Pathogenesis Of Airway Disorders Research Articles

Effect of Selenium and Vitamin C on Clinical Outcomes, Trace Element Status, and Antioxidant Enzyme Activity in Horses with Acute and Chronic Lower Airway Disease. A Randomized Clinical Trial

Excess production of reactive oxygen species is involved in the pathogenesis of airway disorders in horses. Trace element antioxidants have a beneficial role in oxidant/antioxidant balance. The aim of the present study was to evaluate the effect of a combination of sodium selenite and ascorbic acid on clinical outcome, antioxidant enzymes, and trace elements status in horses with lower airway disease. For this purpose, 40 draft horses with lower airway disease were randomly selected (acute, n = 20; chronic, n = 20). Both acute and chronic cases were randomly allocated into two subgroups (ten each). Groups 1 and 2 were the horses with acute disease, while groups 3 and 4 were chronically ill. For all groups, each horse was administered antibiotic, non-steroidal anti-inflammatory, and mucolytic drug. In addition, groups 2 and 4 were injected with 15mg/kg sodium selenite and 30mg/kg ascorbic acid every 24h for successive 4weeks. Venous blood samples were obtained from diseased horses on three occasions; at first examination, and at 2 and 4weeks post-treatment. Clinically, antioxidant supplementation improved the clinical signs with significant decrease (p < 0.05) of the clinical index score in both acute and chronic cases. In supplemented groups compared with non-supplemented, there was a significant increase (p < 0.05) in the levels of copper, zinc, selenium, and iron as well as in the activity of glutathione-S-transferase and catalase. Meanwhile, there was a significant decrease (p < 0.05) in the levels of manganese, malondialdehyde, hydrogen peroxide, and low-density lipoprotein and in the activity of glutathione reductase. The results of the present study indicate that administration of sodium selenite and ascorbic acid may have beneficial effect on clinical outcome and antioxidant balance in horses with acute and chronic lower airway disease.

Bronchial Epithelial Cells in Allergic Reactions

Bronchial epithelial cells (BEC) are known to play an integral role in the airway defense mechanism via mucociliary system as well as mechanical barriers. Recent studies further indicate that BEC produce and release biologically active compounds including lipid mediators, growth factors, endothelin and a variety of cytokines/chemokines important in the pathogenesis of airway disorders. Cytokines and chemokines produced by BEC include IL-6, IL-8, G-CSF, GM-CSF, RANTES, eotaxin and TARC. Pro-inflammatory cytokines IL-1 and TNF-alpha, generally upregulate expression and release these cytokines/chemokines. BEC from patients with bronchial asthma showed increased levels of mRNA for these potent inflammatory peptides. BEC also interact with immune and inflammatory cells by direct adhesion as well as by humoral factors including cytokines. For example, eosinophil adhesion to BEC may be an important signal for the activation and degranulation of eosinophils. BEC is also believed to take part in the airway mucosal immunity via Toll-like receptors. Finally, BEC may play a crucial role in the processes of airway remodeling by cross-talk with mesenchymal cells. These findings strongly suggest that BEC are actively involved as regulators of allergic inflammatory responses, and become a target for therapeutic intervention.

Neutrophils Potentiate Platinum-Mediated Injury to Human Ciliated Epithelium In Vitro

Exposure to platinum salts, such as may occur in the platinum refining industry, can be associated with the development of airway disorders such as asthma. However, there have been no studies investigating the direct effects of platinum salts on human ciliated epithelium. We have investigated the effects of platinic chloride on human ciliated epithelium, obtained by brushing the inferior nasal turbinate of healthy human volunteers. Ciliary beat frequency was measured using a phototransistor technique, and damage to the structural integrity of the epithelium was measured using a visual scoring index. Platinic chloride at concentrations between 0.25 and 25 μ M caused a dose-dependent slowing of ciliary beating and damage to the structural integrity of the epithelium. These direct injurious effects were not affected by catalase, but were almost completely attenuated by preincubation of the epithelium with cysteine. The effects of platinic chloride on ciliary beating and structural integrity were enhanced by the presence of neutrophils and were partially attenuated by preincubation of the epithelial strips with catalase, suggesting that the direct effects of the metal were enhanced in this experimental system by reactive oxidants produced by activated neutrophils. This study documents that platinum salts have an injurious effect on human ciliated epithelium in vitro. If such effects also occur in vivo they may play a role, at least partly, in the pathogenesis of airway disorders that may manifest in exposed workers.

Airway epithelial cells as regulators of airway inflammation (Review).

Airway epithelial cells (AEC) are known to play an integral role in the airway defense mechanism via mucociliary system as well as mechanical barriers. Recent studies further indicate that AEC can produce and release biologically active compounds including lipid mediators, growth factors, endothelin and a variety of cytokines/chemokines important in the pathogenesis of airway disorders. Human bronchial epithelial cells were isolated from normal and diseased states, and purely cultured in hormonally defined, serum-free medium. Culture supernatants of AEC contained detectable amounts of cytokines such as IL-1, IL-6, IL-8, G-CSF and GM-CSF. Proinflammatory cytokines IL-1 and TNFalpha generally upregulated expression and release of these cytokines. Moreover, human bronchial epithelial cells from patients with airway diseases such as asthma showed increased levels of mRNA for the cytokines. AEC are considered to interact with immune and inflammatory cells by direct adhesion as well as by humoral factors including cytokines. For example, eosinophil adhesion to AEC may be an important signal for the activation and degranulation of eosinophils. AEC is also believed to take part in the airway mucosal immunity by interacting with lymphocytes. Finally, AEC may play a crucial role in the processes of airway remodelling found in chronic airway inflammatory diseases. These findings strongly suggest that AEC are actively involved as regulators of airway inflammatory responses playing an important role in the pathogenesis of airway disorders, and become a target for therapeutic intervention.