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Biomedical subjects

E F M Wouters

Publications and source records attributed to E F M Wouters.

At least 19 recordsLinked to original sources
PubMed2006

Differences in local versus systemic TNFalpha production in COPD: inhibitory effect of hyaluronan on LPS induced blood cell TNFalpha release.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by both airway inflammation and systemic changes. To elucidate the relationship between local and systemic inflammation, tumour necrosis factor alpha (TNFalpha) production by sputum cells and blood cells of patients with COPD and controls was compared and the effect of the extracellular matrix compound hyaluronan (HA) on TNFalpha release was studied. METHODS: Four study groups were included: 10 steroid free COPD patients, 8 steroid treated patients, 10 healthy smokers, and 11 healthy non-smokers. Sputum cells and blood were incubated for 24 hours with or without lipopolysaccharide (LPS) in the absence or presence of HA (122 kDa or HMW fragment). TNFalpha was measured by ELISA. RESULTS: Sputum cells produced spontaneously high levels of TNFalpha but were unresponsive to LPS. Sputum cells from COPD patients (both steroid free and steroid treated) produced significantly less TNFalpha than cells from healthy non-smoking subjects (p=0.017 and p=0.001, respectively). In contrast, blood cells produced TNFalpha only in response to LPS. No differences were observed in TNFalpha production by blood cells between the patient groups and the control groups. HA (both fragments) partially blocked LPS (1 ng/ml) induced TNFalpha release by blood cells from all study groups, whereas TNFalpha production by sputum cells was not influenced by HA. CONCLUSION: These data indicate a difference between local and systemic TNFalpha production. Sputum cells of patients with COPD produced less TNFalpha than controls, which could contribute to impaired local defence. An inhibitory effect of HA on TNFalpha release in blood cells was observed which was similar in both patients and controls.

Adult↗
PubMed2006

Prevalence of nutritional depletion in a large out-patient population of patients with COPD.

OBJECTIVE: The present study focuses on the prevalence of nutritional depletion in relation to functional performance, airflow limitation, experienced dyspnoea and health status in a large multi-center out-patient population with chronic obstructive pulmonary disease (COPD). METHODS: In 39 out-patient centers in The Netherlands, 389 patients with moderate to severe COPD (217 men) were recruited. The study evaluated on the baseline characteristics of the COSMIC study. Measurements included body composition by bioelectrical impedance analysis, dyspnoea by MRC-score, peripheral muscle function by isometric handgrip strength and disease-specific health status by St. George Respiratory Questionnaire. RESULTS: The prevalence of nutritional depletion (defined as body mass index (BMI)<or=21 kg/m2 and/or fat-free mass index (FFMI)<or=15 (females) or <or=16 (males) kg/m2) was high (27%). Prevalence of normal BMI and low FFMI was 15%, and of low BMI and low FFMI 11%. The prevalence of low BMI as well as low FFMI was significantly higher in female than in male COPD patients, 18% and 40% vs. 10% and 20%, respectively (both P<0.01). No differences in FEV1%predicted, dyspnoea score and health status were observed between depleted and non-depleted COPD patients. Multiple linear regression analysis in the total group showed that handgrip strength correlated with FFMI after correction for sex distribution and age, but not FEV1%predicted. CONCLUSIONS: The prevalence of nutritional depletion was high in a large out-patient COPD population in The Netherlands, especially in female COPD patients. Depletion of FFM was associated with impaired peripheral muscle strength, independent of disease severity.

Adult↗
PubMed2005

Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease.

BACKGROUND: The observations that smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and that nicotine may have antidepressant effects and regulate mood provide a rationale for the use of antidepressant drugs for smoking cessation in patients with COPD. No clinical trial has studied the efficacy of bupropion hydrochloride and nortriptyline hydrochloride for smoking cessation in this patient population, to our knowledge. METHODS: In a placebo-controlled double-dummy randomized trial, 255 adults at risk for COPD or with COPD were prescribed sustained-release bupropion (bupropion SR) (150 mg twice daily) or nortriptyline (75 mg once daily) for 12 weeks. All patients received smoking cessation counseling. The main outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the target quit date. RESULTS: The use of bupropion SR and nortriptyline resulted in higher prolonged abstinence rates compared with placebo, although only the difference between bupropion SR and placebo was statistically significant (differences with placebo, 13.1% [95% confidence interval, 1.2%-25.1%] for bupropion SR and 10.2% [95% confidence interval, -1.7% to 22.2%] for nortriptyline). In patients with COPD, bupropion SR and nortriptyline seem efficacious in achieving prolonged abstinence (differences with placebo, 18.9% [95% confidence interval, 3.6%-34.2%] for bupropion SR and 12.9% [95% confidence interval, -0.8% to 26.4%] for nortriptyline). In participants at risk for COPD, no statistically significant differences with placebo in prolonged abstinence rates were found. CONCLUSIONS: Bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD. Nortriptyline treatment seems to be a useful alternative.

Antidepressive Agents, Second-Generation↗
PubMed2005

Raised CRP levels mark metabolic and functional impairment in advanced COPD.

BACKGROUND: C-reactive protein (CRP) is often used as a clinical marker of acute systemic inflammation. Since low grade inflammation is evident in chronic diseases such as chronic obstructive pulmonary disease (COPD), new methods have been developed to enhance the sensitivity of CRP assays in the lower range. A study was undertaken to investigate the discriminative value of high sensitivity CRP in COPD with respect to markers of local and systemic impairment, disability, and handicap. METHODS: Plasma CRP levels, interleukin 6 (IL-6) levels, body composition, resting energy expenditure (REE), exercise capacity, health status, and lung function were determined in 102 patients with clinically stable COPD (GOLD stage II-IV). The cut off point for normal versus raised CRP levels was 4.21 mg/l. RESULTS: CRP levels were raised in 48 of 102 patients. In these patients, IL-6 (p<0.001) and REE (adjusted for fat-free mass, p = 0.002) were higher while maximal (p = 0.040) and submaximal exercise capacity (p = 0.017) and 6 minute walking distance (p = 0.014) were lower. The SGRQ symptom score (p = 0.003) was lower in patients with raised CRP levels, as were post-bronchodilator FEV1 (p = 0.031) and reversibility (p = 0.001). Regression analysis also showed that, when adjusted for FEV1, age and sex, CRP was a significant predictor for body mass index (p = 0.044) and fat mass index (p = 0.016). CONCLUSIONS: High sensitivity CRP is a marker for impaired energy metabolism, functional capacity, and distress due to respiratory symptoms in COPD.

Body Mass Index↗
PubMed2005

Associations of depressive symptoms with gender, body mass index and dyspnea in primary care COPD patients.

BACKGROUND: It has been suggested that severe COPD is associated with depressive symptoms, possibly linked to exacerbations, dyspnea and hospitalisation. However, scarce data are available in primary care where most patients suffer from mild or moderate disease. OBJECTIVE: We aimed to reveal associations of depressive symptoms with demographic and clinical characteristics in mild to moderate COPD. METHODS: Cross-sectional data on lung function measurements, exacerbation frequency, dyspnea, comorbidity, smoking behaviour, body mass index (BMI), age, gender and depressive symptoms (Beck Depression Inventory) of 147 primary care patients were assessed in multiple logistic regression analyses. RESULTS: Patients suffered from mild to moderate obstruction (FEV1 63.6% pred, range 45.1% to 82.1%). Female gender (OR 4.8, 95% CI 2.1 to 10.8), BMI > 25 (OR 0.4, 95% CI 0.2 to 0.8) and current smoking (OR 2.3, 95% CI 1.01 to 5.3) were univariately associated with depressive symptoms, while in a multivariate logistic model only female gender (OR 4.0, 95% CI 1.6 to 9.9), BMI > 25 (OR 0.3, 95% CI 0.1 to 0.7) and dyspnea (OR 1.8, 95% CI 1.1 to 2.9) were independently associated with depressive symptoms. Conclusion. These data suggest that in primary care depressive symptoms in COPD seem to be related with female gender, BMI and dyspnea. In this study, lung function, exacerbation rate, smoking behaviour, age and comorbidity are not independently associated with depressive symptoms in COPD of mild to moderate severity.

Aged↗
PubMed2005

Leptin as local inflammatory marker in COPD.

INTRODUCTION: Chronic inflammation of the lung is a characteristic finding in chronic obstructive pulmonary disease (COPD). Leptin is a pleiotropic cytokine thought to play a role in host response to inflammation. As recent studies have shown that leptin receptors are present in the lung, this study aimed to determine if leptin is detectable in induced sputum of COPD patients and if there is a relationship between leptin and other inflammatory markers in sputum. METHODS: Sputum was induced in 14 male patients with moderate COPD (FEV1: 56 (15) % pred.). Leptin, total tumour necrosis factor (TNF)-alpha, and C-reactive protein (CRP) were analyzed in induced sputum supernatant by ELISA. Leptin was also determined in EDTA plasma. RESULTS: Leptin was detectable in induced sputum of 10 COPD patients. A significant relationship was found between sputum leptin and CRP (r = 0.943, P < 0.001) and total TNF-alpha (r = 0.690, P < 0.01). Plasma leptin and sputum leptin were inversely correlated (r = -0.643, P < 0.01). CONCLUSION: The present study demonstrated that leptin is detectable in induced sputum of patients with moderate COPD and is related to other inflammatory markers. The observed correlations between leptin and inflammatory markers in sputum may indicate that leptin is involved in the local inflammatory response in COPD.

Adult↗
PubMed2005

Minimal clinically important differences in COPD: body mass index and muscle strength.

Weight loss, muscle wasting, as well as muscle dysfunction are recognized as important problems in COPD, contributing to morbidity and mortality. This paper discusses body weight and muscle function as possible outcome parameters in the management of COPD. The relationship between these outcome measures and COPD-related management goals is discussed. Minimal clinically important differences (MCID) in the approach of patients suffering from COPD for these measures are discussed.

Body Mass Index↗
PubMed2005

Enhanced levels of hyaluronan in lungs of patients with COPD: relationship with lung function and local inflammation.

BACKGROUND: Chronic inflammation and airway remodelling are characteristics of chronic obstructive pulmonary disease (COPD). Hyaluronan (HA) is an extracellular matrix compound with proinflammatory activity. HA levels in induced sputum from patients with COPD were measured and related to local inflammation. The expression of hyaluronan synthase 2 (HAS2) and hyaluronidase 2 (HYAL2) was analysed in lung tissue. METHODS: Sputum was obtained from 18 patients with COPD (forced expiratory volume in 1 second (FEV(1)) 62% predicted (range 20-76)) and 14 healthy smokers. HA and inflammatory markers were measured using ELISA assays. Lung sections were obtained from five patients with severe COPD (FEV(1) <30%) and from five smokers, and mRNA levels of HAS2 and HYAL2 were analysed by polymerase chain reaction. RESULTS: HA levels were significantly higher in the sputum from patients with COPD than controls. The COPD population appeared to consist of two subpopulations with either high or moderate HA levels. The subgroup of patients with high HA levels had lower FEV(1) than the moderate HA group. In addition, neutrophil influx and levels of interleukin-8, and the soluble tumour necrosis factor receptors R55 and R75 were significantly higher in patients with high HA levels than in those with moderate HA levels and controls. Semiquantitative analysis revealed enhanced expression of HYAL2 in lung tissue of patients with severe COPD compared with control subjects. CONCLUSION: These data indicate a relationship between HA levels, local inflammation and severity of disease, and suggest enhanced breakdown of HA in the lungs of patients with COPD.

Adult↗
PubMed2005

Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease.

BACKGROUND: Muscle wasting and decreased muscle oxidative capacity commonly occur in patients with chronic obstructive pulmonary disease (COPD). Polyunsaturated fatty acids (PUFA) have been shown to mediate several inflammatory and metabolic pathways which may be involved in the pathogenesis of muscle impairment in COPD. The aim of this study was to investigate the effect of PUFA modulation on systemic inflammation, reversal of muscle wasting, and functional status in COPD. METHODS: Eighty patients with COPD (57 men) with forced expiratory volume in 1 second (FEV1) 37.3 (13.8)% predicted received 9 g PUFA or placebo daily in a double blind randomised fashion during an 8 week rehabilitation programme. Body composition (bioelectrical impedance), functional capacity (lung function, incremental cycle ergometry test, submaximal cycle test, isokinetic quadriceps strength) and inflammatory markers (C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha) were assessed at baseline and after 8 weeks. RESULTS: Both groups had similar increases in weight, fat-free mass (FFM), and muscle strength. The peak load of the incremental exercise test increased more in the PUFA group than in the placebo group (difference in increase 9.7 W (95% CI 2.5 to 17.0), p = 0.009) even after adjustment for FFM. The duration of the constant work rate test also increased more in patients receiving PUFA (difference in increase 4.3 min (95% CI 0.6 to 7.9), p = 0.023). The positive effects of PUFA could not be attributed to a decrease in systemic levels of CRP, IL-6 and TNF-alpha. CONCLUSIONS: This is the first study to show beneficial effects of PUFA on exercise capacity in patients with COPD.

C-Reactive Protein↗
PubMed2005

Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial.

BACKGROUND: Guidelines recommend inhaled corticosteroids (ICS) as maintenance treatment for patients with chronic obstructive pulmonary disease (COPD) with a post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and frequent exacerbations, although they have only a small preventive effect on the accelerated decline in lung function. Combined treatment with ICS and long acting beta2 agonists (LABA) may provide benefit to the stability of COPD, but it is unknown if withdrawal of ICS will result in disease deterioration. METHODS: The effects of 1 year withdrawal of the ICS fluticasone propionate (FP) after a 3 month run-in treatment period with FP combined with the LABA salmeterol (S) (500 microg FP + 50 microg S twice daily; SFC) were investigated in patients with COPD in a randomised, double blind study. 497 patients were enrolled from 39 centres throughout the Netherlands; 373 were randomised and 293 completed the study. RESULTS: The drop out rate after randomisation was similar in the two groups. Withdrawal of FP resulted in a sustained decrease in FEV1: mean (SE) change from baseline -4.4 (0.9)% (S) v -0.1 (0.9)% (SFC); adjusted difference 4.1 (95% CI 1.6 to 6.6) percentage points (p<0.001). Corresponding figures for the FEV1/FVC ratio were -3.7 (0.8)% (S) v 0.0 (0.8)% (SFC) (p = 0.002). The annual moderate to severe exacerbation rate was 1.6 and 1.3 in the S and SFC groups, respectively (adjusted rate ratio 1.2; 95% CI 0.9 to 1.5; p = 0.15). The mean annual incidence rate of mild exacerbations was 1.3 (S) v 0.6 (SFC), p = 0.020. An immediate and sustained increase in dyspnoea score (scale 0-4; mean difference between groups 0.17 (0.04), p<0.001) and in the percentage of disturbed nights (6 (2) percentage points, p<0.001) occurred after withdrawal of fluticasone. CONCLUSIONS: Withdrawal of FP in COPD patients using SFC resulted in acute and persistent deterioration in lung function and dyspnoea and in an increase in mild exacerbations and percentage of disturbed nights. This study clearly indicates a key role for ICS in the management of COPD as their discontinuation leads to disease deterioration, even under treatment with a LABA.

Administration, Inhalation↗
PubMed2005

Are patients with COPD psychologically distressed?

This study was designed to assess the level of psychological distress in a heterogeneous group of patients with chronic obstructive pulmonary disease (COPD), and compare them with the general population and psychiatric outpatients. A total of 118 patients with COPD, a random sample of 500 subjects from the general population and 500 psychiatric outpatients participated in this study. The Dutch version of the Symptom Checklist-90-Revised was used to assess general psychological distress. The sample of patients with COPD experienced significantly more psychological distress than the general population and significantly less than psychiatric outpatients. Furthermore, no significant association was found between the severity of the pulmonary disease and the level of psychological distress, although patients with severe or very severe COPD appeared to be at increased risk of depression. Lastly, the pattern of psychological complaints seems comparable in depressed patients with COPD and psychiatric outpatients. Once patients with COPD report suffering from depressive symptoms, the level of distress seems to increase to that found in psychiatric outpatients. In conclusion, in clinical settings in which psychological complaints are not routinely assessed, the Beck Depression Inventory and Symptom Checklist-90-Revised are very useful for drawing attention to depression and psychological distress.

Aged↗
PubMed2005

A dynamic population model of disease progression in COPD.

To contribute to evidence-based policy making, a dynamic Dutch population model of chronic obstructive pulmonary disease (COPD) progression was developed. The model projects incidence, prevalence, mortality, progression and costs of diagnosed COPD by the Global Initiative for Chronic Obstructive Lung Disease-severity stage for 2000-2025, taking into account population dynamics and changes in smoking prevalence over time. It was estimated that of all diagnosed COPD patients in 2000, 27% had mild, 55% moderate, 15% severe and 3% very severe COPD. The severity distribution of COPD incidence was computed to be 40% mild, 55% moderate, 4% severe and 0.1% very severe COPD. Disease progression was modelled as decline in forced expiratory volume in one second (FEV1) % predicted depending on sex, age, smoking and FEV1 % pred. The relative mortality risk of a 10-unit decrease in FEV1 % pred was estimated at 1.2. Projections of current practice were compared with projections assuming that each year 25% of all COPD patients receive either minimal smoking cessation counselling or intensive counselling plus bupropion. In the projections of current practice, prevalence rates between 2000-2025 changed from 5.1 to 11 per 1,000 inhabitants for mild, 11 to 14 per 1,000 for moderate, 3.0 to 3.9 per 1,000 for severe and from 0.5 to 1.3 per 1,000 for very severe COPD. Costs per inhabitant increased from 1.40 Euro to 3.10 for mild, 6.50 Euro to 9.00 for moderate, 6.20 Euro to 8.50 for severe and from 3.40 Euro to 9.40 for very severe COPD (price level 2000). Both smoking cessation scenarios were cost-effective with minimal counselling generating net savings. In conclusion, the chronic obstructive pulmonary disease progression model is a useful instrument to give detailed information about the future burden of chronic obstructive pulmonary disease and to assess the long-term impact of interventions on this burden.

Aged↗
PubMed2004

Nutritional support in patients with chronic obstructive pulmonary disease during hospitalization for an acute exacerbation; a randomized controlled feasibility trial.

BACKGROUND & AIMS: Previous studies reported a severely impaired energy balance in COPD patients during the first days of an acute exacerbation, mainly due to a decreased energy and protein intake. The aim of the study was to investigate the feasibility and effectiveness of energy- and protein-rich nutritional supplements during hospitalization for an acute exacerbation in nutritionally depleted COPD patients. METHODS: In a randomized double-blind, placebo-controlled two-center trial, 56 COPD patients were randomized and 47 patients completed the study. Nutritional intervention consisted of 3 x 125 ml (2.38 MJ/day) and the placebo group received similar amounts of a non-caloric fluid. Medical therapy and dietetic consultation were standardized and dietary intake was measured daily. Body composition, respiratory and skeletal muscle strength, lung function and symptoms were measured on admission and on days 4 and 8 of hospitalization. RESULTS: Forty-seven percent of the patients had experienced recent involuntary weight loss prior to admission. The degree of weight loss was inversely related to resting arterial oxygen tension (r = 0.31; P < 0.05). Nutritional intervention resulted in a significant increase in energy (16% vs. placebo) and protein intake (38% vs. placebo). Mean duration of hospitalization was 9 +/- 2 days. Relative to usual care, no additional improvements in lung function or muscle strength were seen after nutritional intervention. CONCLUSIONS: Oral nutritional supplementation during hospitalization for an acute exacerbation is feasible in nutritionally depleted COPD patients and does not interfere with normal dietary intake.

Aged↗
PubMed2004

Probability and determinants of relapse after discontinuation of inhaled corticosteroids in patients with COPD treated in general practice.

OBJECTIVE: The objective of the study was to assess the probability, and explore determinants of adverse respiratory outcome after discontinuation of inhaled corticosteroid (ICS) treatment in subjects with chronic obstructive pulmonary disease (COPD) diagnosed and treated in general practice. DESIGN: Prospective unblinded ICS withdrawal study. SUBJECTS: 201 ICS treated COPD patients with various degrees of airflow limitation from 45 Dutch general practices. MAIN OUTCOME MEASURES: Probability of and time to exacerbation or unremitting worsening of respiratory symptoms after ICS discontinuation. RESULTS: Mean age was 60.6 (S.D. 9.5) years, post-bronchodilator forced expiratory volume in 1s (FEV1) 65.6 (S.D. 15.7) % predicted. Overall probability of adverse respiratory outcome after ICS discontinuation was 0.37 (95% confidence interval (CI) 0.31, 0.44). Survival analysis showed that age, gender, smoking status and reversibility of airflow limitation were independent predictors of adverse respiratory outcome. For females, the adjusted hazard ratio was 2.14 (95% CI 1.31, 3.50) compared to males. For age, the hazard ratio was 1.05 (95% CI 1.02, 1.08) per year lived. CONCLUSION: Discontinuation of inhaled corticosteroids may harm patients with COPD. The probability of an adverse respiratory outcome may be higher in women, elderly patients, smokers and patients with higher bronchodilator reversibility while on inhaled steroid treatment.

Journal Article↗
PubMed2004

Glutathione and glutamate levels in the diaphragm of patients with chronic obstructive pulmonary disease.

Recently, decreased glutamate (Glu) and reduced glutathione (GSH) levels were reported in the quadriceps femoris of patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate whether Glu and GSH levels are also modified in the diaphragm of these patients. Nine male COPD patients (forced expiratory volume in one second (FEV1) range 28-68% of the predicted value) and seven male patients with normal pulmonary function (mean +/- SD FEV1 86 +/- 3% pred) submitted to thoracotomy were included. Biopsy specimens were taken from the diaphragm (both groups) and the quadriceps femoris (COPD group alone) in order to assess fibre size, myosin heavy chain expression, GSH levels and amino acid profile. The COPD group was characterised by preserved fibre size, a higher proportion of type I fibres (mean +/- SEM 70 +/- 3 versus 26 +/- 4%), and higher Glu and GSH content in the diaphragm compared to the quadriceps muscle. However, Glu and GSH levels were similar in diaphragm from the COPD and control groups. Glu level correlated with GSH level in both muscles. No significant correlation was found between Glu or GSH level and fibre size or proportions. This study shows that glutamate and reduced glutathione levels are preserved in the diaphragm of chronic obstructive pulmonary disease patients. Alterations in glutamate and reduced glutathione metabolism are muscle-specific in chronic obstructive pulmonary disease, affecting the quadriceps femoris but not the diaphragm. Glutamate and reduced glutathione levels are strongly interrelated in both muscles, independent of fibre type distribution and fibre size.

Aged↗
PubMed2003

ROS in the local and systemic pathogenesis of COPD.

An imbalance between oxidants and antioxidants is proposed in the pathogenesis of COPD. Potential alterations responsible for an imbalance in oxidant production and intra- and extracellular antioxidant defense systems are discussed with respect to COPD-related changes in the pulmonary compartment. In line with the current view of COPD as a disease with multiple systemic consequences, there is increasing evidence that imbalances in the redox milieu extend beyond the diseased lung in COPD patients. Skeletal muscle dysfunction is often observed in COPD and may result from imbalances in the redox environment of skeletal muscle. Potential triggers of oxidative stress in the muscle compartment include inflammation and hypoxia, and local sources of reactive oxygen and nitrogen species are discussed, as well the mechanisms by which skeletal muscle trophical state, contractility and fatigability may be affected by oxidative stress, resulting in skeletal muscle dysfunction.

Animals↗