Oxidative Stress and Bronchial Asthma in Children-Causes or Consequences?
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ABSTRACT:
SUBMITTER: Jesenak M
PROVIDER: S-EPMC5523023 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Influence of bronchial asthma (BA) severity on physical development in children patients was evaluated in comparison with healthy population. Materials and Methods. 1042 children and adolescents (768 boys) with atopic BA were evaluated. All children underwent standard examination in a clinical setting, including anthropometry. The control group included 875 healthy children of a comparable age (423 boys). Results. The fraction of patients with the normal, lower, and increased height among the whole group of patients with BA is close to the corresponding values in the healthy population (χ2 = 3.32, p = 0.65). The fraction of BA patients with the reduced physical development is increased monotonically and significantly when the BA severity increases: healthy group, 8.2% (72/875), BA intermittent, 4.2% (6/144), BA mild persistent 9% (47/520), BA moderate persistent, 11.7% (36/308), and BA severe persistent, 24.3% (17/70) (χ2 = 45.6, p = 0,0009). Conclusion. The fraction of the children with the reduced height is increased monotonically and significantly in the groups of increasing BA severities. At the same time, the fraction of such children in groups of intermittent and mild persistent BA practically does not differ from the conditionally healthy peers.
| S-EPMC5549479 | biostudies-other
Project description:COPD and asthma exacerbations are commonly triggered by rhinovirus infection. Potentially promoting exacerbations, impaired anti-viral signaling and attenuated viral clearance have been observed in diseased bronchial epithelium. Oxidative stress is a feature of inflammation in asthma and COPD and is prominent during exacerbations. It is not known whether oxidative stress affects the anti-viral signaling capacity. Bronchial epithelial cells from asthmatic and COPD donors were infected with rhinovirus or treated with the oxidative stressor H2O2 followed by exposure to the synthetic viral replication intermediate poly(I:C). Poly(I:C) was used to ascertain a constant infection-like burden. Gene and protein levels of antioxidants as well as anti-viral responses were measured 3 and 24 h post poly(I:C) exposure. Rhinovirus infection and poly(I:C) stimulation induced protein levels of the antioxidants SOD1 and SOD2. In asthmatic bronchial epithelial cells pre-treatment with H2O2 dose-dependently decreased the antioxidant response to poly(I:C), suggesting exaggerated oxidative stress. Further, poly(I:C)-induced IFN? gene expression was reduced after pre-treatment with H2O2. This epithelial effect was associated with a reduced expression of the pattern recognition receptors RIG-I, MDA5 and TLR3 both on gene and protein level. Pre-treatment with H2O2 did not alter antioxidant responses in COPD bronchial epithelial cells and, more modestly than in asthma, reduced poly(I:C)-induced IFN? gene expression. Knockdown of TLR3 but not RIG-I/MDA5 abrogated impairment of poly(I:C)-induced IFN? gene expression by H2O2. We developed a method by which we could demonstrate that oxidative stress impairs anti-viral signaling in bronchial epithelial cells from asthmatic and COPD patients, most pronounced in asthma. The impairment apparently reflects reduced responsiveness of TLR3. These present findings shed light on molecular mechanisms potentially causing reduced interferon responses to rhinovirus infection at exacerbations in asthma and COPD. Together, our findings suggest a possible self-perpetuating vicious cycle underlying recurrent exacerbations, leading to an impaired anti-viral response, which in turn leads to viral-induced exacerbations, causing more airway inflammation.
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Project description:This study was designed to investigate the correlation of vitamin D receptor (VDR) gene polymorphism with bronchial asthma in children. Seventy patients admitted to Daqing Longnan Hospital and diagnosed as bronchial asthma for the first time from April 2015 to May 2017 were selected as observation group. Patients received routine treatment and intervention. Seventy healthy subjects admitted to hospital during the same period were enrolled as the control group. Vitamin D gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism assay; the levels of total serum immunoglobulin E (IgE) in the two groups were determined by electrochemiluminescence immunoassay; lung function levels in patients were measured using PowerCube (Germany) pulmonary function instrument before and after treatment, and the relationship between VDR gene polymorphism and lung function in children with bronchial asthma was analyzed. The difference in comparison of base frequency of rs1544410 locus of VDR gene had no statistical significance between the two groups (P>0.05). The locus CC frequency of rs7975232 of VDR gene in observation group was lower in the observation group than that in the control group (P<0.05); the locus AC and AA frequencies of rs7975232 of VDR gene were higher in the observation group than those in the control group (P<0.05). The level of vitamin D was lower in the observation group than that in the control group (P<0.05); the level of total serum IgE was higher in the observation group than that in the control group (P<0.05). The forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF) and the ratio of FEV1 to forced vital capacity (FVC) in children with bronchial asthma in the observation group were higher after treatment than those before treatment (P<0.05). The correlation research displayed that VDR gene polymorphism was negatively correlated with lung function levels in children with bronchial asthma (P<0.05). The results showed that children with bronchial asthma are often accompanied by different degrees of changes in VDR gene polymorphism, which is negatively correlated with the severity of asthma, so vitamin D should be strengthened to ameliorate the prognosis of children.
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Project description:Background: Uncontrolled asthma (BA) can be complicated by cardiac conduction disturbances and arrhythmias. It is typical mainly for adult asthmatics patients. In asthmatics children the effect of bronchoconstriction on cardiac conduction, including the supraventricular component of the ECG, is currently under discussion. The objective of the research is to analyze ECG parameters of the atrial complex and atrioventricular conduction and to assess their relationship with spirometric indicators in children with BA. Methods: Hundred three patients with BA from the age of 6–17 years were examined. The spirometric parameters were evaluated, including the Tiffeneau index (TI): FEV1/FVC (%), according to the level of which the patient groups were distinguished. Group 1 (G1): with TI more than 85%, (n = 15); Group 2 (G2): with TI from 85 to 75%, (n = 40); Group 3 (G3): with TI <75%, (n = 48). The ECG parameters that characterize supraventricular conduction, including the PQ interval (sec) and the sPQ segment (sec), were analyzed. We had calculated relative PQ (rPQ) by the formula rPQ=PQ/PQmed, where PQ is the patient's PQ, PQmed are the median PQ values of healthy children of age selected. Results: The duration of the PQ in groups G1 and G2 was 0.13 (0.11; 0.14) s; and 0.13 (0.12; 0.14) s, respectively, which is statistically significantly less than in patients of groups G3–0.14 (0.13; 0.15] s, p = 0.01. The duration of the sPQ segment in children of groups G1 and G2 was also generally shorter than in patients of groups G3, and amounted, respectively, to 0.05 (0.04; 0.06) s, 0.04 (0.04; 0.05) s, and 0.06 (0.04; 0.07) s, p = 0.02. The rPQ increased progressively as TI decreased and amounted in G1 to 92.9 (85.7; 106.3) %, in G2 100.0 (92.9; 103.0) %, and in G3 104 (100.0; 107.7) %, p = 0.009. A statistically significant negative correlation between IT and PQ–r = ?0.23, p = 0.02; with sPQ–r = ?0.20, p = 0.045; and with rPQ–r = ?0.25, p = 0.01 was revealed. Conclusion: A decrease in TI in asthmatics children is associated with a prolongation of the PQ. This may indicate a slowdown in supraventricular conduction in patients with uncontrolled asthma and, thus, be considered as a risk for the formation of subsequent supraventricular arrhythmias.
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Project description:The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood-retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1?, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.
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Project description:Bronchial thermoplasty (BT) is a novel therapy for patients with severe asthma. Using radio frequency thermal energy, it aims to reduce the airway smooth muscle mass. Several clinical trials have demonstrated improvements in asthma-related quality of life and a reduction in the number of exacerbations following treatment with BT. In addition, recent data has demonstrated the long-term safety of the procedure as well as sustained improvements in rates of asthma exacerbations, reduction in health care utilization, and improved quality of life. Further study is needed to elucidate the underlying mechanisms that result in these improvements. In addition, improved characterization of the asthma subphenotypes likely to exhibit the largest clinical benefit is a critical step in determining the precise role of BT in the management of severe asthma.
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