Effect of an inhaled glucocorticoid on reactive oxygen species production by bronchoalveolar lavage cells from smoking COPD patients

Oxidative stress in the lung is important in the pathogenesis of COPD. Published data indicate that glucocorticoids inhibit blood cells in their capacity to produce reactive oxygen species (ROS). We investigated the effect of Fluticasone propionate (FP) on the ROS production capabilities of pulmonary cells. Bronchoalveolar lavage (BAL) was performed in smoking COPD patients, before and after a six month, placebo-controlled treatment with FP. BAL cells were stimulated with phorbol myristrate acetate (PMA) alone, and together with superoxide dismutase (SOD). From kinetic plots of ferricytochrome-c conversion we calculated the maximal rate of superoxide production: Vmax. We also examined BAL cell subsets and performed correlation analyses on ROS production and relevant clinical determinants. Paired results were obtained from 6 FP- and 9 placebo-treated patients. No significant change of Vmax was found in both patient groups. Also BAL cellularity was unchanged. Correlation analyses showed a significant (inverse) association of Vmax with the number of cigarettes smoked per day. We concluded that a potent inhaled glucocorticoid had no effect on the ROS production capability of BAL cells from smoking COPD patients. Apparently, heavy smoking impaired the ability of alveolar macrophages to produce ROS, which was not further decreased by FP

Pleuro-pulmonary tumours detected by clinical and chest X-ray analyses in rats transplanted with mesothelioma cells

New strategies for cancer therapy must be developed, especially in severe neoplasms such as malignant pleural mesothelioma. Animal models of cancer, as close as possible to the human situation, are needed to investigate novel therapeutical approaches. Orthotopic transplantation of cancer cells is then relevant and efforts should be made to follow up tumour evolution in animals. In the present study, we developed a method for the orthotopic growth of mesothelioma cells in the pleural cavity of Fischer 344 and nude rats, along with a procedure for clinical survey. Two mesothelioma cell lines, of rat and human origin, were inoculated by transthoracic puncture. Body weight determination and chest X-ray analyses permitted the follow-up of tumour evolution by identifying different stages. Autopsies showed that tumours localized on the whole pleural cavity (diaphragm, parietal pleura), mediastinum and pericardium. Tumour morphology and antigenic characteristics were consistent with those of the inoculated cells and were similar in both types of rats inoculated with the same cell type. These results demonstrate that mesothelioma formation in rats can be followed up by clinical and radiographic survey after gentle intrathoracic inoculation of mesothelioma cells, thus allowing the definition of stages of interest for further experimental trials. © 1999 Cancer Research Campaig

Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen-presenting dendritic cell: influence of treatment with fluticasone propionate

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory Row and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose-response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV1), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV1 remained stable, while FEV1 deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of EP is obtained through modulation of different cell populations in asthma and COPD

Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen-presenting dendritic cell: influence of treatment with fluticasone propionate (vol 29, pg 116, 1999)

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory Row and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose-response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV1), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV1 remained stable, while FEV1 deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of EP is obtained through modulation of different cell populations in asthma and COPD

LYMPHOCYTE AND MACROPHAGE ACTIVATION IN BRONCHOALVEOLAR LAVAGE FLUID IN NOCTURNAL ASTHMA

Increased nocturnal airway narrowing is thought to occur as a consequence of an intensification of inflammatory processes at night. Lymphocyte and alveolar macrophage (AM) activation are thought to be associated with the clinical expression of asthma, and may be important in the occurrence of nocturnal asthma as well. The expression of CD25 and HLA-DR receptors on lymphocytes from bronchoalveolar lavage (BAL) and peripheral blood (PB) CD4(+), as well as of CD14, IgG Fc, and CD11/CD18 leukocyte adhesion receptors on AM in BAL fluid and monocytes in PB, were determined at 16.00 and 04.00 h by flow cytometry. Their relationship with the occurrence of nocturnal asthma was investigated in eight nonatopic controls (Group 1) and 17 atopic asthmatic subjects, prospectively assigned to groups with a mean circadian peak expiratory flow (PEF) variation <15% (Group 2) and greater than or equal to 15% (Group 3). The occurrence of an increased circadian variation in PEF in asthmatic subjects was on the whole not associated with a day-night fluctuation in lymphocyte numbers and subsets in PB or BAL fluid, nor with day-night changes in receptor expression on AM from BAL or monocytes from PB. The only exception was the presence of a greater day-night change in the proportion of HLA-DR-expressing CD4(+) lymphocytes in the BAL fluid along with an increasing circadian PEF rhythm in asthmatic subjects (r = 0.68, p = 0.03). A further finding was that a lower number of BAL CD4(+) lymphocytes at daytime was significantly related to a higher circadian PEF variation in asthmatic subjects (r = -0.66, p = 0.01). Additionally, asthmatics in Group 3 showed a greater expression of CD11b on AM from BAL fluid at 16.00 h (p = 0.05), and a significantly positive correlation was found for this parameter with the circadian variation in PEF of all asthmatic subjects (r = 0.72, p = 0.03). These findings show that increased nocturnal airway obstruction in asthma is not associated with an increased influx of lymphocytes and macrophages into BAL fluid at night, nor with marked activation of these cells. Daytime presence of enhanced AM CD11b expression may predispose to the occurrence of nocturnal asthma