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Biomedical subjects

B Wallaert

Publications and source records attributed to B Wallaert.

At least 91 records · Page 5Linked to original sources
PubMed1999

Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus.

Status asthmaticus (SA) is an acute respiratory failure combining an acute bronchospastic reaction with a severe airway inflammation. We previously reported an important influx of neutrophils and an increased secretion of interleukin-8 (IL-8) in patients with SA. The aim of this prospective study was to evaluate in bronchial lavage (BL) of patients with SA (n = 9) under mechanical ventilation (MV) the concentrations of cytokines and related mediators which have the ability to modulate inflammation, either proinflammatory (interleukin-1beta [IL-1beta], IL-6, tumor necrosis factor-alpha [TNF-alpha]), or anti-inflammatory mediators (IL-10, transforming growth factor-beta1 [TGF-beta1]), interleukin-1 receptor antagonist [IL-1Ra], soluble TNF receptor I and II [sTNFRI and II]). To determine the relative importance of both pro- and anti-inflammatory mediators, the net inflammatory activity was analyzed by the capacity of BL fluids (BLF) to increase intercellular adhesion molecule-1 (ICAM-1) expression in the human lung A549 epithelial cell line. These data were compared with those obtained from patients who required MV without respiratory disease (V, n = 4), controlled asthma (A, n = 11), and nonsmoking healthy volunteers (C, n = 8). Levels of IL-1, IL-6, TNF-alpha, and of the active form of TGF-beta1 were significantly higher in SA compared with the other groups. The concentrations of IL-1Ra, IL-10, the latent form of TGF-beta1, and of the sTNFRI and II were not significantly different between SA and V, albeit higher in SA than in A and C. The ratio between IL-1Ra and IL-1beta was significantly higher in patients with SA compared with the other groups, whereas there was no difference for the ratio between both types of sTNFR and TNF-alpha. Despite a marked increase of anti-inflammatory mediators in BL from patients with SA, the net inflammatory activity was found to be proinflammatory and mainly due to the presence of bioactive IL-1beta (79% inhibition of ICAM-1 expression with anti-IL-1beta antibodies) and to a lesser extent TNF-alpha (32% inhibition with anti-TNF-alpha antibodies).

Adult↗
PubMed1999

Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation during status asthmaticus.

In order to assess inflammatory features related to severe asthma as compared with mild asthma, we investigated the secretion of 92 kDa gelatinase matrix metalloproteinase (MMP-9) in bronchial lavages of six patients undergoing mechanical ventilation (MV) for status asthmaticus (SA) and in six patients with mild asthma. Ten healthy nonventilated patients and four patients under MV without preexisting respiratory disease were also investigated. Patients with SA were characterized by prominent neutrophilic inflammation (82 +/- 4% versus 10% in mild asthma). On the basis of enzymatic and immunological analysis, results showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9) concentration in epithelial lining fluid (ELF) from patients with SA, together with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase (MMP-3) and detectable concentration of free metallogelatinolytic activity (1-5 micrograms gelatin hydrolyzed/48 h/ml ELF). Concomitant elevated level of tissue inhibitor of metalloproteinase-1 (TIMP-1) was shown only in patients with SA, thus counterbalancing, at least partially, excess of activated 92 kDa gelatinase. Acutely enhanced albumin levels were only observed in patients with SA; in addition, 92 kDa gelatinase and albumin levels were significantly and positively correlated (r = 0.96, p < 0.0001), suggesting that 92 kDa gelatinase may account for increased bronchial permeability in patients with SA. Several arguments support that 92 kDa gelatinase during SA originates both from numerous activated chemoattracted neutrophils and from activated bronchial epithelial cells in response to in situ lung injury. The fact that no relevant change in ELF, albumin, MMP-9, MMP-3, TIMP-1, or laminin degradation products was observed during mild asthma, strongly supports that the mechanism of airway inflammation in SA is quite distinct from that observed in mild asthma.

Adult↗
PubMed1999

Increased glucocorticoid receptor beta in airway cells of glucocorticoid-insensitive asthma.

Glucocorticoid (GC)-insensitive asthma is a challenging clinical problem that can be associated with life-threatening disease progression. The molecular basis of GC insensitivity is unknown. Alternative splicing of the GC receptor (GCR) pre-mRNA generates a second GCR, termed GCRbeta, which does not bind GC but antagonizes the transactivating activity of the classic GCR. Thus increased expression of GCRbeta could account for glucocorticoid insensitivity. Bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) were examined for GCRbeta immunoreactivity using a GCRbeta-specific antibody by immunohistochemical staining. Cell localization of GCRbeta expression was performed using a double immunostaining technique. Patients with GC-insensitive asthma expressed a significantly higher number of GCRbeta-immunoreactive cells in their BAL and peripheral blood than GC-sensitive asthmatics or normal control subjects. Furthermore, GCRbeta expression in GC-insensitive asthma was particularly high in airway T cells, which are thought to play a major role in the pathogenesis of asthma. We also examined the expression of GCRbeta in specimens from the airways of patients with chronic bronchitis. In chronic bronchitis, few cells were GCRbeta-positive and their numbers did not differ significantly from normal control subjects. We conclude that GC-insensitive asthma is associated with increased expression of GCRbeta in airway T cells.

Adult↗
PubMed1999

Increased expression of IL-12 receptor mRNA in active pulmonary tuberculosis and sarcoidosis.

Cytokines have been implicated in the pathophysiology and development of pulmonary diseases such as tuberculosis and sarcoidosis. In particular, the numbers of cells expressing Th1-type cytokines such as IFN-gamma and IL-12 are increased within the lungs of patients with these granulomatous diseases. As a factor promoting the commitment of naive lymphocytes to a Th1-type profile of cytokine expression, IL-12 may be pivotal in the cascade of proinflammatory events within the airways. In this study, we examined the expression of the IL-12 receptor (IL-12R) mRNA in bronchoalveolar lavage (BAL) fluid from patients with active pulmonary tuberculosis (n = 6) and active pulmonary sarcoidosis (n = 6), and from allergic asthmatics (n = 6) and normal control subjects (n = 6). Bronchoscopy with BAL was undertaken, and cell cytospins were examined using the technique of in situ hybridization. There was a significant increase in the numbers of cells expressing mRNA for both beta(1) and beta(2) subunits of the IL-12R in active pulmonary sarcoidosis (p < 0.02, p < 0.01, respectively) and active pulmonary tuberculosis (p < 0.01, p < 0.005, respectively) compared with normal control subjects. In contrast, the allergic asthmatic patients exhibited a significant decrease in the number of IL-12R mRNA-positive cells (both beta(1) and beta(2) subunits (p < 0.01, p < 0.005, respectively), compared with the normal control subjects. These patients did, however, exhibit a significant increase in IL-4R mRNA, which was not evident in those with either tuberculosis or sarcoidosis when compared with normal subjects (p < 0.05). Colocalization studies demonstrated that CD8+ve cells are a principal site for the expression of IL-12R in tuberculosis. In sarcoidosis, IL-12R was expressed both on CD4+ve and CD8+ve cells. The increased expression of receptors for IL-12 in granulomatous diseases such as pulmonary tuberculosis and sarcoidosis provides evidence supporting the commitment of lymphocytes to a Th1-type cytokine profile in vivo.

Adult↗
PubMed1999

Overexpression of alveolar macrophage gelatinase B (MMP-9) in patients with idiopathic pulmonary fibrosis: effects of steroid and immunosuppressive treatment.

Alveolar macrophages (AM) express gelatinase B, a member of the matrix metalloproteinase family involved in the degradation and remodeling of extracellular matrix components. We evaluated the expression of gelatinase B in the course of idiopathic pulmonary fibrosis (IPF) by studying alveolar macrophages in culture AM and bronchoalveolar lavage fluid from 12 untreated patients with IPF, 11 patients with IPF under treatment with steroid and immunosuppressive agents, and 10 control subjects. By using zymography and quantitative image analysis, latent gelatinase B, as well an 88-kD active form, were investigated in culture medium (24 h) of AMs and were found to be significantly increased (P < 0.01) in untreated patients exhibiting severe IPF when compared with control subjects (4.1 +/- 1.7 versus 0.3 +/- 0.2 10(5) arbitrary units [AU]/10(4) AM for the 92-kD form). Concomitant studies of gelatinase B levels associated with cultured AM extracts or freshly harvested AM showed similar results, both at the mRNA and protein levels, respectively. Immunocytochemical studies on freshly harvested AM demonstrated that the enzyme was located mainly at the cell, suggesting some involvement of gelatinase B in AM migration. In contrast, gelatinase B activity secreted by AM tended to be normal in patients with IPF under steroid and immunosuppressive treatment. Simultaneously, level of the gelatinase B activity in epithelial lining fluid was increased in untreated IPF patients, whereas it was normal in treated patients. These results suggest that AM of patients with IPF are primed for gelatinase B expression and that steroid and immunosuppressive treatment induces negative modulation of the gelatinase B overexpression. We conclude that gelatinase B may play a role in lung remodeling in IPF.

Base Sequence↗
PubMed1999

Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis.

STUDY OBJECTIVES: Allergic bronchopulmonary aspergillosis (ABPA) is the result of an immune reaction to antigens of Aspergillus fumigatus, which colonizes the bronchial lumen of affected individuals. Presently, the recommended treatment of ABPA, mainly for acute episodes of exacerbations, is administration of glucocorticoids. We initiated this study to analyze the effects of itraconazole on the clinical, biological, and functional parameters in patients with ABPA. PATIENTS: in this report, we describe the follow-up of 14 asthmatic patients who presented with ABPA. During the 2-year reference period (a 2-year period before the introduction of itraconazole), 14 patients were treated with inhaled corticosteroids and 12 of the 14 received oral glucocorticoids. During the itraconazole treatment period, the patients were treated with oral itraconazole, 200 mg/d, for at least 12 months. RESULTS: During the 2-year reference period, no significant clinical, immunologic, and functional improvement was observed on a long-term basis. During the itraconazole treatment period, a clinical improvement was observed. Blood eosinophilia, serum total IgE levels, and serum precipitating antibodies against A fumigatus antigen significantly decreased. No decrease of specific IgE against A fumigatus spp was observed. All patients experienced a partial improvement in pulmonary function tests: FEV(1) significantly increased from 1,433 +/- 185 to 1,785 +/- 246 mL/s (p < 0.01). All patients successfully lowered oral glucocorticoid dose when receiving itraconazole. In 7 of 14 patients receiving itraconazole, the removal of oral glucocorticoids was possible. CONCLUSION: These results demonstrate the efficacy of itraconazole in ABPA in reducing or eliminating the need for glucocorticoid therapy, along with clinical, biological, and functional improvement.

Adult↗
PubMed1999

[Interstitial lung disease induced by timolol eye solution].

Timolol maleate is a beta-blocker widely used in topical administration for open angle glaucoma. We report a case of interstitial pneumopathy which developed in a 58-year-old patient who was given timolol eyedrops (2 drops b.i.d. since 1986). The patient presented with cough and dyspnea and was found to have a restrictive disorder leading to hypoxemia (68 mmHg at rest and 51 mmHg during exercise). Bronchial lavage fluid had high lymphocyte (28%) and neutrophil (7%) counts. Transbronchial biopsies demonstrated moderate fibrous thickening of the interalveolar walls. Timolol eyedrops were stopped. Three months later, the patient was asymptomatic with normal lung function, chest x-ray and thoracic CT-scan.

Adrenergic beta-Antagonists↗
PubMed1999

[Sjögren's syndrome and necrotizing sarcoid-like granulomatosis].

We report the first description of a Sjögren's syndrome associated with nectrotizing sarcoid-like granulmatosis. A 62-year old woman was admitted for diagnostic exploration of fatigue, weight loss, and fever at 38 degrees C which had progressed for more than 3 months. Chest X-ray showed several pulmonary opacities. There was a history of tuberculosis and thyroiditis at the age of 20 years. Physical examination revealed a sicca syndrome. There was no objective evidence of respiratory disease. Her heart and chest were clear on auscultation. The patient had autoantibodies for SSa and SSb specific antigens. Minor salivary gland biopsy gave a score of 3 in the Chisholm classification. Chest X-ray and CT-scan showed diffuse infiltrative opacities which were dense and peripheral with no retraction. Bronchoalveolar lavage, and bronchial and transbronchial biopsies were non-specific. Surgical lung biopsy showed typical aspects of necrotizing sarcoid-like granulomatosis. After high-dose pulse corticosteroid therapy, the opacities disappeared with no recurrence under oral steroids at three years.

Adrenal Cortex Hormones↗
PubMed1999

[Pulmonary hemorrhagic syndrome after inhalation of cocaine].

Frequency of recreational abuse of cocaine is increasing. We report the case of a patient who developed an acute anemia associated with an alveolar hemorrhage after repeated inhalation of cocaine. He presented with daily hemoptysis and dyspnea. Chest-X ray and CT scan showed bilateral micronodular opacities. The fibroscopic alveolar lavage fluid showed fresh blood. DLCO/VA was 117% predicted. With oxygen therapy and no blood transfusion the evolution was positive within 48 hours, without relapse. The occurrence of hemoptysis in subjects who inhale cocaine must lead to suspect cocaine induced-pulmonary hemorrhage.

Adolescent↗
PubMed1998

Modulation of cell adhesion molecules on human endothelial cells by eosinophil-derived mediators.

Mechanisms that allow a selective eosinophil emigration in different eosinophilic lung diseases remain poorly understood. In this study, we tested the hypothesis that eosinophils might participate in their own recruitment, particularly through adhesion molecule expression on human endothelial cells (EC). Blood eosinophils from donors with blood eosinophilia were purified and maintained in culture medium for 1 and 18 h. The expression of ICAM-1, E-selectin, and VCAM-1 on human umbilical vein endothelial cells (HUVEC) was evaluated by ELISA and flow cytometry analysis after addition of eosinophil supernatants. Eosinophil supernatants collected after 1 h induced a weak increase of CAM expression on HUVEC. In contrast, supernatants from eosinophils cultured for 18 h considerably amplified ICAM-1, E-selectin, and VCAM-1 expression on the surface of EC. These levels of CAM expression (in optical density determined by ELISA) were about two- or threefold more important than those obtained with eosinophil supernatants collected after a 1-h culture. The characterization of the implicated molecules showed that anti-IL-1beta antibodies significantly inhibited ICAM-1, E-selectin, and VCAM-1 expression, whereas anti-TNF-alpha antibodies only induced a moderate inhibition. Our data support the hypothesis that eosinophils, through the release of at least IL-1beta and TNF-alpha, might participate in the amplification of the inflammatory reaction by activating the vascular endothelium.

Cell Membrane↗
PubMed1998

Early modifications of chemokine production and mRNA expression during rush venom immunotherapy.

The mechanism by which specific immunotherapy exerts its beneficial effect remains unclear. Chemokines are implicated in inflammatory and allergic diseases, in particular via their ability to induce histamine release from basophils, a potential early target of rush venom immunotherapy (RVIT), In this study, the authors evaluated ex vivo regulated upon activation normal T-cell expressed and secreted (RANTES), interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) production and mRNA expression by mononuclear cells (MNC) from nine patients undergoing a 3.5-h ultra rush treatment, before treatment at Day 0 (D0), at the end of the 3.5-h of the rush at Day 4h (D4h), at Day 15 (D15) and Day 45 (D45) after treatment. Increased RANTES release and mRNA expression were observed in 24-h culture of peripheral blood MNC collected at D4h. This was followed by a decrease in the production of RANTES, IL-8 and MCP-1, 45 days after initiation of RVIT. The same pattern was observed after in vitro venom stimulation of MNC. At the mRNA level, similar profiles were observed except for IL-8 mRNA which inversely increased during RVIT. These results suggest that RVIT is associated with a general decrease in chemokines which may explain, in part, the clinical efficacy of specific immunotherapy.

Animals↗
PubMed1998

Respiratory involvement in relapsing polychondritis. Clinical, functional, endoscopic, and radiographic evaluations.

Although respiratory involvement occurs in 50% of patients with relapsing polychondritis (RP) and augurs a poor prognosis, few previous studies have provided complete descriptions of respiratory tract involvement. For this reason, we investigated the respective role of clinical, functional, endoscopic, and radiographic (computed tomography [CT]) examinations in 9 consecutive patients with RP and lower respiratory tract localization. All exhibited cough, dyspnea, and wheezing. Eight had a nonreversible obstructive pattern with a marked decrease of the maximal flow ratio at 75% and 25% of vital capacity. Rotman functional criteria were evaluated to differentiate upper from lower respiratory tract involvement; they were consistent with the results of other examinations in 4/9 cases. Endoscopic examination showed moderate to severe inflammation in 8/9 patients; tracheal stenosis was present in 6/9 patients, bronchial stenosis in 4/9 patients, and tracheal collapse in 7 cases. CT showed tracheal stenosis in 8/9 patients (diffuse, 7; localized, 1) and bronchial stenosis in 6/9 patients. Tracheobronchial wall thickening and/or calcifications were observed in 7 cases. Clinical symptoms are of poor specificity for defining respiratory involvement precisely, although degree of dyspnea is correlated to the decrease in forced expiratory volume in 1 second (FEV1). Functional criteria were helpful in evaluating the obstructive ventilatory defect but did not differentiate, in most cases, the respective part of lower and upper respiratory involvement when using Rotman criteria. Compared to CT findings, endoscopic examination failed to identify tracheal and bronchial stenosis and tracheal wall alterations at an early stage of the disease. In our series CT appears to be a reliable method to identify tracheal and bronchial involvement and can be repeated safely during the course of the disease.

Adult↗
PubMed1998

Bronchial neutrophilia in patients with noninfectious status asthmaticus.

Cellular events that occur in status asthmaticus (SA) remain poorly investigated. Autopsy studies frequently emphasized about the presence of eosinophils in bronchial airway wall, whereas recent studies reported increased number of neutrophils in patients dying of sudden-onset fatal asthma. Mucus plugs occluding the bronchial lumen are almost constant features during SA. Bronchial lavage (BL) may be useful to remove mucus plugs in cases of atelectasis and/or refractory SA. We investigated the contribution of different cell types and cellular mediators (neutrophil elastase, eosinophil cationic protein [ECP], histamine, interleukin-8 [IL-8]) to the pathogenesis of SA. We studied 16 BL from eight patients undergoing mechanical ventilation (MV) for SA (time interval from onset of MV = Day 0 to Day 11), four BL from patients undergoing MV without preexisting respiratory disease (V), 11 BL from patients with stable asthma (A) and eight BL from healthy controls (C). SA exhibited higher number and percentage of neutrophils (81.5 +/- 4.5%) than V (44.3 +/- 12.2) (p < 0.05), A (6.9 +/- 2.7) and C (9.5 +/- 3.8) (p < 0.0001), and higher number of eosinophils than V, A, and C (p < 0.01). Neutrophil elastase, ECP, and IL-8 levels were dramatically increased in SA. Histamine was higher in SA than in C and V (p < 0.05). Bronchial neutrophilia was not related to concomitant bacterial infection as bacteriological cultures were positive in only three BL. Eosinophils, mast cells and histamine were higher in BL performed within the first 48 h of MV (p < 0.05) than in BL performed later on. Our results indicate that bronchial inflammation in SA differs from bronchial inflammation in mild asthma. Persistent bronchial neutrophilia is associated with increased eosinophils and mast cells in the early phase of SA. Neutrophils may result in tissue damage and participate to the shedding of the epithelium in SA.

Adult↗
PubMed1998

Bronchiolitis obliterans organizing pneumonia syndrome primed by radiation therapy to the breast. The Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires (GERM"O"P)

Reports of bronchiolitis obliterans organizing pneumonia (BOOP) occurring in women after radiation therapy for breast cancer have suggested that radiation to the lung could participate in the development of BOOP. We now describe the clinical, radiographic, functional, and bronchoalveolar lavage characteristics of this syndrome in a series of 15 patients reported to the Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P) in France. All 15 women (60 +/- 6 yr of age) fulfilled the following inclusion criteria: (1) radiation therapy to the breast within 12 mo, (2) general and/or respiratory symptoms lasting for at least 2 wk, (3) lung infiltrates outside the radiation port, and (4) no specific cause. The patients presented with fever, nonproductive cough, mild dyspnea, and peripheral alveolar opacities on chest radiograph with a characteristic migratory pattern. In five patients, BOOP was found at lung pathologic analysis. In all the patients dramatic improvement was obtained with corticosteroids, but relapses occurred in 12 patients while tapering or after stopping corticosteroids. This report demonstrates that a characteristic BOOP syndrome may occur after radiation therapy to the breast, including tangential radiation to the lung, thus suggesting that radiation therapy may prime the development of BOOP.

Aged↗
PubMed1998

Apoptosis, proliferation, and expression of Bcl-2, Fas, and Fas ligand in bronchial biopsies from asthmatics.

The in situ apoptosis and the expression of molecules involved in this process, such as Bcl-2, Fas, and its ligand, Fas ligand (FasL), were examined in bronchial biopsies from healthy control subjects and from steroid-untreated or -treated asthmatics, using terminal transferase-mediated deoxyuridyltriphosphate nick-end labeling and immunohistochemical techniques, respectively. Bronchial submucosa from steroid- untreated asthmatics showed an increase in the number of eosinophils and a decrease in that of apoptotic cells compared with that of control subjects, but no significant changes in the number of T lymphocytes or in that of cells expressing Bcl-2, Fas, or FasL. Treatment with steroids reduced airway eosinophilia and augmented the proportion of apoptotic eosinophils. Compared with control subjects or untreated patients, steroid-treated asthmatics exhibited increased expression of Bcl-2, Fas, FasL, and of proliferating cell nuclear antigen (PCNA) in their bronchial epithelium, without changes in the number of apoptotic cells. Moreover, the intensity of the expression of Bcl-2, Fas, and FasL correlates well with that of PCNA. We conclude that steroids may reduce the inflammatory cell infiltrate in the bronchial submucosa in part by promoting eosinophil apoptosis and by inducing the expression of FasL on bronchial epithelial cells. Treatment with steroids may also augment survival and proliferation of epithelial cells, possibly via the expression of Bcl-2 and PCNA.

Adult↗
PubMed1998

Transforming growth factor-beta1 in sarcoidosis.

Transforming growth factor-beta (TGF-beta) is a cytokine that promotes extracellular matrix accumulation and inhibits matrix degradation. Although the natural course of sarcoidosis is usually favourable, granuloma healing in the lung may result in pulmonary fibrosis and respiratory impairment in some patients. In this study TGF-beta1 was evaluated in bronchoalveolar lavage (BAL) fluid and culture supernatants of alveolar macrophages (AM) from 73 patients with biopsy-proven sarcoidosis. Disease activity was defined when patients recently developed or increased symptoms (cough, dyspnoea, systemic symptoms) and/or demonstrated increasing opacities on chest radiography. Pulmonary function tests were performed in all patients including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and the diffusing capacity of the lung for carbon monoxide (DL,CO). Fourteen patients with idiopathic pulmonary fibrosis (IPF) and 14 healthy subjects were investigated as a control group. Immunohistochemistry was used to evaluate the cell distribution of TGF-beta1 on lung specimens. TGF-beta1 levels in BAL and in AM supernatants were not different between sarcoidosis and healthy subjects, whereas they were markedly increased in IPF. However, the TGF-beta1 level was significantly increased in BAL fluid but not in AM supernatants from sarcoidosis with altered lung function, compared with patients with normal lung function. The TGF-beta1 level in BAL was increased in active sarcoidosis but this increased level was mainly related to the higher level observed in patients with altered lung function. TGF-beta1 levels in BAL correlated significantly with the lymphocyte percentage. TGF-beta1 staining assessed by immunohistochemistry was intense in epithelioid histiocytes comprising non-necrotizing granuloma and in bronchiolar epithelial cells, in hyperplastic type II pneumocytes and occasionally in AM. This study supports the hypothesis that overproduction of transforming growth factor-beta1 is associated with functional impairment in patients with pulmonary sarcoidosis.

Adult↗