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P Chanez

Publications and source records attributed to P Chanez.

At least 37 records · Page 2Linked to original sources
PubMed2004

Can endobronchial biopsy analysis be recommended to discriminate between asthma and COPD in routine practice?

BACKGROUND: International guidelines stress the importance of accurately discriminating between asthma and chronic obstructive pulmonary disease (COPD). Although characteristic pathological features have been described for both conditions, their discriminatory power has never been systematically assessed. METHODS: Endobronchial biopsy (EBB) specimens from patients with a clear clinical diagnosis of asthma and COPD (50 per group) were examined by three pathologists in a double blind manner. They were asked to propose a pathological diagnosis of either asthma or COPD and to analyse qualitatively the most frequent abnormalities reported in the literature. RESULTS: The sensitivity and specificity of EBB ranged from 36% to 48% and from 56% to 79%, respectively. Eosinophils strongly biased the pathological diagnoses in favour of asthma, whereas their estimated prevalence was similar (11-37% in asthma and 13-41% in COPD). Metaplasia (11-39% in COPD, 1-18% in asthma) and epithelial inflammation (28-61% in COPD, 11-38% in asthma) tended to be specific to COPD, whereas epithelial desquamation (80-98% in asthma, 61-88% in COPD) and basement membrane thickening (71-94% in asthma, 53-88% in COPD) tended to be associated with asthma. There was acceptable intra- and inter-observer agreement only for metaplasia and epithelial eosinophils. CONCLUSIONS: Specific histopathological features of asthma and COPD probably exist, but current routine analysis procedures to assess EBB specimens are not sufficiently discriminatory. This might be rectified by improving pathological definitions.

Adult↗
PubMed2004

Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD.

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airways.

Adult↗
PubMed2004

Does systemic inflammation trigger local exercise-induced oxidative stress in COPD?

Inflammatory abnormalities may be involved in the inadequate basal oxidant/antioxidant balance and local exercise-induced oxidative stress in chronic obstructive pulmonary disease (COPD) patients. The time course of oxidative stress and inflammation was investigated in 10 COPD patients and seven healthy subjects before and after local dynamic quadriceps endurance exercise at 40% of maximal strength. Venous samples were collected before, immediately after and up to 48 h after exercise. At rest, levels of an oxidant released by stimulated phagocytes, the superoxide anion, were significantly higher in patients, as were plasma levels of C-reactive protein, tumour necrosis factor-alpha and interleukin-6, inflammatory markers. An inverse relationship was found between baseline C-reactive protein levels and endurance time in patients. Six hours after exercise, superoxide anion release and levels of protein oxidation products, an index of oxidative stress, increased similarly in both groups, whereas thiobarbituric acid reactive substance levels, another index of oxidative stress, increased significantly only in patients. Plasma nonenzymatic antioxidant and inflammatory cytokine levels were unchanged by the exercise protocol. The increased baseline systemic inflammation in chronic obstructive pulmonary disease patients could be related to disturbed oxidant/antioxidant balance, and, together, these may have triggered the exercise-induced oxidative stress. The absence, however, of local exercise-induced systemic inflammation suggests that additional mechanisms explain local exercise-induced oxidative stress.

Antioxidants↗
PubMed2003

Glucocorticoid receptor-binding characteristics in severe asthma.

The cellular mechanisms associated with severe asthma are still poorly understood. This study investigated the association between glucocorticoid-receptor (GR) alterations and continuous oral glucocorticoid therapy requirement in severe asthma. GR-binding affinity (Kd) and receptor number (n) in peripheral blood monocytes (PBM) obtained from 10 normal subjects, 10 untreated, intermittent asthmatics and 10 severe asthmatics were assessed. Moreover, one ability of dexamethasone to inhibit regulated on activation, T-cells expressed and secreted (RANTES) release by these cells in vitro was investigated. GR-binding characteristics were studied in PBM using a 3H dexamethasone ligand-binding assay and Scatchard analysis. RANTES release was measured in the supernatant of PBM at 24 h using an enzyme-linked immunosorbent assay. No significant differences in Kd and n were found between the three groups of patients. Dexamethasone in vitro was able to inhibit RANTES release (mean+/-SEM), with the same concentration/response curve in intermittent, untreated asthmatics (0.47+/-0.22 versus 1.64+/-0.31 ng x mL(-1)) and severe asthmatics (1.49+/-0.64 versus 2.59+/-0.77 ng x mL(-1)). This study showed that, despite long-term treatment with oral glucocorticoids, there was no evidence of abnormalities in glucocorticoid receptor-binding characteristics in severe asthma, and moreover, it was demonstrated that glucocorticoid receptors were functional in vitro.

Administration, Oral↗
PubMed2003

Assessment of variations in control of asthma over time.

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

Adolescent↗
PubMed2003

Idiopathic chronic eosinophilic pneumonia and asthma: how do they influence each other?

Since idiopathic chronic eosinophilic pneumonia (ICEP) and asthma are frequently associated, their possible reciprocal influence on clinical presentation and evolution were investigated. The clinical and follow-up features of 53 cases of ICEP, of which 41 (77%) had asthma, were reviewed retrospectively. Asthma preceded the diagnosis of ICEP in 26 patients, was contemporaneous in eight patients, and developed 17 +/- 12 months after ICEP in seven patients. Presentation of ICEP was similar in asthmatics and nonasthmatics with the exception of a higher level of total immunoglobulin E in the former group. Patients with asthma at the time of diagnosis of ICEP were more likely to remain free of relapse of ICEP (56 versus 23%) and had a lower number of relapses per year of follow-up (median 0 versus 0.24). Moreover, they were treated more frequently with long-term inhaled corticosteroids (88 versus 31%) at last follow-up. Asthma got worse after the diagnosis of ICEP and frequently required long-term oral corticosteroids. To conclude, among patients with idiopathic chronic eosinophilic pneumonia, asthmatics have a lower frequency of relapse than nonasthmatics, possibly because of a higher use of inhaled corticosteroids. The occurrence of idiopathic chronic eosinophilic pneumonia in asthmatics is often associated with the development of severe asthma.

Adult↗
PubMed2003

The response of two different dosages of beclometasone dipropionate suspension for nebulization versus a standard dose of beclometasone dipropionate via a metered-dose inhaler on bronchoprovocation testing in adults with asthma.

The objective of this double-blind, randomized, placebo-controlled, parallel-group study was to compare the pharmacodynamic effects and safety of beclometasone dipropionate (BDP) given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 1-week run-in period, 40 patients, aged 18-60 years, with intermittent bronchial asthma were randomized to one of four treatment groups for 3 weeks (n = 10 in each group): beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. via a nebulizer, BDP suspension for nebulization 3,200 microg day(-1) b.i.d. via a nebulizer, BDP 800 microg day(-1) b.i.d. via a metered-dose inhaler (MDI) plus spacer, or placebo. At study end, comparable effects were reported for all active treatment groups on the primary pharmacodynamic endpoint of FEV1 in response to methacholine bronchial provocation testing, with a statistically significant improvement shown in the BDP 3,200 microg day(-1) suspension for nebulization group compared with pre-treatment for other parameters, including FEV1 and peak expiratory flow rates. All treatments were comparable. All treatments were equally well tolerated. No significant effects on cortisol levels were reported in any of the treatment groups.

Administration, Inhalation↗
PubMed2002

Endogenous anti-inflammatory mediators from arachidonate in human neutrophils.

Eicosanoids have been historically involved in the pathogenesis of various inflammatory diseases. Lipoxins (LXs) and epi-LXs show physiological effects relevant to inflammation regulation. In this study, we focused on LX precursors based on the hypothesis that their entrance and metabolism into the cell may facilitate their targeting at the inflammation site. Because compound chirality is of considerable importance in the efficacy of therapeutic agents, our aim was to study the anti-inflammatory effects of various epimers of LXA(4) precursors compared to LXA(4). Blood polymorphonuclear cells (PMNs) were incubated with 15(S)- or 15(R)-hydroxyeicosatetraenoic acid (HETE), 14(R)-,15(S)-, or 14(S),15(S)-diHETE, and LXA(4) and then stimulated with the calcium ionophore A23187. We found that 15(R)-HETE rather than 15(S)-HETE was preferentially metabolized and that 15-epi-LXs were produced in larger amounts than LXs. In contrast, when PMNs were incubated with the diastereoisomers of 14,15(S)-diHETE, 14-epi-LXB(4) was produced in lower amounts than LXB(4). Enantiomers of 15-HETE and diastereoisomers of 14,15-diHETE and LXA(4) were able to significantly decrease LTB(4) release by PMNs. These results suggest a potential resolution of the inflammatory process through endogenous anti-inflammatory mediators released by the way of trans-cellular metabolism.

Anti-Inflammatory Agents↗
PubMed2002

Sputum induction.

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Administration, Inhalation↗
PubMed2002

Regulation of E-cadherin expression by dexamethasone and tumour necrosis factor-alpha in nasal epithelium.

Asthma and rhinitis often coexist and share many clinical features. The extent of epithelial alteration in nasal inflammation is controversial. Cell-cell adhesion plays an important role in tissue morphogenesis and homeostasis and is mediated by the cadherin family. In human bronchial epithelial cells the authors have shown that tumour necrosis factor (TNF)-alpha induced a significant decrease of E-cadherin and beta-catenin expression. The addition of dexamethasone inhibited this decrease. The aim of the present study was to investigate the effect of TNF-alpha and dexamethasone on the regulation of E-cadherin, gamma-catenin and beta-catenin in human nasal epithelial cells (HNEC). A primary culture of HNEC, obtained from human nasal turbinates after surgery, was used. The quantitative and qualitative modulation of E-cadherin, gamma-catenin and beta-catenin expression was assessed by Western blot and immunofluorescence analysis. In order to assess the TNF-alpha-induced activation of HNEC, interleukin-8 and RANTES (regulated on activation, normal T-cell expressed and secreted) release was assessed by enzyme-linked immunosorbent assay. The results showed that TNF-alpha induced, a decrease in gamma-catenin and beta-catenin expression, but had no effect on E-cadherin expression. Immunofluorescence showed that TNF-alpha induced cytoplasmic localisation of E-cadherin, gamma-catenin and beta-catenin. Dexamethasone inhibited the effect of TNF-alpha and induced a three-fold increase in E-cadherin expression. These results suggest that the difference in nasal and bronchial epithelial cohesion may be due to the differential effect of tumour necrosis factor-alpha and dexamethasone on E-cadherin expression.

Blotting, Western↗
PubMed2002

Eosinophilic inflammation in sputum of poorly controlled asthmatics.

Despite full effective treatment, asthmatic patients often present with poorly controlled asthma. Airway eosinophilia is associated with asthma, but its relationship with asthma control is still undetermined. To investigate the relationship between airway eosinophilia and asthma control, cellular and biochemical markers of airway inflammation were measured in 19 subjects with poorly controlled asthma, 16 subjects with asthma under control and eight normal volunteers. The severity of asthma was mild-to-moderate persistent in 23 patients (14 poorly controlled) and severe prednisone-dependent in 12 subjects (five poorly controlled). Induced sputum was analysed for total and differential cell counts, leukotriene E4 (LTE4), eosinophil cationic protein (ECP), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin (IL)-8. Sputum eosinophils, LTE4, ECP and RANTES levels (but not IL-8) were significantly higher in patients with poorly controlled asthma as compared to patients with controlled asthma. By contrast, sputum cells and sputum inflammatory markers were not different among groups of patients with different severity of asthma. These results suggest that sputum eosinophilia is associated with poorly controlled asthma rather than with the severity of asthma.

Adult↗
PubMed2002

Costs of asthma are correlated with severity: a 1-yr prospective study.

Asthma prevalence is increasing and asthma-related costs are likely to increase, but few studies have analysed the relationship of asthma costs and severity. The impact of severity on costs was quantified in a cohort of 318 asthmatic patients followed up prospectively for 1 yr. Patients presenting with a broad range of severity of the disease (intermittent, mild persistent, moderate persistent, severe persistent) were recruited by chest physicians throughout France and treated for 1 yr according to customary clinical practice and following international guidelines. Severity, direct and indirect costs, and quality of life (QoL) were assessed. A multivariate analysis was conducted to relate factors contributing to the costs measured. Mean direct costs for goods and services excluding hospitalization, numbers of consultations, supplementary examinations, and the use and cost of bronchodilators and corticosteroids, indirect costs of days lost from work, and adverse QoL parameters all increased significantly with increasing severity. This also applied to mean age, body weight, asthma duration, depression of forced expiratory volume in one second, and inhaled corticosteroid posology in the 234 patients completing the study. There was a significant relationship (r=0.614, p<0.001) between direct costs (hospitalization and cures were excluded) and three domains of the QoL questionnaire (mobility, pain and energy). Overall costs of asthma (including individual direct costs, indirect costs, and intangible quality of life costs) are clearly related to severity. This is the first study in asthma to combine rigorous independent classification of grades of severity in statistically valid numbers of patients of grades receiving "real-world" treatment and followed-up prospectively for 1 yr. It allowed severity to be accurately related to direct, indirect and intangible costs of asthma. Quality of life explained a significant part of these costs.

Adolescent↗
PubMed2002

[Nasal involvement in Crohn's disease: report of a case and diagnostic difficulties of systemic diseases affecting the nose].

The authors describe the case of a 32 years old man with Crohn's disease who has developped sinonasal and tracheal localizations. The review of the literature, quite poor, allows to find some cases of nasal involvement in Crohn's disease and few associations between this illness and others systemic diseases as Wegener's disease or relapsing polychondritis. Among these diseases, we can find atypical conditions mixing different features of the most classical systemic diseases, which are called "overlap syndromes". The case we report illustrate these questions relative to the diagnosis. To conclude, it may be important to point at the difficulties of the anatomopathological diagnosis and the interest of the iterative biopsies. Regular follow-up can help us to identify systemic disease with the research of new extra-sinonasal symptoms.

Adult↗
PubMed2001

Sputum eosinophilia in Churg-Strauss syndrome.

Sputum induction (IS) can be used to study airway inflammation in asthmatics and other lung diseases. However, no data are available for patients with Churg-Strauss syndrome (CSS). A study was carried out to evaluate eosinophil counts and eosinophil cationic protein (ECP) levels in induced sputum during the follow-up of three patients with CSS. Induced sputum was carried out in 10 patients with corticosteroid-dependent asthma (used as a control group). Patients with CSS had significantly higher eosinophils percentages and ECP levels in sputum than those with stable corticosteroid-dependent asthma. During the follow-up, patients with CSS presented increased ECP levels sputum and eosinophils in sputum as well as increased blood eosinophils, despite their oral corticosteroid and immunosuppressive treatment. Eosinophil percentage in sputum and the total number of eosinophils in peripheral blood were more predictive of exacerbations of CSS than sputum ECP.

Acute Disease↗
PubMed2001

Rhinosinusitis in severe asthma.

BACKGROUND: Chronic rhinosinusitis is a common comorbidity of asthma. However, sinonasal involvement in severe steroid-dependent asthma is still undefined. OBJECTIVE: The aim of the study was to evaluate chronic rhinosinusitis in 35 patients with severe steroid-dependent asthma by using a clinical score and coronal computed tomography (CT) scanning. METHODS: Thirty-five subjects (16 female subjects) with severe asthma requiring daily doses of oral corticosteroids were compared with 34 patients (19 female patients) with mild-to-moderate asthma. Sinonasal involvement was studied by using clinical and CT scores. Airflow obstruction, therapy requirement, and asthma triggering factors were carefully assessed. RESULTS: The proportion of patients with symptoms of rhinosinusitis was similar in both groups of asthmatic subjects (74% in patients with severe steroid-dependent asthma and 70% in patients with mild-to-moderate asthma). All subjects with steroid-dependent asthma versus 88% of subjects with mild-to-moderate asthma had abnormal CT scan results. The clinical (P <.05) and CT scan (P <.0005) severity scores were higher in the subjects with severe steroid-dependent asthma. In both groups the CT scan scores were correlated to the clinical scores (P <.0001 and P <.006), but only in the mild-to-moderate group were both scores correlated with high significance (P <.002 and P <.0005) to the absolute number of blood eosinophils. CONCLUSION: Frequency of rhinosinusitis in patients with mild-to-moderate or severe steroid-dependent asthma is similar; however, sinonasal involvement, as evaluated by clinical symptoms and CT scan imaging, is significantly greater in the patients with severe steroid-dependent asthma than in those with mild-to-moderate asthma.

Adolescent↗
PubMed2001

Effects of glucocorticoids on endogenous and transcellular metabolism of eicosanoids in asthma.

BACKGROUND: Human blood polymorphonuclear cells, which biosynthesize eicosanoids from the 5-lipoxygenase (5-LO) pathway, are likely to be involved in asthma, in which glucocorticoids represent the first line of therapy. Their effects on leukotriene release after a short course of treatment, which have been reported in several studies, are controversial. OBJECTIVE: We sought to investigate whether long-term oral glucocorticoids inhibit lipid mediators from the 5-LO pathway. METHODS: Twelve normal control subjects, 29 asthmatic subjects, and 50 glucocorticoid-dependent asthmatic subjects were included in the study. Polymorphonuclear cells were studied for endogenous and transcellular metabolism of eicosanoids. RESULTS: Total leukotriene B(4) production was significantly lower in cells from glucocorticoid-dependent asthmatic subjects (mean +/- SD, 177 +/- 26 ng/10(7) cells) than in control subjects (406 +/- 27), untreated asthmatic subjects (421 +/- 34), and asthmatic subjects treated with inhaled glucocorticoids (290 +/- 56). When incubated with arachidonic acid, these polymorphonuclear cells released very low amounts of 5(S)- and 12(S)-hydroxy-eicosatetraenoic acid (HETE), whereas endogenous 15(S)-HETE was found in substantial amounts. The transformation of exogenous 15(S)-HETE into 5(S),15(S)-diHETE and lipoxins was significantly more important in untreated asthmatic subjects than in control subjects and glucocorticoid-dependent asthmatic subjects. CONCLUSION: This study showed that long-term oral corticotherapy affects the 5-LO activity and leads to a decrease production of all metabolites in contrast to short-term or inhaled glucocorticoids. This study also questions the site of action of glucocorticoids in regulating the availability of arachidonic acid and potential eicosanoid regulation, as previously held in phospholipase A2 studies.

5-Lipoxygenase-Activating Proteins↗
PubMed2001

Proliferation and activation of bronchial epithelial cells in corticosteroid-dependent asthma.

BACKGROUND: Structural and functional characteristics of bronchial epithelial cells in corticosteroid-dependent asthma are unknown. OBJECTIVE: In bronchial biopsy specimens from 16 control, 9 untreated asthmatic, 9 inhaled corticosteroid-treated asthmatic, and 19 corticosteroid-dependent asthmatic subjects, we evaluated epithelium morphology and patterns of cell apoptosis, proliferation, and activation. METHODS: We used the terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) technique to study apoptosis. Immunohistochemistry was used to evaluate the expression of molecules related to apoptosis (such as Bcl-2 and P53), cell proliferation (PCNA), and cell activation (NFkappaB and CD40/CD40-L). RESULTS: Epithelium thickness was higher in corticosteroid-dependent asthmatic and control subjects than in inhaled corticosteroid-treated and untreated asthmatic subjects (P < .0001 and P <.0003). Very few TUNEL-positive epithelial cells were found in the 4 groups. Bcl-2 expression was higher in all groups of asthmatic subjects than in controls (P < .001). In corticosteroid-dependent asthmatic subjects, PCNA, NFkappaB, and CD40-L expression was higher than in inhaled corticosteroid-treated asthmatic (P < .001), untreated asthmatic (P <.001 and P < .04), and control (P < .01) subjects. CD40 expression was greater in corticosteroid-dependent asthmatic and untreated asthmatic subjects than in inhaled corticosteroid-treated asthmatic subjects (P < .0001 and P < .0006) and controls (P < .02 and P < .03). In corticosteroid-dependent asthma, PCNA expression was correlated with the epithelium thickness (P < .007). CONCLUSION: This study shows that in bronchial epithelial cells of corticosteroid-dependent asthma, markers of cell survival and proliferation are coexpressed with markers of cell activation, suggesting that in this disease epithelium repair is associated with a persistent activation state of epithelial cells.

Administration, Inhalation↗