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.

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 New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Giuseppe Spaziano ◽  
Donato Cappetta ◽  
Konrad Urbanek ◽  
Elena Piegari ◽  
Grazia Esposito ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Macrophage Polarization ◽  
Airflow Obstruction ◽  
Local Environment ◽  
Inflammatory Cells ◽  
Cell Contact

Structural changes contribute to airway hyperresponsiveness and airflow obstruction in asthma. Emerging evidence points to the involvement of c-kit+ cells in lung homeostasis, although their potential role in asthma is unknown. Our aim was to isolate c-kit+ cells from normal mouse lungs and to test whether these cells can interfere with hallmarks of asthma in an animal model. Adult mouse GFP-tagged c-kit+ cells, intratracheally delivered in the ovalbumin-induced airway hyperresponsiveness, positively affected airway remodeling and improved airway function. In bronchoalveolar lavage fluid of cell-treated animals, a reduction in the number of inflammatory cells and in IL-4, IL-5, and IL-13 release, along with an increase of IL-10, was observed. In MSC-treated mice, the macrophage polarization to M2-like subset may explain, at least in part, the increment in the level of anti-inflammatory cytokine IL-10. After in vitro stimulation of c-kit+ cells with proinflammatory cytokines, the indoleamine 2,3-dioxygenase and TGFβ were upregulated. These data, together with the increased apoptosis of inflammatory cells in vivo, indicate that c-kit+ cells downregulate immune response in asthma by influencing local environment, possibly by cell-to-cell contact combined to paracrine action. In conclusion, intratracheally administered c-kit+ cells reduce inflammation, positively modulate airway remodeling, and improve function. These data document previously unrecognized properties of c-kit+ cells, able to impede pathophysiological features of experimental airway hyperresponsiveness.

Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes

Respiration ◽  
2020 ◽  
pp. 1-11
Author(s):  
Louis-Philippe Boulet ◽  
Marie-Eve Boulay ◽  
Harvey O. Coxson ◽  
Cameron J. Hague ◽  
Joanne Milot ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Obstruction ◽  
Airway Inflammation ◽  
Wall Thickness ◽  
Structural Changes ◽  
Smoking History ◽  
Airway Wall ◽  
Tobacco Exposure ◽  
Airway Wall Thickness ◽  
Irreversible Airway Obstruction

<b><i>Background:</i></b> The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. <b><i>Objective:</i></b> To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. <b><i>Methods:</i></b> We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with &#x3c;5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. <b><i>Results:</i></b> Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (<i>p</i> = 0.0242). Visual analysis showed a higher prevalence of emphysema (<i>p</i> = 0.0001) and higher emphysema score (<i>p</i> &#x3c; 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. <b><i>Conclusions:</i></b> Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.

scholarly journals Airway wall thickness associated with forced expiratory volume in 1 second decline and development of airflow limitation

2015 ◽  
Vol 45 (3) ◽  
pp. 644-651 ◽  
Author(s):  
Firdaus A.A. Mohamed Hoesein ◽  
Pim A. de Jong ◽  
Jan-Willem J. Lammers ◽  
Willem P.T.M. Mali ◽  
Michael Schmidt ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Forced Expiratory Volume ◽  
Airflow Limitation ◽  
Airway Wall ◽  
Lung Function Decline ◽  
Wall Area ◽  
Percentile Method ◽  
Airway Wall Thickness ◽  
Fev1 Decline

Airway wall thickness and emphysema contribute to airflow limitation.We examined their association with lung function decline and development of airflow limitation in 2021 male smokers with and without airflow limitation. Airway wall thickness and emphysema were quantified on chest computed tomography and expressed as the square root of wall area of a 10-mm lumen perimeter (Pi10) and the 15th percentile method (Perc15), respectively. Baseline and follow-up (median (interquartile range) 3 (2.9–3.1) years) spirometry was available.Pi10 and Perc15 correlated with baseline forced expiratory volume in 1 s (FEV1) (r= −0.49 and 0.11, respectively (p<0.001)). Multiple linear regression showed that Pi10 and Perc15 at baseline were associated with a lower FEV1 after follow-up (p<0.05). For eachsdincrease in Pi10 and decrease in Perc15 the FEV1 decreased by 20 mL and 30.2 mL, respectively. The odds ratio for developing airflow limitation after 3 years was 2.45 for a 1-mm higher Pi10 and 1.46 for a 10-HU lower Perc15 (p<0.001).A greater degree of airway wall thickness and emphysema was associated with a higher FEV1 decline and development of airflow limitation after 3 years of follow-up.

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.

scholarly journals Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Fang Liu ◽  
Nan-Xia Xuan ◽  
Song-Min Ying ◽  
Wen Li ◽  
Zhi-Hua Chen ◽  
...  
Keyword(s):  
Asthma Control ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Herbal Medicines ◽  
Allergic Airway Inflammation ◽  
Inhaled Corticosteroid ◽  
Mechanistic Studies ◽  
Alternative Medicines ◽  
Long Acting ◽  
Reversible Airflow Obstruction

Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long actingβ2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control.

scholarly journals Heterogeneity of airway wall dimensions in humans: a critical determinant of lung function in asthmatics and nonasthmatics

2017 ◽  
Vol 312 (3) ◽  
pp. L425-L431 ◽  
Author(s):  
Christopher D. Pascoe ◽  
Chun Y. Seow ◽  
Tillie L. Hackett ◽  
Peter D. Paré ◽  
Graham M. Donovan
Keyword(s):  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Small Airways ◽  
Airway Wall ◽  
Critical Determinant ◽  
Mean Values ◽  
Airway Narrowing ◽  
Wall Area ◽  
First Time ◽  
Fixed Airflow Obstruction

Airway remodeling, a key feature of asthma, alters every layer of the airway wall but most strikingly the airway smooth muscle (ASM) layer. Airway remodeling in asthmatics contributes to fixed airflow obstruction and can amplify airway narrowing caused by ASM activation. Previous modeling studies have shown that the increase in ASM mass has the largest effect on increasing maximal airway narrowing. Simulated heterogeneity in the dimensions and properties of the airway wall can further amplify airway narrowing. Using measurements made on histological sections from donor lungs, we show for the first time that there is profound heterogeneity of ASM area and wall area in both nonasthmatics and asthmatics. Using a mathematical model, we found that this heterogeneity, together with changes in the mean values, contributes to an increased baseline resistance and elastance in asthmatics as well as a leftward shift in the responsiveness of the airways to a simulated agonist in both nonasthmatics and asthmatics. The ability of heterogeneous wall dimensions to shift the dose-response curve is largely due to an increased susceptibility for the small airways to close. This research confirms that heterogeneity of airway wall dimensions can contribute to exaggerated airway narrowing and provides an actual assessment of the magnitude of these effects.

scholarly journals Extracellular Vesicles and Asthma—More Than Just a Co-Existence

2021 ◽  
Vol 22 (9) ◽  
pp. 4984
Author(s):  
Bilal Alashkar Alhamwe ◽  
Daniel P. Potaczek ◽  
Sarah Miethe ◽  
Fahd Alhamdan ◽  
Lukas Hintz ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Association Studies ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Cell Communication ◽  
Therapeutic Interventions ◽  
Inflammatory Disorder ◽  
Diagnostic Potential ◽  
Functional Relevance ◽  
Reversible Airflow Obstruction

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.

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