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See detailLe medicament du mois. L'association budesonide 160 micrograms/formoterol 4.5 micrograms (Symbicort TH)
Louis, Renaud ULg

in Revue Médicale de Liège (2002), 57(11), 741-4

The combination of budesonide 160 micrograms/formoterol 4.5 micrograms (Symbicort TH) in the same dry powder inhaler (turbohaler) results in a drug that possesses powerful bronchial anti-inflammatory ... [more ▼]

The combination of budesonide 160 micrograms/formoterol 4.5 micrograms (Symbicort TH) in the same dry powder inhaler (turbohaler) results in a drug that possesses powerful bronchial anti-inflammatory, bronchoprotective and bronchodilating activities. Symbicort TH is registered as a maintenance treatment for asthma from the age of 12 years. This drug is indicated in the treatment of moderate and severe persistent asthma as well as in asthma which remains mild persistent despite the regular use of low doses of inhaled corticoids alone. Symbicort TH rapidly improves asthma control by reducing symptoms, relief medication consumption and by improving lung function. Importantly, when taken regularly over a prolonged period, the drug reduces the number of mild and severe exacerbations. The dose of Symbicort TH is adjustable according to the disease severity and generally fluctuates between 2 x 1/24 h and 4 x 2/24 h. Symbicort TH is a simple and a efficient treatment likely to improve the compliance of asthmatics to their treatment in real life. [less ▲]

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See detailSputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness
Louis, Renaud ULg; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Allergy (2002), 57(10), 907-912

BACKGROUND: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This ... [more ▼]

BACKGROUND: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This study aimed to assess the distribution of sputum eosinophil count and its relationship with methacholine bronchial hyperresponsiveness in mild to moderate steroid-naive asthmatic people. METHODS: Sputum was induced by inhalation of hypertonic saline (NaCl 4.5%) in 118 mild to moderate steroid-naive asthmatic people consecutively recruited from our outpatient clinic, and in 44 healthy people. The asthma group was selected on the basis of an forced expiratory volume in 1 s (FEV(1)) of > or = 70% predicted, and a provocative methacholine concentration causing a fall of 20% in FEV(1) (PC20 methacholine; PC(20)M) < or = 16 mg/ml. RESULTS: In the asthma group, the median (range) of the percentage and the absolute values of sputum eosinophils were 4.8% (0-75) and 38 10(3)/g (0-14,191), respectively, vs 0% (0-2.3) (P < 0.001) and 0 10(3)/g (0-53) (P < 0.001) in healthy participants. Based on the 95% percentile for normal values calculated from our healthy group, 69% of the asthma group had significantly raised sputum eosinophil count (that is > 2%). In the asthma group, multiple regression analysis followed by a stepwise procedure revealed that sputum eosinophil count was significantly and inversely associated with PC(20)M accounting for 16% of its total variance (P < 0.001) while neutrophil counts positively related to PC(20)M accounting for 4% of total variance (P < 0.05). By contrast, no significant relationship was found between either eosinophil or neutrophil counts and the slope of forced vital capacity (FVC) vs FEV(1) from the methacholine challenge. CONCLUSIONS: We conclude that two-thirds of people in the mild to moderate asthma group had increased sputum eosinophilia, which plays a limited role in determining the degree of methacholine airway hyperresponsiveness. [less ▲]

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See detailMethods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation
Efthimiadis, A.; Spanevello, A.; Hamid, Q. et al

in European Respiratory Journal (2002), 20(Suppl. 37), 19-23

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See detailClinical applications of assessment of airway inflammation using induced sputum
Pavord, I. D.; Sterk, P. J.; Hargreave, F. E. et al

in European Respiratory Journal (2002), 20(Suppl. 37), 40-43

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See detailMatrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation
Cataldo, Didier ULg; Tournoy, K. G.; Vermaelen, K. et al

in American Journal of Pathology (2002), 161(2), 491-498

We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and ... [more ▼]

We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and their corresponding wild-type (WT) littermates. After a single intraperitoneal sensitization to ovalbumin, the mice were exposed daily either to ovalbumin (1%) or phosphate-buffered saline aerosols from days 14 to 21. Significantly less peribronchial mononuclear cell infiltration of the airways and less lymphocytes in the bronchoalveolar lavage fluid were detected in challenged MMP-9(-/-) as compared to WT mice. In contrast, comparable numbers of bronchoalveolar lavage fluid eosinophils; were observed in both genotypes. After allergen exposure, the WT mice developed a significant airway hyperresponsiveness to carbachol whereas the MMP-9(-/-) mice failed to do so. Allergen exposure induced an increase of MMP-9-related gelatinolytic activity in WT lung extracts. Quantitative reverse transcriptase-polymerase chain reaction showed increased mRNA levels of MMP-12, MMP-14, and urokinase-type plasminogen activator after allergen exposure in the lung extracts of WT mice but not in MMP-9-deficient mice. in contrast, the expression of tissue inhibitor of metalloproteinases-1 was enhanced after allergen exposure in both groups. We conclude that MMP-9 plays a key role in the development of airway inflammation after allergenexposure. [less ▲]

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See detailEvidence of mast-cell activation in a subset of patients with eosinophilic chronic obstructive pulmonary disease
Louis, Renaud ULg; Cataldo, Didier ULg; Buckley, M. G. et al

in European Respiratory Journal (2002), 20(2), 325-331

Although asthma has been viewed mainly, as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in ... [more ▼]

Although asthma has been viewed mainly, as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in severe asthma and sputum eosinophilia in sonic COPD patients. In an attempt to further characterise these two syndromes according to pathology, the current authors have conducted a study of induced sputum in 15 subjects with COPD, 17 asthmatics, and 17 nonatopic healthy individuals. Sputum was analysed for cytology and levels of eosinophil cationic protein (ECP), albumin, tryptase and soluble intercellular adhesion molecule-1. The COPD subjects differed from the asthmatics as they had higher sputum neutrophil and lower columnar epithelial cell counts, but there were no differences in any soluble marker studied. When compared to control subjects, both the asthmatic and COPD subjects had raised eosinophil counts and ECP levels. In a subset of COPD subjects with Sputum eosinophilia (>3% of total cells), significantly increased levels of tryptase were detected. In conclusion, although chronic obstructive pulmonary disease is a more neutrophilic disease than asthma, the two diseases are difficult to distinguish on the basis of sputum levels of the soluble markers traditionally associated with asthma. However, a subset of patients with chronic obstructive pulmonary disease with airway eosinophilia and mast-cell activation might represent a distinct pathological phenotype. [less ▲]

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See detailClinique et cytologie sputaire de l'asthme intrinseque
Bettiol, J.; Radermecker, Maurice ULg; Louis, Renaud ULg

in Revue Médicale de Liège (2002), 57(4), 223-7

The diagnosis of intrinsic asthma is evoked in patients with clinical criteria of asthma but, who contrarily to atopic asthmatics, lack history of allergy, specific IgE and skin positive reaction towards ... [more ▼]

The diagnosis of intrinsic asthma is evoked in patients with clinical criteria of asthma but, who contrarily to atopic asthmatics, lack history of allergy, specific IgE and skin positive reaction towards common aeroallergens of the environment. While the bronchial cytology of these two types of asthma is comparable, the immunological mechanisms of intrinsic asthma remain poorly understood because the factors responsible for the bronchial inflammation are unknown. Intrinsic asthma normally begins in adulthood and carries often a more severe prognosis. This disease is more frequent in women and is often associated to nasal polyposis and/or aspirin hypersensitivity. In this work, we have retrospectively studied the demographic and clinical characteristics, as well as the lung function and the sputum cell counts of intrinsic asthmatic outpatients seen during the period of 1996 to 1998 in the Pneumology Department of the CHU Sart Tilman. [less ▲]

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: possible involvement in allergic inflammation
Bureau, Fabrice ULg; Seumois, G.; Jaspar, F. et al

in Pflügers Archiv : European Journal of Physiology (2002), 443

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: Possible involvement in allergic inflammation.
Bureau, Fabrice ULg; Seumois, Gregory; Jaspar, Fabrice et al

in Journal of Allergy and Clinical Immunology (The) (2002), 110(3), 443-9

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by ... [more ▼]

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by inducing the expression of antiapoptotic proteins. Three members of the inhibitor of apoptosis protein (IAP) family, namely cellular (c)-IAP1, c-IAP2, and XIAP, and 2 antiapoptotic proteins of the Bcl-2 family, namely Bcl-x(L) and Bfl-1/A1, were investigated. METHODS: Blood and sputum were obtained from healthy subjects and atopic asthmatic patients. Blood eosinophils were isolated by means of magnetic selection. Expression of CD40, IAPs, and Bcl-2 proteins was investigated by using flow cytometry, immunoblotting, or both. CD40 stimulation was achieved with agonistic antibodies or soluble ligands. Apoptosis was assessed by staining with propidium iodide and FITC-conjugated annexin-V. c-IAP2 expression was inhibited with antisense oligonucleotides. RESULTS: Freshly isolated eosinophils from healthy and asthmatic patients did not express CD40. Conversely, eosinophils expressed CD40 spontaneously when cultured for 48 hours. At this time point, CD40 stimulation significantly delayed eosinophil apoptosis. Inhibition of eosinophil apoptosis was accompanied by induction of c-IAP2 but not c-IAP1, XIAP, Bcl-x(L), or Bfl-1/A1 expression. Antisense knockdown of c-iap2 abolished CD40-induced enhancement of eosinophil survival. Sputum cells from asthmatic patients, unlike those from healthy subjects, substantially expressed CD40 and c-IAP2. Moreover, a strong correlation was found between the percentage of eosinophils in the sputum from asthmatic patients and the sputum level of CD40 and c-IAP2 expression. CONCLUSION: The results demonstrate that CD40 engagement enhances eosinophil survival through induction of c-IAP2 expression and suggest a role for this mechanism in allergic inflammation. [less ▲]

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See detailInduced sputum - Comparison between isotonic and hypertonic saline solution inhalation in patients with asthma
Cataldo, Didier ULg; Foidart, Jean-Michel ULg; Lau, L. et al

in CHEST (2001), 120(6), 1815-1821

Background: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect ... [more ▼]

Background: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect bronchoconstrictor. Study objectives: We studied the validity of isotonic saline solution (0.9%) inhalation as a means to induce sputum by comparing it to hypertonic saline solution (4.5%) inhalation. Patients: Sixteen patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion. Methods: Subjects underwent sputum induction twice at 1-week intervals. Saline solution (hypertonic or isotonic) was inhaled For three periods of 5 min. The parameters assessed in sputum samples were cell counts, sodium, eosinophil cationic protein (ECP), and albumin concentrations, osmolality, and pro-matrix metalloproteinase (MMP)-9 activity by zymography. Results: The maximal fall in peak expiratory flow during sputum induction was greater after inhalation of hypertonic saline solution than after inhalation of isotonic saline solution (p < 0.01). Each subject produced analyzable sputum on both visits. There were no statistically significant differences in total and differential sputum cell counts, and the reproducibility coefficients were high for eosinophils and neutrophils when comparing the two methods. Likewise, sputum levels of ECP and albumin as well as sputum pro-MMP-9 activity were not different between the two methods, and were highly reproducible as shown by high intraclass coefficients (Ri) of correlation (0.72, 0.74, and 0.77 for ECP, albumin, and pro-MMP-9, respectively). Sputum sodium concentrations and osmolality were higher after inhalation of hypertonic saline solution (p < 0.05). Conclusion: In patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion, inducing sputum by isotonic or hypertonic saline solution inhalation leads to comparable results in eosinophil and neutrophil cell counts and fluid phase mediators/proteins. [less ▲]

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See detailLa bronchopneumopathie chronique obstructive (BPCO): concepts actuels
Louis, Renaud ULg

in Revue Médicale de Liège (2001), 56(10), 689-95

COPD is a widespread disease in western countries affecting 10% of adults and linked to tobacco consumption in 90% of cases. This disorder is characterized by a reduced maximal expiratory flow which is ... [more ▼]

COPD is a widespread disease in western countries affecting 10% of adults and linked to tobacco consumption in 90% of cases. This disorder is characterized by a reduced maximal expiratory flow which is irreversible and slowly progressive over the years. In those who are genetically prone to develop a COPD, chronic exposure to toxic fumes or particles generates a bronchiolitis and an emphysema which cause disturbances in ventilation mechanics and alveolar gaz exchange. This leads to symptoms of breathlessness, hypoxemia, pulmonary hypertension and, in end stage disease, cor pulmonale. The smoking cessation is the only way to prevent the occurrence of COPD. [less ▲]

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See detailLe cas clinique du mois. A propos d'un cas d'hypertension portopulmonaire
Blaise, Pierre ULg; Louis, Renaud ULg; Quaden, C. et al

in Revue Médicale de Liège (2001), 56(9), 607-11

A case of portopulmonary hypertension discovered during exploration of an atypical faint is described and the pathophysiology and management are discussed.

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See detailPharma clinics. Le medicament du mois. Le montelukast (Singulair)
Louis, Renaud ULg

in Revue Médicale de Liège (2001), 56(6), 460-2

Montelukast (Singulair, Merck Sharp

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See detailIncreased Response of Blood Eosinophils to Various Chemotactic Agents in Quiescent Crohn Disease
Denis, M. A.; Louis, Renaud ULg; Malaise, Michel ULg et al

in Scandinavian Journal of Gastroenterology (2001), 36(2), 190-5

BACKGROUND: The number of eosinophils is increased in the mucosae of the digestive and the respiratory tracts in Crohn disease, even clinically quiescent. The mechanisms underlying this panmucosal ... [more ▼]

BACKGROUND: The number of eosinophils is increased in the mucosae of the digestive and the respiratory tracts in Crohn disease, even clinically quiescent. The mechanisms underlying this panmucosal eosinophilia are unknown. METHODS: The response of blood eosinophils to various chemotactic agents was assessed in 15 patients with clinically quiescent Crohn disease. The results were compared with 15 healthy controls. After purification, eosinophils were placed in Boyden microchambers and the chemotactic effect of PAF (10(-7) M), RANTES (50 ng/ml), IL-5 (0-20 ng/ml), IL-8 (0-50 ng/ml), Eotaxin (0-50 ng/ml) was evaluated. The number of eosinophils in induced sputum of these Crohn disease patients and controls was also assessed and the correlation between chemotaxis and eosinophil count in induced sputum was studied. RESULTS: PAF and RANTES induced a chemotactic effect both in Crohn disease patients and controls. The chemotactic index was significantly higher in Crohn than controls for PAF (2.09+/-0.24 versus 1.37+/-0.14; P < 0.05) but not RANTES. With IL-5, IL-8 and Eotaxin, there was no detectable chemotactic effect in controls while in Crohn, we observed a significant dose-dependent chemotactic effect. Furthermore, with Eotaxin 50 ng/ml, the chemotactic index was significantly higher in Crohn disease patients than controls (2.42+/-0.18 versus 1.56+/-0.28; P < 0.05). A significant increase in sputum eosinophil count and a significant decrease in sputum macrophage count in Crohn disease were observed. However, there was no correlation between eosinophil chemotaxis and sputum eosinophil count in individual patients. CONCLUSION: There is an increased response of blood eosinophils to various chemotactic agents, mainly PAF and Eotaxin, in clinically quiescent Crohn disease. This may participate in the mucosal infiltration by eosinophils in this disease. [less ▲]

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See detailMatrix Metalloproteinases and TIMP-1 production by peripheral blood granulocytes from COPD patients and asthmatics
Cataldo, Didier ULg; Munaut, Carine ULg; Noël, Agnès ULg et al

in Allergy (2001), 56(2), 145-51

Both asthmatic and COPD patients were found to have increased amounts of granulocytes and matrix metalloproteinase-9 (MMP-9) in their sputum. The present study was conducted to investigate whether the ... [more ▼]

Both asthmatic and COPD patients were found to have increased amounts of granulocytes and matrix metalloproteinase-9 (MMP-9) in their sputum. The present study was conducted to investigate whether the elevated amounts of MMP-9 and TIMP-1 found in such patients' airways may be linked to an enhanced secretion by granulocytes. Blood granulocytes from asthmatics (n = 10), COPD patients (n = 11), and healthy controls (n = 11) were isolated and cultured under basal conditions or after stimulation by phorbol 12-myristate 13-acetate (PMA) or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). MMP-9 activity was detected by zymography while MMP-8 and TIMP-1 levels were measured by ELISA. In zymography, pro- and activated forms of MMP-9 were present in each group (healthy subjects, asthmatics, and COPD patients). Spontaneous release was not different between the three groups. Stimulation by fMLP and PMA increased to a similar extent the release of MMP-9 by granulocytes in all the three groups. TIMP-1 levels were also increased after stimulation by PMA and fMLP only in healthy subjects and COPD patients. MMP-8 levels were barely detectable. We conclude that circulating granulocytes from COPD patients and asthmatics do not display an abnormal secretion of MMP-9, and that granulocytes from asthmatics have an impaired ability to release TIMP-1 upon stimulation. [less ▲]

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See detailCytokine Production from Peripheral Whole Blood in Atopic and Nonatopic Asthmatics: Relationship with Blood and Sputum Eosinophilia and Serum Ige Levels
Bettiol, J.; Bartsch, Pierre ULg; Louis, Renaud ULg et al

in Allergy (2000), 55(12), 1134-41

BACKGROUND: The cytokine network is thought to be essential in orchestrating airway inflammation in asthma. Although evidence has accumulated to suggest that atopic asthma is a Th2 disease, much less is ... [more ▼]

BACKGROUND: The cytokine network is thought to be essential in orchestrating airway inflammation in asthma. Although evidence has accumulated to suggest that atopic asthma is a Th2 disease, much less is known about nonatopic asthma. METHODS: We have compared the production of IL-4, IL-6, IFN-gamma, and TNF-alpha from peripheral blood leukocytes between atopic (n=21) and nonatopic (n=22) asthmatics and healthy nonatopic subjects (n=20). Peripheral blood was incubated for 24 h either without stimulus or with LPS or PHA. Cytokines were measured by the immunotrapping technique (Dynamic Immunoassay). RESULTS: When compared to healthy nonatopic subjects, both atopic and nonatopic asthmatics showed increased blood and sputum eosinophilia associated with raised total serum IgE levels. Similarly, both asthma groups displayed spontaneous, endotoxin-induced overproduction of IL-6. Enhanced spontaneous, endotoxin-induced release of IL-4 combined with reduced spontaneous IFN-gamma production was seen only in atopic asthma. In this group of patients, the production of IL-4 was related to the extent of blood and sputum eosinophilia. In nonatopic asthmatics, serum levels of IgE were inversely related to the production of IFN-gamma. CONCLUSIONS: Both atopic and intrinsic asthma display raised blood and airway eosinophilia, raised total serum IgE, and overproduction of IL-6 from peripheral blood. Atopic asthma is also characterized by impaired spontaneous release of IFN-gamma and increased production of IL-4 that correlates with the magnitude of eosinophilic inflammation. [less ▲]

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See detailLes fibroses pulmonaires idiopathiques: nouvelle classification histopathologique et aspects cliniques
Blaise, Pierre ULg; Louis, Renaud ULg; Bartsch, Pierre ULg

in Revue Médicale de Liège (2000), 55(11), 986-90

Idiopathic pulmonary fibrosis (IPF) comprises different interstitial lung diseases of unknown origin. They are classified into four groups based on pathologic criteria: UIP, DIP, AIP and NSIP. This ... [more ▼]

Idiopathic pulmonary fibrosis (IPF) comprises different interstitial lung diseases of unknown origin. They are classified into four groups based on pathologic criteria: UIP, DIP, AIP and NSIP. This classification helps in terms of prognosis and treatment. In addition to history, physical examination and common investigations (chest X ray, pulmonary function testing), a bronchoalveolar lavage (BAL), a high-resolution CT scan and ideally a open-lung biopsy are needed to establish a precise diagnosis. The patients are usually treated by immunosuppressive agents, and mainly by corticoids. However, in UIP, lung transplantation is the only way to improve survival. [less ▲]

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See detailMMP-2 and MMP-9-Linked Gelatinolytic Activity in the Sputum from Patients with Asthma and Chronic Obstructive Pulmonary Disease
Cataldo, Didier ULg; Munaut, Carine ULg; Noël, Agnès ULg et al

in International Archives of Allergy & Immunology (2000), 123(3), 259-67

BACKGROUND: The course of asthma and chronic obstructive pulmonary disease (COPD) is associated with bronchial morphological changes. Metalloproteinases are thought to play a role in these structural ... [more ▼]

BACKGROUND: The course of asthma and chronic obstructive pulmonary disease (COPD) is associated with bronchial morphological changes. Metalloproteinases are thought to play a role in these structural changes. METHODS: We studied the gelatinolytic activity present in the induced sputum from 20 patients with asthma, 20 with COPD and 19 healthy controls. The assessment of gelatinolytic activity was performed by quantitative zymography, and gelatinolytic species were identified by Western blot analysis. Tissue inhibitor of metalloproteinase-1 (TIMP-1) was detected by reverse zymography and ELISA. RESULTS: From zymography, we found significantly higher gelatinolytic activity linked to pro-matrix metalloproteinase-9 (pro-MMP-9) in the sputum from asthmatics (p < 0.0001) and COPD patients (p < 0.0001) compared to the control group. Furthermore, the activated form of MMP-9 (85 kD) was found in the sputum from 60% of asthmatics and 85% of COPD patients, but was absent in that of control subjects (p < 0.0001). Importantly, although less frequently detectable than pro-MMP-9, pro- MMP-2 (72 kD) was found more frequently in asthmatics (50%) than in control subjects (5%) (p < 0. 005). We also described two unusual gelatinolytic species of 45 and 120 kD and showed that they derived from MMP-9 according to their ability to bind gelatin and anti-MMP-9 antibody. Levels of TIMP-1 were higher in asthmatics (p < 0.05) and COPD patients (p < 0.05) than in controls. CONCLUSION: Asthmatics and COPD patients display an increased gelatinolytic activity linked to MMP-2 and MMP-9 and higher levels of TIMP-1 in their sputum. [less ▲]

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See detailLack of Association between Adult Asthma and the Tumour Necrosis Factor Alpha-308 Polymorphism Gene
Louis, Renaud ULg; Leyder, E.; Malaise, Michel ULg et al

in European Respiratory Journal (2000), 16(4), 604-8

Tumour necrosis factor (TNF)alpha is a cytokine endowed with potent inflammatory properties that may contribute to airway inflammation in asthma. It has previously been shown that the single base pair ... [more ▼]

Tumour necrosis factor (TNF)alpha is a cytokine endowed with potent inflammatory properties that may contribute to airway inflammation in asthma. It has previously been shown that the single base pair polymorphism-308 (G to A substitution) in the promoter of TNFalpha gene results in enhanced cytokine secretion. Whether this polymorphism is associated with the presence of phenotypic expression of asthma is questioned. In this study the relative frequency of TNF1 and TNF2 alleles in a population of adult healthy subjects (n=98) and adult Caucasian asthmatics (n=95) was compared taking into account their disease severity, atopic status and their smoking habit. For the whole group of asthma the genotype frequency for 1/1, 1/2, 2/2 were 67%, 33% and 0%, respectively, and not significantly different from those found in the control group that reached 70%, 28% and 2% respectively (p>0.05). The allele frequencies in asthma were 86% and 14% for TNF1 and TNF2 respectively while the corresponding figures were 85% and 15% in the control group (p>0.05). Furthermore, subdividing asthmatics into severe forced expiratory volume in one second <60% pred), atopic or smoking patients did not show any significant association with this TNFalpha polymorphism. To conclude the polymorphism -308 in the promoter of the TNFalpha gene does not confer a susceptibility to develop asthma nor to grade its severity. [less ▲]

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