Search PubMed⌕ Search

Biomedical subjects

P Chanez

Publications and source records attributed to P Chanez.

At least 109 records · Page 6Linked to original sources
PubMed1996

Different cytokine patterns in bronchial biopsies in asthma and chronic bronchitis.

Bronchial biopsies have made possible the detailed study of the pathology of the airways of humans with respiratory disease. Much data has been accumulated on asthmatics or normal controls but much less is known about chronic bronchitics. The aim of this study was to characterize the cellular and cytokine pattern seen in chronic bronchitics and to compare these with control and asthmatic subjects. The patients were also characterized clinically. In this study, immunocytochemistry on cryostat sections from bronchial biopsies were used to determine the level of inflammatory cells and cells of the immune system as well as the pattern of cytokines. This study revealed a distinct cellular and cytokine pattern for each of the three different patient groups, although the diversity of the cytokines analysed was limited by the size of the biopsies. In the inflammatory infiltrate of patients with asthma, CD4+ T-cells and eosinophils were the most prominent cell types discerned. All of the expected cytokines such as IL-1, TNF-alpha, IL-4, IL-5 and IFN-gamma were found. In contrast, the emphasis in chronic bronchitic patients was quite different. The predominant cell types were macrophages, neutrophils, mast cells and CD8+ T-cells, but eosinophils were also abundant. In addition, IL-4 and TNF-alpha were the only cytokines present of those tested.

Adult↗
PubMed1996

Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma.

Although their precise mechanism of action remains to be elucidated, glucocorticoids represent the most effective therapy in the treatment of asthma. Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes, including glucocorticoid receptor itself. The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days. mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semiquantitative competitive hybridization assay. All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment (per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41, P < 0.02), and a significant decrease for glucocorticoid receptor mRNA expression (P < 0.02) was observed in their monocytes. This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression, following corticosteroid treatment.

Adult↗
PubMed1996

Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar macrophages in airway diseases.

Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-beta and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-beta and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-beta and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-beta and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-beta and fibronectin than those from control subjects. The spontaneous release of TGF-beta is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-beta release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-beta in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma.

Adult↗
PubMed1996

Ex vivo pharmacologic modulation of basophil histamine release in asthmatic patients.

Histamine is one of a range of mediators which play an important role in asthma, and the "releasability" of basophils has been shown to be upregulated in this disease. In vitro, beta 2-agonists and to a lesser extent corticosteroids have been shown to reduce histamine release. The ex vivo effects of salmeterol and inhaled corticosteroids on histamine release were studied in 78 asthmatic patients with variable disease severity and 20 control subjects. Spontaneous and anti-IgE-induced histamine release was measured in all subjects. Fifteen patients were not receiving any form of treatment, 42 were treated with inhaled corticosteroids, and 21 received inhaled corticosteroids and salmeterol. Seven patients treated with inhaled corticosteroids and seven patients treated with inhaled corticosteroids and salmeterol were tested twice to assess the effect of salmeterol on histamine release. Nine patients treated with inhaled corticosteroids were tested before and after 1 month of salmeterol treatment to determine the possible inhibition by salmeterol. Patients who were treated with inhaled corticosteroids and salmeterol showed significantly lower levels of spontaneous histamine release (median: 2.5%) than untreated (5.2%) and inhaled corticosteroids-treated asthmatics (3.4%). No tachyphylaxis to salmeterol was observed when patients were tested twice at a 3-month interval. This study suggests that salmeterol may have an additive anti-inflammatory effect with inhaled corticosteroids, although this hypothesis must be tested by further studies involving cells obtained by bronchoalveolar lavage and studies with bronchial biopsies.

Administration, Inhalation↗
PubMed1996

Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. V. Duration of the efficacy of immunotherapy after its cessation.

Specific immunotherapy (SIT) using a standardized mite extract is effective and safe when administered under optimal conditions. However, the duration of its effectiveness after cessation of treatment remains unknown. Forty asthmatic subjects who had received SIT with a standardized Dermatophagoides pteronyssinus (Der p) extract under the same protocol were studied. All had received SIT for a period of 12-96 months and were not receiving pharmacologic treatment. The FEV1 was within normal range in all patients. After cessation of treatment, patients were followed for up to 3 years at 6-month intervals. The patient was considered to have relapsed when symptoms of asthma and/or rhinitis occurred and/or when pulmonary function tests were impaired. Skin tests with increasing concentrations of Der p were carried out before and at the end of SIT. Forty-five percent of the patients did not relapse. The duration of efficacy of SIT was related to the duration of SIT itself (P < 0.04). Most patients who did not relapse had a decrease in skin test reactivity at the end of SIT, whereas most patients who relapsed did not show any change (P < 0.003). The duration of efficacy of SIT after its cessation depends upon the duration of SIT and may be predicted by the effect of SIT on skin tests.

Adolescent↗
PubMed1996

Interleukin 8 in bronchoalveolar lavage of asthmatic and chronic bronchitis patients.

Interleukin 8 (IL-8) is a chemoattractant cytokine having a distinct target specificity for the neutrophil. However, it was also found to be active on primed eosinophils. IL-8 was measured by enzyme immunoassay in the bronchoalveolar lavage fluid (BALF) of 9 control subjects, 19 asthmatics and 36 chronic bronchitis patients. Its levels were correlated with neutrophil and eosinophil counts as well as levels of myeloperoxidase (MPO) and eosinophil cationic protein in the BALF. Asthmatic and chronic bronchitis patients had elevated levels of IL-8 in comparison with normal subjects. There was no correlation between the severity of asthma or chronic bronchitis and IL-8 levels. In asthmatic subjects there was a correlation between IL-8 and MPO levels (p < 0.0001, Spearman test). There was no significant correlation between eosinophils and IL-8. In chronic bronchitis there was a correlation between IL-8 and MPO levels as well as between IL-8 and neutrophil counts (p < 0.004 and p < 0.0152, respectively, Spearman test). IL-8 is involved in neutrophilic inflammation in asthma and chronic bronchitis, but differences in the IL-8 regulation of neutrophils were observed in both diseases.

Adolescent↗
PubMed1996

Computed tomography of the lungs in asthma: influence of disease severity and etiology.

Airways remodelling is a feature of longstanding asthma, but may differ in persons with allergic and nonallergic asthma. To assess airways remodelling indirectly, we compared permanent CT-scan abnormalities in 70 subjects with allergic (median age: 30 yr) and 56 with nonallergic asthma (median age: 54.5 yr) who had had asthma of similar duration. None of the subjects were smokers. Asthma severity was assessed by Aas score and FEV1. Permanent high-resolution computed tomographic (HR-CT) scan abnormalities were characterized. In comparison with allergic asthmatic subjects, those with nonallergic asthma had a significantly greater frequency of cylindric (p < 0.0007, Mann-Whitney U test) and varicose (p < 0.004) bronchiectasis, emphysema (p < 0.0003), bronchial recruitment (p < 0.0001), and sequellar linear shadows (p < 0.0001). There was a significant correlation between Aas score and emphysema (p < 0.0001 for nonallergic and p < 0.0005 for allergic asthma; Kendall's test method) or Aas score and sequellar linear shadows (p < 0.007, nonallergic asthma). There was a significant increase in the extent of permanent abnormalities with increasing severity and duration of asthma in both groups. Patients with brittle asthma had few permanent abnormalities. This study confirms that after a similar course of the disease, patients with nonallergic asthma have a more extensive remodelling of the airways than those with allergic asthma.

Adolescent↗
PubMed1996

Bronchial elastic fibers in normal subjects and asthmatic patients.

Elastic fibers required to maintain bronchial patency during ventilation may be damaged in asthma as a result of repair following inflammation or stretching during exacerbations. Fifteen normal subjects and 40 asthmatics of variable severity were studied. Bronchial biopsies were obtained from a subsegmental bronchus using a flexible bronchoscope. The elastic fibers were examined using orceine-eosine sustaining and/or immunohistochemistry with two monoclonal antibodies against elastin or transmission electron microscopy (six asthmatics and four control subjects). Orceine-eosine staining revealed that most normal subjects had normal fibers throughout the submucosa whereas of the 21 asthmatics analyzed only three had a normal superficial elastin network. In five patients, elastin had virtually disappeared. In the remaining patients, fibers appeared fragmented. The deeper layer of elastic fibers was abnormal in 17 asthmatics, fibers being patchy, tangled, and thickened. The fragmentation of the superficial network of elastic fibers shown in asthmatics was confirmed by immunohistochemistry. Electron microscopy studies suggested that the elastinolytic process and fragmentation of elastic fibers occurred in asthmatics. Elastinolysis occurs in the airways of asthmatics possibly as a result of repair elicited by chronic inflammation. Mechanical stretch induced by breathing and edema may lead to the fragmentation of fibers in asthmatic airways.

Adult↗
PubMed1996

[Value of imaging in asthma].

While the definition of asthma is based on clinical manifestations and respiratory function, imaging is widely used in acute asthma. We attempted to exploit the resources of high-resolution computed tomography to better study the fine structure of the airways. In acute asthma and at the first consultation for asthma, standard radiograms provide little precise information on the bronchi excepting cases with major lesions. High-resolution computed tomography can identify persistent bronchial and lung lesions which significantly correlate with clinical expression. These lesions are more frequent in non-allergic persons. We were able to obtain dynamic images demonstrating the anatomic variations in bronchial obstruction occurring after a provocation test. These applications are now in the clinical research stage. High-resolution computed tomography may soon play a role in clinical management of patients with asthma.

Asthma↗
PubMed1995

[Community acquired pneumonias in the region of Montpellier. Increase of pneumococci with reduced sensitivity to penicillins].

OBJECTIVES: Bacteriological data indicate that there is an increased incidence of Streptococcus pneumoniae strains with an intermediate sensitivity to penicillin. The goals of the present study was i) to investigate the profile of sensitivity of Streptococcus pneumoniae isolated from patients with bacterial pneumonia in the area of Montpellier and ii) to compare this profile with the findings of the national center registry to better appreciate geographical specificity. METHODS: Fifty-six patients with bacterial pneumonia were enrolled into the study. From September 1989 to March 1994, we performed bacterial sampling including blood cultures, protected brushes and bronchoalveolar lavage specimens. We examined the antibiotic sensitivity of the germs which were isolated. All patients were followed using clinical and radiological criteria. RESULTS: A precise bacteriological diagnosis was established in 83.6% of the population. Streptococcus pneumoniae was found in 47.2% of the samples. In 19%, the strains displayed an intermediate sensitivity to penicillin. All patients recovered. CONCLUSION: We found a higher rate of resistance to penicillin in Montpellier than the common rate of the national reference center in France. The location of Montpellier closed to the Spanish border might, at least in part, explain this difference.

Adolescent↗
PubMed1995

5-15-diHETE and lipoxins generated by neutrophils from endogenous arachidonic acid as asthma biomarkers.

5-Lipoxygenase (5-LO) activation of human blood polymorphonuclear cells (PMN) from healthy subjects (HS) and from asthmatic patients (AP) was investigated comparing their respective capacities to produce lipoxins, 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) and leukotrienes, under in vitro stimulation by ionophore A23187. PMN from AP were able to generate higher leukotriene levels from endogenous sources than PMN from HS. Moreover they produced 5,15-diHETE (from 50 to 280ng/10(7) cells) and lipoxins (from 1 to 30ng/10(7) cells), in a linear manner, whereas in the same experimental conditions no detectable amounts of these compounds appeared in PMN from HS. The enhanced 5-LO activation of blood PMN may reflect transcellular signalisation priming indicating that lipoxins and 5,15-diHETE could be much more specific inflammatory state biomarkers than leukotriene B4.

Arachidonic Acid↗
PubMed1995

Evaluation of the effects of ambroxol on the ofloxacin concentrations in bronchial tissues in COPD patients with infectious exacerbation.

Infectious excerbations of COPD are generally due to Streptococcus pneumoniae, Haemophilus species, and other Gram-negative bacteria. Ofloxacin has potent activity against Gram-negative species but is less effective against Gram-positive species including Streptococcus pneumoniae. It has also been shown that the administration of ambroxol increases the concentration of some antibiotics in pulmonary tissues. The aim of the study was to determine whether ambroxol increases the bronchial tissue concentrations of ofloxacin to a level exceeding the MIC90 of the bacterial species less susceptible to ofloxacin. 24 patients with COPD were randomized in two groups. Drug regimens of ofloxacin alone (200 mg twice daily) or ofloxacin (200 mg twice daily)+ambroxol (30 mg thrice daily) were administered over 10 d. A fibroscopy was performed on day 10 with bronchial biopsies and broncho-alveolar lavage. At steady state, concentrations of drug in plasma and bronchial samples were assayed by HPLC with fluorometric detection. There was no significant difference in the bronchial levels of ofloxacin between the two groups; however, in alveolar cells, ofloxacin concentration was three times higher in the group with ambroxol. Ambroxol does not increase ofloxacin concentrations in bronchial tissue because high concentrations are already present in the lung.

Administration, Oral↗
PubMed1995

Fos immunoreactivity assessment on human normal and pathological bronchial biopsies.

The transcription factor Fos is involved in cell proliferation and differentiation. Its expression in normal and pathological adult human tissues and cells has rarely been studied. We therefore studied bronchial biopsies obtained from 14 normal subjects (NS), 18 non-steroid-treated asthmatics, 10 corticosteroid-treated asthmatics and 10 patients with chronic bronchitis (CB), in addition to 34 patients with lung cancer (LC), by immunofluorescence for Fos immunoreactivity, using a highly specific polyclonal antibody. Bronchial tissue of 0/10 NS, 11/18 non-steroid-treated asthmatics, 1/10 steroid-treated asthmatics, 0/10 CB and 1/34 LC expressed Fos. In asthmatic patients, the expression was heterogeneous, localized to epithelial cells and correlated with the epithelium shedding (tau = 0.45, P = 0.0001). Corticosteroid-treated patients rarely expressed Fos, suggesting a role for this proto-oncogene in asthmatic bronchial inflammation. Fos was rarely expressed in the normal and pathological (CB, LC) proliferative compartment of the human bronchi, suggesting its low role in cell proliferation of the large airways.

Adenocarcinoma↗
PubMed1995

Detection of a novel macrophage-derived mucus secretagogue (MMS-68) in bronchoalveolar lavage fluid of patients with asthma.

BACKGROUND: We have previously described a novel high-molecular-weight macrophage-derived mucus secretagogue (MMS-68) that causes mucuslike glycoconjugate release from cultured airways, nasal explants, and the Ishikawa adenocarcinoma cell line. We have generated monoclonal antibodies against MMS-68 and have developed an antigen-capture ELISA to measure MMS-68 levels in biologic fluids. Using this ELISA, we have demonstrated elevated levels of MMS-68 in the bronchoalveolar lavage fluid (BALF) of smokers and persons chronic bronchitis, in a patient with asthma and bronchorrhea, and in nasal lavage from patients with allergic rhinitis challenged with histamine and methacholine. We have also demonstrated that both spontaneous and lipopolysaccharide induced MMS-68 production is increased in the culture supernatants of monocytes from patients with steroid-dependent asthmas compared with those from normal control subjects. METHODS: To delineate further a role for MMS-68 in the regulation of mucus secretion in asthma, we measured MMS-68 levels in the BALF of 37 patients with non-steroid-dependent asthma and of 16 control subjects. RESULTS: There were 21 men and 16 women in the asthma group (age range, 17 to 62 years; mean, 33.8 years) and 11 men and five women in the control group (age range, 18 to 42 years; mean, 27.8 years). There were no statistical differences in either total cell count (145.5 x 103 +/- 75.7 cells/mm3 x 10(3) cells/mm3 vs 134 x 103 +/- 65.9 x 10(3) cells/mm3, p < 0.234) or numbers of alveolar macrophages (103.7 x 10(3) +/- 71.7 x 10(3)/mm3 vs 98.7 x 10(3) +/- 65 x 10(3) cells/mm3, p < 0.244) when the asthmatic group was compared with the control group. The MMS-68 level in the asthmatic group was 2.1 +/- 0.25 micrograms MMS-68 per milligram protein compared with 2.09 +/- 0.26 micrograms MMS-68 per milligram protein (p < 0.256) in the control group. CONCLUSIONS: There was no correlation between MMS-68 levels and total protein content, numbers of alveolar macrophages, or the production of other macrophage-derived cytokines including interleukin-1, interleukin-6, or tumor necrosis factor in the asthmatic BALF. Mild asthma, which is clinically not associated with mucus hypersecretion, was not associated with elevated levels of MMS-68. We believe that direct correlation exists between mucus hypersecretion and MMS-68 levels.

Adolescent↗
PubMed1995

Protein content in bronchoalveolar lavage fluid of patients with asthma and control subjects.

BACKGROUND: Secretory component (SC), Clara cell protein (CC10) and to some extent, IgM are proteins locally synthetized in airways. Albumin, alpha 2-macroglobulin and alpha 1-antitrypsin are mainly plasma proteins. In patients with asthma, blood proteins may occur in greater amounts in bronchoalveolar lavage fluid (BALF) than in control subjects because of plasma extravasation. These proteins were measured in BALF to define markers of local synthesis and plasma exudation. METHODS: Twenty-four patients with asthma (mean age, 40 +/- 3.1 years) and 24 control subjects (mean age, 29 +/- 11 years) were tested. Five aliquots of saline solution (50 ml) were instilled, and the recovered BALF was stored. Clara cell protein was measured by a sensitive immunoassay technique based on the agglutination of latex particles. SC, immunoglobulins, alpha 2-macroglobulin, alpha 1-antitrypsin, and albumin were measured by an immunoradiometric assay. Protein concentrations were normalized to albumin. RESULTS: In BALF from patients with asthma there was a significant increase in alpha 2-macroglobulin and IgM and a significant decrease of SC, alpha 1-antitrypsin, and Clara cell protein compared with control subjects. Also, the ratio to albumin was significantly increased for alpha 2-macroglobulin and IgM and decreased for SC. There was no correlation between the severity of asthma and the amount of proteins. CONCLUSIONS: BALF protein content is significantly different in patients with asthma and control subjects, for proteins produced locally and derived from plasma.

Adolescent↗
PubMed1995

Seasonal variations of interleukin-4 and interferon-gamma release by peripheral blood mononuclear cells from atopic subjects stimulated by polyclonal activators.

IgE synthesis is controlled by interleukin (IL)-4 and interferon (IFN)-gamma, but there is heterogeneity in the IL-4 response depending on the sensitization of patients and natural allergen exposure. In patients sensitized to various allergens, we studied the synthesis of IL-4, IFN-gamma, and IgE to determine to what extent their in vitro immune response may be influenced by pollen season, depending on their sensitization. We studied 12 nonallergic individuals, seven patients sensitized to cypress pollen, 12 sensitized to grass pollen, 14 sensitized to several pollens, and 42 patients with polysensitization. The release of IL-4 and IFN-gamma from peripheral blood mononuclear cells stimulated by polyclonal agents (calcium ionophore A23187 and phorbol myristate acetate) was measured by ELISA. The spontaneous and IL-4-induced release of IgE was measured by ELISA. In patients with cypress pollen allergy, IL-4 and IgE release were significantly lower than in patients with other allergies. In the pollen-sensitized group, IL-4 and IgE release were significantly higher during the pollen season than out of it. No variation in IL-4 or IgE release was observed in the polysensitized group. IFN-gamma production was not affected by the pollen season. These data show that the seasonal variations of IL-4 and IgE synthesis differ according to the sensitization of patients.

Adolescent↗