Harry Gosker

Harry Gosker
Maastricht University | UM · Department of Respiratory Medicine

PhD

About

138
Publications
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Publications

Publications (138)
Article
Introduction: Physical and mental health are often affected in chronic obstructive pulmonary disease (COPD) adversely affecting disease course and quality of life. Abnormalities in whole body and cellular energy metabolism, dietary and plasma nutrient status and intestinal permeability have been well established in these patients as systemic deter...
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Background Cognitive impairment (CI) is highly prevalent in chronic obstructive pulmonary disease (COPD) and is associated with a sedentary lifestyle, unhealthy diet and increased cognitive stress susceptibility. Enhancement of cognitive performance by working memory training (WMT) may reverse these effects. Therefore, this study aimed to investiga...
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Context Chronic obstructive lung disease (COPD) is a progressive lung disease characterized by persistent airflow limitation. An increasing amount of evidence suggests an effect of dietary quality on the risk of COPD in the general population and pulmonary function decline in patients with COPD. Objective The association of dietary intake and nutr...
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The awareness of the presence and consequences of sarcopenia has significantly increased over the past decade. Sarcopenia is defined as gradual loss of muscle mass and strength and ultimately loss of physical performance associated with aging and chronic disease. The prevalence of sarcopenia is higher in chronic obstructive pulmonary disease (COPD)...
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Introduction: Muscle impairments are prevalent in COPD and have adverse clinical implications in terms of physical performance capacity, disease burden, quality of life and even mortality. During acute exacerbations of COPD (AECOPDs) the respiratory symptoms worsen and this might also apply to the muscle impairments. Areas covered: This report incl...
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Background & aims Cognitive impairment (CI) and metabolic abnormalities, including the metabolic syndrome (MetS) and sarcopenia, are more prevalent in COPD patients compared to controls without diagnosed lung disease. Because earlier studies have shown these metabolic abnormalities may affect cognitive performance, this study investigated whether c...
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Iron homeostasis is essential for mitochondrial function, and iron deficiency has been associated with skeletal muscle weakness and decreased exercise capacity in patients with different chronic disorders. We hypothesized that iron deficiency‐induced loss of skeletal muscle mitochondria is caused by increased mitochondrial clearance. To study this,...
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Background: Physical inactivity contributes to muscle wasting and reductions in mitochondrial oxidative phenotype (OXPHEN), reducing physical performance and quality of life during aging and in chronic disease. Previously, it was shown that inactivation of glycogen synthase kinase (GSK)-3β stimulates muscle protein accretion, myogenesis, and mitoc...
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Background: Both mitophagy, a selective mechanism for clearance of mitochondria, and mitochondrial biogenesis are key processes determining mitochondrial content and oxidative capacity of the musculature. Abnormalities in these processes could therefore contribute to deterioration of peripheral muscle oxidative capacity as observed in e.g. chronic...
Article
Background: Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of...
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Objective: In muscle cells, the peroxisome proliferator-activated receptor γ co-activator 1 (PGC-1) signaling network, which has been shown to be disturbed in the skeletal muscle in several chronic diseases, tightly controls mitochondrial biogenesis and oxidative substrate metabolism. Previously, we showed that inactivation of glycogen synthase ki...
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Introduction: Physical inactivity significantly contributes to loss of muscle mass and performance in bed-bound patients. Loss of skeletal muscle mitochondrial content has been well-established in muscle unloading models, but the underlying molecular mechanism remains unclear. We hypothesized that apparent unloading-induced loss of muscle mitochon...
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Background: Loss of peripheral muscle oxidative phenotype, cognitive impairment, and depression are well-recognized systemic manifestations of chronic obstructive pulmonary disease (COPD). Kynurenine (KYN), known to be associated with disturbed mental health, can be metabolized in muscle by kynurenine aminotransferases (KAT) 1-4. These KATs are re...
Data
Table S1. Compositions of network‐constrained clusters of molecular rehabilitation responses. Table S2. Component loadings of markers on each process Table S3. Rehabilitation responses per cluster, process scores Table S4. Rehabilitation responses per cluster, molecular markers Table S5. Medication use
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Background and aims: The efficacy of nutritional intervention to enhance short- and long-term outcomes of pulmonary rehabilitation in COPD is still unclear, hence this paper aims to investigate the clinical outcome and cost-effectiveness of a 12-month nutritional intervention strategy in muscle-wasted COPD patients. Methods: Prior to a 4-month p...
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Background: Pulmonary rehabilitation (PR) is a cornerstone in the management of chronic obstructive pulmonary disease (COPD), targeting skeletal muscle to improve functional performance. However, there is substantial inter-individual variability in the effect of PR on functional performance, which cannot be fully accounted for by generic phenotypi...
Article
Skeletal muscle regeneration after disuse is essential for muscle maintenance and involves the regulation of both mass- and metabolic plasticity-related processes. However, the relation between these processes during recovery from disuse remains unclear. In this study, we explored the potential interrelationship between the molecular regulation of...
Article
Background & aims: Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD. Methods: This double-blind, randomized cros...
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Loss of skeletal muscle mitochondrial oxidative capacity is well-established in patients with COPD, but the role of mitochondrial breakdown herein is largely unexplored. Currently, we studied if mitochondrial breakdown signalling is increased in skeletal muscle of COPD patients and associates with the loss of mitochondrial content, and whether it i...
Article
Introduction: Cognitive impairment (CI) is an important but an under-recognized extra-pulmonary feature of chronic obstructive pulmonary disease (COPD). It is related to the burden of disability, worse health outcomes and impaired self-management. Areas covered: CI includes deterioration of a wide range of cognitive functions, such as memory and va...
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COPD is a chronic lung disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities. Furthermore, COPD is often characterized by extrapulmonary manifestations and comorbidities worsening COPD progression and quality of life. A neglected comorbidity in COPD management is mental health im...
Article
Background: Mitochondrial biogenesis is crucial for myogenic differentiation and regeneration of skeletal muscle tissue and is tightly controlled by the peroxisome proliferator-activated receptor-γ co-activator 1 (PGC-1) signaling network. In the present study, we hypothesized that inactivation of glycogen synthase kinase (GSK)-3β, previously sugg...
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Purpose of review: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with a high prevalence of extrapulmonary manifestations and, frequently, cardiovascular comorbidity. Resveratrol is a food-derived compound with anti-inflammatory, antioxidant, metabolic and cardioprotective potential. Therefore, resveratrol might improve...
Article
Background: Aberrant skeletal muscle mitochondrial oxidative metabolism is a debilitating feature of chronic diseases such as chronic obstructive pulmonary disease, type 2 diabetes and chronic heart failure. Evidence in non-muscle cells suggests that glycogen synthase kinase-3β (GSK-3β) represses mitochondrial biogenesis and inhibits PPAR-γ co-act...
Article
Health-related quality of life or health status is significantly impaired in bronchiectasis. There is a paucity of brief, simple-to-use, disease-specific health status measures. The aim of this study was to develop and validate the Bronchiectasis Health Questionnaire (BHQ), a new health status measure that is brief and generates a single overall sc...
Article
Background Sarcopenia was recently recognized as an independent condition by an International Classification of Diseases, Tenth Revision, Clinical Modification code, and is a frequently observed comorbidity in chronic obstructive pulmonary disease (COPD). Muscle mass is primarily dictated by the balance between protein degradation and synthesis, bu...
Poster
Objective: COPD is hallmarked by a loss of skeletal muscle oxidative capacity which is already present in less advanced disease stages. In this study, we hypothesized that mitophagy (selective mitochondrial autophagy) is enhanced in skeletal muscle of COPD patients, and is associated with the loss of muscle oxidative capacity. Methods: Vastus later...
Poster
Objective: Systemic inflammation has been implicated in skeletal muscle mitochondrial impairment of patients with COPD. Both mitophagy, a selective mitochondrial clearance mechanism, and mitochondrial biogenesis are required for mitochondrial homeostasis. We hypothesized that inflammation-induced loss of muscle mitochondrial capacity is associated...
Article
Purpose of review: Loss of skeletal muscle oxidative capacity is a common feature of chronic diseases such as chronic obstructive pulmonary disease, type 2 diabetes, and congestive heart failure. It may lead to physical impairments and has been suggested to contribute to metabolic inflexibility-induced cardiometabolic risk. The mechanism underlyin...
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Rationale: Critical illness survivors often experience permanent functional disability due to intensive care unit (ICU)-acquired weakness. The mechanisms responsible for long-term weakness persistence versus resolution are unknown. Objectives: To delineate cellular mechanisms underlying long-term weakness persistence in ICU survivors. Methods:...
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Background: The King's Sarcoidosis Questionnaire (KSQ) is a brief questionnaire assessing health status using five modules (General Health Status, Lung, Eyes, Skin, Medication) in patients with sarcoidosis. The KSQ was only validated in one English sarcoidosis cohort. Objective: The aim of this study was to validate the KSQ in a Dutch sarcoidosi...
Article
Background: Quadriceps muscle fiber atrophy and a loss of oxidative type I muscle fibers and mitochondrial content often occur in chronic obstructive pulmonary disease (COPD), which adversely affects exercise performance. Sarcopenia is an age-related syndrome characterized by wasting and weakness of muscle mass. We recently showed in a large cohor...
Conference Paper
Background: Linked to physical inactivity, loss of muscle oxidative metabolism is a consistent finding in COPD. Evidence in non-muscle cells shows that glycogen synthase kinase-3β (GSK-3β) represses mitochondrial biogenesis and inhibits PPAR-γ co-activator 1 (PGC-1), a main regulator of cellular oxidative metabolism. Aims: We hypothesized that GSK...
Conference Paper
The KSQ is a validated quality of life questionnaire (HRQOL) for patients with sarcoidosis. HRQOL can be calculated from patient raw scores or following their transformation to a linear logit scale, which has improved measurement characteristics and sample size calculations. We compared the validity of KSQ using raw scores (KSQraw) with KSQlogit sc...
Conference Paper
Cachexia has devastating effects on quality of life and augments cancer-related mortality. Preclinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate loss of muscle oxidative phenotype in newly diagnosed pat...
Article
Skeletal muscle of patients with chronic respiratory failure is prone to loss of muscle mass and oxidative phenotype. Tissue hypoxia has been associated with cachexia and emphysema in humans. Experimental research on the role of hypoxia in loss of muscle oxidative phenotype however has yielded inconsistent results. Animal studies are frequently per...
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Background Cachexia augments cancer-related mortality and has devastating effects on quality of life. Pre-clinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype (OXPHEN) stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate the presence of muscle OXPHEN loss i...
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A shift in quadriceps muscle metabolic profile towards decreased oxidative metabolism and increased glycolysis is a consistent finding in chronic obstructive pulmonary disease (COPD). Chronic inflammation has been proposed as a trigger of this pathological metabolic adaptation. Indeed, the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) i...
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Exercise training (ExTr) is largely used to improve functional capacity of chronic obstructive pulmonary disease (COPD) patients. However, ExTr partially restores muscle function in COPD patients, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by...
Article
The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor. Alternative splicing and enzymatic shedding produce soluble forms that protect against damage by ligands including Advanced Glycation End products (AGEs). A link between RAGE and oxygen levels is evident from studies showing RAGE-mediated injury following hyperoxia....
Article
Hypoxia as a consequence of acute and chronic respiratory disease has been associated with muscle atrophy. This study investigated the sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy. Male mice were exposed to 8% normobaric oxygen for up to 21 days. Oxidative soleus and glycolytic extensor digitorum longus (EDL) mu...
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In COPD, matrix remodeling contributes to airflow limitation. Recent evidence suggests that next to fibroblasts, the process of epithelial-mesenchymal transition can contribute to matrix remodeling. CSE has been shown to induce EMT in lung epithelial cells, but the signaling mechanisms involved are largely unknown and subject of this study. EMT was...
Article
Nutrition and metabolism have been the topic of extensive scientific research in chronic obstructive pulmonary disease (COPD) but clinical awareness of the impact dietary habits, nutritional status and nutritional interventions may have on COPD incidence, progression and outcome is limited. A multidisciplinary Task Force was created by the European...
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Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important prog...
Article
Loss of skeletal muscle oxidative fiber types and mitochondrial capacity is a hallmark of chronic obstructive pulmonary disease and chronic heart failure. Based on in vivo human and animal studies, tissue hypoxia has been hypothesized as determinant, but the direct effect of hypoxia on muscle oxidative phenotype remains to be established. Hence, we...
Article
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Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD) are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen). Physical activity is a well-known stimulus of muscle Oxphen and crucia...
Article
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Physical inactivity-induced loss of skeletal muscle oxidative phenotype (OXPHEN), often observed in chronic disease, adversely affects physical functioning and quality of life. Potential therapeutic targets remain to be identified as the molecular mechanisms involved in reloading-induced recovery of muscle OXPHEN remain incompletely understood. We...
Article
Dietary intake attracts increasing interest in the risk for and progression of chronic obstructive pulmonary disease (COPD). In particular, dietary fibre and fatty acids have drawn specific attention for their immunomodulating potential. The study aimed to review the current evidence on the potential roles of dietary fibre or fatty acid intake in t...
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Rationale: Locomotor muscle atrophy develops in patients with chronic obstructive pulmonary disease (COPD) partly because of increased protein degradation by the ubiquitin-proteasome system. It is not known if autophagy also contributes to protein degradation. Objectives: To investigate whether autophagy is enhanced in locomotor muscles of stable C...
Article
Background: Loss of quadriceps muscle oxidative phenotype (OXPHEN) is an evident and debilitating feature of chronic obstructive pulmonary disease (COPD). We recently demonstrated involvement of the inflammatory classical NF-κB pathway in inflammation-induced impairments in muscle OXPHEN. The exact underlying mechanisms however are unclear. Intere...
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Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation. We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis. We studied changes in mitochondrial morphology and in expression of ma...
Article
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Introduction: Quadriceps muscle dysfunction is common in COPD. Determining, and, if possible, predicting quadriceps phenotype in COPD is important for patient stratification for therapeutic trials. Methods: In biopsies from 114 COPD patients and 30 controls, we measured fiber size and proportion and assessed the relationship with quadriceps func...
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Transcutaneous neuromuscular electrical stimulation (NMES) can be applied as a complementary intervention to regular exercise training programs. A distinction can be made between high-frequency (HF) NMES and low-frequency (LF) NMES. In order to increase understanding of the mechanisms of functional improvements following NMES, the purpose of this s...
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to the editor: Recently Gouzi et al. ([3][1]) reported reference values and lower limits of normal (LLNs) for vastus lateralis fiber size and type in healthy subjects over 40 years old. LLNs are useful to distinguish pathology from physiological variation in high-risk patient groups such as chronic
Article
Skeletal muscle wasting contributes to impaired exercise capacity, reduced health-related quality of life and is an independent determinant of mortality in chronic obstructive pulmonary disease. An imbalance between protein synthesis and myogenesis on one hand, and muscle proteolysis and apoptosis on the other, has been proposed to underlie muscle...
Article
Background: Impairments in skeletal muscle oxidative phenotype (OXPHEN) have been linked to the development of insulin resistance, metabolic inflexibility and progression of the metabolic syndrome and have been associated with progressive disability in diseases associated with chronic systemic inflammation. We previously showed that the inflammato...