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Biomedical subjects

P Chanez

Publications and source records attributed to P Chanez.

At least 73 records · Page 4Linked to original sources
PubMed1998

Generation of eicosanoids from 15(S)-hydroxyeicosatetraenoic acid in blood monocytes from steroid-dependent asthmatic patients.

The aim of this study was to investigate eicosanoid metabolism by human peripheral blood monocytes (PBM) from steroid-dependent asthmatic patients as compared to control subjects and untreated asthmatic patients. Eicosanoid biosynthesis by PBM isolated from venous blood using Percoll gradient centrifugation was evaluated following stimulation of 5 x 10(6) cells with calcium ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), and analyzed by reverse phase high performance liquid chromatography (RP-HPLC). Without 15(S)-HETE, PBM synthesized leukotriene B4 (LTB4) only (40 +/- 12 ng and 59 +/- 11 ng for untreated and steroid-dependent asthmatics, respectively). In the presence of 15(S)-HETE, PBM produced six-fold smaller amounts of leukotriene B4 (P < 0.0001). They also released 5(S),15(S)-dihydroxyeicosatetraenoic acid (5(S),15(S)-diHETE) in similar amounts for all the populations, whereas low amounts of lipoxins (LXs) were produced by PBM from asthmatics only (2.7 +/- 0.7 ng and 4.6 +/- 2.8 ng for untreated and steroid-dependent asthmatics, respectively). Moreover, PBM were also able to release an unknown compound containing conjugated triene chromophore. Cells from steroid-dependent asthmatic patients synthesized this unknown metabolite in higher amounts than controls and untreated asthmatics (133 +/- 18 ng vs 52 +/- 19 ng and 68 +/- 15 ng, respectively, P < 0.02). This work shows for the first time that human PBM are able to metabolize 15(S)-HETE and lead to lipoxins and to an unknown metabolite, with the amounts of the latter being enhanced by long-term corticosteroid treatment.

Adrenal Cortex Hormones↗
PubMed1998

Airway inflammation in mild intermittent and in persistent asthma.

The severity of asthma can be graded from mild intermittent to severe persistent. Airway inflammation is a feature of persistent asthma. We compared several markers of inflammation in mucosal biopsies and bronchoalveolar lavage fluid (BAL fluid) from 12 healthy control subjects, 24 patients with intermittent asthma, and 18 patients with mild-to-moderate persistent asthma. Epithelial shedding, eosinophil (EG2-positive cells), and activated T-cell (UCHL1) counts in biopsies, and ECP levels in BAL fluids were significantly increased in patients with intermittent asthma by comparison with control subjects and this increase was significantly greater for patients with persistent asthma. Alveolar macrophage activation (percentage of hypodense cells) and the thickness of the basement membrane were significantly increased in asthmatic subjects as compared with controls but there was no difference between the two asthmatic groups. Hyaluronic acid levels in BAL fluids were significantly increased in patients with persistent asthma by comparison with control subjects and patients with intermittent asthma. Mast cell numbers (toluidine blue) in biopsies and histamine or levels in BAL fluids were similar in the three groups. This study shows that airways inflammation is present in patients with intermittent asthma but to a lesser extent than in patients with persistent asthma.

Adult↗
PubMed1998

Safety of inducing sputum in patients with asthma of varying severity.

Inducing sputum using hypertonic saline is a noninvasive method to investigate airway inflammation in people with asthma. However, hypertonic saline may also induce bronchoconstriction in some patients. The aim of the study was to examine whether the overall safety of using hypertonic saline to induce sputum in patients with mild to moderate asthma could be extended to patients with severe and/or uncontrolled asthma. Nine control subjects and 64 asthmatic patients with varying severity of the disease (FEV1 40-126% predicted values) were studied. Twenty-one of those patients had uncontrolled asthma. Sputum was induced in a standardized manner using hypertonic saline. The safety of the procedure was evaluated by assessing the clinical response and measuring FEV1 just before and during sputum induction. The procedure was well tolerated in most patients, but it had to be stopped due to side effects in 11.6% of patients with severe asthma. None of the side reactions were severe. Few patients with uncontrolled (17.3%) or severe asthma (18.6%) had a drop in FEV1 of 10-20%. The fall in FEV1 was significantly greater in patients with severe asthma than those with mild disease (p < 0.02 Mann-Whitney U test). We conclude that hypertonic saline-induced sputum is a safe technique even in patients with severe asthma.

Adult↗
PubMed1998

Bronchial mucosal immunoreactivity of sensory neuropeptides in severe airway diseases.

Neuropeptides act on most of the components of the bronchial environment. They influence bronchomotor tone and bronchial vascular caliber and permeability. To investigate the nonadrenergic, noncholinergic system within the airways in asthma and chronic bronchitis, we performed endobronchial biopsies in 16 normal human volunteers, 49 patients with asthma of varying severity, including 16 patients treated with oral corticosteroids, and 13 patients with chronic bronchitis. Frozen sections of biopsies stained with specific antibodies against the neural marker PGP 9.5, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were analyzed for the presence of nerves through indirect immunofluorescence. Nerves were present in most of the biopsies and were found within and below the epithelium and adjacent to smooth muscle, glands, and blood vessels. By comparison with those in normal subjects, the numbers of VIP-immunoreactive nerves were not significantly decreased in patients with asthma and chronic bronchitis, but NPY-immunoreactive nerves were significantly decreased in the smooth muscle of these latter two groups of patients (p < 0.005). There was no correlation between disease severity and the number of nerves found in the biopsies. This study does not confirm previous findings in autopsy material of some defects in sensory and VIP-containing nerves in severe asthma.

Administration, Oral↗
PubMed1998

Glucocorticoid receptors in bronchial epithelial cells in asthma.

The expression of the glucocorticoid receptor (GR) in untreated or in steroid-dependent asthmatic patients is poorly understood. We therefore studied GR mRNA and protein levels in bronchial biopsies obtained from seven untreated asthmatic patients, seven control volunteers, and seven patients with chronic bronchitis. We also studied in bronchial epithelial cells obtained by brushing from 13 untreated asthmatics, 18 steroid-dependent asthmatics, 11 control volunteers, and 12 patients with chronic bronchitis, GR and heat shock protein 90 kD (hsp90) mRNA as well as the immunoreactivity of GR, intercellular adhesion molecule (ICAM-1), and granulocyte macrophage-colony-stimulating factor (GM-CSF). GR mRNA and protein level was similar in all subject groups in both biopsies and bronchial epithelial cells. Hsp90 mRNA level was also similar in all subject groups. ICAM-1 expression was significantly increased in bronchial epithelial cells from untreated asthmatics, but ICAM-1 was not expressed in those from steroid-dependent asthmatic patients. GM-CSF expression was significantly increased in bronchial epithelial cells from untreated and steroid-dependent asthmatic patients. GR expression within the airways is unaltered by oral long-term steroid treatment in asthma, but the expression of some but not all specific markers for asthma is modified by oral steroid.

Administration, Oral↗
PubMed1998

Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis.

Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECM) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreated asthmatic, and 16 chronic bronchitic subjects. We first performed zymographic analysis to identify the profile of MMPs. Zymography revealed a similar MMPs profile in all populations studied and that MMP-9 was the major enzyme released. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and of its inhibitor TIMP-1 and evaluated whether airflow limitation may be associated with an imbalance between these enzymes. MMP-9 and TIMP-1 concentrations were greater in sputum of patients with asthma and chronic bronchitis than in control subjects. The molar ratio between MMP-9 and TIMP-1 was lower in asthmatics and chronic bronchitics than in control subjects, and positively correlated with FEV1 values. In asthma, MMP-9 levels were significantly correlated with the number of macrophages and neutrophils. This study shows that airway inflammation in asthma and chronic bronchitis is associated with an imbalance between MMP-9 and TIMP-1 which may have a role in the pathogenesis of ECM remodeling and airflow obstruction.

Adolescent↗
PubMed1998

Expression of the high-affinity receptor for IgE on bronchial epithelial cells of asthmatics.

Bronchial epithelial cells are the first cells to come into contact with inhaled pneumoallergens. It has been suggested that these cells may play an important role in the allergic response, and indeed bronchial epithelial cells of some atopic asthmatic subjects have been shown to express the low-affinity receptor for IgE on their surface. In this report we demonstrate, using bronchial biopsies, that bronchial epithelial cells of some asthmatic subjects express both the alpha and gamma chains of the high-affinity receptor for IgE (Fcepsilon RI) on their surface and that they are capable of fixing IgE. Second, using reverse transcription-polymerase chain reaction, we show that both control and asthmatic subjects have messenger RNA for Fcepsilon RI. Finally, we demonstrate that this receptor may be functional since stimulation of the cells with the antibody to the alpha chain of Fcepsilon RI results in the liberation of 15-hydroxyeicosatetraenoic acid from epithelial cells of asthmatic, but not control, subjects or subjects suffering from chronic bronchitis. These data suggest that bronchial epithelial cells from at least some asthmatic subjects express a functional high-affinity receptor for IgE and it is therefore possible that these cells may be able to interact directly with inhaled allergens.

Adolescent↗
PubMed1998

Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients.

Reactive oxygen species play an important role in promoting inflammation. Blood monocytes have been described to release higher amounts of superoxide anion in uncontrolled and untreated asthmatics. Corticosteroids are widely used in asthma, but little is known about their molecular mechanism of action. The aim of our study was to analyse the ex vivo effect of corticosteroid treatments on superoxide anion release by blood monocytes. Superoxide anion release was measured by a spectrophotometric method based on the superoxide dismutase (SOD) -inhibitable reduction of ferricytochrome C by blood monocytes from untreated patients and asthmatics treated with i.v., inhaled and oral corticosteroids. Monocytes from uncontrolled and untreated asthmatics, released high amounts of superoxide anions. After short-term treatment with i.v., corticosteroids, this release was found to decrease significantly (1.410 versus 0.340 nM, p<0.05). Cells from asthmatics who had undergone long-term treatment with inhaled or oral steroids presented low amounts of superoxide anion production, with a significant difference as compared to untreated asthmatics (0.375 nM p<0.01 and 0.620 nM p<0.02 respectively). In general, patients with controlled asthma (treated with short-term oral steroids, or with long-term inhaled steroids) released lesser amounts of superoxide anion than uncontrolled and untreated asthmatics. In the case of steroid-dependent asthmatics there was no difference between patients with a controlled or uncontrolled disease.

Administration, Inhalation↗
PubMed1998

[The value and limits of Palmaz's prosthesis in the treatment of tracheobronchial stenosis].

The use of endobronchial prosthesis may be indispensable to maintain patency of the airways. We report our experience using Palmaz's prosthesis in four patients. The results were satisfactory in one patient but we have been confronted with three failures and one grave complication. The failures were linked to unsuitable properties of this prosthesis which has led us limit its use whilst waiting for newer studies.

Adolescent↗