Search PubMed⌕ Search

Biomedical subjects

Isabelle Vachier

Publications and source records attributed to Isabelle Vachier.

11 recordsLinked to original sources
PubMed2006

Interference of psychological factors in difficult-to-control asthma.

BACKGROUND: Most patients with asthma can be controlled with suitable medication, but 5-10% of them remain difficult to control despite optimal management. OBJECTIVE: We investigated whether patients with difficult-to-control asthma (DCA) or controlled asthma (CA) differ with respect to psychological factors, such as general control beliefs on life events. METHODS: DCA was defined as an absence of control despite optimal management. Recent control was measured using the Asthma Control Questionnaire. General control beliefs were investigated using a Locus of Control scale (LOC). RESULTS: Patients with DCA had a significantly higher external LOC as compared to patients with CA (P=0.01). In the DCA group, the hospital admission rate was highly significant in association with the external LOC (P=0.004) as compared to the internal LOC trend. CONCLUSION: This study showed that patients with DCA had different general control beliefs which might have hampered their management and interfered with their therapeutic adherence. The present findings could enhance management of DCA in a clinical setting.

Adult↗
PubMed2006

[Difficult asthma].

Difficult asthma is a major issue in pulmonary medicine today because of its cost for patients and society. Difficult asthma is asthma that remains uncontrolled despite optimal specialist management. The validity of the diagnosis must be reconsidered in these cases: associated or differential diagnoses may be involved in the lack of control, and it is always necessary to assess the patient's treatment adhesion. Sufficient time--at least a year--must be taken to get to know the patient and to meet the objectives set. The standard asthma therapies should be tested objectively. Severe asthma is the reality of difficult asthma that endures despite a reaffirmed diagnosis, optimal compliance and controlled comorbidities. Better knowledge is needed of the pathophysiology of these patients' asthma. Improved knowledge of these phenotypes will make it possible to develop innovative treatments. They will need to be validated in clinical research for subsequent use that is wider but more rational because targeted at phenotypes likely to benefit from them.

Administration, Oral↗
PubMed2005

Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound.

BACKGROUND: Lipoxins and 15-epi-lipoxins are lipid mediators that modulate leukocyte trafficking and promote the inflammation resolution. They are produced by different enzymatic pathways. Patients with severe asthma present ongoing airway inflammation despite chronic long-term treatment including oral glucocorticoids. OBJECTIVES: The aim of this study was to assess the presence of proinflammatory and anti-inflammatory mediators in the supernatants of induced sputum. METHODS: Induced sputum supernatants were collected from 10 normal subjects; 12 subjects with mild, 15 with moderate, and 24 with severe asthma; and 13 patients with chronic obstructive pulmonary disease. First, we validated the measurements of IL-8, leukotriene B 4 , lipoxin A 4 , and 15-epi-lipoxin A 4 in these samples. Then we measured these mediators by using immunoenzymatic methods. RESULTS: IL-8 levels were highly increased in patients with severe asthma ( P < .0001), and leukotriene B 4 levels were significantly increased in patients with severe asthma and patients with chronic obstructive pulmonary disease. Lipoxin A 4 was significantly increased in the supernatant obtained from patients with mild asthma ( P < .0001), whereas 15-epi-lipoxin A 4 levels were higher in patients with severe asthma ( P = .05). More interestingly, we found a positive correlation between the level of lipoxin A 4 and IL-8 in patients with mild asthma. CONCLUSION: These results indicate that induced sputum is a suitable method to assess lipoxin and 15-epi-lipoxin measurements in bronchi. The mechanisms involved in the synthesis of these 2 eicosanoid mediators would be helpful to understand better the imbalance between proinflammatory and anti-inflammatory mediators occurring in severe asthma. Lipoxin production involves interaction between lipoxygenases, whereas 15-epi-lipoxin production might involve CytP450 activity.

Adult↗
PubMed2004

[The measurement of exhaled nitric oxide, a new tool in the management of asthma?].

A GOOD DIAGNOSTIC TEST FOR ASTHMA: Chronic airway inflammation, main feature of asthma, can be assessed by measuring the exhaled nitric oxide (NO) level. Measurement of NO is standardized, non-invasive and easy to use in both children and adults. Studies have shown that it is a good diagnostic test for asthma when NO is high. However, other conditions or pathologies must be searched for because they may influence the results. ITS PLACE IN TREATMENT: Although exhaled NO helps to characterise the patients with asthma, other studies are required to show that it can help to improve the follow-up of such patients. Nevertheless, this tool has not yet been validated in the daily treatment of asthma and further research is still ongoing.

Adult↗
PubMed2004

Effects of inhaled corticosteroids on pathology in asthma and chronic obstructive pulmonary disease.

The effects of inhaled corticosteroids (ICSs) have been investigated in asthma and chronic obstructive pulmonary disease (COPD) using endobronchial biopsies. In asthma, most studies have shown reductions in infiltrating eosinophils, mast cells, and T lymphocytes. Cell-associated mediators, such as cytokines derived from type 2 T-helper lymphocytes, are decreased as assessed by immunostaining and molecular biology techniques. More recently, attention has been devoted to the effect of ICSs on structural changes. In asthma, ICSs have been shown in some studies to affect collagen deposition (size of the reticular basement membrane), the number of vessels, or epithelial integrity. The correlations between those findings and various clinical and functional outcomes are far from clear. A long-term study has shown a decrease in the basement membrane size in a group of patients with asthma treated according to their level of airway hyperreactivity. In COPD, ICSs generally do not decrease neutrophils, macrophages, and CD8(+) T lymphocytes. The effects of these drugs on structural changes in COPD have not been investigated extensively. Long-term prospective studies are needed to demonstrate the potential for ICSs to affect the natural history of chronic bronchial diseases.

Administration, Inhalation↗
PubMed2003

Persistent activation of nuclear factor-kappaB signaling pathway in severe uncontrolled asthma.

The transcription factor nuclear factor-kappaB (NF-kappaB) is inactive when bound to its inhibitory protein IkappaBalpha. On cell stimulation with inflammatory signals, IkappaBalpha is phosphorylated by IkappaB kinases and subsequently degraded. Freed NF-kappaB then induces expression of cytokines such as granulocyte-macrophage colony-stimulating factor, interleukin-8, and regulated upon activation, normal T cell expressed and secreted. These mediators are overexpressed in asthma and are downregulated by glucocorticoids through NF-kappaB activity repression. However, high levels of granulocyte-macrophage colony-stimulating factor, interleukin-8, and regulated upon activation, normal T cell expressed and presumably secreted are released by peripheral blood mononuclear cells isolated from patients with severe asthma despite continuous systemic glucocorticoid treatment. We report that these mediators are markedly decreased by pyrrolidinedithiocarbamate, an inhibitor of NF-kappaB activation. To further characterize the persistent NF-kappaB activation in severe asthma, we analyzed the expression of various components of this activation pathway in healthy subjects and in asthmatics with mild controlled, and moderate and severe uncontrolled disease. We found high amounts of phosphorylated IkappaBalpha characterizing the three asthmatic groups. Western blot analyses indicated that in peripheral blood mononuclear cells the IkappaB kinase beta and p65 levels were greater in moderate and severe asthmatics than in normal subjects. Electrophoretic mobility shift assay and immunocytochemistry showed a greater activation status of p65 in severe asthmatics. Our data suggest that exaggerated NF-kappaB activation perpetuates inflammatory mediators production in severe asthma.

Adult↗
PubMed2003

High levels of urinary leukotriene E4 excretion in steroid treated patients with severe asthma.

Urinary LTE4 reflects the whole body production of the cysteinyl-leukotrienes (LTC4, LTD4 and LTE4) that are established mediators in asthma. The influence of chronic inhaled and oral glucocorticoid treatment on urinary excretion of leukotriene (LT) E4 was investigated in subjects with asthma. Enzyme immunoassay analysis of LTE4 was performed in spot urine samples collected from 40 patients with severe asthma, 25 patients with mild-moderate asthma and 20 non-asthmatic control subjects. Urinary LTE4 was significantly higher in patients with severe asthma (69.7 +/- 5.5) as compared to mild-moderate asthma (45.7 +/- 3.3 with P < 0.0004) and control (42.5 +/- 2.5 with P < 0.0001). Despite chronic systemic treatment with glucocorticoids, chronically severe asthma had presented with higher levels of LTE4 compared to mild moderate asthma and healthy controls. The findings support previous indications that one important component in asthmatic airway inflammation, the cysteinyl-leukotriene pathway remains relatively unopposed by oral glucocorticoids.

Administration, Oral↗
PubMed2002

Lipoxins are potential endogenous antiinflammatory mediators in asthma.

Lipoxins, endogenous eicosanoids biosynthetized in vivo at inflammation sites, are potential antiinflammatory mediators. Subjects with severe asthma present chronic inflammation of the airways despite long-term treatment with oral glucocorticoids. Therefore it is of interest to investigate the potential antiinflammatory effects of lipoxin A4 (LXA4) and lipoxin B4 (LXB4) that could attenuate chronic inflammation. In a first time, we detected interleukin (IL)-8 and LXA4 in supernatants of induced sputum. IL-8 was heightened in severe asthma (p = 0.001), whereas high concentrations of lipoxin A4 were present in mild asthma (p = 0.001). We then studied the effects of LXA4 on IL-8 released in vitro. Nanomolar concentrations of LXA4 and LXB4 inhibited the IL-8 released by peripheral blood mononuclear cells from the two groups of patients with asthma: a maximal inhibition of 29.4% (p < 0.01) was observed for patients with mild asthma, and 41.5% inhibition (p < 0.001) for patients with severe asthma at 1 nM and 100 nM LXA4 concentrations, respectively. Polymerase chain reaction analysis indicated that peripheral blood mononuclear cells from patients with asthma expressed the LXA4 receptor mRNA. Moreover, pertussis toxin reversed LXA4- and LXB4-inhibited IL-8 release. These findings suggest that lipoxins have potential antiinflammatory action in asthma.

Asthma↗
PubMed2002

Modulation of cadherin and catenins expression by tumor necrosis factor-alpha and dexamethasone in human bronchial epithelial cells.

Asthma is an inflammatory disease, and the epithelial mesenchymal unit appears to be of importance in regulating the disease mechanisms. Cell-cell adhesion plays an important role in tissue morphogenesis and homeostasis and is commonly mediated by cadherins, a family of Ca(2+)-dependent transmembrane adhesion receptors. The cadherin family is involved in control of the cellular architecture. Proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha are involved in asthma and may interfere with epithelial integrity. In the present study, we investigated the role of TNF-alpha and dexamethasone on the expression of E-cadherin, beta-catenin, and gamma-catenin. We used two bronchial epithelial cell models: primary small airway epithelial cell cultures and primary culture obtained from human bronchial tubes. After 48 h of TNF-alpha stimulation with or without dexamethasone expression of E-cadherin, beta-catenin and gamma-catenin were analyzed using Western blot analysis and immunofluorescence. This study showed a decrease in the expression of adhesion molecules in both epithelial cell cultures after stimulation. Dexamethasone and anti-TNF-alpha inhibited this effect. In unstimulated cells, E-cadherin and beta- and gamma-catenin expression was membranous, expressed only on the lateral cell wall with minimal cytoplasmic expression. Immunoreactivity was cytoplasmic in stimulated cells. We demonstrated, using Western blot analysis and immunofluorescence, that proinflammatory cytokines could be responsible for structural damage to the epithelium and that this process was potentially reversed by steroids.

Anti-Inflammatory Agents↗