scholarly journals Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma

2020 ◽  
Vol 21 (3) ◽  
pp. 757 ◽  
Author(s):  
Lei Fang ◽  
Qinzhu Sun ◽  
Michael Roth
Keyword(s):  
Allergic Asthma ◽  
Immune Cells ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Airway Wall ◽  
Epigenetic Events ◽  
Wide Range ◽  
Direct Binding ◽  
Tissue Cells ◽  
Definition Of

Asthma increases worldwide without any definite reason and patient numbers double every 10 years. Drugs used for asthma therapy relax the muscles and reduce inflammation, but none of them inhibited airway wall remodeling in clinical studies. Airway wall remodeling can either be induced through pro-inflammatory cytokines released by immune cells, or direct binding of IgE to smooth muscle cells, or non-immunological stimuli. Increasing evidence suggests that airway wall remodeling is initiated early in life by epigenetic events that lead to cell type specific pathologies, and modulate the interaction between epithelial and sub-epithelial cells. Animal models are only available for remodeling in allergic asthma, but none for non-allergic asthma. In human asthma, the mechanisms leading to airway wall remodeling are not well understood. In order to improve the understanding of this asthma pathology, the definition of “remodeling” needs to be better specified as it summarizes a wide range of tissue structural changes. Second, it needs to be assessed if specific remodeling patterns occur in specific asthma pheno- or endo-types. Third, the interaction of the immune cells with tissue forming cells needs to be assessed in both directions; e.g., do immune cells always stimulate tissue cells or are inflamed tissue cells calling immune cells to the rescue? This review aims to provide an overview on immunologic and non-immunologic mechanisms controlling airway wall remodeling in asthma.

scholarly journals Repeated airway constrictions in mice do not alter respiratory function

2018 ◽  
Vol 124 (6) ◽  
pp. 1483-1490 ◽  
Author(s):  
Samuel Mailhot-Larouche ◽  
Louis Deschênes ◽  
Morgan Gazzola ◽  
Katherine Lortie ◽  
Cyndi Henry ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Respiratory System ◽  
Structural Changes ◽  
Respiratory Mechanics ◽  
Airway Remodeling ◽  
Structural Components ◽  
Airway Wall ◽  
Cell Hyperplasia ◽  
Shed Light

It is suggested that the frequent strain the airways undergo in asthma because of repeated airway smooth muscle (ASM)-mediated constrictions contributes to airway wall remodeling. However, the effects of repeated constrictions on airway remodeling, as well as the ensuing impact of this presumptive remodeling on respiratory mechanics, have never been investigated in subjects without asthma. In this study, we set out to determine whether repeated constrictions lead to features that are reminiscent of asthma in mice without asthma. BALB/c mice were subjected to a 30-min constriction elicited by aerosolized methacholine every other day over 6 wk. Forty-eight hours after the last constriction, the mechanics of the respiratory system was evaluated at baseline and in response to incremental doses of nebulized methacholine with the flexiVent. The whole-lung lavages, the tracheas, and the lungs were also collected to evaluate inflammation, the contractile capacity of ASM, and the structural components of the airway wall, respectively. The resistance and the compliance of the respiratory system, as well as the Newtonian resistance and the resistive and elastic properties of the lung tissue, were not affected by repeated constrictions, both at baseline and in response to methacholine. All the other examined features also remained unaltered, except the number of goblet cells in the epithelium and the number of macrophages in the whole-lung lavages, which both increased with repeated constrictions. This study demonstrates that, despite causing goblet cell hyperplasia and a mild macrophagic inflammation, repeated constrictions with methacholine do not lead to structural changes that adversely impact the physiology. NEW & NOTEWORTHY Repeated airway constrictions led to signs of remodeling that are typically observed in asthma, which neither altered respiratory mechanics nor the contractile capacity of airway smooth muscle. These findings shed light on a debate between those claiming that constrictions induce remodeling and those convinced that methacholine challenges are harmless. Insofar as our results with mice relate to humans, the findings indicate that repeated challenges with methacholine can be performed safely.

Structural basis for exaggerated airway narrowingThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

2007 ◽  
Vol 85 (7) ◽  
pp. 653-658 ◽  
Author(s):  
Peter D. Paré ◽  
Brent E. McParland ◽  
Chun Y. Seow
Keyword(s):  
Airway Hyperresponsiveness ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Structural Basis ◽  
Airway Wall ◽  
Special Issue ◽  
Airway Narrowing ◽  
Quantitative Changes ◽  
Or Organization ◽  
Selection Of

Airway hyperresponsiveness, particularly the ability of airways to narrow excessively in response to stimuli that normally cause little airway narrowing in nonasthmatic subjects, is a characteristic feature of asthma and the basis of its symptoms. Although airway hyperresponsiveness may be partly the result of alterations in the contractile phenotype of the airway smooth muscle, there is evidence that it may also be caused by structural changes in the airway wall, collectively termed airway remodeling. Airway remodeling is defined as changes in composition, quantity, and (or) organization of cellular and molecular constituents of the airway wall. Airway wall remodeling that occurs in asthma can result in functional alterations because of quantitative changes in airway wall compartments, and (or) because of changes in the biochemical composition or material properties of the various constituents of the airway wall. This brief review summarizes the quantitative changes in the dimensions and organization of the airway wall compartments that have been described and explains how structural alterations may lead to the exaggerated airway narrowing.

scholarly journals Airway remodeling in asthma

2001 ◽  
Vol 41 (3) ◽  
pp. 125
Author(s):  
Roni Naning ◽  
MTS Darmawan
Keyword(s):  
Lung Function ◽  
Combination Therapy ◽  
Airway Obstruction ◽  
Chronic Inflammation ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Airway Wall ◽  
Inhaled Corticosteroid ◽  
Irreversible Airway Obstruction

Airway remodeling is the term given to a series of structural changes characterized by chronic, irreversible airway obstruction. Structural changes in the airway wall caused by chronic inflammation of asthma. Evidence for asthma airway remodeling demonstrating an accelerated decline of lung function that cannot be completely reversed with therapy. Combination therapy produced at least as much protection against inflammation as theuse of the higher dose of the inhaled corticosteroid.

scholarly journals The Three A’s in Asthma – Airway Smooth Muscle, Airway Remodeling & Angiogenesis

2015 ◽  
Vol 9 (1) ◽  
pp. 70-80 ◽  
Author(s):  
L.F. Keglowich ◽  
P. Borger
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Vascular Density ◽  
Airway Wall ◽  
Cell Hyperplasia ◽  
Asthma Symptoms ◽  
Basement Membrane Thickening ◽  
Cell Shedding

Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet cell hyperplasia, hyperplasia and hypertrophy of the airway smooth muscle (ASM) bundles, basement membrane thickening and increased vascular density. Airway wall remodeling starts early in the pathogenesis of asthma and today it is suggested that remodeling is a prerequisite for other asthma pathologies. The beneficial effect of bronchial thermoplasty in reducing asthma symptoms, together with the increased potential of ASM cells of asthmatics to produce inflammatory and angiogenic factors, indicate that the ASM cell is a major effector cell in the pathology of asthma. In the present review we discuss the ASM cell and its role in airway wall remodeling and angiogenesis.

scholarly journals Mechanisms of Remodeling in Asthmatic Airways

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Adrian Shifren ◽  
Chad Witt ◽  
Chandrika Christie ◽  
Mario Castro
Keyword(s):  
Airway Hyperresponsiveness ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Asthma Treatment ◽  
Airway Wall ◽  
Lung Function Decline ◽  
Airway Wall Thickness ◽  
Asthma Patients ◽  
Reversible Airflow Obstruction

Asthma is a chronic inflammatory airway disorder characterized by airway hyperresponsiveness and reversible airflow obstruction. Subgroups of asthma patients develop airflow obstruction that is irreversible or only partially reversible and experience an accelerated rate of lung function decline. The structural changes in the airways of these patients are referred to as airway remodeling. All elements of the airway wall are involved, and remodeled airway wall thickness is substantially increased compared to normal control airways. Airway remodeling is thought to contribute to the subphenotypes of irreversible airflow obstruction and airway hyperresponsiveness, and it has been associated with increased disease severity. Reversal of remodeling is therefore of paramount therapeutic importance, and mechanisms responsible for airway remodeling are feasible therapeutic targets for asthma treatment. This paper will focus on our current understanding of the mechanisms of airway remodeling in asthma and potential targets for future intervention.

Typologization of security regulation

2020 ◽  
pp. 20-27
Author(s):  
Denis Tikhomirov
Keyword(s):  
Social Relations ◽  
Scientific Literature ◽  
Legal Regulation ◽  
Procedural Understanding ◽  
Limited Ability ◽  
Methodological Basis ◽  
Wide Range ◽  
The Subject ◽  
Definition Of ◽  
Legal Understanding

The purpose of the article is to typologize terminological definitions of security, to find out the general, to identify the originality of their interpretations depending on the subject of legal regulation. The methodological basis of the study is the methods that made it possible to obtain valid conclusions, in particular, the method of comparison, through which it became possible to correlate different interpretations of the term "security"; method of hermeneutics, which allowed to elaborate texts of normative legal acts of Ukraine, method of typologization, which made it possible to create typologization groups of variants of understanding of the term "security". Scientific novelty. The article analyzes the understanding of the term "security" in various regulatory acts in force in Ukraine. Typological groups were understood to understand the term "security". Conclusions. The analysis of the legal material makes it possible to confirm that the issues of security are within the scope of both legislative regulation and various specialized by-laws. However, today there is no single conception on how to interpret security terminology. This is due both to the wide range of social relations that are the subject of legal regulation and to the relativity of the notion of security itself and the lack of coherence of views on its definition in legal acts and in the scientific literature. The multiplicity of definitions is explained by combinations of material and procedural understanding, static - dynamic, and conditioned by the peculiarities of a particular branch of legal regulation, limited ability to use methods of one or another branch, the inter-branch nature of some variations of security, etc. Separation, common and different in the definition of "security" can be used to further standardize, in fact, the regulatory legal understanding of security to more effectively implement the legal regulation of the security direction.

Music after the Fall

2017 ◽  
Author(s):  
Tim Rutherford-Johnson
Keyword(s):  
New Media ◽  
Contemporary Music ◽  
The United States ◽  
Art Music ◽  
Sound Art ◽  
Musical Composition ◽  
Western Art ◽  
Wide Range ◽  
Definition Of ◽  
The Cold War

By the start of the 21st century many of the foundations of postwar culture had disappeared: Europe had been rebuilt and, as the EU, had become one of the world’s largest economies; the United States’ claim to global dominance was threatened; and the postwar social democratic consensus was being replaced by market-led neoliberalism. Most importantly of all, the Cold War was over, and the World Wide Web had been born. Music After The Fall considers contemporary musical composition against this changed backdrop, placing it in the context of globalization, digitization, and new media. Drawing on theories from the other arts, in particular art and architecture, it expands the definition of Western art music to include forms of composition, experimental music, sound art, and crossover work from across the spectrum, inside and beyond the concert hall. Each chapter considers a wide range of composers, performers, works, and institutions are considered critically to build up a broad and rich picture of the new music ecosystem, from North American string quartets to Lebanese improvisers, from South American electroacoustic studios to pianos in the Australian outback. A new approach to the study of contemporary music is developed that relies less on taxonomies of style and technique, and more on the comparison of different responses to common themes, among them permission, fluidity, excess, and loss.

scholarly journals Size-adjusted aortic valve area: refining the definition of severe aortic stenosis

2020 ◽  
Author(s):  
Branka Vulesevic ◽  
Naozumi Kubota ◽  
Ian G Burwash ◽  
Claire Cimadevilla ◽  
Sarah Tubiana ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Predictive Accuracy ◽  
Severe Aortic Stenosis ◽  
Aortic Valve Area ◽  
Obese Patients ◽  
Derivation Cohort ◽  
Wide Range ◽  
Definition Of ◽  
Diagnostic And Prognostic Value ◽  
Valve Area

Abstract Aims Severe aortic valve stenosis (AS) is defined by an aortic valve area (AVA) <1 cm2 or an AVA indexed to body surface area (BSA) <0.6 cm/m2, despite little evidence supporting the latter approach and important intrinsic limitations of BSA indexation. We hypothesized that AVA indexed to height (H) might be more applicable to a wide range of populations and body morphologies and might provide a better predictive accuracy. Methods and results In 1298 patients with degenerative AS and preserved ejection fraction from three different countries and continents (derivation cohort), we aimed to establish an AVA/H threshold that would be equivalent to 1.0 cm2 for defining severe AS. In a distinct prospective validation cohort of 395 patients, we compared the predictive accuracy of AVA/BSA and AVA/H. Correlations between AVA and AVA/BSA or AVA/H were excellent (all R2 > 0.79) but greater with AVA/H. Regressions lines were markedly different in obese and non-obese patients with AVA/BSA (P < 0.0001) but almost identical with AVA/H (P = 0.16). AVA/BSA values that corresponded to an AVA of 1.0 cm2 were markedly different in obese and non-obese patients (0.48 and 0.59 cm2/m2) but not with AVA/H (0.61 cm2/m for both). Agreement for the diagnosis of severe AS (AVA < 1 cm2) was significantly higher with AVA/H than with AVA/BSA (P < 0.05). Similar results were observed across the three countries. An AVA/H cut-off value of 0.6 cm2/m [HR = 8.2(5.6–12.1)] provided the best predictive value for the occurrence of AS-related events [absolute AVA of 1 cm2: HR = 7.3(5.0–10.7); AVA/BSA of 0.6 cm2/m2 HR = 6.7(4.4–10.0)]. Conclusion In a large multinational/multiracial cohort, AVA/H was better correlated with AVA than AVA/BSA and a cut-off value of 0.6 cm2/m provided a better diagnostic and prognostic value than 0.6 cm2/m2. Our results suggest that severe AS should be defined as an AVA < 1 cm2 or an AVA/H < 0.6 cm2/m rather than a BSA-indexed value of 0.6 cm2/m2.

scholarly journals Entangling Lattice-Trapped Bosons with a Free Impurity: Impact on Stationary and Dynamical Properties

Entropy ◽  
2021 ◽  
Vol 23 (3) ◽  
pp. 290
Author(s):  
Maxim Pyzh ◽  
Kevin Keiler ◽  
Simeon I. Mistakidis ◽  
Peter Schmelcher
Keyword(s):  
Structural Changes ◽  
Many Body ◽  
Wide Range ◽  
Entropy Measures ◽  
Particle Level ◽  
The Many ◽  
The One ◽  
Tunneling Dynamics ◽  
The Individual ◽  
Trapped Bosons

We address the interplay of few lattice trapped bosons interacting with an impurity atom in a box potential. For the ground state, a classification is performed based on the fidelity allowing to quantify the susceptibility of the composite system to structural changes due to the intercomponent coupling. We analyze the overall response at the many-body level and contrast it to the single-particle level. By inspecting different entropy measures we capture the degree of entanglement and intraspecies correlations for a wide range of intra- and intercomponent interactions and lattice depths. We also spatially resolve the imprint of the entanglement on the one- and two-body density distributions showcasing that it accelerates the phase separation process or acts against spatial localization for repulsive and attractive intercomponent interactions, respectively. The many-body effects on the tunneling dynamics of the individual components, resulting from their counterflow, are also discussed. The tunneling period of the impurity is very sensitive to the value of the impurity-medium coupling due to its effective dressing by the few-body medium. Our work provides implications for engineering localized structures in correlated impurity settings using species selective optical potentials.

Cubical Agda: A dependently typed programming language with univalence and higher inductive types

2021 ◽  
Vol 31 ◽  
Author(s):  
ANDREA VEZZOSI ◽  
ANDERS MÖRTBERG ◽  
ANDREAS ABEL
Keyword(s):  
Programming Language ◽  
Type Theory ◽  
Type Checking ◽  
Dependent Type Theory ◽  
Wide Range ◽  
General Schema ◽  
Direct Definition ◽  
Inductive Types ◽  
Definition Of ◽  
Cubical Type Theory

Abstract Proof assistants based on dependent type theory provide expressive languages for both programming and proving within the same system. However, all of the major implementations lack powerful extensionality principles for reasoning about equality, such as function and propositional extensionality. These principles are typically added axiomatically which disrupts the constructive properties of these systems. Cubical type theory provides a solution by giving computational meaning to Homotopy Type Theory and Univalent Foundations, in particular to the univalence axiom and higher inductive types (HITs). This paper describes an extension of the dependently typed functional programming language Agda with cubical primitives, making it into a full-blown proof assistant with native support for univalence and a general schema of HITs. These new primitives allow the direct definition of function and propositional extensionality as well as quotient types, all with computational content. Additionally, thanks also to copatterns, bisimilarity is equivalent to equality for coinductive types. The adoption of cubical type theory extends Agda with support for a wide range of extensionality principles, without sacrificing type checking and constructivity.

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