19 results on '"Verleden GM"'
Search Results
2. Azithromycin during Acute Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization (BACE). A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial.
- Author
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Vermeersch K, Gabrovska M, Aumann J, Demedts IK, Corhay JL, Marchand E, Slabbynck H, Haenebalcke C, Haerens M, Hanon S, Jordens P, Peché R, Fremault A, Lauwerier T, Delporte A, Vandenberk B, Willems R, Everaerts S, Belmans A, Bogaerts K, Verleden GM, Troosters T, Ninane V, Brusselle GG, and Janssens W more...
- Subjects
- Administration, Inhalation, Adrenergic beta-Agonists therapeutic use, Aged, Clindamycin therapeutic use, Disease Progression, Double-Blind Method, Drug Therapy, Combination, Female, Forced Expiratory Volume, Glucocorticoids therapeutic use, Hospitalization, Humans, Macrolides therapeutic use, Male, Middle Aged, Mortality, Muscarinic Antagonists therapeutic use, Patient Readmission, Pulmonary Disease, Chronic Obstructive physiopathology, Quinolones therapeutic use, Vital Capacity, beta-Lactams therapeutic use, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, Pulmonary Disease, Chronic Obstructive drug therapy, Treatment Failure
- Abstract
Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring hospitalization remains to be defined. Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for an AECOPD and had a smoking history of ≥10 pack-years and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated the TF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or all-cause mortality. Measurements and Main Results: A total of 301 patients were randomized to azithromycin ( n = 147) or placebo ( n = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% ( P = 0.0272), 13% versus 28% ( P = 0.0024), and 2% versus 4% ( P = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal. Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits. more...
- Published
- 2019
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Catalog
3. How Would You Grade Our Progress in Primary Graft Dysfunction after Lung Transplantation?
- Author
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Neyrink A and Verleden GM
- Subjects
- Humans, Retrospective Studies, Lung Transplantation, Primary Graft Dysfunction
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- 2018
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4. Daily Home Spirometry: A New Milestone in the Field of Pulmonary Fibrosis.
- Author
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Wuyts WA, Spagnolo P, Bonella F, Yserbyt J, and Verleden GM
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- Humans, Pulmonary Fibrosis, Spirometry
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- 2016
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5. Morphometric Analysis of Explant Lungs in Cystic Fibrosis.
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Boon M, Verleden SE, Bosch B, Lammertyn EJ, McDonough JE, Mai C, Verschakelen J, Kemner-van de Corput M, Tiddens HA, Proesmans M, Vermeulen FL, Verbeken EK, Cooper J, Van Raemdonck DE, Decramer M, Verleden GM, Hogg JC, Dupont LJ, Vanaudenaerde BM, and De Boeck K more...
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- Adult, Aged, Airway Obstruction physiopathology, Bronchi, Bronchioles, Case-Control Studies, Cystic Fibrosis physiopathology, Cystic Fibrosis surgery, Female, Forced Expiratory Volume, Humans, Male, Maximal Midexpiratory Flow Rate, Middle Aged, Multidetector Computed Tomography, Organ Size, Plethysmography, Pneumonectomy, Residual Volume, Spirometry, Total Lung Capacity, Vital Capacity, X-Ray Microtomography, Young Adult, Airway Obstruction diagnostic imaging, Airway Remodeling, Cystic Fibrosis diagnostic imaging, Lung diagnostic imaging, Lung Transplantation
- Abstract
Rationale: After repeated cycles of lung infection and inflammation, patients with cystic fibrosis (CF) evolve to respiratory insufficiency. Although histology and imaging have provided descriptive information, a thorough morphometric analysis of end-stage CF lung disease is lacking., Objectives: To quantify the involvement of small and large airways in end-stage CF., Methods: Multidetector computed tomography (MDCT) and micro-CT were applied to 11 air-inflated CF explanted lungs and 7 control lungs to measure, count, and describe the airway and parenchymal abnormalities in end-stage CF lungs. Selected abnormalities were further investigated with thin section histology., Measurements and Main Results: On MDCT, CF explanted lungs showed an increased median (interquartile range) number (631 [511-710] vs. 344 [277-349]; P = 0.003) and size of visible airways (cumulative airway diameter 217 cm [209-250] vs. 91 cm [80-105]; P < 0.001) compared with controls. Airway obstruction was seen, starting from generation 6 and increasing to 40 to 50% of airways from generation 9 onward. Micro-CT showed that the total number of terminal bronchioles was decreased (2.9/ml [2.6-4.4] vs. 5.3/ml [4.8-5.7]; P < 0.001); 49% were obstructed, and the cross-sectional area of the open terminal bronchioles was reduced (0.093 mm(2) [0.084-0.123] vs. 0.179 mm(2) [0.140-0.196]; P < 0.001). On micro-CT, 41% of the obstructed airways reopened more distally. This remodeling was confirmed on histological analysis. Parenchymal changes were also seen, mostly in a patchy and peribronchiolar distribution., Conclusions: Extensive changes of dilatation and obstruction in nearly all airway generations were observed in end-stage CF lung disease. more...
- Published
- 2016
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6. An Official American Thoracic Society/European Respiratory Society Statement: Research questions in chronic obstructive pulmonary disease.
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Celli BR, Decramer M, Wedzicha JA, Wilson KC, Agustí A, Criner GJ, MacNee W, Make BJ, Rennard SI, Stockley RA, Vogelmeier C, Anzueto A, Au DH, Barnes PJ, Burgel PR, Calverley PM, Casanova C, Clini EM, Cooper CB, Coxson HO, Dusser DJ, Fabbri LM, Fahy B, Ferguson GT, Fisher A, Fletcher MJ, Hayot M, Hurst JR, Jones PW, Mahler DA, Maltais F, Mannino DM, Martinez FJ, Miravitlles M, Meek PM, Papi A, Rabe KF, Roche N, Sciurba FC, Sethi S, Siafakas N, Sin DD, Soriano JB, Stoller JK, Tashkin DP, Troosters T, Verleden GM, Verschakelen J, Vestbo J, Walsh JW, Washko GR, Wise RA, Wouters EF, and ZuWallack RL more...
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- Europe, Evidence-Based Medicine methods, Evidence-Based Medicine organization & administration, Humans, Organizational Objectives, Policy Making, United States, Biomedical Research organization & administration, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive therapy, Societies, Medical organization & administration
- Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management., Methods: Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified., Results: Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus., Conclusions: Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes. more...
- Published
- 2015
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7. The site and nature of airway obstruction after lung transplantation.
- Author
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Verleden SE, Vasilescu DM, Willems S, Ruttens D, Vos R, Vandermeulen E, Hostens J, McDonough JE, Verbeken EK, Verschakelen J, Van Raemdonck DE, Rondelet B, Knoop C, Decramer M, Cooper J, Hogg JC, Verleden GM, and Vanaudenaerde BM more...
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- Adult, Aged, Bronchiolitis Obliterans diagnostic imaging, Bronchiolitis Obliterans etiology, Bronchography, Case-Control Studies, Female, Graft Rejection diagnostic imaging, Graft Rejection etiology, Humans, Male, Middle Aged, Pulmonary Alveoli diagnostic imaging, Bronchioles pathology, Bronchiolitis Obliterans pathology, Graft Rejection pathology, Lung Transplantation, Multidetector Computed Tomography, Pulmonary Alveoli pathology, X-Ray Microtomography
- Abstract
Rationale: The chronic rejection of lung allografts is attributable to progressive small airway obstruction., Objectives: To determine precisely the site and nature of this type of airway obstruction., Methods: Lungs from patients with rejected lung allografts treated by a second transplant (n = 7) were compared with unused donor (control) lungs (n = 7) using multidetector computed tomography (MDCT) to determine the percentage of visible airways obstructed in each airway generation, micro-computed tomography (microCT) to visualize the site of obstruction, and histology to determine the nature of this obstruction., Measurements and Main Results: The number of airways visible with MDCT was not different between rejected and control lungs. However, 10 ± 7% of observed airways greater than 2 mm in diameter, 50 ± 22% of airways between 1 and 2 mm in diameter, and 73 ± 10% of airways less than 1 mm in diameter were obstructed in the rejected lungs. MicroCT confirmed that the mean lumen diameter of obstructed airways was 647 ± 317 μm but showed no difference in either total number and cross-sectional area of the terminal bronchioles or in alveolar dimensions (mean linear intercept) between groups (P > 0.05). In addition, microCT demonstrated that only segments of the airways are obstructed. Histology confirmed a constrictive form of bronchiolitis caused by expansion of microvascular-rich granulation tissue in some locations and collagen-rich scar tissue in others., Conclusions: Chronic lung allograft rejection is associated with a progressive form of constrictive bronchiolitis that targets conducting airways while sparing larger airways as well as terminal bronchioles and the alveolar surface. more...
- Published
- 2014
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8. The clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease.
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Wuyts WA, Dooms C, and Verleden GM
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- Humans, Bronchoalveolar Lavage standards, Bronchoalveolar Lavage Fluid cytology, Lung Diseases, Interstitial diagnosis
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- 2013
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9. New idiopathic pulmonary fibrosis guidelines: some unresolved questions.
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Wuyts WA, Thomeer M, Demedts MG, and Verleden GM
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- Humans, Evidence-Based Medicine, Idiopathic Pulmonary Fibrosis diagnosis, Idiopathic Pulmonary Fibrosis therapy
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- 2012
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10. Integration of clinical, radiological, and histopathological data in the diagnosis of diffuse parenchymal lung diseases.
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Wuyts WA and Verleden GM
- Subjects
- Diagnosis, Differential, Humans, Observer Variation, Radiography, Lung Diseases, Interstitial diagnostic imaging, Lung Diseases, Interstitial pathology
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- 2009
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11. An algorithm to tackle acute exacerbations in idiopathic pulmonary fibrosis.
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Wuyts WA, Thomeer M, Dupont LJ, and Verleden GM
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- Acute Disease, Humans, Algorithms, Pulmonary Fibrosis diagnosis, Pulmonary Fibrosis therapy
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- 2008
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12. Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease.
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Demedts IK, Bracke KR, Van Pottelberge G, Testelmans D, Verleden GM, Vermassen FE, Joos GF, and Brusselle GG
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- Aged, Chemokine CCL20, Chemokines, CC analysis, Chemokines, CC genetics, Female, Humans, Lung pathology, Macrophage Inflammatory Proteins analysis, Macrophage Inflammatory Proteins genetics, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive pathology, RNA, Messenger analysis, RNA, Messenger metabolism, Receptors, CCR6, Receptors, Chemokine analysis, Receptors, Chemokine genetics, Receptors, Chemokine metabolism, Sputum chemistry, Sputum immunology, Chemokines, CC metabolism, Dendritic Cells immunology, Lung immunology, Macrophage Inflammatory Proteins metabolism, Pulmonary Disease, Chronic Obstructive immunology
- Abstract
Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process., Objectives: To evaluate the presence of DC in small airways of patients with COPD., Methods: We evaluated DC infiltration in small airways by immunohistochemistry in patients with COPD (stage I-IV), never-smokers, and smokers without COPD. Chemokine ligand 20 (CCL20, the most potent chemokine in attracting DC) was determined in total lung by RT-PCR and in induced sputum by enzyme-linked immunsorbent assay. Chemokine receptor 6 (CCR6, the receptor for CCL20) expression on human pulmonary DC was evaluated by RT-PCR and flow cytometry., Measurements and Main Results: There is a significant increase in DC number in the epithelium (p = 0.007) and adventitia (p = 0.009) of small airways of patients with COPD compared with never-smokers and smokers without COPD. DC number in epithelium and adventitia increases along with disease severity. CCL20 mRNA expression in total lung and CCL20 protein levels in induced sputum are significantly higher in patients with COPD compared with never-smokers (p = 0.034 for CCL20 mRNA and p = 0.0008 for CCL20 protein) and smokers without COPD (p = 0.016 for CCL20 mRNA and p = 0.001 for CCL20 protein). DC isolated from human lung express CCR6 both at mRNA and at protein level., Conclusions: This is the first description of airway infiltration by DC in COPD. Moreover, interaction between CCL20 and CCR6 provides a possible mechanism for accumulation of DC in the lungs in COPD. more...
- Published
- 2007
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13. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome.
- Author
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Verleden GM, Vanaudenaerde BM, Dupont LJ, and Van Raemdonck DE
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- Adult, Anti-Bacterial Agents pharmacology, Azithromycin pharmacology, Bronchiolitis Obliterans etiology, Bronchiolitis Obliterans metabolism, Bronchoalveolar Lavage, Female, Forced Expiratory Volume, Humans, Interleukin-8 genetics, Male, Middle Aged, Neutrophil Infiltration drug effects, RNA, Messenger metabolism, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, Bronchiolitis Obliterans drug therapy, Interleukin-8 metabolism, Lung Transplantation adverse effects
- Abstract
Rationale: Bronchiolitis obliterans syndrome (BOS) remains the leading cause of death after lung transplantation. Treatment is difficult, although azithromycin has recently been shown to improve FEV(1). The exact mechanism of action is unclear., Hypotheses: (1) Azithromycin reduces airway neutrophilia and interleukin (IL)-8 and (2) airway neutrophilia predicts the improvement in FEV(1)., Methods: Fourteen lung transplant patients with BOS (between BOS 0-p and BOS 3) were treated with azithromycin, in addition to their current immunosuppressive treatment. Before and 3 mo after azithromycin was introduced, bronchoscopy with bronchoalveolar lavage (BAL) was performed for cell differentiation and to measure IL-8 and IL-17 mRNA ratios., Results: The FEV(1) increased from 2.36 (+/- 0.82 L) to 2.67 L (+/- 0.85 L; p = 0.007), whereas the percentage of BAL neutrophilia decreased from 35.1 (+/- 35.7%) to 5.7% (+/- 6.5%; p = 0.0024). There were six responders to azithromycin (with an FEV(1) increase of > 10%) and eight nonresponders. Using categorical univariate linear regression analysis, the main significant differences in characteristics between responders and nonresponders were the initial BAL neutrophilia (p < 0.0001), IL-8 mRNA ratio (p = 0.0009), and the postoperative day at which azithromycin was started (p = 0.036). There was a significant correlation between the initial percentage of BAL neutrophilia and the changes in FEV(1) after 3 mo (r = 0.79, p = 0.0019)., Conclusion: Azithromycin significantly reduces airway neutrophilia and IL-8 mRNA in patients with BOS. Responders have a significantly higher BAL neutrophilia and IL-8 compared with nonresponders and had commenced treatment earlier after transplantation. BAL neutrophilia can be used as a predictor for the FEV(1) response to azithromycin. more...
- Published
- 2006
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14. Azithromycin: a plea for multicenter randomized studies in lung transplantation.
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Williams TJ and Verleden GM
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- Humans, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, Lung Transplantation, Multicenter Studies as Topic, Randomized Controlled Trials as Topic
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- 2005
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15. Mechanisms of interleukin 1beta-induced human airway smooth muscle hyporesponsiveness to histamine. Involvement of p38 MAPK NF-kappaB.
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Pype JL, Xu H, Schuermans M, Dupont LJ, Wuyts W, Mak JC, Barnes PJ, Demedts MG, and Verleden GM
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- Blotting, Western, Bronchi drug effects, Bronchi physiology, Cells, Cultured, Drug Interactions, Humans, Mitogen-Activated Protein Kinases drug effects, Muscle Contraction drug effects, Muscle, Smooth enzymology, Phosphoric Monoester Hydrolases, p38 Mitogen-Activated Protein Kinases, Bronchial Hyperreactivity physiopathology, Histamine pharmacology, Interleukin-1 metabolism, Mitogen-Activated Protein Kinases metabolism, Muscle, Smooth drug effects, Tumor Necrosis Factor-alpha metabolism
- Abstract
We have investigated the effect of IL-1beta on histamine H(1)-receptor (H(1)R)-mediated inositol phosphate (IP) accumulation in human airway smooth muscle cells (HASMC) and on histamine-induced contraction of human bronchial rings. Stimulation of HASMC for 24 h with IL-1beta resulted in significant loss of histamine-induced IP formation, which was associated with a reduction of histamine- induced contraction of IL-1beta-treated human bronchial rings. An inhibitor of NF-kappaB activation, pyrrolidine dithiocarbamate, and a p38 MAPK inhibitor, blocked the IL-1beta-induced H(1)R desensitization, whereas anisomycin, an SAPK/JNK and p38 MAPK activator, mimicked the effect of IL-1beta. IL-1beta has been demonstrated to induce cox-2 expression and PGE(2) synthesis. In our study, indomethacin a cox antagonist, completely inhibited the effect of IL-1beta on H(1)R, whereas exogenously added PGE(2) was able to desensitize H(1)R. Furthermore, H-89, a selective PKA inhibitor, antagonized the effect of IL-1beta. Here, we have demonstrated that IL-1beta desensitizes H(1)R, which involves the activation of p38 MAPK and NF-kappaB, leading to the expression of cox-2 and the synthesis of PGE(2). PGE(2) increases intracellular cAMP resulting in PKA activation, which phosphorylates and functionally uncouples H(1)R. Our results suggest that IL-1beta protects airway smooth muscle against histamine-induced contractile responses and that bronchial hyperreactivity to histamine is not associated with proinflammatory cytokine-induced enhancement in H(1)R signaling. more...
- Published
- 2001
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16. The effects of 8-hydroxy-2-(di-n-propylamino)tetralin on the cholinergic contraction in guinea pig and human airways in vitro.
- Author
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Dupont LJ, Pype JL, Demedts MG, De Leyn P, Deneffe G, and Verleden GM
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- 8-Hydroxy-2-(di-n-propylamino)tetralin administration & dosage, Acetylcholine metabolism, Animals, Bronchoconstriction drug effects, Capsaicin pharmacology, Culture Techniques, Cyclohexane Monoterpenes, Dose-Response Relationship, Drug, Electric Stimulation, Guinea Pigs, Humans, Indoles pharmacology, Ketanserin pharmacology, Methysergide pharmacology, Muscle Contraction drug effects, Muscle, Smooth drug effects, Neuropeptides antagonists & inhibitors, Pindolol analogs & derivatives, Pindolol pharmacology, Serotonin analogs & derivatives, Serotonin pharmacology, Serotonin Antagonists pharmacology, Serotonin Receptor Agonists administration & dosage, Thiazoles pharmacology, Tropisetron, 8-Hydroxy-2-(di-n-propylamino)tetralin pharmacology, Bronchi drug effects, Cholinergic Fibers drug effects, Serotonin Receptor Agonists pharmacology, Trachea drug effects
- Abstract
Electrical field stimulation of guinea pig tracheal strips and human bronchial rings, in vitro, evokes a cholinergic contraction mediated by the release of acetylcholine. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a 5-HT1A and 5-HT7 agonist. In this study, we have investigated whether 8-OH-DPAT could modulate the cholinergic contraction in guinea pig and human airways in vitro. 8-OH-DPAT (1 to 30 microM) produced a concentration-dependent inhibition of the cholinergic contraction in guinea pig tracheal strips with a maximal inhibition of 75.8% +/- 4. 7% (30 microM, 0.5 Hz). Pretreatment of the tissues with the 5- HT1/2/7 antagonist methysergide (10 to 30 microM) significantly attenuated the inhibitory effects of 8-OH-DPAT (10 to 30 microM) on the cholinergic contraction. Pretreatment with ketanserin (10 microM), a 5-HT2 antagonist, tropisetron (1 microM), a 5-HT3/4 antagonist, SDZ 216-525 (1 to 10 microM) and pindobind (10 microM), both selective 5-HT1A antagonists, or capsaicin (10 microM), which depletes sensory nerves from neuropeptides, had no effect on the inhibition of the cholinergic contraction by 8-OH-DPAT (10 to 30 microM). 5-carboxamidotryptamine (5-CT) (10 to 100 microM), a 5-HT1/2/7 agonist, partially mimicked the inhibitory effects of 8-OH-DPAT on the cholinergic contraction. 8-OH-DPAT (10 to 30 microM) also inhibited the cholinergic contraction in human bronchial rings in vitro with a maximal inhibition of 46.2% +/- 7.2% (30 microM, 1 Hz). SDZ 216-525 (10 microM) had no effect, whereas methysergide (30 microM) partially prevented the effect of 8-OH-DPAT in human airways. 8-OH-DPAT (30 microM) did not displace the concentration-response curve to acetylcholine (10 nM-30 mM) in guinea pig and human airways in vitro. These results suggest that 8-OH-DPAT inhibits the cholinergic contraction in guinea pig and human airways in vitro through stimulation of prejunctional atypical 5-HT receptors, possibly of the 5-HT7 subtype, located on postganglionic cholinergic nerves. more...
- Published
- 1998
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17. Recurrence of desquamative interstitial pneumonia after lung transplantation.
- Author
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Verleden GM
- Subjects
- Humans, Lung Diseases, Interstitial pathology, Male, Middle Aged, Recurrence, Lung Diseases, Interstitial surgery, Lung Transplantation
- Published
- 1998
- Full Text
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18. Exhaled nitric oxide correlates with airway hyperresponsiveness in steroid-naive patients with mild asthma.
- Author
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Dupont LJ, Rochette F, Demedts MG, and Verleden GM
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- Adrenergic beta-Agonists administration & dosage, Adrenergic beta-Agonists therapeutic use, Adult, Airway Obstruction metabolism, Airway Obstruction physiopathology, Anti-Asthmatic Agents administration & dosage, Anti-Asthmatic Agents therapeutic use, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents therapeutic use, Asthma drug therapy, Asthma physiopathology, Beclomethasone administration & dosage, Beclomethasone therapeutic use, Biomarkers analysis, Bronchial Hyperreactivity physiopathology, Bronchial Provocation Tests, Chronic Disease, Cough metabolism, Cough physiopathology, Dyspnea metabolism, Dyspnea physiopathology, Female, Forced Expiratory Volume drug effects, Glucocorticoids administration & dosage, Glucocorticoids therapeutic use, Histamine administration & dosage, Humans, Male, Nitric Oxide analysis, Respiratory Sounds physiology, Asthma metabolism, Bronchial Hyperreactivity metabolism, Nitric Oxide metabolism, Respiration
- Abstract
Endogenously released nitric oxide (NO) has been detected in the exhaled air of humans. Exhaled NO (NOexh) levels have been significantly increased in patients with inflammatory airways disorders such as asthma, and NOexh has been suggested to be a usable marker of airway inflammation. In the present study, NOexh levels were measured both in steroid-treated and untreated subjects with mild asthma, and were correlated with the degree of airway hyperresponsiveness (AHR), measured as the dose of histamine that produced a 20% decrease in FEV1 (PC20histamine). NOexh levels, which were significantly increased in steroid-naive patients (Group A1: NOexh = 21 +/- 11 ppb; n = 56) in comparison with levels in control subjects (Group B: NOexh = 10 +/- 2 ppb; n = 20; p < 0.001), correlated significantly with the PC20histamine (r = -0.65; p < 0.0001). The NOexh level was significantly lower in patients with chronic cough of other causes than bronchial asthma (Group A2: NOexh = 11 +/- 3 ppb; n = 18) when compared with the level in subjects with mild asthma (Group A1: p < 0.001). Therefore, the noninvasive measurement of NOexh allowed us to discriminate, among patients with respiratory complaints, between those with and without AHR. In asthmatic subjects treated with inhaled steroids, the NOexh levels were significantly lower (Group A3: NOexh = 13 +/- 5 ppb; n = 25) than in untreated subjects (Group A1; p < 0.01), and there was no relationship with the PC20histamine (r = -0.18, p = NS). These findings confirm that NOexh reflects AHR in patients with mild asthma who have not already been treated with inhaled steroids. Patients treated with inhaled steroids had an NOexh level comparable to levels in control subjects, although AHR could still be demonstrated. more...
- Published
- 1998
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19. Furosemide and bumetanide, but not nedocromil sodium, modulate nonadrenergic relaxation in guinea pig trachea in vitro.
- Author
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Verleden GM, Pype JL, and Demedts MG
- Subjects
- Animals, Arginine analogs & derivatives, Arginine pharmacology, Atropine pharmacology, Chymotrypsin pharmacology, Drug Therapy, Combination, Electric Stimulation, Female, Guinea Pigs, In Vitro Techniques, Indomethacin pharmacology, Male, Muscle Relaxation physiology, Nitric Oxide antagonists & inhibitors, Nitroprusside pharmacology, Premedication, Propranolol pharmacology, Trachea physiology, Vasoactive Intestinal Peptide pharmacology, omega-N-Methylarginine, Bumetanide pharmacology, Furosemide pharmacology, Muscle Relaxation drug effects, Nedocromil pharmacology, Trachea drug effects
- Abstract
Furosemide has recently been shown to be effective in inhibiting various indirect challenges in asthmatic patients, but its mode of action is not yet clear. There is some evidence that furosemide has an inhibitory effect on sensory and cholinergic nerves in the airways. We have investigated the effects of furosemide, bumetanide, and nedocromil sodium on inhibitory nonadrenergic, noncholinergic (iNANC) responses in guinea pig trachea in vitro using electrical field stimulation (50 V, 0.5 ms, 2 to 32 Hz for 30 s) and exogenously applied vasoactive intestinal peptide (VIP) or nitroprusside. In the presence of atropine (1 microM), indomethacin (10 microM), and propranolol (1 microM), both furosemide and bumetanide but not nedocromil sodium produced a concentration-dependent inhibition of the iNANC response (maximum inhibition, 31.2 +/- 5.6% with 100 microM furosemide at 16 Hz and 44.2 +/- 4.1% with 10 microM bumetanide at 4 Hz). Furthermore, after pretreatment of the tissues with L-NG-monomethyl arginine (90 microM), alpha-chymotrypsin (2 U/ml), or both, furosemide and bumetanide produced a further inhibition of the iNANC relaxation. Neither loop diuretic had any effect on the concentration-response curves to exogenous VIP (10(-9) to 10(-7) M) or nitroprusside (10(-8) to 10(-6) M). These results indicate that loop diuretics may inhibit nonadrenergic relaxation in guinea pig trachea in vitro by a prejunctional mechanism, probably through inhibition of nerve activation, the exact mechanism of which is still undefined. more...
- Published
- 1994
- Full Text
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