5 results on '"Bem RA"'
Search Results
2. Breath Markers of Oxidative Stress in Children with Severe Viral Lower Respiratory Tract Infection.
- Author
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Lilien TA, Brinkman P, Fenn DW, van Woensel JBM, Bos LDJ, and Bem RA
- Subjects
- Humans, Male, Female, Child, Preschool, Infant, Child, Prospective Studies, Oxidative Stress, Breath Tests methods, Biomarkers metabolism, Volatile Organic Compounds metabolism, Volatile Organic Compounds analysis, Respiratory Tract Infections virology, Respiratory Tract Infections metabolism
- Abstract
Severe viral lower respiratory tract infection (LRTI), resulting in both acute and long-term pulmonary disease, constitutes a substantial burden among young children. Viral LRTI triggers local oxidative stress pathways by infection and inflammation, and supportive care in the pediatric intensive care unit may further aggravate oxidative injury. The main goal of this exploratory study was to identify and monitor breath markers linked to oxidative stress in children over the disease course of severe viral LRTI. Exhaled breath was sampled during invasive ventilation, and volatile organic compounds (VOCs) were analyzed using gas chromatography and mass spectrometry. VOCs were selected in an untargeted principal component analysis and assessed for change over time. In addition, identified VOCs were correlated with clinical parameters. Seventy breath samples from 21 patients were analyzed. A total of 15 VOCs were identified that contributed the most to the explained variance of breath markers. Of these 15 VOCs, 10 were previously linked to pathways of oxidative stress. Eight VOCs, including seven alkanes and methyl alkanes, significantly decreased from the initial phase of ventilation to the day of extubation. No correlation was observed with the administered oxygen dose, whereas six VOCs showed a poor to strong positive correlation with driving pressure. In this prospective study of children with severe viral LRTI, the majority of VOCs that were most important for the explained variance mirrored clinical improvement. These breath markers could potentially help monitor the pulmonary oxidative status in these patients, but further research with other objective measures of pulmonary injury is required.
- Published
- 2024
- Full Text
- View/download PDF
3. Experimental Acute Lung Injury in Animals: With Age Comes Knowledge.
- Author
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Schouten LR, Vlaar APJ, Bos LDJ, and Bem RA
- Subjects
- Humans, Lung, Acute Lung Injury
- Published
- 2022
- Full Text
- View/download PDF
4. Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit.
- Author
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Linssen RS, Chai G, Ma J, Kummarapurugu AB, van Woensel JBM, Bem RA, Kaler L, Duncan GA, Zhou L, Rubin BK, and Xu Q
- Subjects
- Adult, Airway Obstruction immunology, Airway Obstruction metabolism, Extracellular Traps metabolism, Humans, Mucus metabolism, Neutrophils metabolism, Oxidative Stress immunology, Peroxidase immunology, Peroxidase metabolism, Reactive Oxygen Species immunology, Reactive Oxygen Species metabolism, Respiratory System metabolism, Extracellular Traps immunology, Mucus immunology, Neutrophils immunology, Respiratory System immunology
- Abstract
Mucus obstruction is a key feature of many inflammatory airway diseases. Neutrophil extracellular traps (NETs) are released upon neutrophil stimulation and consist of extracellular chromatin networks studded with cytotoxic proteins. When released in the airways, these NETs can become part of the airway mucus. We hypothesized that the extracellular DNA and/or oxidative stress (e.g., by the release of reactive oxygen species and myeloperoxidase during NETs formation in the airways) would increase mucus viscoelasticity. We collected human airway mucus from endotracheal tubes of healthy patients admitted for elective surgery and coincubated these samples with NETs from phorbol 12-myristate 13-acetate-stimulated neutrophils. Unstimulated neutrophils served as controls, and blocking experiments were performed with dornase alfa for extracellular DNA and the free radical scavenger dimethylthiourea for oxidation. Compared with controls, the coincubation of mucus with NETs resulted in 1 ) significantly increased mucus viscoelasticity (macrorheology) and 2 ) significantly decreased mesh pore size of the mucus and decreased movement of muco-inert nanoparticles through the mucus (microrheology), but 3 ) NETs did not cause visible changes in the microstructure of the mucus by scanning EM. Incubation with either dornase alfa or dimethylthiourea attenuated the observed changes in macrorheology and microrheology. This suggests that the release of NETs may contribute to airway mucus obstruction by increasing mucus viscoelasticity and that this effect is not solely due to the release of DNA but may in part be due to oxidative stress.
- Published
- 2021
- Full Text
- View/download PDF
5. Potential role of soluble TRAIL in epithelial injury in children with severe RSV infection.
- Author
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Bem RA, Bos AP, Wösten-van Asperen RM, Bruijn M, Lutter R, Sprick MR, and van Woensel JB
- Subjects
- Acute Lung Injury microbiology, Acute Lung Injury pathology, Apoptosis, Bronchoalveolar Lavage Fluid immunology, Case-Control Studies, Cells, Cultured, Epithelial Cells immunology, Epithelial Cells pathology, Female, Humans, Infant, Infant, Newborn, Leukocytes microbiology, Male, Receptors, TNF-Related Apoptosis-Inducing Ligand metabolism, Receptors, Tumor Necrosis Factor metabolism, Recombinant Proteins metabolism, Respiration, Artificial, Respiratory Insufficiency microbiology, Respiratory Insufficiency pathology, Respiratory Insufficiency therapy, Respiratory Mucosa microbiology, Respiratory Mucosa pathology, Respiratory Syncytial Virus Infections microbiology, Respiratory Syncytial Virus Infections pathology, Respiratory Syncytial Virus Infections therapy, Severity of Illness Index, Signal Transduction, Time Factors, Up-Regulation, Acute Lung Injury immunology, Leukocytes immunology, Respiratory Insufficiency immunology, Respiratory Mucosa immunology, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Virus, Human pathogenicity, TNF-Related Apoptosis-Inducing Ligand metabolism
- Abstract
Lower respiratory tract infection by respiratory syncytial virus (RSV) is a frequent cause of acute lung injury in young children and infants. Studies in adults and animals suggest that tumor necrosis factor receptor (TNFR) ligands may mediate lung injury by causing apoptosis of epithelial cells. The main goal of the present study was to determine whether the TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) pathway may be implicated in epithelial injury during severe RSV infection in children. We report elevated levels of soluble (s)TRAIL released by leukocytes in bronchoalveolar lavage fluid (BALF) of patients with RSV-associated respiratory failure (n = 22) as compared with mechanically ventilated patients without pulmonary illness (n = 7). Primary bronchial epithelial cells of children without pulmonary disease obtained by nonbronchoscopic cytobrushing expressed both death receptors TRAIL-R1 and -R2, and were found to be susceptible for cell death by human recombinant sTRAIL in vitro. Furthermore, BALF from a patient with RSV induced cell death in these cells, which was partly attenuated by inhibiting TRAIL signaling. These data suggest that the TRAIL pro-apoptotic pathway may contribute to lung epithelial injury in severe RSV infection in children.
- Published
- 2010
- Full Text
- View/download PDF
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