References of "LOUIS, Renaud"
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See detailMatrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation
Guéders, Maud ULg; Balbin, M.; Rocks, Natacha ULg et al

in Journal of Immunology (2005), 175(4), 2589-2597

Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has recently been reported to be increased in ... [more ▼]

Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has recently been reported to be increased in the bronchoalveolar lavage fluid (BALF) from asthmatic patients. To evaluate the role of MMP-8 in asthma, we measured MMP-8 expression in lung tissue in an OVAsensitized mouse model of asthma and addressed the effect of MMP-8 deletion on allergen-induced bronchial inflammation. MMP-8 production was increased in lungs from C57BL/6 mice exposed to allergens. After allergen exposure, MMP-8-1-mice developed an airway inflammation characterized by an increased neutrophilic inflammation in BALF and an increased neutrophilic and eosinophilic infiltration in the airway walls. MMP-8 deficiency was associated with increased levels of IL-4 and antiOVA IgE and IgG1 in BALF and serum, respectively. Although allergen exposure induced an enhancement of LPS-induced CXC chemokine, KC, and MIP-2 levels in BALF and lung parenchyma, no difference was observed between the two genotypes. Inflammatory cell apoptosis was reduced in the lungs from MMP-8(-/-) mice. For the first time, our study evidences an important role of MMP-8 in the control of neutrophilic and eosinophilic infiltration during allergen-induced lung inflammation, and demonstrates that the anti-inflammatory effect of MMP-8 is partly due to a regulation of inflammatory cell apoptosis. [less ▲]

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See detailMéta-analyse des études de qualite de vie internationales.
Louis, Renaud ULg

in Revue des Maladies Respiratoires (2005), 22(2 Pt 3), 446-8

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See detailLes protheses tracheobronchiques: experience au CHU de Liege
Corhay, Jean-Louis ULg; Duysinx, Bernard ULg; Louis, Renaud ULg et al

in Revue Médicale de Liège (2004), 59(10), 577-83

During recent years the endobronchial prostheses has become an essential part of the therapeutic bronchoscopy in order to remove obstructions from the proximal airways, in malignant diseases, (principally ... [more ▼]

During recent years the endobronchial prostheses has become an essential part of the therapeutic bronchoscopy in order to remove obstructions from the proximal airways, in malignant diseases, (principally lung cancer) are in benign disorders. In this article we report our last ten year experience in stenting of the tracheo-bronchial tree. We will retrospectively review the indications of the stents, the type of prostheses and their modes of insertion, their complications, the clinical and functional results. [less ▲]

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See detailLe medicament du mois. Le tiotropium (SPIRIVA)
Corhay, Jean-Louis ULg; Louis, Renaud ULg

in Revue Médicale de Liège (2004), 59(9), 530-3

SPIRIVA (tiotropium) is a long-acting anticholinergic bronchodilatator, inhaled once a day, which produces relaxation of airway smooth muscle through antagonism of acetylcholine at M3-muscarinic receptors ... [more ▼]

SPIRIVA (tiotropium) is a long-acting anticholinergic bronchodilatator, inhaled once a day, which produces relaxation of airway smooth muscle through antagonism of acetylcholine at M3-muscarinic receptors. Its duration of action is at least 24h with once daily administration of tiotropium. Several studies have shown its efficacy and its good tolerance in the treatment of patients who are suffering from moderate to very severe chronic obstructive pulmonary disease (COPD). SPIRIVA improves spirometric measurements and quality of life, and reduces dyspnea and exacerbation rate in COPD patients. [less ▲]

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See detailAnti-IgE: a significant breakthrough in the treatment of airway allergic diseases
Louis, Renaud ULg

in Allergy (2004), 59(7), 698-700

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See detailContribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum
Dent, G.; Hadjicharalambous, C.; Yoshikawa, T. et al

in American Journal of Respiratory & Critical Care Medicine (2004), 169(10), 1110-1117

The CC chemokine eotaxin-1 (CCL11) is chemotactic for eosinophils, basophils, and type 2 helper T cells and may play a role in allergic inflammation. We investigated its contribution as an eosinophil ... [more ▼]

The CC chemokine eotaxin-1 (CCL11) is chemotactic for eosinophils, basophils, and type 2 helper T cells and may play a role in allergic inflammation. We investigated its contribution as an eosinophil chemoattractant in asthmatic airway secretions (sampled as induced sputum), which possess chemotactic activity for eosinophils and T cells. Sputum samples collected from healthy subjects and subjects with mild, stable-moderate, unstable-moderate, and severe asthma were processed with phosphate-buffered saline and assayed for eotaxin by ELISA and for eosinophil chemotactic activity by fluorescence-based chemotaxis assay. The contribution of eotaxin to chemotactic activity was studied by using a high-affinity neutralizing human anti-eotaxin antibody, CAT-213. Sputum eotaxin concentration was significantly raised in moderate and severe asthma (p < 0.05 versus healthy control subjects) but not in mild asthma. Chemotactic activity was significantly increased in all asthmatic groups relative to healthy subjects (p < 0.05) and was significantly inhibited by CAT-213 (1100 nM) in subjects with moderate and severe asthma, with median inhibition of 52% (p < 0.05), 78% (p < 0.0001), and 86% (p < 0.0001), respectively, in samples representing stable-moderate, unstable-moderate, and severe asthma. Eotaxin contributed to the eosinophil chemotactic activity of sputum from subjects with more severe forms of asthma but not mild asthma, suggesting that its contribution is more important in more severe disease. This activity is inhibited significantly by CAT-213. [less ▲]

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See detailDyspnee paroxystique chez le sujet sain: le pneumothorax spontane
Duysinx, Bernard ULg; Nguyen, Delphine; Corhay, Jean-Louis ULg et al

in Revue Médicale de Liège (2004), 59(4), 205-8

In a healthy individual, a dyspnoea of abrupt onset raises the suspicion of a spontaneous pneumothorax. The clinical examination and standard chest X-ray usually permit the correct diagnosis. The risk of ... [more ▼]

In a healthy individual, a dyspnoea of abrupt onset raises the suspicion of a spontaneous pneumothorax. The clinical examination and standard chest X-ray usually permit the correct diagnosis. The risk of reccurence can be assessed by the clinical history and examination. The functional consequences (which can be lethal) and the risk of recurrence will guide the short- and long-term therapy. [less ▲]

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See detailPrise en charge des exacerbations d'asthme
Mommens, Véronique; Louis, Renaud ULg; D'Orio, Vincenzo ULg

in Revue Médicale de Liège (2004), 59(4), 209-14

Asthma exacerbations constitute a common medical emergency, which in the past has been shown to be poorly managed. Although its management has recently improved, it remains suboptimal. For instance, acute ... [more ▼]

Asthma exacerbations constitute a common medical emergency, which in the past has been shown to be poorly managed. Although its management has recently improved, it remains suboptimal. For instance, acute life-threatening asthma is still responsible for 2000 death each year in France. More than two thirds of deaths should be avoided by a prompt and adjusted treatment. Initial assessment of the severity of the exacerbation is fundamental. The clinical story, physical examination and objective measurement of airflow obstruction by peak flow meter should permit to quickly establish an adapted treatment. The aim of this paper is, once general considerations about clinical approach and currently used treatments have been made, to propose a home and a hospital-based management of the asthma exacerbations. [less ▲]

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See detailMatrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics
Cataldo, Didier ULg; Guéders, Maud ULg; Munaut, Carine ULg et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2004), 84(4), 418-424

Asthma is a chronic inflammatory disease characterized by profound extracellular matrix changes referred to as bronchial remodelling. In this study, we evaluated matrix metalloproteinases (MMPs) and ... [more ▼]

Asthma is a chronic inflammatory disease characterized by profound extracellular matrix changes referred to as bronchial remodelling. In this study, we evaluated matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) mRNA expression in bronchial secretions of asthmatics and correlated MMPs modulations with the lung function as a reflection of the bronchial extracellular matrix remodelling. Quantitative RT-PCR was performed on cell pellets obtained from induced sputum in order to detect the mRNAs for MMP-1, -2, -3, -8, -9, -12, -13 TIMP-1, -2, while semiquantitative RT-PCR was performed to assess the expression of MMP-7, monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta(1) (TGF-beta(1)). The mRNA transcripts for MMP-1, TIMP-1 and monocyte chemoattractant protein-1 (MCP-1) were increased in cell pellets of induced sputum from asthmatics when compared to controls (P<0.05), and the intensity of MMP-1 mRNA expression inversely correlated with the FEV(1) in asthmatics (r=-0.49, P<0.05). The MMP-1 mRNA/TIMP-1 mRNA ratio correlated with the levels of MCP-1 mRNA in asthmatics (r=0.47, P<0.05). There were no differences between the groups with respect to mRNA coding for MMP-2, -3, -7, -8, -9, -12, -13, -14, TIMP-2 and TGF-beta(1). We conclude that cells contained in the bronchial secretions from asthmatics express higher amounts of mRNA for MMP-1 and TIMP-1, perhaps related to an increased expression of MCP-1, which might contribute to the extracellular matrix changes observed during airway remodelling. [less ▲]

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See detailNebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma
Delvaux, Muriel ULg; Henket, Monique ULg; Lau, L. et al

in Thorax (2004), 59(2), 111-115

Background: Inhalation of hypertonic or even isotonic saline during sputum induction may cause bronchospasm in susceptible patients with asthma, despite premedication with 400 mug inhaled salbutamol ... [more ▼]

Background: Inhalation of hypertonic or even isotonic saline during sputum induction may cause bronchospasm in susceptible patients with asthma, despite premedication with 400 mug inhaled salbutamol delivered by pressurised metered dose inhaler (pMDI). The bronchoprotection afforded by additional inhaled salbutamol administered through the ultrasonic nebuliser during sputum induction was investigated. Methods: Twenty patients with moderate to severe asthma underwent sputum induction by inhaling saline 4.5% (or 0.9% if post-bronchodilation forced expiratory volume in 1 second (FEV1) <65% predicted) for 10 minutes according to two protocols given 1 week apart in random order. At visit A the patients received 400 mg salbutamol administered through a pMDI + spacer 20 minutes before induction while at visit B the premedication was supplemented by 1500 mg nebulised salbutamol inhaled throughout the induction procedure. Both the investigator and the patients were blind to the nebulised solution used. FEV1 was recorded during sputum induction at 1, 3, 5, and 10 minutes. Sputum cell counts and histamine, tryptase and albumin levels in the supernatants were determined. Results: The mean (SE) maximal reduction in FEV1 over the 10 minute period of sputum induction was 11.7 (2.8)% at visit A, which was significantly greater than at visit B (2.6 (1.2)%; mean difference 9% (95% CI 2.7 to 15.4), p < 0.01). Total and differential sputum cell counts as well as albumin, tryptase, and histamine levels did not differ between the two visits. Conclusion: The addition of inhaled salbutamol through an ultrasonic nebuliser markedly improves bronchoprotection against saline induced bronchoconstriction in patients with moderate to severe asthma undergoing sputum induction without affecting cell counts and inflammatory markers. [less ▲]

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See detailEvaluation of pleural disease with 18-fluorodeoxyglucose positron emission tomography imaging
Duysinx, Bernard ULg; Nguyen, Delphine; Louis, Renaud ULg et al

in CHEST (2004), 125(2), 489-493

STUDY OBJECTIVES: To study the ability of positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG) to distinguish between benign and malignant disease in exudative pleural effusions and ... [more ▼]

STUDY OBJECTIVES: To study the ability of positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG) to distinguish between benign and malignant disease in exudative pleural effusions and pleural thickening. DESIGN: Prospective study of 98 consecutive patients presenting with either pleural thickening or an exudative pleural effusion. SETTING: Department of pulmonary medicine of a university hospital. METHODS: FDG-PET was performed on each subject before invasive procedures were used to determine the etiologic diagnosis. FDG-PET data were analyzed by visual interpretation. RESULTS: Sixty-three of 98 patients were found to have malignant pleural disease after histologic analysis. Sixty-one of 63 patients with histologically confirmed malignant disease showed FDG uptake within the area of pleural thickening. Uptake was graded as intense in 51 cases and moderate in 10 cases. Only two patients with malignant pleural disease did not show increased FDG uptake. FDG-PET imaging showed an absence of FDG uptake, and correctly classified 31 of 35 benign lesions. For the remaining four lesions, intense FDG uptake was seen in one case of parapneumonic effusion, while moderate and localized uptake was observed in one parapneumonic, one tuberculous, and one uremic pleurisy. The sensitivity of the method to identify malignancy was 96.8% with a negative predictive value of 93.9%, while its specificity was 88.5% and its positive predictive value was 93.8%. CONCLUSIONS: Our results suggest that FDG-PET is an effective tool for differentiating between benign and malignant pleural diseases. [less ▲]

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See detailDual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients
Joos, G. F.; Vincken, W.; Louis, Renaud ULg et al

in European Respiratory Journal (2004), 23(1), 76-81

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the ... [more ▼]

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2 receptor antagonist, DNK333, on NKA-induced bronchoconstriction in asthma. A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled crossover trial. Increasing concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol(.)mL(-1)) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo. It was observed that DNK333 did not affect baseline lung function but did protect against NKA-induced bronchoconstriction in those patients. The mean log(10) provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was -5.6 log(10) mol(.)mL(-1) at 1 h after DNK333 treatment and -6.8 log(10) mol(.)mL(-1) after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment. The results shown in this report indicate that DNK333 blocks neurokinin A-induced bronchoconstriction in patients with asthma. [less ▲]

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See detailPathogenic role of matrix metalloproteases and their inhibitors in asthma and chronic obstructive pulmonary disease and therapeutic relevance of matrix metalloproteases inhibitors
Cataldo, Didier ULg; Guéders, Maud ULg; Rocks, Natacha ULg et al

in Cellular and Molecular Biology (2003), 49(6), 875-884

Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and zinc dependent enzymes implicated in many physiological and pathological processes. Asthma, chronic obstructive pulmonary ... [more ▼]

Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and zinc dependent enzymes implicated in many physiological and pathological processes. Asthma, chronic obstructive pulmonary disease (COPD) and emphysema are diseases associated with an inflammation of the airways and lung parenchyma. In this review, we focus on the role played by MMPs in the pathogenesis of inflammation, airway remodelling and alveolar destruction, depicting the observational studies in humans and the experimental studies in animal models. During the course of asthma, MM P-2,-8,-9 and TIMP-1 are expressed at baseline and the allergen exposure or exacerbations of the disease lead to an increase of MMP-9 secretion being at this time much higher than that of TIMP-1, allowing temporarily a matrix damage, possibly followed by abnormal repair. Animal models suggest a predominant role for MMP-9 and MMP-12 in the pathogenesis of pulmonary inflammation and link an absence of MMP-2 to an increased parenchymal inflammation. In COPD and emphysema, human studies indicate an over-secretion of MMP-2,-8,-9 and animal models point out MMP-1 and MMP-12 as being key players in the pathogenesis of emphysema. Taken together, these data identify specific MW inhibition as appropriate target for therapeutic intervention in asthma or COPD/emphysema. They also strongly argue against the widespread use of large spectrum non specific inhibitors that could be detrimental. [less ▲]

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See detailMatrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma
Vermaelen, K. Y.; Cataldo, Didier ULg; Tournoy, K. et al

in Journal of Immunology (2003), 171(2), 1016-1022

Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory leukocytes across basement ... [more ▼]

Dendritic cells (DCs) appear to be strategically implicated in allergic diseases, including asthma. Matrix metalloproteinase (MMP)-9 mediates transmigration of inflammatory leukocytes across basement membranes. This study investigated the role of MMP-9 in airway DC trafficking during allergen-induced airway inflammation. MMP-9 gene deletion affected the trafficking of pulmonary DCs in a specific way: only the inflammatory transmigration of DCs into the airway lumen was impaired, whereas DC-mediated transport of airway Ag to the thoracic lymph nodes remained unaffected. In parallel, the local production of the Th2-attracting chemokine CC chemokine ligand 17/thymus and activation-regulated chemokine, which was highly concentrated in purified lung DCs, fell short in the airways of allergen-exposed MMP-9(-/-) mice. This was accompanied by markedly reduced peribronchial eosinophilic infiltrates and impaired allergen-specific IgE production. We conclude that the specific absence of MMP-9 activity inhibits the development of allergic airway inflammation by impairing the recruitment of DCs into the airways and the local production of DC-derived proallergic chemokines. [less ▲]

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See detailLa vaccination a base de mycobacteries: vaincra-t-elle les allergies?
Louis, Renaud ULg

in Revue Médicale de Liège (2003), 58(6), 392-5

In developed countries, the prevalence of tuberculosis has evolved in an opposite direction as to the one of allergy over the last century. The immunological response is mainly Th1 in tuberculosis while ... [more ▼]

In developed countries, the prevalence of tuberculosis has evolved in an opposite direction as to the one of allergy over the last century. The immunological response is mainly Th1 in tuberculosis while it features a Th2 pattern in allergy. Vaccination with BCG in early life is associated with a reduction in the prevalence of allergy later in childhood. In an experimental mouse model of asthma, administration of BCG or killed Mycobacterium vaccae inhibits the sensitisation process as well as the bronchial inflammation and hyperresponsiveness that follows allergen exposure. In children and adolescents suffering from atopic dermatitis, subcutaneous injection of killed Mycobacterium vaccae attenuates the severity of skin lesions. [less ▲]

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See detailOzone et asthme: un couple dans l'air du temps
Kleis, S.; Louis, Renaud ULg; Bartsch, Pierre ULg

in Revue Médicale de Liège (2003), 58(3), 132-8

Ozone is a pollutant the production of which depends on weather conditions and car engine combustion. Numerous epidemiological studies have indicated that high ozone levels correlated with morbidity in ... [more ▼]

Ozone is a pollutant the production of which depends on weather conditions and car engine combustion. Numerous epidemiological studies have indicated that high ozone levels correlated with morbidity in asthma. Experimental studies have shown that exposure of healthy subjects and asthmatics to ozone levels comparable to those measured in ambient air during hot summer days can generate respiratory symptoms, neutrophilic airways inflammation and lung function impairment. Lung function changes following ozone exposure are more pronounced in asthmatics and are dependent on the duration and intensity of exposure, a previous exposure and the nutritional status of the subjects. The airway epithelial cell layer is likely to play a pivotal role in initiating the inflammatory process following ozone exposure. Control of ambient air ozone levels must be a target for public health authorities. [less ▲]

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See detailInduced sputum studies in asthma
LOUIS, Renaud ULg; Chanez, P

in Djukanovic, Ratko; Sterk, Peter J. (Eds.) An Atlas of INDUCED SPUTUM : an Aid for Research and Diagnosis. (2003)

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See detailInteret des expectorations induites dans l'exploration de l'asthme.
Louis, Renaud ULg; Bettiol, Jane; Cataldo, Didier ULg et al

in Revue des Maladies Respiratoires (2003), 20(2 Pt 1), 215-23

INTRODUCTION: The technique of induced expectoration generates sputum by the inhalation of hypertonic saline. On account of its non-invasive character, its simplicity, its relative harmlessness, its cost ... [more ▼]

INTRODUCTION: The technique of induced expectoration generates sputum by the inhalation of hypertonic saline. On account of its non-invasive character, its simplicity, its relative harmlessness, its cost effectiveness and its reproducibility this technique, that appeared in the early 1990's, has rapidly established itself as the technique of choice in the investigation of bronchial inflammation in asthma. STATE OF THE ART: We present the results of our studies that have contributed to the validation of the technique at the methodological level and to the exploitation of the cellular contents as much as the fluid phase of the expectorations in characterising bronchial inflammation in asthmatics. Our results confirm an infiltration of the airways of asthmatics with eosinophils that appears to be proportional to the severity of the illness. We evaluate the effect of inhaled steroids and of theophylline on sputum eosinophilia and bronchial reactivity and discuss the role of eosinophils on bronchial hyperreactivity. Finally we discuss the use of induced expectoration in clinical practice in asthma. PERSPECTIVES: The analysis of induced sputum could well become a valuable tool in the clinical evaluation and monitoring of asthma in the same way as symptoms and abnormalities of lung function. CONCLUSIONS: Induced expectoration has certainly contributed to the understanding of the cellular and molecular mechanisms of asthma as well as the role of bronchial inflammation in the clinical manifestations of the disease. [less ▲]

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See detailCytokine production from sputum cells after allergenic challenge in IgE-mediated asthma
Bettiol, Jeanne; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Allergy (2002), 57(12), 1145-1150

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ... [more ▼]

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ammation. Methods: By applying the technique of induced sputum to collect airways cells, we have assessed the spontaneous production of a set of cytokines, including interleukin-4, 6, 10, interferon-gamma and tumour necrosis factor-alpha 6 h after a bronchial allergenic hallenge with Dermatophagoides pteronyssinus (Dpt) in 12 sensitized asthmatics and compared the results obtained after inhalation of saline as control. A group of eight healthy non-allergic subjects was enrolled to control for any non-specific effect of Dpt. Cytokines were measured by a dynamic immunoassay during a 24-h sputum cell culture. Results: Allergen challenge in sensitized asthmatics caused an acute and a late bronchospasm together with a rise in sputum eosinophil counts. Afterwards allergen sputum cells from allergic asthmatics displayed a rise in their production of IL-4 (P < 0.01), IL-6 (P < 0.05) and IL- 10 (P < 0.05) when compared to saline. By this time sputum generation of IL- 4 in atopic asthmatics was greater than in healthy subjects (P < 0.001). Furthermore, in allergic asthmatics there was a strong correlation between the rise in interleukin-4 production from sputum cells and the rise in sputum eosinophils (r = 0.87, P < 0.001). Conclusions: Sputum cell culture is a useful model to assess cytokine production in allergic asthmatics who show a marked up-regulation of Th2 cytokines following acute allergen exposure. The rise in sputum eosinophil count following allergen challenge strongly correlates with the rise in IL-4 generation from sputum cells. [less ▲]

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See detailMatrix metalloproteinase-9, but not tissue inhibitor of matrix metalloproteinase-1, increases in the sputum from allergic asthmatic patients after allergen challenge
Cataldo, Didier ULg; Bettiol, J.; Noël, Agnès ULg et al

in CHEST (2002), 122(5), 1553-1559

Objective: The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metallloproteinase (TIMP)-1 in the ... [more ▼]

Objective: The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metallloproteinase (TIMP)-1 in the induced sputum recovered from patients during a late-phase reaction. Method: Eight allergic asthma patients and five healthy control subjects inhaled a dose of Dermatophagoides pteronyssinus extract corresponding to the provocative concentration of the allergen causing a 20% fall in FEV1 and saline solution. Lung function was carefully monitored for 6 h, and an induced sputum test was performed at 6 h after sham challenge or allergen challenge. The total and differential cell counts were analyzed, and the levels of MMP-9 (by enzyme-linked immunosorbent assay [ELISA] and zymography), TIMP-1 (by ELISA), and albumin (by rocket immunoelectrophoresis) were measured. Results: The sputum eosinophil counts (p < 0.01) and MMP-9 levels (p < 0.05) increased significantly in atopic asthma patients after undergoing the allergen challenge but did not in the control subjects. By contrast, TIMP-1 and albumin levels were not significantly increased in any group. MMP-9 levels, measured after the allergen challenge in asthmatic patients, were significantly correlated with FEV1 variations after allergen inhalation (r = 0.51; p < 0.05) and with the sputum neutrophil percentage (r = 0.71; p < 0.01). Conclusion: The levels of MMP-9, but not TIMP-1, increase after inhaled allergen challenge in the sputum of allergic asthmatic patients. This protease increase may lead to a transient imbalance between MMP-9 and TIMP-1 favoring proteolytic extracellular matrix degradation. [less ▲]

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