Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040586 (tracheobronchitis)
 449 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human bronchial epithelium is exquisitely sensitive to high O2 levels, with tracheobronchitis usually developing after 12 h of exposure to 100% O2. To evaluate whether this vulnerability results from inability of the bronchial epithelium to provide adequate antioxidant protection, we quantified antioxidant gene expression in bronchial epithelium of normal volunteers at baseline and after exposure to 100% O2 in vivo. After 14.8 +/- 0.2 h of 100% O2, 24 of 33 individuals had evidence of tracheobronchitis. Baseline gene expression of CuZn superoxide dismutase (SOD), MnSOD, and catalase in bronchial epithelium was very low (CuZnSOD 4.1 +/- 0.8 transcripts/cell, MnSOD 5.1 +/- 0.9, catalase 1.3 +/- 0.2), with control gamma-actin expression relatively abundant (50 +/- 6 transcripts/cell). Importantly, despite 100% O2 exposure sufficient to cause tracheobronchitis in most individuals, antioxidant mRNA transcripts/cell in bronchial epithelium did not increase (P > 0.5). Catalase activity in bronchial epithelium did not change after exposure to hyperoxia (P > 0.05). Total SOD activity increased mildly (P < 0.01) but not sufficiently to protect the epithelium. Together, the very low levels of expression of intracellular antioxidant enzymes and the inability to upregulate expression at the mRNA level with oxidant stress likely have a role in human airway epithelium susceptibility to hyperoxia.
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PMID:In vivo antioxidant gene expression in human airway epithelium of normal individuals exposed to 100% O2. 822 38

Reactive oxygen species (ROS) is increased in the airway during the inhalation of 100% O(2) or cigarette smoke and participates in the development of tracheobronchitis. We hypothesized that inhaled ROS upregulates local extracellular ROS scavenging systems or reactive molecules, e.g., nitric oxide (NO). Extracellular glutathione peroxidase (eGPx) is synthesized by airway epithelium and alveolar macrophages, secreted into the surface epithelial lining fluid, and functions as a first-line defense against inhaled ROS. NO, produced by NO synthase 2 (NOS2), combines rapidly with ROS to form reactive nitrogen species (RNS). In this study, human airway epithelial cells and alveolar macrophages from healthy individuals before and after exposure to 100% O(2) for 12 h, or from cigarette-smoking individuals, were evaluated for eGPx and NOS2 messenger RNA (mRNA) expression. Hyperoxia increased NOS2 mRNA in airway epithelial cells by 2.5-fold but did not increase eGPx mRNA. In contrast, cigarette smoke upregulated eGPx mRNA over 2-fold in airway epithelial cells and alveolar macrophages but did not affect NOS2 expression. In vitro exposure of respiratory epithelial cells to ROS or RNS also increased eGPx expression. These findings define distinct molecular responses in the airway to different inhaled ROS, which likely influences the susceptibility of the airway to oxidative injury.
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PMID:Differential induction of extracellular glutathione peroxidase and nitric oxide synthase 2 in airways of healthy individuals exposed to 100% O(2) or cigarette smoke. 1097 Aug 26

Oxygen administration is uniformly used in emergency and intensive care medicine and has life-saving potential in critical conditions. However, excessive oxygenation also has deleterious properties in various pathophysiological processes and consequently both clinical and translational studies investigating hyperoxia during critical illness have gained increasing interest. Reactive oxygen species are notorious by-products of hyperoxia and play a pivotal role in cell signaling pathways. The effects are diverse, but when the homeostatic balance is disturbed, reactive oxygen species typically conserve a vicious cycle of tissue injury, characterized by cell damage, cell death, and inflammation. The most prominent symptoms in the abundantly exposed lungs include tracheobronchitis, pulmonary edema, and respiratory failure. In addition, absorptive atelectasis results as a physiological phenomenon with increasing levels of inspiratory oxygen. Hyperoxia-induced vasoconstriction can be beneficial during vasodilatory shock, but hemodynamic changes may also impose risk when organ perfusion is impaired. In this context, oxygen may be recognized as a multifaceted agent, a modifiable risk factor, and a feasible target for intervention. Although most clinical outcomes are still under extensive investigation, careful titration of oxygen supply is warranted in order to secure adequate tissue oxygenation while preventing hyperoxic harm.
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PMID:Bench-to-bedside review: the effects of hyperoxia during critical illness. 2627 83