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Biomedical subjects

P Chanez

Publications and source records attributed to P Chanez.

At least 19 recordsLinked to original sources
PubMed2000

[Corticosteroid therapy of asthma].

UNLABELLED: BRONCHIAL INFLAMMATION AND GLUCOCORTICOIDS: Bronchial inflammation plays an important role in asthma and contributes to bronchoconstriction, hypersecretion and bronchial hyperreactivity. Glucocorticoids are the gold standard treatment in asthma affecting most of the components involved in bronchial inflammation. Inhaled steroids are recommended early in most countries. MECHANISM OF ACTION: The molecular and cellular mechanisms of glucocorticoids action are still better understood. However, it remains difficult to evaluate individual sensitivity when initiating treatment. Glucocorticoids have an effect on all inflammatory cells and bronchial structure cells. They bind to cytoplasmic receptors and then the complex links to DNA, inducing or inhibiting gene transcription in the target cell. DIFFERENT GLUCOCORTICOID SENSITIVITY: Very few patients are totally insensitive to the effect of glucocorticoids and require specific explorations for an identification. Although individual variability in corticosensitivity is similar in asthmatic patients and in the general population, the underlying mechanisms remain to be fully elucidated. The difference observed between responders and non-responders is not clearly identified and their definitions must be fully adapted.

Administration, Inhalation↗
PubMed2000

Structural consequences of airway inflammation in asthma.

Asthma represents a chronic inflammatory process of the airways followed by healing, the end-result of which is an altered structure referred to as a remodeling of the airways. Repair usually involves 2 distinct processes: regeneration (which is the replacement of injured tissue by parenchymal cells of the same type) and replacement by connective tissue and its eventual maturation into scar tissue. In many instances both processes contribute to the healing response and inflammation. In asthma the processes of cell dedifferentiation, migration, differentiation, and maturation and connective tissue deposition can be followed either by complete or altered restitution of airway structure and function, the latter often seen as fibrosis and increase in smooth muscle and mucus gland mass. These features result in an increased resistance to airflow, particularly when there is bronchial contraction and bronchial hyperresponsiveness. The effect on airflow is compounded by the presence of increased mucous secretion and inflammatory exudate, which not only blocks the airway passages but also causes an increased surface tension that favors airway closure.

Animals↗
PubMed2000

Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma.

Patients with glucocorticoid (GC)-dependent asthma present an ongoing inflammation of the airways despite chronic long-term treatment with oral GC. Interleukin (IL)-8 and granulocyte/macrophage colony-stimulating factor (GM-CSF) have been implicated in airway inflammation in severe asthma and their synthesis is normally repressed by GC. To further characterize the inflammatory process in GC-dependent asthma, we measured the release of IL-8 and GM-CSF by peripheral blood mononuclear cells (PBMC) of eight normal subjects, six untreated controlled asthmatics, six untreated uncontrolled asthmatics, and nine GC-dependent asthmatics. We show that PBMC from GC-dependent asthmatics released high amounts of these cytokines despite chronic in vivo exposure to GC (p < 0.001 versus normal subjects). In contrast, when untreated uncontrolled asthmatics were given a short course of oral GC, IL-8 and GM-CSF production was inhibited (p = 0.0078). Release of IL-8 and GM-CSF by PBMC of GC-dependent asthmatics was reduced after in vitro GC treatment (p < 0.002). We investigated whether the incapacity of GC to inhibit production of these cytokines in vivo was the result of a dysregulation of the glucocorticoid receptor (GR) in GC-dependent asthma. GRalpha and GRbeta are, respectively, the functional receptor and a putative dominant negative form of the receptor. Western blot and polymerase chain reaction (PCR) analyses indicated that GRalpha was expressed at similar level in all groups and was largely predominant over GRbeta. Thus, persistent release of IL-8 and GM-CSF in GC-dependent asthma is not associated with low expression of GRalpha or overexpression of GRbeta.

Adult↗
PubMed1999

[Corticosteroid-resistant asthma: basic aspects].

A CONTROVERSIAL DEFINITION: The current definition of corticosteroid-resistant asthma is a spirometry definition. There is however, no consensus on dose, treatment duration, steroid administration route and the degree of FEV1 non-reversibility allowing the diagnosis of corticosteroid-resistant asthma. Finally, the beneficial effect of steroids in clinical terms (symptom frequency, number of hospitalizations, quality of life) is not taken into consideration, thus nearly one-half al all patients included in studies on corticosteroid resistance are taking long-term oral steroids. This subgroup of patients must be considered individually when examining these studies. COMPLEX PATHOGENESIS: There are a wide range of anomalies described in the literature involving: glucocorticoid pharmacokinetics, cytokine regulation, cell function (monocytes, lymphocytes, eosionophils), and transcription factors (glucocorticoid and AP-1 receptors). DIFFICULT THERAPEUTIC MANAGEMENT: There are several prerequisites before proposing exceptional regimens using cyclosporine, gold salts, methotrexate, or immunoglobulins: i) certain diagnosis of asthma (with CT scan and ultrasonographic explorations if needed, ii) proper control of environmental factors and good compliance, iii) proof of the absence of clinical benefit with long-term corticosteroids. These exceptional therapeutic schemes have their disadvantages and are only warranted by clinically patent corticosteroid resistance (whatever the "biological" cause).

Adrenal Cortex Hormones↗
PubMed1999

Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients with asthma and chronic bronchitis.

BACKGROUND: Apoptosis regulates inflammatory cell survival, and its reduction contributes to the chronicity of an inflammatory process. Apoptosis is controlled by suppressing or inducing genes, such as bcl-2 and p53, respectively. OBJECTIVE: We sought to assess apoptosis of eosinophils, macrophages, and T lymphocytes in bronchial biopsy specimens from asthmatic subjects and to examine its regulation by evaluating the expression of B-cell lymphoma leukemia-2 (Bcl-2) and P53 proteins. We also sought to explore the relationships between cell apoptosis and GM-CSF, a cytokine able to increase eosinophil and macrophage survival. METHODS: Apoptosis in eosinophils, macrophages, and T lymphocytes was evaluated in bronchial biopsy specimens obtained from 30 asthmatic subjects, 26 subjects with chronic bronchitis, and 15 control subjects by combining the terminal deoxynucleotidyl transferase-mediated dNTP nick end-labeling technique and immunohistochemistry. The expression of P53, Bcl-2, and GM-CSF was studied through immunohistochemistry by using specific mAbs. RESULTS: The number of apoptotic eosinophils and macrophages was lower in subjects with asthma than in those with chronic bronchitis (P <.007 and P <.001, respectively) and inversely correlated with the clinical severity of asthma (P <.001 and P <.002, respectively). Few T lymphocytes were apoptotic in all groups studied. In asthma GM-CSF+ cells correlated with the number of nonapoptotic eosinophils and macrophages (P =.0001) and with the severity of the disease (P <.003). In asthma Bcl-2+ cells were higher than in control subjects and subjects with chronic bronchitis (P <.002 and P <.015, respectively), they outnumbered P53+ cells, and they correlated with the number of T lymphocytes (P <.001) and with the severity of the disease (P <.003). CONCLUSION: Airway inflammation in asthma is associated with an enhanced survival of different cell types caused by reduced apoptosis.

Adult↗
PubMed1999

Eosinophilic inflammation assessed by induced sputum in corticosteroid-dependent asthma.

Sputum induction can be used to study airway inflammation in asthmatics. However, it has not been used in patients with corticosteroid-dependent asthma requiring long-term oral corticosteroids. The aim of the study was to assess the number of eosinophils and the levels of eosinophil cationic protein (ECP) in sputum of 17 corticosteroid-dependent asthmatics by comparison with nine mild untreated asthmatics, 10 moderate asthmatics receiving inhaled steroids (ICS) and 11 healthy subjects. In the 17 corticosteroid-dependent asthmatics, we examined sputum eosinophil markers on two occasions and correlated with the control of asthma. Eosinophils were undetectable in controls and were detected in 63.8% of asthmatics. There were no significant differences between the three groups of asthmatics. ECP levels were significantly increased in ICS or corticosteroid-dependent asthmatics by comparison to controls and mild asthmatics. There was no significant difference between ICS and corticosteroid-dependent asthmatics. During follow-up, corticosteroid-dependent asthmatics with a controlled disease had no significant change in eosinophil numbers or ECP levels. On the other hand, corticosteroid-dependent asthmatics with recent exacerbations had a non-significant increase in eosinophil numbers and a significant increase in ECP levels. This study shows that ECP levels may be more accurate than eosinophil numbers in assessing exacerbations in corticosteroid-dependent asthmatics.

Adolescent↗
PubMed1999

Safety and cellular assessment of bronchial brushing in airway diseases.

Bronchial brushing is a useful method for morphological and functional studies of bronchial epithelial cells (BECs) in various diseases. This technique has been found to be generally safe, but its safety in asthma and chronic bronchitis has not been fully assessed. The purpose of this study was to determine 1, whether bronchial brushing is a safe method in asthmatic and chronic bronchitis patients of differing severity and 2, to characterize the BECs obtained in terms of number, viability and purity. We evaluated 25 asthmatics of variable severity, 19 chronic bronchitis patients and 26 normal volunteers. Bronchoscopy and bronchial brushing were performed in a standardized manner by the same investigator. Safety was assessed by clinical follow-up of all subjects; continuous monitoring of arterial oxygen saturation during the procedure with a digital oximeter was carried out in a subsample of subjects. No complications were observed clinically during the procedure. There was a minimal fall in arterial oxygen saturation without a significant difference between the three groups of subjects. A consistent number of BECs was recovered and their viability, assessed by the trypan blue exclusion test, in asthmatics and chronic bronchitis patients was significantly lower than in controls (P < 0.05). Bronchial brushing is well tolerated and may be a valuable method of obtaining BECs in asthmatic and chronic bronchitis patients.

Adult↗
PubMed1999

Compliance in asthma.

Low rates of compliance with medication pose a major challenge to the effective management of most chronic diseases, including asthma. The high medical and social costs of non-compliance, and the apparent lack of effective methods for dealing with it, has stimulated renewed interest in this complex issue. Two broad categories of non-compliance have been identified, namely unintentional (or 'accidental') and intentional (or 'deliberate'). Unintentional non-compliance may result from poor doctor-patient communication or a lack of ability to follow advice. Intentional non-compliance occurs when the patient knows what is required but decides not to follow this to some degree. Healthcare professionals need to be aware of the various issues affecting compliance in all patients. The reasons for non-compliance are many and varied, and include factors such as complexity of the treatment regimen, administration route, patient beliefs about therapy and other psychological factors. Improvement in patient compliance with therapy will require better doctor-patient communication, improved patient education, the tailoring of therapy to the individual and possible novel strategies such as offering feedback to the patients on their level of compliance.

Anti-Asthmatic Agents↗
PubMed1999

Comparison between nasal and bronchial inflammation in asthmatic and control subjects.

Although asthma and rhinitis often coexist, it is still unknown whether they are characterized by a similar inflammatory profile. We studied eosinophilic infiltration, epithelial shedding and reticular basement membrane thickness in nasal and bronchial biopsies of six control subjects, 15 untreated allergic asthmatics with perennial rhinitis, and six corticosteroid-dependent (CSD) asthmatics. In nasal and bronchial biopsies, eosinophils were greater in untreated asthmatics than in control subjects and CSD asthmatics (p = 0.001). In untreated asthmatics, eosinophils were higher in bronchial than in nasal biopsies (p = 0.002). In nasal and bronchial biopsies, reticular basement membrane thickness was greater in untreated and CSD asthmatics than in control subjects (nasal: p < 0.008 and p < 0. 004; bronchial: p < 0.001 and p < 0.008). In untreated and CSD asthmatics, reticular basement membrane thickness was greater in bronchial than in nasal biopsies (p = 0.001; Wilcoxon's W test). Nasal epithelium was not shed in all the study groups. In untreated asthmatics, bronchial epithelium shedding was greater than in control subjects or CSD asthmatics (p < 0.005), and it was greater than nasal epithelium shedding (p < 0.006). This study has shown that, although concomitant, the extent of eosinophilic inflammation of reticular basement membrane thickness and of the epithelium shedding is greater in bronchial than in nasal mucosa of asthmatic patients with perennial rhinitis.

Adolescent↗
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↗