Emiel F M Wouters

Maastricht Universitair Medisch Centrum, Maestricht, Limburg, Netherlands

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Publications (612)2755.94 Total impact

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    ABSTRACT: Background Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored. Methods In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored. Results As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group. Conclusions In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195 .).
    New England Journal of Medicine 09/2014; · 51.66 Impact Factor
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    ABSTRACT: Remodeling in COPD has at least two dimensions: small airway wall thickening and destruction of alveolar walls. The aim of this study was to characterize and assess similarities in alveolar and small airway wall matrix remodeling in chronic COPD models. From this comparative characterization of matrix remodeling we derived and elaborated underlying mechanisms to the matrix changes reported in COPD. Lung tissue sections of chronic models for COPD, either induced by exposure to cigarette smoke, chronic intratracheal LPS instillation or local TNF expression (SPC-TNFα mice), were stained for elastin, collagen and hyaluronan. Furthermore TNFα, MMP2, 9 and 12 mRNA expression was analyzed using qPCR and localized using immunohistochemistry. Both collagen and hyaluronan were increased in alveolar and small airway walls of all three models. Interestingly, elastin contents were differentially affected, with a decrease in both alveolar and airway walls in SPC-TNFα mice. Furthermore TNFα, and MMP2 and 9 mRNA and protein levels were found to be increased in alveolar walls and around airway walls only in SPC-TNFα mice. We show that only SPC-TNFα mice show changes in elastin remodeling which are comparable to what has been observed in COPD patients. This reveals that the SPC-TNFα model is a suitable model to study processes underlying matrix remodeling and in particular elastin breakdown as seen in COPD. Furthermore we indicate a possible role for MMP2 and MMP9 in the breakdown of elastin in airways and alveoli of SPC-TNFα mice.
    American journal of physiology. Lung cellular and molecular physiology. 08/2014;
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    ABSTRACT: Depression is highly prevalent among patients with Chronic Obstructive Pulmonary Disease (COPD). The relationship of depression with systemic inflammation in COPD remains unknown. The objective of this observational study was to compare depression scores at baseline and after 36 months follow-up between COPD patients with persistent systemic inflammation (PSI) and never inflamed patients (NI) in the ECLIPSE cohort.
    Respiratory medicine. 08/2014;
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    ABSTRACT: Computed tomography (CT) of the chest can be used to assess pectoralis muscle area (PMA) and subcutaneous adipose tissue (SAT) area. Adipose tissue content is associated with inflammatory mediators in chronic obstructive pulmonary disease (COPD) subjects. Based on gender differences in body composition, we aimed to assess the hypothesis that in subjects with COPD, the relationships between PMA, SAT, and blood biomarkers of inflammation differ by gender.
    Academic radiology. 08/2014;
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    ABSTRACT: Little is known about changes in physical activity in subjects with chronic obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we aimed to study changes in physical activity in subjects with and without COPD and the impact of physical activity on mortality risk. Subjects from the Copenhagen City Heart Study with at least two consecutive examinations were selected. Each examination included a self-administered questionnaire and clinical examination. 1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1 s 67±18 and 91±15% predicted, respectively) were included. COPD subjects with moderate or high baseline physical activity who reported low physical activity level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35, respectively; both p<0.001). In COPD subjects with low baseline physical activity, no differences were found in survival between unchanged or increased physical activity at follow-up. In addition, subjects without COPD with low physical activity at follow-up had the highest hazard ratio of mortality, irrespective of baseline physical activity level (p≤0.05). A decline to low physical activity at follow-up was associated with an increased mortality risk in subjects with and without COPD. These observational data suggest that it is important to assess and encourage physical activity in the earliest stages of COPD in order to maintain a physical activity level that is as high as possible, as this is associated with better prognosis.
    The European respiratory journal. 07/2014;
  • The European respiratory journal. 07/2014; 44(1):264-5.
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    Chest 06/2014; 145(6):1437-8. · 5.85 Impact Factor
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    ABSTRACT: Exercise tolerance can be assessed by the cycle endurance test (CET) and six-minute walk test (6MWT) in patients with Chronic Obstructive Pulmonary Disease (COPD). We sought to investigate the characteristics of functional exercise performance and determinants of the CET and 6MWT in a large clinical cohort of COPD patients.
    BMC Pulmonary Medicine 05/2014; 14(1):97. · 2.76 Impact Factor
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    ABSTRACT: Low fat-free mass (FFM) is a risk factor for morbidity and mortality in elderly and patient populations. Therefore, measurement of FFM is important in nutritional assessment. Bioelectrical impedance analysis (BIA) is a convenient method to assess FFM and FFM index (FFMI; FFM/height(2)). Although reference values have been established for individuals with normal body weight, no specific cutoff values are available for overweight and obese populations. Also, limited studies accounted for the age-related decline in FFM. To determine BMI- and age-specific reference values for abnormal low FFM(I) in white-ethnic men and women free of self-reported disease from the general population. The UK Biobank is a prospective epidemiological study of the general population from the United Kingdom. Individuals in the age category 45 to 69 years were analyzed. In addition to body weight, FFM and FFMI were measured using a Tanita BC-418MA. Also, self-reported chronic conditions and ethnic background were registered, and lung function was assessed using spirometry. After exclusion of all individuals with missing data, nonwhite ethnicity, self-reported disease, body mass index (BMI) less than 14 or 36 kg/m(2) or higher, and/or an obstructive lung function, reference values for FFM and FFMI were derived from 186,975 individuals (45.9% men; age: 56.9 ± 6.8 years; BMI: 26.5 ± 3.6 kg/m(2); FFMI 18.3 ± 2.4 kg/m(2)). FFM and FFMI were significantly associated with BMI and decreased with age. Percentiles 5, 10, 25, 50, 75, 90, and 95 were calculated for FFM, FFMI, and fat mass (index), after stratification for gender, age, and BMI. Using the UK Biobank dataset, new reference values for body composition assessed with BIA were determined in white-ethnic men and women aged 45 to 69 years. Because these reference values are BMI specific, they are of broad interest for overweight and obese populations.
    Journal of the American Medical Directors Association 04/2014; · 5.30 Impact Factor
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    ABSTRACT: The identification of specific volatile organic compounds (VOCs) produced by microorganisms may assist in developing a fast and accurate methodology for the determination of pulmonary bacterial infections in exhaled air. As a first step, pulmonary bacteria were cultured and their headspace analyzed for the total amount of excreted VOCs to select those compounds which are exclusively associated with specific microorganisms. Development of a rapid, noninvasive methodology for identification of bacterial species may improve diagnostics and antibiotic therapy, ultimately leading to controlling the antibiotic resistance problem. Two hundred bacterial headspace samples from four different microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumoniae) were analyzed by gas chromatography-mass spectrometry to detect a wide array of VOCs. Statistical analysis of these volatiles enabled the characterization of specific VOC profiles indicative for each microorganism. Differences in VOC abundance between the bacterial types were determined using ANalysis of VAriance-principal component analysis (ANOVA-PCA). These differences were visualized with PCA. Cross validation was applied to validate the results. We identified a large number of different compounds in the various headspaces, thus demonstrating a highly significant difference in VOC occurrence of bacterial cultures compared to the medium and between the cultures themselves. Additionally, a separation between a methicillin-resistant and a methicillin-sensitive isolate of S. aureus could be made due to significant differences between compounds. ANOVA-PCA analysis showed that 25 VOCs were differently profiled across the various microorganisms, whereas a PCA score plot enabled the visualization of these clear differences between the bacterial types. We demonstrated that identification of the studied microorganisms, including an antibiotic susceptible and resistant S. aureus substrain, is possible based on a selected number of compounds measured in the headspace of these cultures. These in vitro results may translate into a breath analysis approach that has the potential to be used as a diagnostic tool in medical microbiology.
    Journal of Breath Research 04/2014; 8(2):027106. · 2.57 Impact Factor
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    ABSTRACT: Over the past few decades, chronic obstructive lung disease (COPD) has been considered a disease of the lungs, often caused by smoking. Nowadays, COPD is regarded as a systemic disease. Both physical effects and effects on brains, including impaired psychological and cognitive functioning, have been demonstrated. Patients with COPD may have cognitive impairment, either globally or in single cognitive domains, such as information processing, attention and concentration, memory, executive functioning, and self-control. Possible causes are hypoxemia, hypercapnia, exacerbations, and decreased physical activity. Cognitive impairment in these patients may be related to structural brain abnormalities, such as gray-matter pathologic changes and the loss of white matter integrity which can be induced by smoking. Cognitive impairment can have a negative impact on health and daily life and may be associated with widespread consequences for disease management programs. It is important to assess cognitive functioning in patients with COPD in order to optimize patient-oriented treatment and to reduce personal discomfort, hospital admissions, and mortality. This paper will summarize the current knowledge about cognitive impairment as extrapulmonary feature of COPD. Hereby, the impact of smoking on cognitive functioning and the impact of cognitive impairment on smoking behaviour will be examined.
    BioMed Research International 03/2014; 2014:1-8. · 2.88 Impact Factor
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    ABSTRACT: Over the past few decades, chronic obstructive lung disease (COPD) has been considered a disease of the lungs, often caused by smoking. Nowadays, COPD is regarded as a systemic disease. Both physical effects and effects on brains, including impaired psychological and cognitive functioning, have been demonstrated. Patients with COPD may have cognitive impairment, either globally or in single cognitive domains, such as information processing, attention and concentration, memory, executive functioning, and self-control. Possible causes are hypoxemia, hypercapnia, exacerbations, and decreased physical activity. Cognitive impairment in these patients may be related to structural brain abnormalities, such as gray-matter pathologic changes and the loss of white matter integrity which can be induced by smoking. Cognitive impairment can have a negative impact on health and daily life and may be associated with widespread consequences for disease management programs. It is important to assess cognitive functioning in patients with COPD in order to optimize patient-oriented treatment and to reduce personal discomfort, hospital admissions, andmortality. This paper will summarize the current knowledge about cognitive impairment as extrapulmonary feature of COPD. Hereby, the impact of smoking on cognitive functioning and the impact of cognitive impairment on smoking behaviour will be examined.
    BioMed Research International 03/2014; 2014:1-8. · 2.88 Impact Factor
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    ABSTRACT: Rationale: Plasma soluble Receptor for Advanced Glycation End Product (sRAGE) is considered as a biomarker in COPD. The contribution of endogenous sRAGE (esRAGE) to the pool of plasma sRAGE and the implication of both markers in COPD pathogenesis is however not clear yet. The aim of the current study was therefore to measure plasma levels of esRAGE comparative to total sRAGE in patients with COPD and a control group. Further, we established the relations of esRAGE and total sRAGE with disease specific characteristics such as lung function and DLCO, and with different circulating AGEs. Plasma levels of esRAGE and sRAGE were measured in an 88 patients with COPD and in 55 healthy controls. FEV1 (%predicted) and FEV1/VC (%) were measured in both groups; DLCO (%predicted) was measured in patients only. In this study population we previously reported that the AGE Nepsilon-(carboxymethyl) lysine (CML) was decreased, and Nepsilon-(carboxyethyl) lysine and pentosidine were increased in patients. Plasma esRAGE (COPD: 533.9 +/- 412.4, Controls: 848.7 +/- 690.3 pg/ml; p = 0.000) was decreased in COPD compared to controls. No significant correlations were observed between plasma esRAGE levels and lung function parameters or plasma AGEs. A positive correlation was present between esRAGE and total sRAGE levels in the circulation. Confirming previous findings, total sRAGE (COPD: 512.6 +/- 403.8, Controls: 1834 +/- 804.2 pg/ml; p < 0.001) was lower in patients compared to controls and was positively correlated FEV1 (r = 0.235, p = 0.032), FEV1/VC (r =0.218, p = 0.047), and DLCO (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive association with CML (r = 0.321, p = 0.003). Although plasma esRAGE is decreased in COPD patients compared to controls, only total sRAGE showed a significant and independent association with FEV1, FEV1/VC and DLCO, indicating that total sRAGE but not esRAGE may serve as marker of COPD disease state and severity.
    Respiratory research 02/2014; 15(1):24. · 3.64 Impact Factor
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    ABSTRACT: Rationale: Muscle wasting in Chronic Obstructive Pulmonary Disease is associated with a poor prognosis and is not readily assessed by measures of body mass index (BMI). BMI does not discriminate between relative proportions of adipose tissue and lean muscle and may be insensitive to early pathologic changes in body composition. Computed tomographic (CT) based assessments of the pectoralis muscles may provide insight into the clinical significance of skeletal muscles in smokers. Objectives: We hypothesized that the objective assessment of the pectoralis muscle area on chest CT scans provides information that is clinically relevant and independent of BMI. Study Design: Data from the ECLIPSE study (n=73) was used to assess the relationship between pectoralis muscle area and fat-free mass. We then used data in a subset (n=966) of larger cohort, the COPDGene study, to explore the relationship between pectoralis muscle area and COPD-related traits. Measurements and Main Results: We first investigated the correlation between pectoralis muscle area and fat-free mass using data from a subset of participants in the ECLIPSE study. We then further investigated pectoralis muscle area in COPDGene and found that higher pectoralis muscle area values were associated with greater height, male sex and younger age. On subsequent clinical correlation, pectoralis muscle area was more significantly associated than BMI with COPD-related traits, including spirometric measures, dyspnea and 6-minute walk distance (6MWD). For example, on average each 10 cm2 increase in pectoralis muscle area was associated with a 0.8 unit decrease in BODE (95% Confidence Interval: -1.0 to -0.6, p<0.001). Furthermore, statistically significant associations between pectoralis muscle area and COPD-related traits remained even after adjustment for BMI. Conclusions: CT derived pectoralis muscle area provides relevant indices of COPD morbidity that may be more predictive of important COPD-related traits than BMI. However, the relationship with clinically relevant outcomes such as hospitalization and death requires additional investigation. Pectoralis muscle area is a convenient measure that can be collected in the clinical setting in addition to BMI.
    Annals of the American Thoracic Society. 02/2014;
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    ABSTRACT: Arm activities are required for maintenance of self-care and independent living. This study aimed to investigate whether and to what extent arm activities of daily living (ADL) in chronic obstructive pulmonary disease (COPD) patients differ compared to healthy controls and the extent to which they perform arm ADL at a relatively higher upper limb muscle effort.Daily arm and leg activities were assessed using accelerometers in the home environment (COPD: n = 21, healthy: n = 24; part 1). The relative efforts of the trapezius, deltoid and biceps muscles were studied using electromyography during domestic arm ADL in a laboratory setting (COPD: n = 17, healthy: n = 15; part 2).After correction for walking time, the time spent on arm ADL was similar between COPD patients and healthy control subjects (p = 0.52), while the intensity of arm activities was lower in COPD patients (p = 0.041). In the laboratory setting, arm ADL were performed at a lower intensity by COPD patients, while the trapezius muscle effort was significantly higher during several arm ADL compared to healthy control subjects (p<0.05).COPD patients have a similar duration of arm ADL compared to healthy subjects after correction for walking time, but perform arm activities at a lower intensity. Moreover, patients perform some arm ADL at a relatively higher muscle effort.
    European Respiratory Journal 02/2014; · 6.36 Impact Factor
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    ABSTRACT: Coronary artery calcification is pathognomonic of coronary artery disease (CAD). Whether CAD in patients with COPD is linked to lung function, functional capacity and/or clinically relevant outcomes is unknown. The objective was to assess the association between CAD and disease severity, functional capacity and outcomes in patients with COPD. Coronary artery calcium score (CACS; Agatston score) was measured using chest CT in patients with COPD, smokers with normal spirometry and non-smokers from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. CACS was measured in 942 subjects: 672 with COPD (mean age±SD, 63±7 years; FEV1 49±16% predicted), 199 smokers with normal spirometry (54±9 years; FEV1 110±12% predicted) and 71 non-smokers (55±9 years; FEV1 114±14% predicted). CACS was higher in patients with COPD than smokers or non-smokers (median (IQR), 128 (492) vs 0 (75) vs 0 (3) Agatston units (AU), p<0.001). In patients with COPD, CACS correlated with age, pack-years, 6 min walking distance, modified Medical Research Council Dyspnoea score and circulating levels of interleukin (IL)-6, IL-8, Clara Cell protein 16, surfactant protein D and peripheral blood neutrophil count, but not with emphysema, exacerbation frequency, % predicted FEV1 or decline in FEV1. CACS was higher in patients with COPD who died than in those who survived until 3-year follow-up (CACS 406 vs 103 AU, p<0.001), and was associated with mortality in a Cox proportional hazards model (p=0.036). Patients with COPD have more CAD than controls and this is associated with increased dyspnoea, reduced exercise capacity and increased mortality. These data indicate that the presence of CAD in patients with COPD is associated with poor clinical outcomes.
    Thorax 01/2014; · 8.38 Impact Factor
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    ABSTRACT: Radiation-esophagitis and weight loss are frequently observed toxicities in patients treated with concurrent chemo-radiotherapy (CT-RT) for non-small cell lung cancer (NSCLC) and might be related. The purpose was to investigate whether weight loss already starts early after initiation of CT-RT and precedes radiation-esophagitis. In a retrospective cohort, weight and esophagitis grade ≥2 were assessed during the first weeks of (CT-)RT in patients treated with concurrent (n = 102) or sequential (n = 92) therapy. In a prospective validation study, data on body weight, esophagitis grade ≥2, nutritional intake and muscle strength were obtained before, during and following CT-RT. In the retrospective cohort, early weight loss was observed in concurrently treated patients (p = 0.002), independent of esophagitis ≥ grade 2. Early weight loss was also observed in the prospective cohort (p = 0.003) and was not accompanied by decreases in nutritional intake. In addition lower limb muscle strength rapidly declined (p = 0.042). In the later weeks of treatment, further body weight loss occurred (p < 0.001) despite increased nutritional supplementation and body weight was only partly recovered after 4 weeks post CT-RT (p = 0.003). Weight loss during concurrent CT-RT for NSCLC starts early and prior to onset of esophagitis, requiring timely and intense nutritional rehabilitation.
    Journal of cachexia, sarcopenia and muscle. 01/2014;
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    ABSTRACT: Strength training and neuromuscular electrical stimulation (NMES) improve lower-limb muscle function in dyspnoeic individuals with chronic obstructive pulmonary disease (COPD). However, high-frequency NMES (HF-NMES) and strength training have never been compared head-to-head; and effects of low-frequency NMES (LF-NMES) have never been studied in COPD. Therefore, the optimal training modality to improve lower-limb muscle function, exercise performance and other patient-related outcomes in individuals with severe COPD remains unknown. To study prospectively the efficacy of HF-NMES (75 Hz), LF-NMES (15 Hz) or strength training in severely dyspnoeic individuals with COPD with quadriceps muscle weakness at baseline. 120 individuals with COPD (FEV1: 33±1% predicted, men: 52%, age: 64.8±0.8 years) were randomised to HF-NMES, LF-NMES or strength training as part of a comprehensive inpatient pulmonary rehabilitation programme. No treadmill walking or stationary cycling was provided. Groups were comparable at baseline. Quadriceps muscle strength increased after HF-NMES (+10.8 Newton-metre (Nm)) or strength training (+6.1 Nm; both p<0.01), but not after LF-NMES (+1.4 Nm; p=0.43). Quadriceps muscle endurance, exercise performance, lower-limb fat-free mass, exercise-induced symptoms of dyspnoea and fatigue improved significantly compared with baseline after HF-NMES, LF-NMES or strength training. The increase in quadriceps muscle strength and muscle endurance was greater after HF-NMES than after LF-NMES. HF-NMES is equally effective as strength training in severely dyspnoeic individuals with COPD and muscle weakness in strengthening the quadriceps muscles and thus may be a good alternative in this particular group of patients. HF-NMES, LF-NMES and strength training were effective in improving exercise performance in severely dyspnoeic individuals with COPD and quadriceps weakness. NTR2322.
    Thorax 01/2014; · 8.38 Impact Factor
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    ABSTRACT: Objectives To compare domains of cognitive functioning between persons with and without obstructive lung disease (OLD) and to analyze the relationship between cognitive functioning and the degree of airflow limitation. Design An observational population-based study. Setting This research was conducted using the United Kingdom Biobank Resource. Participants The study population consisted of 43,039 persons with complete data on cognitive functioning and spirometry. Measurements Cognitive functioning was compared between persons with and without OLD using linear regression analysis. The relationship between impairment in lung function and cognitive impairment was assessed among persons with OLD. Results Persons with OLD had significantly worse scores than persons without OLD on prospective memory [β = –0.15 (–0.22 to –0.09)], visuospatial memory [β round 1 = 0.06 (0.03‒0.10)]; β round 2 = 0.09 (<0.001‒0.18)), numeric short-term memory [β = ‒0.05 (‒0.10 to <0.001)] and cognitive processing speed [β = 4.62 (1.25‒8.01)] after correction for possible confounders. Impairment in prospective memory [β = 0.004 (<0.001‒0.01)] and numeric short-term memory [β = 0.01 (0.003‒0.01)] were weakly related to FEV1 (adjusted P < .05). Conclusions Persons with OLD experience cognitive impairment in different domains, which is partially related to airway obstruction. In particular, memory and information processing are affected. Further assessment of the relationship with patient-related outcomes is needed to optimize patient-oriented treatment.
    Journal of the American Medical Directors Association 01/2014; 15(3):214–219. · 5.30 Impact Factor
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    ABSTRACT: Intact cognitive functioning is necessary for patients with chronic obstructive pulmonary disease (COPD) to understand the value of healthy lifestyle guidelines, to make informed decisions and subsequently act on it. Nevertheless, brain abnormalities and cognitive impairment have been found in patients with COPD. To date, it remains unknown which cognitive domains are affected and what the possible consequences are of cognitive impairment. Therefore, objectives of the study described are to determine neuropsychological functioning in patients with COPD, and its influence on health status, daily functioning and pulmonary rehabilitation outcome. Furthermore, structural and functional brain abnormalities and the relationship with cognitive and daily functioning will be explored. A longitudinal observational comparative study will be performed in 183 patients with COPD referred for pulmonary rehabilitation and in 90 healthy control participants. Demographic and clinical characteristics, activities of daily living and knowledge about COPD will be assessed. Baseline cognitive functioning will be compared between patients and controls using a detailed neuropsychological testing battery. An MRI substudy will be performed to compare brain abnormalities between 35 patients with COPD with cognitive impairment and 35 patients with COPD without cognitive impairment. Patients will be recruited between November 2013 and November 2015. The study has been approved by the Medical Ethics Committee of the University Hospital Maastricht and Maastricht University (NL45127.068.13/METC 13-3-035) and is registered in the Dutch trial register. All participants will provide written informed consent and can withdraw from the study at any point in time. Assessment and home visit data material will be managed anonymously. The results obtained can be used to optimise patient-oriented treatment for cognitively impaired patients with COPD. The findings will be disseminated in international peer-reviewed journals and through research conferences.
    BMJ Open 01/2014; 4(3):e004495. · 1.58 Impact Factor

Publication Stats

15k Citations
2,755.94 Total Impact Points

Institutions

  • 1990–2014
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 2010–2013
    • Southern Medical Clinic
      San Fernando, City of San Fernando, Trinidad and Tobago
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2009–2013
    • Catharina Hospital
      Eindhoven, North Brabant, Netherlands
    • King's College London
      Londinium, England, United Kingdom
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 2006–2013
    • CIRO
      • Program Development Centre
      Roermond, Provincie Limburg, Netherlands
  • 1986–2013
    • Maastricht University
      • • NUTRIM School for Nutrition, Toxicology and Metabolism
      • • Pulmonologie
      • • Department of Respiratory Medicine
      • • Farmacologie
      • • Humane Biologie
      • • Department of Epidemiology
      Maastricht, Provincie Limburg, Netherlands
  • 2012
    • Biometrics
      Saint-Clair, Île-de-France, France
    • University of Barcelona
      Barcino, Catalonia, Spain
    • University of Arkansas for Medical Sciences
      Little Rock, Arkansas, United States
  • 2010–2012
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2011
    • Philipps University of Marburg
      Marburg, Hesse, Germany
    • University of Northern Parana
      Londrina, Paraná, Brazil
  • 2001–2011
    • University of Vermont
      • Department of Pathology
      Burlington, VT, United States
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 2008
    • University of Rome Tor Vergata
      Roma, Latium, Italy
  • 2006–2008
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2007
    • Leiden University Medical Centre
      • Department of Pulmonology
      Leiden, South Holland, Netherlands
    • Cardiff University
      Cardiff, Wales, United Kingdom
  • 2005
    • Solvay
      Bruxelles, Brussels Capital Region, Belgium
    • KU Leuven
      • Department of Rehabilitation Sciences
      Leuven, VLG, Belgium
  • 2004
    • University of Otago
      Taieri, Otago Region, New Zealand
  • 1998–2002
    • Zeeuws Radiotherapeutisch Instituut
      Flushing, Zeeland, Netherlands
    • Tilburg University
      • Department of Medical and Clinical Psychology
      Tilburg, North Brabant, Netherlands
  • 1997
    • Open Universiteit Nederland
      Heerlen, Limburg, Netherlands
  • 1996
    • Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin
      Aachen, North Rhine-Westphalia, Germany
  • 1995
    • Wageningen University
      Wageningen, Gelderland, Netherlands