scholarly journals Elevation of serum soluble E-selectin and VCAM-1 in severe asthma

2001 ◽  
Vol 10 (6) ◽  
pp. 339-342 ◽  
Author(s):  
Agnes Hamzaoui ◽  
Jamel Ammar ◽  
Fethi El Mekki ◽  
Olfa Borgi ◽  
Hédia Ghrairi ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Serum Levels ◽  
Assay Method ◽  
Moderate Asthma ◽  
Asthmatic Patients ◽  
Immunological Markers ◽  
Healthy Donors ◽  
Severe Asthmatic ◽  
Enzymelinked Immunosorbent Assay ◽  
Cell Adhesion Molecule 1

Objective:To investigate the significance of circulating adhesion molecules associated with leucocyteendothelial cell interactions in asthma, serum levels of soluble E (sE)-selectin, soluble P (sP)-selectin, soluble L (sL)-selectin, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in mild, moderate and severe asthma.Method:Serum levels of sE-selectin, sP-selectin, sLselectin, and sVCAM-1 were measured in 32 women with asthma and 30 healthy donors using an enzymelinked immunosorbent assay method. Twenty patients were suffering from severe asthma, and 12 from mild/moderate asthma.Results:Serum sE-selectin and sVCAM-1 levels from patients with asthma were significantly higher than those observed in healthy donors(p<0.01). The levels of sP-selectin were the same as those of controls. The level of sE-selectin exhibited an important increase in the severe asthmatic patients compared with mild/moderate asthma(p<0.01). The sVCAM-1 level was increased in severe asthma when compared with healthy controls. There was no correlation between the levels of soluble selectins and the age of the patients. A significant correlation was found between sE-selectin and sVCAM-1 levels.Conclusion:These data indicate that circulating soluble forms of the selectins may have different kinetics during the clinical course of asthma, suggesting that they may reflect different inflammatory pathways in severe asthma. Both sVCAM-1 and sE-selectin may be useful immunological markers for monitoring disease activity in asthma.

scholarly journals Small RNA Species and microRNA Profiles are Altered in Severe Asthma Nanovesicles from Broncho Alveolar Lavage and Associate with Impaired Lung Function and Inflammation

2019 ◽  
Vol 5 (4) ◽  
pp. 51 ◽  
Author(s):  
Ana S. Francisco-Garcia ◽  
Eva M. Garrido-Martín ◽  
Hitasha Rupani ◽  
Laurie C. K. Lau ◽  
Rocio T. Martinez-Nunez ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Filtration Method ◽  
Asthmatic Patients ◽  
Expression Of Genes ◽  
Severe Asthmatic ◽  
Asthma Patients ◽  
Impaired Lung Function ◽  
The Impact

MicroRNAs are known to regulate important pathways in asthma pathology including the IL-6 and IFN pathways. MicroRNAs have been found not only within cells but also within extracellular vesicles such as exosomes. In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients. We extracted nanovesicle RNA using a serial filtration method. RNA content was analyzed with small RNA sequencing and mapped to pathways affected using WebGestalt 2017 Software. We report that severe asthma patients have deficient loading of microRNAs into their airway luminal nanovesicles and an altered profile of small RNA nanovesicle content (i.e., ribosomal RNA and broken transcripts, etc.). This decrease in microRNA cargo is predicted to increase the expression of genes by promoting inflammation and remodeling. Consistently, a network of microRNAs was associated with decreased FEV1 and increased eosinophilic and neutrophilic inflammation in severe asthma. MicroRNAs in airway nanovesicles may, thus, be valid biomarkers to define abnormal biological disease processes in severe asthma and monitor the impact of interventional therapies.

Evaluation of bronchial wall thickness in asthma using magnetic resonance imaging

2021 ◽  
pp. 2100329
Author(s):  
Ilyes Benlala ◽  
Gaël Dournes ◽  
Pierre-Olivier Girodet ◽  
Thomas Benkert ◽  
François Laurent ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Severe Asthma ◽  
Altman Analysis ◽  
Resonance Imaging ◽  
Bronchial Wall ◽  
Bland Altman Analysis ◽  
Wall Area ◽  
Asthmatic Patients ◽  
Severe Asthmatic

BackgroundBronchial thickening is a pathological feature of asthma that has been evaluated using computed tomography (CT), an ionised radiation technique. Magnetic Resonance Imaging (MRI) with Ultrashort Echo Time (UTE) pulse sequences could be an alternative to CT.ObjectivesTo measure bronchial dimensions using MRI-UTE in asthmatic patients, by evaluating the accuracy and agreement with CT, by comparing severe and non-severe asthma and by correlating with pulmonary function tests.MethodsWe assessed bronchial dimensions (wall area (WA), lumen area (LA), normalised wall area (WA%), and wall thickness (WT)) by MRI-UTE and CT in 15 non-severe and 15 age- and sex-matched severe asthmatic patients (NCT03089346). Accuracy and agreement between MRI and CT was evaluated by paired t-tests and Bland-Altman analysis. Reproducibility was assessed by intra-class correlation coefficient and Bland-Altman analysis. Comparison between non-severe and severe asthmatic parameters was performed by Student-t, Mann-Whitney or Fisher's Exact tests. Correlations were assessed by Pearson or Spearman coefficients.ResultsLA, WA%, and WT were not significantly different between MRI-UTE and CT, with good correlations and concordance. Inter- and intra-observer reproducibility was moderate to good. WA% and WT were both higher in severe than in non-severe asthmatic patients. WA, WA% and WT were all negatively correlated with FEV1.ConclusionWe demonstrated that MRI-UTE is an accurate and reliable radiation-free method to assess bronchial wall dimensions in asthma, with enough spatial resolution to differentiate severe from non-severe asthma.

scholarly journals Oral Corticosteroids Dependence and Biologic Drugs in Severe Asthma: Myths or Facts? A Systematic Review of Real-World Evidence

2021 ◽  
Vol 22 (13) ◽  
pp. 7132
Author(s):  
Luigino Calzetta ◽  
Marina Aiello ◽  
Annalisa Frizzelli ◽  
Giuseppina Bertorelli ◽  
Paola Rogliani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Severe Asthma ◽  
Real World ◽  
Symptom Control ◽  
Airflow Limitation ◽  
Biologic Drugs ◽  
Asthmatic Patients ◽  
Severe Asthmatic ◽  
Oral Corticosteroids ◽  
Sparing Effect

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.

scholarly journals Possible role of a hydrogen peroxide-mediated mechanism in glucocorticoid receptor functional alterations associated with moderate asthma

2008 ◽  
Vol 60 (4) ◽  
pp. 531-539 ◽  
Author(s):  
Tatjana Perisic ◽  
M. Sreckovic ◽  
Gordana Matic
Keyword(s):  
Hydrogen Peroxide ◽  
Glucocorticoid Receptor ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Pulmonary Inflammation ◽  
Peripheral Blood Mononuclear ◽  
Moderate Asthma ◽  
Asthmatic Patients ◽  
Healthy Donors ◽  
Induced Changes

It is well known that pathogenesis and maintenance of chronic asthma is associated with alterations of glucocorticoid receptor (GR) function, and also with persistent pulmonary inflammation, the important mediators of which are reactive oxygen and nitrogen species. In this paper, we tested a hypothesis that GR functional alterations in asthma result from the action of oxidants. To that end, we conducted a series of ex vivo treatments of peripheral blood mononuclear cells (PBMCs) of healthy donors with oxidizing agents (3 morpholinosydnonimine, SIN1; S-nitroso-N-acetyl-penicillamine, SNAP; and hydrogen peroxide, H2O2) and compared the resulting GR modifications with those previously noticed in asthmatic patients. The results show that treatment of PBMCs by H2O2 provoked an increase in the level of GR protein, accompanied by a rise in the number of hormone-binding sites and a decline in the receptor's affinity for the hormone. The H2O2 induced changes, including a characteristic GR isoprotein expression pattern, were found to be very similar to the GR changes previously observed in PBMCs of moderate asthmatic patients, but not in mild asthmatics and healthy subjects. Treatment with the other oxidants applied herein produced different effects or exerted no influence on GR. Thus, this study provides preliminary data suggesting that functional alterations of the GR associated with moderate asthma may be mediated by redox mechanisms that are based on oxidative and regulatory actions of H2O2.

New oxazolidines inhibit the secretion of IFN-γ and IL-17 by PBMCS from moderate to severe asthmatic patients

2020 ◽  
Vol 16 ◽  
Author(s):  
Renata Virgínia Cavalcanti Santos ◽  
Eudes Gustavo Constantino Cunha ◽  
Gabriela Souto Vieira de Mello ◽  
José Ângelo Rizzo ◽  
Jamerson Ferreira de Oliveira ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Treatment Resistance ◽  
In Silico Analysis ◽  
Asthmatic Patients ◽  
Novel Approach ◽  
Severe Asthmatic ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Neurokinin 1 ◽  
Common Target

Background: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-γ, which are also related to treatment resistance and airway hyperresponsiveness. Oxazolidines emerged as a novel approach for asthma treatment, since some chemical peculiarities were suggested by previous studies. Objective: The present study aimed to evaluate the IL-17A and IFN-γ modulatory effect of two new oxazolidine derivatives (LPSF/NB-12 and -13) on mononucleated cells of patients with moderate and severe asthma. Methods: The study first looked at potential targets for oxazolidine derivatives using SWISS-ADME. After the synthesis of the compounds, cytotoxicity and cytokine levels were analyzed. Results: We demonstrated that LPSF/NB-12 and -13 reduced IFN-γ and IL-17 production in peripheral blood mononucleated cells from asthmatic patients in a concentrated manner. Our in silico analysis showed the neurokinin-1 receptor as a common target for both compounds, which is responsible for diverse proinflammatory effects of moderate and severe asthma. Conclusion: The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.

scholarly journals Effect of grape seed proanthocyanidin extract in peripheral blood mononuclear cells of severe asthmatic patients

2019 ◽  
Author(s):  
Yun Sun ◽  
Bin Gu ◽  
Yan Qian ◽  
Yi Chen ◽  
Zheng-dao Mao ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Mononuclear Cells ◽  
Grape Seed ◽  
Control Group ◽  
Binding Ability ◽  
Peripheral Blood Mononuclear ◽  
Asthmatic Patients ◽  
Severe Asthmatic ◽  
Blood Mononuclear Cells ◽  
Grape Seed Proanthocyanidin

Abstract Backgroud To explore the Effect of grape seed proanthocyanidin extract（GSPE） in peripheral blood mononuclear cells of severe asthmatic patients. Methods 40 severe asthmatic patients were randomly and averagely divided into 2 groups: DXM group (n=20) and GSPE+DXM group (n=20), and 20 healthy volunteers as control gorup. Heparinized peripheral venous blood from each subject was collected in a sterile vacuum tube. The levels of interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 were detected by ELISA. The protein and mRNA expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2), glutamatecysteine ligase modifier subunit (GCLM) inducible nitric oxide synthase (iNOS) and inactivation of histone deacetylase-2 (HDAC2) were detected by Western blot and qRT-PCR respectively. Glutathion(GSH) was measured by using Glutathione Fluorometric Detection Kit, and Nrf2-ARE binding ability was measured by using TransAM Nrf2 Transcription Factor ELISA Kit. Results The results showed that the levels of IL-8 and MCP-1 in normal control group were lower than those in severe asthma group (P <0.05). Treatment with GSPE+DXM reduced the levels of IL-8 and MCP-1 significantly when compared with DXM only ( P <0.05).The mRNA expression of iNOS in DXM group was significantly higher than that in control group. However, after adding GSPE treatment, the expression dramatically decreased ( P <0.001). On the contrary, lower mRNA expressions of Nrf2, GCLM and HDAC2 were found in DXM group than in control group ( P <0.001). Accordingly, when treated with GSPE, these expressions elevated and reached a statistical significance ( P <0.05). Consistently, the results from western blot analysis confirmed the role of GSPE on the protein expressions of iNOS, Nrf2, GCLM and HDAC2 in PBMCs of patients with severe asthma ( P <0.001). The PBMCs from patients with severe asthma exhibited lower Nrf2-ARE binding ability and produced less GSH than normal controls. GSPE treatment effectively augmented the Nrf2-ARE binding ability and the expression of GSH, which demonstrated the biological antioxidant potential of GSPE ( P <0.001). Conclusion GSPE can alleviate glucocorticoid resistance by regulating Nrf2-iNOS-HDAC2 signaling pathway in severe asthma, suggesting that GSPE have potential clinical application prospects in the treatment of severe asthma.

scholarly journals Risk factors for the development of bronchiectasis in patients with asthma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donghai Ma ◽  
María-Jesús Cruz ◽  
Iñigo Ojanguren ◽  
Christian Romero-Mesones ◽  
Diego Varona-Porres ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Asthma Control ◽  
Severe Asthma ◽  
Factors Associated ◽  
Asthmatic Patients ◽  
Asthma Exacerbations ◽  
Severe Asthmatic ◽  
Asthma Patients ◽  
High Age

AbstractThough asthma and bronchiectasis are two different diseases, their coexistence has been demonstrated in many patients. The aim of the present study is to compare the characteristics of asthmatic patients with and without bronchiectasis and to assess risk factors for the development of this condition. Two hundred and twenty-four moderate-severe asthmatic patients were included. The severity of bronchiectasis was assessed by Reiff and FACED parameters. Logistic regression was used to identify independent factors associated with bronchiectasis. Bronchiectasis was identified in 78 asthma patients. In severe asthma patients, its prevalence was 56.9%. Bronchiectasis was defined as mild in81% of patients using modified Reiff criteria and in 74% using FACED criteria. Asthmatic patients with bronchiectasis had decreasing FEV1, FVC and FEV1/FVC (p = 0.002, 0.005 and 0.014 respectively), presented more frequent asthma exacerbations (p < 0.001) and worse asthma control (ACT 21 vs 16pts, p < 0.001). Factors independently associated with bronchiectasis were older age (42–65 years: OR, 3.99; 95% CI 1.60 to 9.95, P = 0.003; ≥ 65 years: OR, 2.91; 95% CI 1.06 to 8.04, P = 0.039), severe asthma grade (OR, 8.91; 95% CI 3.69 to 21.49; P < 0.001) and frequency of asthma exacerbations (OR, 4.43; 95% CI 1.78 to 11.05; P < 0.001). In patients with severe asthma, age of asthma onset (OR, 1.02; 95% CI 1.01 to 1.04; P = 0.015) and asthma exacerbations (OR, 4.88; 95% CI 1.98 to 12.03; P = 0.001) were independently associated with the development of bronchiectasis. The prevalence of bronchiectasis in severe asthmatic patients is high. Age of asthma onset and exacerbations were independent factors associated with the occurrence of bronchiectasis.

scholarly journals Serum 25-hydroxy vitamin D in asthmatic children and its relation to disease severity

2019 ◽  
Vol 6 (2) ◽  
pp. 454
Author(s):  
Ihab Hafez El Sawy ◽  
Passant Al-Said Moaz ◽  
Ghada Mohamed Farouk El Deriny ◽  
Mohamed Sami Abd El Moniem El Kholy
Keyword(s):  
Vitamin D ◽  
Severe Asthma ◽  
Control Group ◽  
Healthy Children ◽  
Vitamin D Status ◽  
Moderate Asthma ◽  
Asthmatic Children ◽  
Asthmatic Patients ◽  
Vitamin D Levels ◽  
The Difference

Background: Asthma is a chronic immunological disorder of the lungs. Vitamin D has several effects on the innate and adaptive immune systems. Little is known about vitamin D level and its impact on severity of asthma in children. This study aimed to determine vitamin D levels in asthmatics versus control children; studying the relation if any between these levels and asthma severity.Methods: This cross-sectional study was conducted on 60 asthmatic children and 20 apparently healthy children as controls. Asthma patients were divided into 3 groups (mild, moderate, severe; 20 each). Asthma severity was based on GINA criteria. Vitamin D level was measured to all study group.Results: The difference between the mean values of vitamin D level in control and asthmatic patients was statistically significant (p<0.001). This difference between control group and each asthma subgroup and between asthma subgroups versus each other were statistically significant being highest in control and lowest in patients with severe asthma (p<0.001). Differences in vitamin D status in control and all asthmatic patients were statistically significant (p<0.001). The difference between control group and each asthma subgroup according to vitamin D status were statistically significant (p<0.001). Concerning asthma subgroups the difference in vitamin D status between severe versus mild and moderate asthma were statistically significant (p<0.001), while between mild and moderate asthma it was not.Conclusions: Significantly lower vitamin D level in asthmatic children compared to controls and a differential decrease in vitamin D levels in asthmatic children being lowest in severe asthma was confirmed.

scholarly journals Association of Toll-like receptors 4 (TLR-4) gene expression and polymorphisms in patients with severe asthma

2021 ◽  
Vol 14 (4) ◽  
pp. 544-548
Author(s):  
Wasan Shukur ◽  
◽  
Kifah Alyaqubi ◽  
Rasha Dosh ◽  
Ali Al-Ameri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Severe Asthma ◽  
Interleukin 1 ◽  
Serum Levels ◽  
High Serum ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Asthmatic Patients ◽  
Healthy Control

Innate immunity plays a central role in the pathogenesis of severe asthma, and it is closely linked to elevated IgE and Toll-like receptor 4 (TLR-4) levels. However, there is a scarcity of information about the association of the TLR-4 receptor polymorphism in the pathogenesis of severe asthma. This study highlights the level of gene expression of different alleles in asthmatic patients compared to healthy control individuals. This was a randomized control trial, which included 150 patients with asthma (with high serum levels of IgE) with a matching 150 healthy control individuals. Participants had a series of blood tests to measure various immune parameters: interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), intercellular adhesion molecule-1 (ICAM1) and detect allele type and gene expression of the TLR-4 gene. Patients with asthma had significantly higher levels of IL-8 when compared to the healthy control participants. In addition, in the rs91 genotyping, there were significant differences in the levels of IL-8 and TNF between CC and TT genotyping. While in rs90 TLR-4, TNF levels were significantly higher in AA vs. AG and GG genotypes among the asthmatic patients when compared to the control group. The results showed that in TLR-4, rs4986791 were significantly associated with asthma risk. Polymorphisms in TLRs play essential roles in asthma.

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