases (3.9%). An average depth of inserting in an early pneumothorax is 6.56 (+/- 0.73), in a late pneumothorax--8.6 cm (+/- 1.75), (p = 0.0015). An average depth of inserting in a drained pneumothorax was 8.9 cm (+/- 2.17), in a non-drained pneumothorax 7.7 cm (+/- 1.3) (p = 0.024). Patients that had to be transported for the operation had pneumothoraxes that needed to be drained considerably more often: 14 cases in 199 comparing to 2 in 135 among patients not demanding to be transported (p = 0.02). Pneumothoraxes appeared more often after indicating tumors of smaller size, from 3 cm--21.6%; 3.1-6 cm--13.3% (p = 0.036). From another complications one could notice: hemoptysis--4 cases; subcutaneous emphysema--1 case; fever and shivers--1 case; hypotonia--2 cases; cough--1 case. Those complications were treated symptomatically or vanished themselves.

[Chemotactic monocyte and activation factor (MCAF/MCP1)in material from bronchoalveolar lavage fluid of patients with chronic bronchitis]. / Czynnik chemotaktyczny i aktywujacy monocyty (MCAF/MCP1) w materiale z plukania oskrzelowo-pecherzykowego u chorych na przewlekle zapalenie oskrzeli.

UNLABELLED: The aim of this study was to evaluate concentrations of monocyte chemotactic and activating factor (MCAF/MCP1) in bronchoalveolar lavage fluid (BAL) from patients with chronic bronchitis. 32 patients (aged 46 +/- 2 years) with chronic bronchitis and 14 patients (aged 30.5 +/- 3.4 years) of control group took part in this study. ELISA test (kits from R&D, USA) was used to measure concentrations of this chemokine in BALF. The results indicate for significant increase of MCAF/MCP1 in BALF from patients with chronic bronchitis (mean +/- SEM = 393 +/- 105.9 pg/ml) as compared from those of control group (middle +/- SEM = 36.4 +/- 10.9 pg/ml). CONCLUSION: MCAF/MCP1 may participate in creation of inflammatory changes of airways in patients with chronic bronchitis.

[Interleukin-6 and interleukin-8 in bronchoalveolar lavage fluid material from patients with chronic bronchitis]. / Interleukina-6 i interleukina-8 w materiale z plukania oskrzelowo-pecherzykowego u chorych na przewlekle zapalenie oskrzeli.

The aim of this study was evaluation of interleukin-6 (IL-6) and interleukin-8 (IL-8) in creation of inflammation of lower airways in patients with chronic bronchitis. 32 patients with chronic bronchitis and 14 subjects of control group took part in this study. Spirometry (Jaeger eq.), bronchofibroscopy and bronchoalveolar lavage (Olympus eq.) were performed in every patient. Cytology and concentration of IL-6 and IL-8 (kits from R&D) were measured in 1 ml of lavage fluid recovered. The increased levels of IL-6 and IL-8 in BAL were correlated with clinical parameters. We conclude that these two cytokines participate in creation of inflammatory changes of lower respiratory tract in chronic bronchitis.

[The effect of specific immunotherapy on serum eotaxin level in patients with pollinosis: preliminary studies]. / Wplyw swoistej immunoterapii na zachowanie sie stezen eotaksyny w surowicy u chorych na pylkowice--doniesienie wstepne.

Eotaxin belongs to CC chemokines with selective activity for eosinophils and basophils. Specific immunotherapy (SIT) represents the only curative approach for allergic inflammation. The aim of this study was an evaluation of the effect of SIT on serum eotaxin level in patients with seasonal allergy. 40 patients (mean age 26 +/- 8.15 with seasonal allergy to birch, 25 with seasonal allergy to grasses) and 35 persons (mean age 27 +/- 8) of the control group took part in this study. Preseasonal immunotherapy (Allergovit, Germany) was performed in conventional schedule in patients with pollinosis. Clinical assessment of symptoms in season (score) was done by all of the patients studied. ELISA test was used to measure serum eotaxin level (pg/ml, kits from R&D) before, after immunotherapy, in pollen season and after season in patients with disease. There was observed increased eotaxin concentration in patients with allergy to birch (140.6 +/- 53.7) as compared to the eotaxin level in the control group (102.1 +/- 53.7) (p < 0.05). There was observed decreased eotaxin level after immunotherapy (115.9 +/- 49.9) (p < 0.05) in patients with allergy to birch, but no with allergy to grasses. When patients with clinical improvement were taken into account, the significant difference (p < 0.05) in eotaxin concentration was showed before (126.7 +/- 52.4) and after immunotherapy (102.5 +/- 44.8). The eotaxin level in pollen season of patients with clinical improvement was significantly (p < 0.05) decreased (116.5 +/- 54.3) as compared to the eotaxin level in patients without clinical improvement (139.8 +/- 46.3). The results suggest an involvement of eotaxin in pathomechanism of SIT. The effect depends on kind of allergen evaluated. Further longitudinal controlled investigations should establish the role measuring serum eotaxin level in the clinical evaluation of SIT.

[Fine needle biopsy in diagnosis of lung tumors]. / Biopsja cienkoiglowa w diagnostyce guzów pluc.

Fine-needle biopsy is one of the method used in diagnosis of lung tumors. In this study the results of 192 biopsies performed by x-ray apparatus inspection were analysed. There was shown that lung cancer was recognized in over 50% of patients studied. In another cases non-specific inflammation (31%), lung fibrosis (1%), tuberculosis (1%), purulent inflammation (1%), blood (7%) were recognized. These results indicate for usefulness of this method in diagnosis of not only peripheral, but also central localized lung tumors.