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P Chanez

Publications and source records attributed to P Chanez.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Leukotriene antagonists. A new therapeutic approach in asthma].

BRONCHIAL INFLAMMATION: Corticosteroids are currently the most important treatment for bronchial inflammation in asthma. SULFIDOPEPTIDE LEUKOTRIENES: These biologically active fatty acids play an important role in the inflammation process in asthma. A NEW THERAPEUTIC APPROACH: Some leukotriene receptor antagonists and synthesis inhibitors are effective and safe treatment for mild to moderate asthma. GLOBAL STRATEGY: The role of these new drugs in the management of asthma remains to be defined on the basis of comparative clinical trials with the standard reliever treatment: inhaled corticosteroids.

Asthma↗
PubMed1997

New developments in the immunology of asthma, with a focus on mechanisms and treatment.

Asthma is a chronic inflammatory disease of the airways involving the activation of many different cell types. The immunologic basis of asthma is widely accepted for allergic asthma, and the synthesis of IgE is dependent on cytokines. A process of healing and repair follows on from inflammation and this leads to a variable degree of remodelling of the airways. The treatment of asthma should take into account that the disease is associated with short-lived symptoms that can be prevented or reversed by bronchodilators, exacerbations that can be treated or reversed by anti-inflammatory drugs, and remodelling of the airways, for which no definite treatment has yet been validated.

Adult↗
PubMed1997

Leukotriene E4 plasma levels in adult asthmatic patients with variable disease severity.

Cysteinyl leukotrienes (C-LTs) are local inflammatory mediators involved in bronchial asthma. Seventeen asthmatic patients (FEV1 ranging from 41 to 99.8% of predicted values) and 11 healthy subjects were studied. The clinical severity of asthma was assessed by the Aas score. Plasma C-LTs were measured by enzyme immunoassay (EIA) after sample purification by solid-phase extraction (SPE), to investigate whether differences may exist between asthmatic and control subjects and whether leukotriene E4 (LTE4) levels were related to the severity of disease. LT measurements showed that 87.6 +/- 1.2% was recovered as LTE4 and 9.4 +/- 1.3% as LTC4. In asthmatic subjects, LTE4 plasma levels were found to be significantly higher than those in the control group (1.073 +/- 0.133 and 0.53 +/- 0.19 ng/ml of plasma, respectively; P < 0.002). Moreover, there was a significant correlation between LTE4 plasma levels and the Aas clinical score (P < 0.005). These data suggest that plasma LTE4 levels might be used to assess the severity of asthma.

Adolescent↗
PubMed1997

Cellular protein kinase C activity in asthma.

Protein kinase C (PKC) is a primary group of enzymes mediating signal transduction for a wide variety of functions in many different cell types. Its activation has been implicated in various inflammatory diseases. In asthma, inflammatory cells, such as alveolar macrophages (AM) and polymorphonuclear neutrophils (PMN), are primed and activated compared with those obtained from control subjects. In particular, they release higher amounts of reactive oxygen species. PKC has been known to play an important role in the respiratory burst of human leukocytes. In this study, the PKC activity was measured in blood neutrophils and alveolar macrophages from control (n = 16) and asthmatic subjects (n = 28). In PMN, the total PKC activity was significantly lower in PMN from stable (182.00 +/- 27.20) and unstable (108.40 +/- 14.15) asthmatic patients, compared with control subjects (257.35 +/- 29.70 pmol/10(7) cells/min with p < 0.05 and p < 0.0005, respectively). In AM, PKC activity was 479.50 +/- 71.80 for controls and 254.00 +/- 25.90 pmol/10(7) cells/min for asthmatic patients. Moreover the percentage of membrane PKC was significantly higher in stable asthmatic patients in both cell types. After stimulation of neutrophils with PMA, a significant decrease in total PKC activity was observed in both control and asthmatic subjects. We have found an abnormal regulation of PKC activity in both blood PMNs and AM in asthmatic patients. These findings are consistent with the functional hyperreactivity of inflammatory cells observed in asthma.

Adult↗
PubMed1997

Corticosteroid reversibility in COPD is related to features of asthma.

Eosinophilic inflammation has been observed in the airways of patients with chronic obstructive pulmonary disease (COPD). A subset of patients clinically diagnosed as having COPD show a reversibility of airflow obstruction when treated with corticosteroids, and may consist of patients with features of asthma including reticular basement membrane thickening and eosinophilic inflammation. Twenty-five unselected patients clinically diagnosed as having COPD received a daily oral dose of 1.5 mg/kg body weight of prednisolone for 15 d to assess the relationships between the functional response to corticosteroids and the presence of features of asthma. Eosinophilic inflammation was characterized before the course of corticosteroid therapy by enumerating eosinophils in peripheral blood, bronchoalveolar lavage fluid (BALF), and bronchial biopsies, using EG2 monoclonal antibody, and by measurement of eosinophil cationic protein (ECP) in BALF. A response to treatment was defined by an increase in FEV1 of at least 12% from baseline values and an absolute value of 200 ml measured at the end of the treatment. Twelve of 25 patients responded to the treatment. By comparison with nonresponders, responders had a significantly larger number of eosinophils (p < 0.015), and higher levels of ECP (p = 0.013) in their BALF. The responders had a thicker reticular basement membrane than the nonresponders (p < 0.04). These results indicate that a response to prednisolone in patients diagnosed as having COPD might occur more readily in a subset of patients presenting with features of asthma.

Adult↗
PubMed1997

Transforming growth factor-beta expression in mucosal biopsies in asthma and chronic bronchitis.

We assessed whether transforming growth factor-beta (TGF-beta), a fibrogenic growth factor, may be involved in remodeling of asthma and chronic bronchitis; its expression was compared with that of epidermal growth factor (EGF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in bronchial mucosal biopsies from 13 normal subjects, 24 asthmatics, and 19 patients with chronic bronchitis. TGF-beta immunoreactivity was highly increased in epithelium and submucosa of those with bronchitis and to a lesser extent in asthmatics. By comparison, with normal subjects, EGF immunoreactivity was significantly increased in the epithelium of bronchitic subjects and submucosa of asthmatics, and, GM-CSF immunoreactivity was increased in both epithelial and submucosal cells of asthmatics and to a lesser extent in submucosa of bronchitics. A significant correlation was found between the number of epithelial or submucosal cells expressing TGF-beta in both asthma and chronic bronchitis and basement membrane thickness and fibroblast number. No such correlation was found for EGF or GM-CSF. in situ hybridization for TGF-beta 1 mRNA confirmed the results obtained by immunohistochemistry. By combining in situ hybridization and immunohistochemistry, it was found that eosinophils and fibroblasts were synthetizing TGF-beta in asthma and bronchitis. These data suggest that TGF-beta, but not EGF or GM-CSF, is involved in airways remodeling in asthma and chronic bronchitis.

Adolescent↗
PubMed1997

Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics.

In order to determine whether matrix metalloproteinases (MMPs) contribute to inflammation in asthma, we have examined the release of MMPs in bronchoalveolar lavage (BAL) fluids and their production and regulation by alveolar macrophages (AM), in short-term culture. BAL was collected from 38 asthmatic subjects (24 untreated and 14 treated with inhaled corticosteroids), 26 healthy nonsmokers, and 18 patients with chronic bronchitis used as a control group for another inflammation. The profile of MMPs present in BAL fluid and AM supernatant, determined by zymographic analysis, was found to be similar in all populations. The main enzyme released was identified immunologically as MMP-9, a potent collagenolytic and elastolytic enzyme. Its release, measured using enzyme immunoassay, was significantly enhanced in fluids and in AM supernatants from untreated asthmatics compared with those from the other populations. Enhanced MMP-9 levels, in asthma, could not be explained by a different sensitivity of AM to interleukin-4, interferon-gamma, or dexamethasone, compounds that have been shown to inhibit MMP-9. The phorbol ester phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, significantly increased MMP-9 in AM from healthy control subjects but not in those from untreated asthmatics. Calphostin C and H7, PKC inhibitors, significantly reduced PMA-stimulated MMP-9 release in AM from healthy control subjects and spontaneous MMP-9 release in AM from untreated asthmatics. H8, a PKA inhibitor, was inactive in both populations. These data suggest that the stimulation of MMP-9 release in AM from untreated asthmatic patients occurs, at least partly, via signals activating PKC.

Adolescent↗
PubMed1997

Diffuse pulmonary calcinosis without calcium metabolism abnormalities in a renal transplant recipient.

Eighteen years after an uneventful renal transplantation, the chest radiograph of an asymptomatic 50 year old man showed diffuse bilateral infiltrations, predominately at the right apex. Computed tomography (CT) scan demonstrated a diffuse alveolar pattern, the alveoli being filled with a very dense material, with some tracheal calcifications. Bronchoalveolar lavage fluid analysis was normal, but bronchial and transbronchial biopsies revealed calcium deposits in the bronchial mucosa and in the alveolar septa. The diagnosis of diffuse pulmonary calcinosis was established, despite normal blood calcium, phosphorus and magnesium levels, based upon computed tomography scan and pathological findings at fibreoptic bronchoscopy, without the need for an open lung biopsy.

Biopsy↗
PubMed1997

Markers of acute airway inflammation.

In asthma, acute inflammation induced by allergen challenge in allergic patients leads to an early and a late phase reaction. Immunoglobulin E (IgE)-mediated cell activation plays a crucial role in acute inflammation and leads to the release of proinflammatory mediators, such as histamine, eicosanoids, platelet-activating factor, oxygen-free radicals, neuropeptides and cytokines. These mediators are capable of inducing constriction of airways smooth muscle, increased secretion of mucus, and vasodilatation, as well as several important biological events, including modulation of the expression of adhesion molecules in endothelial and epithelial cells, and of inflammatory cell recruitment. Clinically, acute airway inflammation is characterized by a bronchoconstrictive response with acute symptoms, including wheezing and dyspnoea which can be reversed by short-acting bronchodilators, among which beta 2-agonists play a major role.

Asthma↗
PubMed1997

Growth factors in asthma.

Asthma is a chronic inflammatory disease of the airways, with associated repair processes. Both inflammatory and repair processes appear to be strictly related, and can lead to several histopathological alterations of the bronchial mucosa, such as the shedding of epithelium and increased thickness of the basement membrane. The integrity as well as the alterations of the bronchial structure are the consequence of several biological events, such as cell proliferation and death, cell activation and inhibition, and extracellular matrix (ECM) production and degradation. These events are critically regulated by polypeptides called growth factors (GFs), which are able, functioning in an autocrine and paracrine fashion, to affect and modulate cell functions and ECM turnover. Although the importance of GFs has been widely demonstrated in other pulmonary conditions, such as lung fibrotic diseases, their possible involvement in the pathogenesis of inflammatory and postinflammatory processes in asthma is still not completely clear. The aim of the present review was to discuss the biological evidence concerning the role of several growth factors, such as transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), granulocyte/macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF) and endothelin, in asthma and chronic bronchitis.

Asthma↗
PubMed1997

[Specific immunotherapy of respiratory allergies].

Specific immunotherapy has been in routine use since 1911 for the treatment of respiratory allergic diseases. There is however a certain amount of controversies regarding its overall indications. Its efficacy has been demonstrated in double-blind placebo controlled studies in both allergic rhinoconjunctivitis and allergic asthma. The improvement of allergenic extracts (in particular by standardization), the better understanding of the mechanisms of action of immunotherapy, the recently proposed use of other administration routes and the publication of guidelines have legitimated its definite role to play in the therapeutic management of allergic respiratory diseases.

Child↗
PubMed1996

[Bronchial asthma: current concepts].

Asthma, a chronic inflammatory disease of the airways, involves activation of various cell types and development of various degres of post-inflammatory lealing and repair processes which remodel the airways. The short duration of the severe episodes is clearly related to the degree of inflammation, but the natural history of the disease itself remains unclear. Treatment must take into account the fact that clinical expression varies, associating short episodes which can be prevented or attenuated with bronchodilatators and severe acute episodes which should be treated or prevented by anti-inflammatory drugs (inhaled corticosteroids are the most effective) preferably given in the early stages of the disease and used for a prolonged period. Long-term use of inhaled corticosteroids may limit airway remodeling, but there have been few long-term studies to date. Further data is required.

Acute Disease↗
PubMed1996

5(S),15(S)-dihydroxyeicosatetraenoic acid and lipoxin generation in human polymorphonuclear cells: dual specificity of 5-lipoxygenase towards endogenous and exogenous precursors.

5-Lipoxygenase activation of human blood polymorphonuclear cells (PMN) from asthmatic patients (asthmatics) was studied to investigate whether differences may exist with healthy subjects (controls). The respective cell capacities to produce lipoxins (LXs), leukotrienes, and 5(S), 15(S)-dihydroxyeicosatetraenoic acid [5(S),15(S)-diHETE] were compared under in vitro stimulation by ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic acid [15(S)-diHETE]. Eicosanoids were analyzed by elution with an isocratic reverse-phase high performance liquid chromatography system, and their profiles, detected by simultaneous monitoring at 302, 280, and 246 nm, were evaluated on the basis of chromatographic behavior: UV spectral characteristics and coelution with synthetic standards. In the presence of exogenous 15(S)-HETE, human PMN were able to produce LXs and 5(S),15(S)-diHETE, PMN from asthmatics were able to produce 5(S), 5(S),15(S)-diHETE, and LXs from endogenous sources, whereas in the same experimental conditions, no detectable amounts of these compounds were released by PMN from controls. The levels of 5(S),15(S)-diHETE, and LXs biosynthesized from endogenous arachidonic acid were highly correlated. Two different LX patterns were observed involving two possible metabolic pathways: (a) via the intermediate 5,6-epoxytetraene alone for LXs generation from exogenous 15(S)-HETE; and (b) via 5,6- and/or 14,15-epoxytetraenes leading to the formation of an enzyme-bound delocalized carbocation for LXs generation from endogenous arachidonate, respectively. The enhanced 5-lipoxygenase activation of blood PMN from asthmatics and the metabolism of exogenous 15(S)-HETE may reflect a priming induced by various mediators released from environmental cells, and could be considered as a model of transcellular signalization between PMN and endothelial cells.

Arachidonate 5-Lipoxygenase↗
PubMed1996

[Asthma and corticotherapy].

There has been a considerable amount of progress in the treatment of asthma providing a highly acceptable quality of life for the majority of patients. Cortisone remains the main medication in severe asthma. But despite the effective reduction in bronchial inflammation provided by cortisone, it is somewhat disappointing that nothing better has been found after a half-century of use. Actually, we have done better. Inhaled cortisone allows application of the active substance in situ, avoiding the inconvenience of systemic administration. In addition, doses can be given in micrograms instead of milligrams. Corticodependency and corticoresistance are the two main problems encountered. Corticodependency is a very heterogeneous highly individual phenomenon. In some corticodependent patients, respiratory function is nearly normal and stable while in others, respiratory function cannot be controlled readily and frequent hospitalizations in the intensive care unit are required. Weaning is a long-term process which must be planned as part of an overall management program. Corticoresistance, in our experience a rather rare condition, involves abnormal cell response to corticoids with abnormal or impaired production of cytokins, interleukin 4 and interleukin 5. A decrease in the number and binding capacity of corticosteroid receptors may also be involved. Cytoplasmic regulation rather than the receptor gene itself would be implicated. By modifying the corticosteroid receptors it would theoretically be possible to override corticorestistance and, by targeting the bronchial epithelium, disassociate the local anti-inflammatory effects of cortisone and the deleterious systemic effects. Understanding the mechanism of action of corticosteroids in patients with severe asthma is one of the challenges facing medicine in the 21st century.

Asthma↗
PubMed1996

Long-term oral corticosteroid therapy does not alter the results of immediate-type allergy skin prick tests.

BACKGROUND: Medications can modulate the results of skin prick tests (SPTs). Short-term corticosteroid therapy does not alter IgE-mediated skin tests, but the impact of long-term oral corticosteroid therapy on SPT results is unclear. A prospective study was carried out in patients with steroid-dependent asthma who received oral corticosteroids for a long period to determine whether this treatment reduced skin test reactivity. METHODS: Thirty-three patients with steroid-dependent asthma (median age, 59 years) were compared with 66 patients with asthma who served as a control group, matched for age, sex, and atopic status. SPTs with codeine phosphate and a screening battery of standardized allergen extracts were performed before commencement and after at least 1 year of daily oral prednisone treatment (median duration, 2 years; median daily dose, 20 mg). RESULTS: Fifteen patients with corticosteroid-dependent asthma were allergic before treatment, and their sensitization was not changed by long-term treatment with oral corticosteroids. The median wheal diameters induced by codeine phosphate were similar in both groups. The median wheal diameters induced by allergens, and more specifically, by Dermatophagoides pteronyssinus and D. farinae were similar in both groups and did not change in the steroid group after treatment. CONCLUSIONS: Systemic corticosteroid therapy (prednisone, 10 to 60 mg/day) for 2 or more years does not seem to alter SPT reactivity.

Adult↗
PubMed1996

Involvement of endothelin in mononuclear phagocyte inflammation in asthma.

BACKGROUND AND AIM: Endothelin has bronchoconstrictive, vasoactive, and inflammatory properties and may be involved in the pathogenesis of asthma. We have studied the involvement of endothelin in asthma by examining its expression and release by mononuclear phagocytes obtained from 56 patients with asthma and 32 control subjects and the activation of mononuclear phagocytes by endothelin. METHODS: Endothelin immunoreactivity was studied by using immunocytochemistry on monocytes and alveolar macrophages. Spontaneous and lipopolysaccharide-induced endothelin release from monocytes and alveolar macrophages was studied by radioimmunoassay. The proportion of intracellular endothelin was assessed after cell disruption by Triton (Union Carbide Corp., Bound Brook, N.J.). The release of fibronectin and tumor necrosis factor-alpha induced by endothelin was studied in alveolar macrophages by enzyme immunoassay. RESULTS: Endothelin immunoreactivity was significantly increased in cells from patients with asthma in comparison with those from the control group, but its release by alveolar macrophages was similar in both groups. Levels in the cell lysates and supernatants were similar for patients with asthma and normal subjects. Endothelin significantly increased the release of tumor necrosis factor-alpha and fibronectin by alveolar macrophages from normal subjects and patients with stable asthma, but it significantly decreased their release in patients with unstable asthma. CONCLUSION: This study suggests a role for endothelin in airway inflammation in asthma. Endothelin may act in a different fashion on alveolar macrophages, depending on the degree of stability of the disease.

Adult↗