scholarly journals Airway Remodelling in Asthma: From Benchside to Clinical Practice

2010 ◽  
Vol 17 (4) ◽  
pp. e85-e93 ◽  
Author(s):  
Céline Bergeron ◽  
Meri K Tulic ◽  
Qutayba Hamid
Keyword(s):  
Structural Changes ◽  
Small Airways ◽  
Airway Remodelling ◽  
Airway Narrowing ◽  
Asthmatic Patients ◽  
Clinical Consequences ◽  
Characteristic Features ◽  
Airway Walls ◽  
The Relationship ◽  
Subepithelial Fibrosis

Airway remodelling refers to the structural changes that occur in both large and small airways relevant to miscellaneous diseases including asthma. In asthma, airway structural changes include subepithelial fibrosis, increased smooth muscle mass, gland enlargement, neovascularization and epithelial alterations. Although controversial, airway remodelling is commonly attributed to an underlying chronic inflammatory process. These remodelling changes contribute to thickening of airway walls and, consequently, lead to airway narrowing, bronchial hyper-responsiveness, airway edema and mucous hypersecretion. Airway remodelling is associated with poor clinical outcomes among asthmatic patients. Early diagnosis and prevention of airway remodelling has the potential to decrease disease severity, improve control and prevent disease expression. The relationship between structural changes and clinical and functional abnormalities clearly deserves further investigation. The present review briefly describes the characteristic features of airway remodelling observed in asthma, its clinical consequences and relevance for physicians, and its modulation by therapeutic approaches used in the treatment of asthmatic patients.

scholarly journals Small airway dysfunction in patients with cough variant asthma: a retrospective cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jie Gao ◽  
Haigui Wu ◽  
Feng Wu
Keyword(s):  
Retrospective Cohort ◽  
Bronchial Hyperresponsiveness ◽  
Diagnostic Value ◽  
Small Airway ◽  
Small Airways ◽  
Cough Variant Asthma ◽  
Asthmatic Patients ◽  
Cell Test ◽  
Sputum Eosinophils ◽  
The Relationship

Abstract Background Cough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA. Methods A total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test. Results The number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively). Conclusions The eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful.

Small airways and bronchial hyper-responsiveness in cough-variant asthma

2020 ◽  
Author(s):  
jie gao ◽  
Feng Wu ◽  
Xing Yang ◽  
Sifang Wu
Keyword(s):  
Area Under Curve ◽  
Pulmonary Function Tests ◽  
Diagnostic Value ◽  
Small Airway ◽  
Small Airways ◽  
Cough Variant Asthma ◽  
Asthmatic Patients ◽  
Bronchial Hyper Responsiveness ◽  
Positive Correlations ◽  
The Relationship

Abstract Background Cough variant asthma (CVA) is one of the special populations of asthma. The study was to compare spirometric parameters of small airways and the degree of bronchial hyper-responsiveness (BHR) between CVA and classic asthma (CA), and examine the relationship between BHR and small airways to determine the accuracy of these markers as indicators of CVA. Methods A total of 825 asthmatic patients were screened for the study and 614 were included. All patients performed spirometry and underwent a bronchial challenge with methacholine. It has been estimated that less than 65% of the small airways must be obstructed before changes can be detected using routine pulmonary function tests. Results CVA patients showed less small airway dysfunction (< 65%) than those of CA patients with MMEF% predicted (70% vs 80.91%, p = 0.002) and FEF50% predicted (62.71% vs 73.5%, p = 0.004). The function of small airways was higher in the CVA group compared with the CA group (p < 0.001). CVA patients had a mild BHR (p = 0.005). Significant positive correlations were observed between PD20 and MMEF% predicted (r = 0.282, p < 0.001), FEF50% predicted (r = 0.2522, p < 0.001), FEF75% predicted (r = 0.2504, p < 0.001) in patients with CVA. The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 was the best diagnostic value for CVA with an AUC of 0.582 (p = 0.001). Conclusions Small airway dysfunction is milder showed in CVA. The value of BHR combined with small airways in CVA prediction, which reflected significant, but not enough to be clinically useful.

Remodelling and Inflammation in Bronchial Asthma

2003 ◽  
Vol 1 (1) ◽  
pp. 9-12 ◽  
Author(s):  
G. Riccioni ◽  
N. D'Orazio ◽  
R. Della Vecchia ◽  
T. Iezzi ◽  
C. Di Ilio
Keyword(s):  
Airway Inflammation ◽  
Bronchial Asthma ◽  
Structural Changes ◽  
Bronchial Hyperresponsiveness ◽  
Lymphocytic Infiltration ◽  
Smooth Muscle Contraction ◽  
Airway Remodelling ◽  
Airway Wall ◽  
Airway Narrowing ◽  
Abnormal Accumulation

Chronic stable asthma is characterized by inflammation of the airway wall, with abnormal accumulation of basophils, eosinophils, lymphocytes, mast cells, macrophages, dendritic cells and myofibroblasts. The airway inflammation is not confined to severe asthma, but is also found in mild and moderate asthma. This inflammation results in a peculiar type of lymphocytic infiltration whereby Th2 lymphocytes secrete cytokines that orchestrate cellular inflammation and promote airway hyperresponsiveness. The term “airway remodelling” in bronchial asthma refers to structural changes that occurr in conjunction with, or because of, chronic airway inflammation. Airway remodelling results in alterations in the airway epithelium, lamina propria, and submucosa, leading to thickening of airway wall. The consequences of airway remodelling in asthma include incompletely reversible airway narrowing, bronchial hyperresponsiveness (BHR), smooth muscle contraction, airway edema, and mucus hypersecretion which may predispose persons with asthma to exacerbations and even death from airway obstruction.

Structural changes in the airways in asthma: observations and consequences

2005 ◽  
Vol 108 (6) ◽  
pp. 463-477 ◽  
Author(s):  
Tony R. BAI ◽  
Darryl A. KNIGHT
Keyword(s):  
Smooth Muscle ◽  
Muscle Mass ◽  
Structural Changes ◽  
Airflow Limitation ◽  
Wall Thickening ◽  
Small Airways ◽  
Airway Wall ◽  
Airway Narrowing ◽  
Matrix Deposition ◽  
Muscle Dynamics

Structural changes reported in the airways of asthmatics include epithelial fragility, goblet cell hyperplasia, enlarged submucosal mucus glands, angiogenesis, increased matrix deposition in the airway wall, increased airway smooth muscle mass, wall thickening and abnormalities in elastin. Genetic influences, as well as fetal and early life exposures, may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of disease and/or long-term uncontrolled inflammation. The increase in smooth muscle mass in both large and small airways probably occurs via multiple mechanisms, and there are probably changes in the phenotype of smooth muscle cells, some showing enhanced synthetic capacity, others enhanced proliferation or contractility. Fixed airflow limitation is probably due to remodelling, whereas the importance of structural changes to the phenomenon of airways hyperresponsiveness may be dependent on the specific clinical phenotype of asthma evaluated. Reduced compliance of the airway wall secondary to enhanced matrix deposition may protect against airway narrowing. Conversely, in severe asthma, disruption of alveolar attachments and adventitial thickening may augment airway narrowing. The encroachment upon luminal area by submucosal thickening may be disadvantageous by increasing the risk of airway closure in the presence of the intraluminal cellular and mucus exudate associated with asthma exacerbations. Structural changes may increase airway narrowing by alteration of smooth muscle dynamics through limitation of the ability of the smooth muscle to periodically lengthen.

scholarly journals Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-β/Smad2/3 pathway intensification and antifibrotic TGF-β/Smad1/5/(8)9 pathway impairment

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dawid Wnuk ◽  
Milena Paw ◽  
Karolina Ryczek ◽  
Grażyna Bochenek ◽  
Krzysztof Sładek ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Bronchial Asthma ◽  
Small Molecule ◽  
Structural Changes ◽  
Signalling Pathways ◽  
Airway Remodelling ◽  
Bronchial Wall ◽  
First Time ◽  
Subepithelial Fibrosis

Abstract Airway remodelling with subepithelial fibrosis, which abolishes the physiological functions of the bronchial wall, is a major issue in bronchial asthma. Human bronchial fibroblasts (HBFs) derived from patients diagnosed with asthma display in vitro predestination towards TGF-β1-induced fibroblast-to-myofibroblast transition (FMT), a key event in subepithelial fibrosis. As commonly used anti-asthmatic drugs do not reverse the structural changes of the airways, and the molecular mechanism of enhanced asthma-related TGF-β1-induced FMT is poorly understood, we investigated the balance between the profibrotic TGF-β/Smad2/3 and the antifibrotic TGF-β/Smad1/5/9 signalling pathways and its role in the myofibroblast formation of HBF populations derived from asthmatic and non-asthmatic donors. Our findings showed for the first time that TGF-β-induced activation of the profibrotic Smad2/3 signalling pathway was enhanced, but the activation of the antifibrotic Smad1/5/(8)9 pathway by TGF-β1 was significantly diminished in fibroblasts from asthmatic donors compared to those from their healthy counterparts. The impairment of the antifibrotic TGF-β/Smad1/5/(8)9 pathway in HBFs derived from asthmatic donors was correlated with enhanced FMT. Furthermore, we showed that Smad1 silencing in HBFs from non-asthmatic donors increased the FMT potential in these cells. Additionally, we demonstrated that activation of antifibrotic Smad signalling via BMP7 or isoliquiritigenin [a small-molecule activator of the TGF-β/Smad1/5/(8)9 pathway] administration prevents FMT in HBFs from asthmatic donors through downregulation of profibrotic genes, e.g., α-SMA and fibronectin. Our data suggest that influencing the balance between the antifibrotic and profibrotic TGF-β/Smad signalling pathways using BMP7-mimetic compounds presents an unprecedented opportunity to inhibit subepithelial fibrosis during airway remodelling in asthma.

scholarly journals Sugar Prices vs. Financial Market Uncertainty in the Time of Crisis: Does COVID-19 Induce Structural Changes in the Relationship?

Agriculture ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 93
Author(s):  
Pavel Kotyza ◽  
Katarzyna Czech ◽  
Michał Wielechowski ◽  
Luboš Smutka ◽  
Petr Procházka
Keyword(s):  
Financial Crisis ◽  
Stock Market ◽  
Financial Market ◽  
Structural Breaks ◽  
Structural Changes ◽  
Global Financial Crisis ◽  
Market Uncertainty ◽  
Volatility Index ◽  
The Global Financial Crisis ◽  
The Relationship

Securitization of the agricultural commodity market has accelerated since the beginning of the 21st century, particularly in the times of financial market uncertainty and crisis. Sugar belongs to the group of important agricultural commodities. The global financial crisis and the COVID-19 pandemic has caused a substantial increase in the stock market volatility. Moreover, the novel coronavirus hit both the sugar market’s supply and demand side, resulting in sugar stock changes. The paper aims to assess potential structural changes in the relationship between sugar prices and the financial market uncertainty in a crisis time. In more detail, using sequential Bai–Perron tests for structural breaks, we check whether the global financial crisis and the COVID-19 pandemic have induced structural breaks in that relationship. Sugar prices are represented by the S&P GSCI Sugar Index, while the S&P 500 option-implied volatility index (VIX) is used to show stock market uncertainty. To investigate the changes in the relationship between sugar prices and stock market uncertainty, a regression model with a sequential Bai–Perron test for structural breaks is applied for the daily data from 2000–2020. We reveal the existence of two structural breaks in the analysed relationship. The first breakpoint was linked to the global financial crisis outbreak, and the second occurred in December 2011. Surprisingly, the COVID-19 pandemic has not induced the statistically significant structural change. Based on the regression model with Bai–Perron structural changes, we show that from 2000 until the beginning of the global financial crisis, the relationship between the sugar prices and the financial market uncertainty was insignificant. The global financial crisis led to a structural change in the relationship. Since August 2008, we observe a significant and negative relationship between the S&P GSCI Sugar Index and the S&P 500 option-implied volatility index (VIX). Sensitivity analysis conducted for the different financial market uncertainty measures, i.e., the S&P 500 Realized Volatility Index confirms our findings.

scholarly journals Electronic Circular Dichroism of the Cas9 Protein and gRNA:Cas9 Ribonucleoprotein Complex

2021 ◽  
Vol 22 (6) ◽  
pp. 2937
Author(s):  
Monika Halat ◽  
Magdalena Klimek-Chodacka ◽  
Jagoda Orleanska ◽  
Malgorzata Baranska ◽  
Rafal Baranski
Keyword(s):  
Circular Dichroism ◽  
Conformational Changes ◽  
Structural Changes ◽  
Electronic Circular Dichroism ◽  
Guide Rna ◽  
Cas9 Protein ◽  
Rnp Complex ◽  
Characteristic Features ◽  
Circular Dichroïsm

The Streptococcus pyogenes Cas9 protein (SpCas9), a component of CRISPR-based immune system in microbes, has become commonly utilized for genome editing. This nuclease forms a ribonucleoprotein (RNP) complex with guide RNA (gRNA) which induces Cas9 structural changes and triggers its cleavage activity. Here, electronic circular dichroism (ECD) spectroscopy was used to confirm the RNP formation and to determine its individual components. The ECD spectra had characteristic features differentiating Cas9 and gRNA, the former showed a negative/positive profile with maxima located at 221, 209 and 196 nm, while the latter revealed positive/negative/positive/negative pattern with bands observed at 266, 242, 222 and 209 nm, respectively. For the first time, the experimental ECD spectrum of the gRNA:Cas9 RNP complex is presented. It exhibits a bisignate positive/negative ECD couplet with maxima at 273 and 235 nm, and it differs significantly from individual spectrum of each RNP components. Additionally, the Cas9 protein and RNP complex retained biological activity after ECD measurements and they were able to bind and cleave DNA in vitro. Hence, we conclude that ECD spectroscopy can be considered as a quick and non-destructive method of monitoring conformational changes of the Cas9 protein as a result of Cas9 and gRNA interaction, and identification of the gRNA:Cas9 RNP complex.

scholarly journals Type B trichothecenes-the relationship between slight structural changes and toxicity

2016 ◽  
Vol 66 (1) ◽  
pp. 45-55
Author(s):  
Tadahiro Suzuki ◽  
Yumiko Iwahashi
Keyword(s):  
Structural Changes ◽  
Type B ◽  
The Relationship

Characteristic features of cockroach hypersensitivity in Turkish asthmatic patients

Allergy ◽  
1998 ◽  
Vol 53 (9) ◽  
pp. 870-873 ◽  
Author(s):  
D. Mungan ◽  
G. Çelik ◽  
B. Sin ◽  
S. Bavbek ◽  
Y. Demirel ◽  
...  
Keyword(s):  
Asthmatic Patients ◽  
Characteristic Features

SOFTWARE FOR CONTROL SYSTEMS FOR «SMART» RESIDENTIAL BUILDING

2021 ◽  
Vol 14 (1) ◽  
pp. 58-67
Author(s):  
Sergey Polyakov ◽  
V. Akimov ◽  
A. Polukazakov ◽  
Vladimir Zolnikov ◽  
P. Enin
Keyword(s):  
Structural Changes ◽  
Life Support ◽  
Assembly Language ◽  
Experimental Studies ◽  
Residential Building ◽  
Heating System ◽  
Liquid Level ◽  
Virtual Object ◽  
Level Control ◽  
The Relationship

The article deals with the issues of modeling and management of life support systems of a residential building. The resulting model of the liquid level in the tank allows you to establish the relationship between the level and the flow rate of the liquid. The results of the selection and justification of the fluid level control structure are presented. An algorithm that implements the operation of a virtual object is given. The structure of the automatic control system (ACS) of the liquid level is technically implemented in an open type. The results confirming the achievability of the proposed structural changes are obtained. The results of experimental studies are presented. The choice and justification of the method of controlling the heating system and the liquid level in the tank are considered. Programs for managing subsystems of a residential building in Assembly language, C++, and ladder diagrams are presented. A model for controlling the liquid level in a Multisim environment is proposed.

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