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Biomedical subjects

D Dusser

Publications and source records attributed to D Dusser.

At least 19 recordsLinked to original sources
PubMed2006

[Characteristics of mild asthma: clinical signs and medication use. Position statement of the Mild Asthma Working Group (174)].

OBJECTIVE: To update on the state of knowledge in mild asthma (intermittent and persistent mild asthma, according to the GINA classification) review the literature, and the position statement of the French Mild Asthma Working Group. METHODS: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the descriptive epidemiology, physiopathology, clinical signs, and management of mild asthma. The position of the working group on the descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation has been presented in a previous article. The present article focuses on the clinical features of mild asthma and the use of medication for it. RESULTS: Mild asthma was more frequent, more symptomatic, and less well controlled in children than in adults. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Patients with mild persistent asthma require controller medication every day: permanent low-dose inhaled corticosteroid monotherapy is the reference foundation treatment for persistent mild asthma. CONCLUSIONS: The present findings should help clinicians and guide them in their approach to managing this condition.

Administration, Inhalation↗
PubMed2006

The effect of tiotropium on exacerbations and airflow in patients with COPD.

This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 microg once daily (n=500) and placebo (n=510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients. The mean+/-sd number of exacerbations during the past year was 2.14+/-1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6+/-96.1 L.min-1 and the mean forced expiratory volume in one second (FEV1) was 1.37+/-0.45 L. Tiotropium significantly delayed the time to first exacerbation by approximately 100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Tiotropium also decreased HRU versus placebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV1, forced vital capacity, slow vital capacity and inspiratory capacity versus placebo. In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.

Aged↗
PubMed2006

[Characteristics of mild asthma: descriptive epidemiology and nature of bronchial inflammation. Position of the Mild Asthma Working Group].

INTRODUCTION: Update on the state of knowledge in the mild asthma (intermittent and persistent mild asthma, according to the GINA classification) literature, and position of a French Mild Asthma Working Group. STATE OF THE ART: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the epidemiology, physiopathology, clinical signs, and management of mild asthma. The present article shows the position of the working group on mild asthma descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation. Clinical signs and medicinal treatments will be presented in a second article. PERSPECTIVES: Between 50% and 75% of asthma patients, depending on the study, present mild asthma. Childhood-to-adulthood cohort monitoring found severity to be unchanged over developmental time. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Inflammation and airway-wall remodelling were always found, although of variable intensity, and non-specific (except for absence of infiltration by polymorphonuclear neutrophils). Corticosteroid therapy by inhalation reduces bronchial inflammation, but with little impact on airway-wall remodelling. CONCLUSION: The present findings should help clinicians in identifying and understanding mild asthma.

Adrenal Cortex Hormones↗
PubMed2005

Malnutrition in adults with cystic fibrosis.

OBJECTIVE: To determine the prevalence and clinical features of malnutrition and its relationship with the CFTR genotype in a cystic fibrosis (CF) adult population. DESIGN: Cross-sectional study. SETTING: Department of Pulmonology, Cochin Hospital, Paris, France. SUBJECTS: 163 CF adults seen between 1997 and 1999. RESULTS: Mean age was 28.8 y. Mean body mass index (BMI) was 19.1 kg/m2. Malnutrition (BMI<18.5 kg/m2) was seen in 81 patients (49.7%). Its severity was associated with diagnosis of CF before the age of 18 y (P<0.01), FEV1 values below 30% (P<0.01), the yearly decline of FEV1 (P<0.01), pancreatic insufficiency (P<0.01) and gastro-oesophageal reflux (P<0.01). Malnutrition was observed in 58.7% of patients with a severe CFTR genotype but in 28.6% of patients with a mild genotype (P<0.001). CONCLUSION: Malnutrition remains frequent in adults with CF except in patients presenting with a mild CFTR genotype (leading to a mild phenotype and to later diagnosis).

Adult↗
PubMed2005

Double-blind, double-dummy, multinational, multicenter, parallel-group design clinical trial of clinical non-inferiority of formoterol 12 microg/unit dose in a b.i.d. regimen administered via an HFA-propellant-pMDI or a dry powder inhaler in a 12-week treatment period of moderate to severe stable persistent asthma in adult patients.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) have traditionally used CFCs as propellants. However, the worldwide phase-out of CFCs has necessitated the development of new pMDIs that use alternative propellants. One such replacement is the hydrofluoroalkane HFA-134a. OBJECTIVES: This study sought to establish the clinical non-inferiority of a new HFA-134a-containing pMDI to a conventional dry powder inhaler (DPI) in the administration of formoterol to adult patients with moderate-to-severe, stable persistent asthma. The secondary aim was to collect safety data in a multiple-dose long-term study. METHODS: During this multicenter, double-blind, parallel study, 500 patients were randomized to receive 12 microg of formoterol twice daily for 12 weeks via either an HFA pMDI or a DPI. If necessary, the dose could be increased to 24 microg twice daily. At baseline, all patients (aged 18-70 years) had an FEV1 40-80% of predicted and a documented positive response to the reversibility test. RESULTS: After 12 weeks' therapy, the adjusted mean morning PEFR was 343.69 l/min in the formoterol HFA pMDI group and 344.56 l/min in the formoterol DPI group. Because the lower limit of the 95% CI for the between-group difference (-11.64 l/min) was well within the non-inferiority margin (-20 l/min), the HFA device was deemed clinically non-inferior to the DPI device. This finding was confirmed when evening PEFR and FEV1 were assessed. Both formulations of formoterol were well tolerated during prolonged multiple dosing. CONCLUSIONS: This study provides evidence that the new HFA-formulated formoterol pMDI has a similar efficacy and safety profile to the conventional formoterol DPI in the treatment of patients with moderate-to-severe asthma.

Adult↗
PubMed2004

[The "Compli'Asthme" therapeutic observation survey on good use of inhaled drugs for asthma: perception by general practitioners].

A cross sectional survey was conducted in 2000 in coordination with the CHIESI medical representatives among 1758 French physicians caring for patients with persistent asthma (80% general practitioners, 20% specialists). This "Compli'Asthme" survey was based on a self-administered questionnaire designed to learn more about the physicians' experience with good use of inhaled drugs and to collect information on therapeutic observance, corticophobia, and use of prescribed inhalers. Poor observance was noted as an important problem by 58-85% of the participants. Most of the problems were related to inability to use the inhaler properly (children, elderly subjects) or to patients forgetting to take their medications (adults, parents). For 58% of the participating physicians, corticophobia is frequent. The patients are worried about the anabolizing effect, secondary effects, and dependence. When there is a potential problem with corticophobia, physicians generally question the patients and provide explanations to achieve good observance. Patient preference is taken into consideration by 86% of the physicians prescribing inhalation devices; 90% demonstrate use of the device at the first prescription and 68% make repeated demonstrations at subsequent consultations. For 56-87% of the physicians, poor therapeutic observance, corticophobia, and poor use of the inhaler can be detected and corrected. Patient education is an important element for 77% of the physicians for improving observance and achieving good use of the inhaler. When poor observance and poor use of the inhaler occur, the physicians responding to this questionnaire applied the currently recommended guidelines.

Administration, Inhalation↗
PubMed2003

[Value of MRI for the diagnosis of cardiac involvement in sarcoidosis].

PURPOSE: The aim of the study was to assess the place of cardiac Magnetic Resonance Imaging (MRI) in patients with sarcoidosis with or without cardiac involvement. MATERIALS AND METHODS: Fifty patients with histologically-proven sarcoidosis underwent initial cardiac evaluation including MRI, ECG, holter ECG, echocardiography. Seven of them had cardiac involvement (cardiac insufficiency, auriculo-ventricular block, bundle-branch block). Fiveteen patients had a second evaluation at 10-month follow-up. MRI was classified in three stages, on the base of literature data (stage 1 "granulomatous", stage 2 "exsudative", stage 3 "fibrotic"). RESULTS: A good correlation between the type of the sarcoidosis and MRI was observed: patients with cardiac involvement had all stage 2 MRI; patients with quiescent sarcoidosis had normal or stage 3 MRI; patients without cardiac involvement had all stages on MRI. A good correlation was observed between cardiac MRI abnormalities and evolution of sarcoidosis. Patients under corticoid, with or without cardiac involvement all had regression of MRI lesions and sarcoidosis. In 2 cases, MRI was predictive of clinical cardiac involvement. CONCLUSION: Cardiac MRI is a useful non-invasive method for the early diagnosis and follow-up of cardiac sarcoidosis.

Adrenal Cortex Hormones↗
PubMed2003

Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-beta kinase pathway.

Inhaled fluticasone propionate (FP) is widely used to reduce pulmonary inflammation in chronic obstructive pulmonary disease, but the potential effects of FP on airway epithelial cells from patients with cystic fibrosis (CF) are unknown. In CF disease, a nonregulated inflammatory lung response occurs through exaggerated nuclear factor (NF)-kappaB activation and elevated pro-inflammatory cytokines production by airway epithelial cells. To determine whether FP reduces cytokine production in bronchial epithelial cells via NF-kappaB, the authors investigated the nonstimulated and the Pseudomonas aeruginosa lipopolysaccharide (LPS) stimulated production of NF-kappaB-dependent interleukin (IL)-6, IL-8 and RANTES (regulated on activation, T-cell expressed and secreted) along with the activation of NF-kappaB in non-CF and CF human bronchial gland epithelial cells. It was demonstrated that a relevant concentration of FP (10(-8) M) inhibited constitutive and P. aeruginosa LPS-induced IL-6 and IL-8 production of non-CF and CF bronchial epithelial cells. Interestingly, the expression of two IkappaB kinases (IKK)-alpha/beta, the degradation of cytosolic IkappaB-beta inhibitor and the NF-kappaB deoxyribonucleic acid binding activity were markedly reduced after FP treatment in both CF and non-CF bronchial epithelial cells. It was shown by the authors that fluticasone propionate exerts an anti-inflammatory effect by blocking a signal transduction leading to a reduced level of IkappaB-alpha/beta kinases in bronchial epithelial cells. In particular the strong effect on the IkappaB-beta kinase, which is known to be elevated in bronchial epithelial cells in cystic fibrosis patients, was observed.

Analysis of Variance↗
PubMed2001

Relationship between IkappaBalpha deficiency, NFkappaB activity and interleukin-8 production in CF human airway epithelial cells.

Several recent reports have suggested that airway inflammation may precede infection and relate to an endogenous dysregulation of pro-inflammatory cytokines in cystic fibrosis (CF) airways. Evidence suggests that activation of the nuclear factor kappa B (NFkappaB), which regulates the inflammatory gene transcription, depends on the degradation of the inhibitory factor IkappaBalpha. We show that, in in situ human DeltaF508 CF bronchial tissues, inhibitor factor IkappaBalpha is not present in gland cells, although endogenous levels of chemokine IL-8 are high. These data are confirmed by studying cultured CF human bronchial gland cells, in which a lack of cytosolic IkappaBalpha and high levels of activated NFkappaB, concomitant with IL-8 overproduction (a 13-fold increase) are found when compared to non-CF bronchial gland cells. Interestingly, treatment of CF gland cells with the isoflavone genistein, a well known CFTR mutant Cl(-) channel stimulator, results in a significant decrease ( P < 0.001) in IL-8 production down to levels released by non-CF gland cells. The addition of genistein also reverses the effects of lipopolysaccharide (LPS) Pseudomonas-aeruginosa-induced nuclear translocation of NFkappaB by increasing IkappaBalpha protein level (65%) in CF gland cells. Our data indicate that the induction of IkappaBalpha protein in CF airway glandular epithelial cells may be a novel mechanism by which IL-8-mediated lung inflammatory events are markedly reduced in CF patients, at least at the airway glandular level.

Bronchi↗
PubMed2001

[First consultation for asthma].

The first medical visit is an essential moment of asthma management because it is a chronic disease needing a long term follow-up. This initial assessment which takes time, can be done gradually, on several days or even weeks. Once the differential diagnosis is excluded, the diagnosis of asthma is confirmed and its severity assessed. The identification of precipitant factors of asthma exacerbations goes through a detailed interview. Planning a therapeutic and supervision strategy with the patient has for goal the control of the disease and improvement of quality of life. Including the patient in the management of his asthma is only possible if he has been educated, patient education must be controlled and reinforced all the long of further medical visits.

Asthma↗
PubMed2001

Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa.

Airway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous DeltaF508+/+CF patients versus non-CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non-CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0.001). The number of T lymphocytes was higher at the CF distal level (P = 0.035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0.033) in the CF surface epithelium, which overexpressed ICAM-1 but not VCAM-1 and E-selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease.

Adult↗
PubMed2001

Improved activity of an actin-resistant DNase I variant on the cystic fibrosis airway secretions.

In cystic fibrosis (CF), actin and DNA originating from inflammatory cells contribute to the thickness of airway secretions. Actin can bind to DNA-rich fibers and potently inhibit the enzymatic activity of rhDNase. The in vitro effects of the actin-resistant rhDNase variant (A114R) were analyzed and compared with those of the wild-type rhDNase. Frozen and thawed CF airway secretions were incubated for 30 min with different concentrations (0.1, 0.5, 1, 5, or 10 microg/ml) of either actin-resistant rhDNase or wild-type rhDNase. We observed that both the wild-type and the actin-resistant rhDNase significantly decreased (p < 0.05 and p < 0.001, respectively) the airway secretion viscosity. The decrease in airway secretion viscosity was significant even at low concentrations (0.1 microg/ml) of the actin-resistant variant. Incubation with the actin-resistant variant resulted in a significant decrease (p < 0.02) of the airway secretion contact angle and cough transport. A significantly higher (p < 0.01) increase in contact angle and cough transport of airway secretions was observed at 10 microg/ml with the actin-resistant variant as compared with the wild-type rhDNase. The present study had demonstrated that the actin-resistant rhDNase variant (A114R) has an enhanced capacity to improve the physical properties and cough transport of airway secretions from patients with cystic fibrosis.

Actins↗
PubMed2001

Brain natriuretic peptide blood levels in the differential diagnosis of dyspnea.

STUDY OBJECTIVES: In dyspneic patients without left ventricular enlargement, it may be difficult to differentiate between obstructive lung disease and diastolic heart failure. Determination of plasma brain natriuretic peptide (BNP) levels, known to increase with ventricular stretch, may be of clinical relevance in this situation. We compared the discriminant power of BNP blood levels and of echocardiography in patients with either chronic obstructive lung disease or diastolic heart failure. PATIENTS: Twenty-six New York Heart Association class III dyspneic patients with normal left ventricular systolic function were enrolled: 17 patients with chronic obstructive lung disease and 9 patients with unequivocal diastolic heart failure. RESULTS: Echocardiographic data were unable to accurately differentiate between the two groups, whereas BNP levels were significantly and markedly higher in patients with diastolic heart failure when compared to those with obstructive lung disease (224 +/- 240 pg/mL vs 14 +/- 12 pg/mL, p < 0.0001). CONCLUSIONS: These preliminary results warrant a prospective, large-scale evaluation of the value of BNP assay for determining diastolic dysfunction, a common cause of dyspnea in elderly patients, and differentiating it from other diagnoses such as obstructive lung disease.

Aged↗
PubMed2000

High susceptibility for cystic fibrosis human airway gland cells to produce IL-8 through the I kappa B kinase alpha pathway in response to extracellular NaCl content.

Increasing evidence suggests that in airways from cystic fibrosis (CF) patients, inflammation may precede bacterial infection and be related to an endogenous dysregulation of proinflammatory cytokines in airway epithelial cells. Several investigators have reported that, in CF airway fluids, elevated NaCl concentrations may also contribute to the diseased state by inhibiting the bactericidal properties of airway fluid. Because many proinflammatory cytokines are transcriptionally regulated by the NF-kappa B, we investigated whether an elevated extracellular NaCl content in airway fluids significantly impaired the regulation of the NF-kappa B/I kappa B alpha complex and the chemokine IL-8 production in primary non-CF and CF human bronchial gland epithelial cells. Exposure of non-CF gland cells to hypotonic (85 mM) NaCl solution, compared with isotonic (115 mM) NaCl and hypertonic (170 mM) NaCl solutions, resulted in a significant decrease in IL-8 production that was paralleled by a strong inhibition of activated NF-kappa B associated with an increased cytosolic expression of I kappa B alpha and a decrease in the I kappa B kinase alpha protein level. In CF gland cells, we demonstrated that, compared with the high IL-8 in an hypertonic solution, the release of IL-8 was significantly reduced 2-fold in an isotonic solution and 5-fold in a hypotonic solution. Strikingly, exposure of CF bronchial gland cells to either hypotonic or isotonic milieu did not result in a marked inhibition of the activated NF-kappa B/I kappa B alpha system. This is the first demonstration that primary human CF bronchial gland cells exhibit abnormally high IL-8 production through constitutively activated NF-kappa B and high I kappa B kinase alpha level, whatever the hypo-, iso-, and hypertonic NaCl milieu.

Adolescent↗