5 results on '"Wijffels M"'
Search Results
2. Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease
- Author
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Lapperre, T. S., Snoeck-Stroband, J. B., Gosman, M. M. E., Jansen, D. F., Schadewijk, A., Thiadens, H. A., Vonk, J. M., Boezen, H. M., Ten Hacken, N. H. T., Sont, J. K., Rabe, K. F., Kerstjens, H. A. M., Hiemstra, P. S., Wim Timens, Postma, D. S., Sterk, P. J., Kauffman, H. F., Reus, D., Barentsen, M. D. W., Zeinstra-Smit, M., Luteijn, A. J., Molen, T., Ter Veen, G., Maaren, M. S., Veltman, C. A., Verbokkem, A., Verhage, I., Vink-Klooster, H. K., Gast-Strookman, J., Janssen, K., Schrumpf, J. A., Smit-Bakker, J., Stolk, J., Tiré, A. C. J. A., Veen, H., Wijffels, M. M. E., Willems, L. N. A., Mauad, T., GLUCOLD Study Grp, Internal Medicine, Epidemiology, Surgery, Erasmus MC other, Pharmacy, Department of Strategic Management and Entrepreneurship, AII - Amsterdam institute for Infection and Immunity, and Pulmonology
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Bronchi ,Cell Count ,Placebo ,Gastroenterology ,Fluticasone propionate ,Drug Administration Schedule ,Pulmonary function testing ,Pulmonary Disease, Chronic Obstructive ,Bronchodilator ,Internal medicine ,Forced Expiratory Volume ,Administration, Inhalation ,Internal Medicine ,Medicine ,Humans ,Albuterol ,Lung ,Salmeterol Xinafoate ,Fluticasone ,Asthma ,Aged ,Inflammation ,COPD ,business.industry ,Smoking ,Sputum ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Bronchodilator Agents ,Androstadienes ,Treatment Outcome ,Drug Therapy, Combination ,Female ,Salmeterol ,Human medicine ,business ,medicine.drug - Abstract
Background: Inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD). Objective: To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD. Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847) Setting: 2 university medical centers in The Netherlands. Patients: 114 steroid-naive current or former smokers with moderate to severe COPD. Measurements: Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months. Intervention: Random assignment by minimization method to receive fluticasone propionate, 500 μg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 μg twice daily, and salmeterol, 50 μg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29). Results: 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3+ cells (-55% [95% CI, -74% to -22%]; P - 0.004), CD4- cells (-78% [CI, -88% to 60%]; P < 0.001), CD8+ cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV1 decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3+ cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV1 level. Limitations: The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months. Conclusion: ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. Primary Funding Source: Netherlands Organization for Scientific Research, Netherlands Asthma Foundation, GlaxoSmithKline of The Netherlands, University Medical Center Groningen, and Leiden University Medical Center.
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- 2009
3. Toll-Like Receptor (TLR2 and TLR4) Polymorphisms and Chronic Obstructive Pulmonary Disease
- Author
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Budulac, Simona E., Boezen, H. Marike, Hiemstra, Pieter S., Lapperre, Therese S., Vonk, Judith M., Timens, Wim, Postma, Dirkje S., Kauffman, H. F., de Reus, D., Jansen, D. F., Barentsen, M. D.W., Zeinstra-Smit, M., Luteijn, A. J., van der Molen, T., ter Veen, G., Gosman, M. M.E., ten Hacken, N. H.T., Kerstjens, H. A.M., van Maaren, M. S., Veltman, C. A., Verbokkem, A., Verhage, I., Vink-Klooster, H. K., Snoeck-Stroband, J. B., Thiadens, H., Sont, J. K., Bajema, I., Gast-Strookman, J., Janssen, K., Rabe, K. F., van Schadewijk, A., Smit-Bakker, J., Stolk, J., Tire', A. C.J.A., van der Veen, H., Wijffels, M. M.E., Willems, L. N.A., Sterk, P. J., Mauad, T., GLUCOLD Study Grp, Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Erasmus School of Economics, Internal Medicine, Epidemiology, Surgery, Erasmus MC other, Pharmacy, Department of Strategic Management and Entrepreneurship, AII - Amsterdam institute for Infection and Immunity, and Pulmonology
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Male ,Pulmonology ,Chronic Obstructive Pulmonary Diseases ,Pulmonary function testing ,Pulmonary Disease, Chronic Obstructive ,Pathology ,Longitudinal Studies ,TOLL-LIKE-RECEPTOR-2 EXPRESSION ,Lung ,SNPS ,COPD ,Multidisciplinary ,Middle Aged ,medicine.anatomical_structure ,Medicine ,Female ,medicine.symptom ,Engineering sciences. Technology ,Research Article ,Clinical Research Design ,Science ,Inflammation ,Single-nucleotide polymorphism ,Models, Biological ,Polymorphism, Single Nucleotide ,SALMETEROL ,Diagnostic Medicine ,Genetics ,medicine ,Humans ,Biology ,Aged ,Polymorphism, Genetic ,business.industry ,Sputum ,Immunity ,medicine.disease ,GENE ,Toll-Like Receptor 2 ,respiratory tract diseases ,Toll-Like Receptor 4 ,TLR2 ,Gene Expression Regulation ,CIGARETTE-SMOKE ,Genetics of Disease ,Immunology ,CELLS ,Genetic Polymorphism ,TLR4 ,Clinical Immunology ,business ,Population Genetics ,Biomarkers ,General Pathology - Abstract
Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD. Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients. Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models. Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells. None of the TLR4 SNPs was associated with FEV1 level. Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time. This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.
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- 2012
4. Inter-observer variation in the diagnosis of coronal articular fracture lines in the lunate facet of the distal radius
- Author
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Wijffels, M. M., Guitton, T. G., Brink, P.R.G., Ring, D., Surgery, and RS: NUTRIM - R2 - Gut-liver homeostasis
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Surgery Articles ,medicine.medical_specialty ,Articular fracture ,Facet (geometry) ,medicine.diagnostic_test ,business.industry ,Radiography ,Computed tomography ,Radius ,Surgery ,Lunate ,Coronal plane ,Orthopedic surgery ,medicine ,Orthopedics and Sports Medicine ,business ,Nuclear medicine - Abstract
Several studies support the use of CT for diagnosing coronal fractures of the distal radius but the inter-observer reliability of these observations is less well studied. We tested the null hypothesis that radiographs alone and the combination of radiographs and two-dimensional computed tomography scans (2DCT) have the same inter-observer variation for the diagnosis of coronal articular fracture lines in the distal radius.Using a web-based survey, 63 surgeons were randomized to evaluate 16 fractures of the distal radius on radiographs alone or radiographs and 2DCT for the presence or absence of a coronal fracture line of the lunate facet and, if present, the stability of the fracture. The kappa multirater measure was calculated to estimate agreement between observers.The inter-observer variation in diagnosis of a coronal fracture line was fair with both radiographs and 2DCT, as was the diagnosis of instability of the volar lunate facet fracture when present.Two-dimensional computed tomography does not improve observer agreement on the diagnosis of coronal plane articular fracture lines in the lunate facet of the distal radius.
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- 2012
5. Smoking cessation and bronchial epithelial remodelling in COPD
- Author
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Lapperre, Therese, Sont, Jacob K., van Schadewijk, Annemarie, Gosman, Margot M. E., Postma, Dirkje S., Bajema, Ingeborg M., Timens, Wim, Mauad, Thais, Hiemstra, Pieter S., Kauffman, H. F., de Reus, D., Boezen, H. M., Jansen, D. F., Vonk, J., Barentsen, M. D. W., Timens, W., Zeinstra-Smit, M., Luteijn, A. J., van der Molen, T., ter Veen, G., Gosman, M. M. E., ten Hacken, N. H. T., Kerstjens, H. A. M., van Maaren, M. S., Postma, D. S., Veltman, C. A., Verbokkem, A., Verhage, I., Vink-Kloosters, H. K., Snoeck-Stroband, J. B., Thiadens, H., Sont, J. K., Bajema, I., Gast-Strookman, J., Hiemstra, P. S., Janssen, K., Lapperre, T. S., Rabe, K. F., van Schadewijk, A., Schrumpf, J. A., Smit-Bakker, J., Stolk, J., Tire, A. C. J. A., van der Veen, H., Wijffels, M. M. E., Willems, L. N. A., Sterk, P. J., Mauad, T., Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), and GLUCOLD Study Grp
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Respiratory Mucosa ,Pulmonary and Respiratory Medicine ,Male ,Pathology ,medicine.medical_specialty ,CHRONIC MUCUS HYPERSECRETION ,Bronchi ,LUNG HEALTH ,GOBLET CELL ,PERIPHERAL AIRWAYS ,OBSTRUCTIVE PULMONARY-DISEASE ,Epithelial squamous cell ,AIR-FLOW OBSTRUCTION ,Pulmonary Disease, Chronic Obstructive ,Metaplasia ,medicine ,EX-SMOKERS ,Humans ,Respiratory system ,Aged ,Cell Proliferation ,lcsh:RC705-779 ,Goblet cell ,COPD ,business.industry ,Cell growth ,Research ,CURRENT SMOKERS ,Cell Differentiation ,lcsh:Diseases of the respiratory system ,Middle Aged ,HUMAN NEUTROPHIL DEFENSINS ,medicine.disease ,Epithelium ,respiratory tract diseases ,medicine.anatomical_structure ,Cross-Sectional Studies ,Female ,Smoking Cessation ,Human medicine ,medicine.symptom ,business ,GROWTH-FACTOR RECEPTOR - Abstract
Background Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation. Methods 114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies. Results Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters ( Conclusion Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years). Trial registration NCT00158847
- Published
- 2007
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