Airway remodelling: the future

Lp, Boulet; Sterk, PJ

doi:10.1183/09031936.00110107

Cited by 35 publications

(31 citation statements)

References 48 publications

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“…The inflammatory process in allergic asthma is typically characterized by increased numbers of Th2 lymphocytes, eosinophils, and activated mast cells. A variety of structural changes in and around the airways, collectively termed airway remodeling, are also observed (4,7,10,39,43). These include mucus metaplasia of goblet cells, hyperplasia and hypertrophy of airway smooth muscle cells, excessive angiogenesis, and airway fibrosis (2).…”

mentioning

confidence: 98%

“…These include mucus metaplasia of goblet cells, hyperplasia and hypertrophy of airway smooth muscle cells, excessive angiogenesis, and airway fibrosis (2). Airway fibrosis reflects the accumulation, activation, and differentiation of fibroblasts which elaborate type I collagen and other extracellular matrix proteins in the subepithelial region of the small airways (4,5,43).…”

mentioning

confidence: 99%

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Airway remodeling in murine asthma correlates with a defect in PGE₂synthesis by lung fibroblasts

Stumm

Wettlaufer

Jancar

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Asthma is a chronic lung disease characterized by local inflammation that can result in structural alterations termed airway remodeling. One component of airway remodeling involves fibroblast accumulation and activation, resulting in deposition of collagen I around small bronchi. Prostaglandin E(2) (PGE(2)) is the main eicosanoid lipid mediator produced by lung fibroblasts, and it exerts diverse anti-fibrotic actions. Dysregulation of the PGE(2) synthesis/response axis has been identified in human pulmonary fibrotic diseases and implicated in the pathogenesis of animal models of lung parenchymal fibrosis. Here we investigated the relationship between the fibroblast PGE(2) axis and airway fibrosis in an animal model of chronic allergic asthma. Airway fibrosis increased progressively as the number of airway challenges with antigen increased from 3 to 7 to 12. Compared with cells from control lungs, fibroblasts grown from the lungs of asthmatic animals, regardless of challenge number, exhibited no defect in the ability of PGE(2) or its analogs to inhibit cellular proliferation and collagen I expression. This correlated with intact expression of the EP(2) receptor, which is pivotal for PGE(2) responsiveness. However, cytokine-induced upregulation of PGE(2) biosynthesis as well as expression of cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 declined with increasing numbers of antigen challenges. In addition, treatment with the COX-2-selective inhibitor nimesulide potentiated the degree of airway fibrosis following repeated allergen challenge. Because endogenous COX-2-derived PGE(2) acts as a brake on airway fibrosis, the inability of fibroblasts to upregulate PGE(2) generation in the inflammatory milieu presented by repeated allergen exposure could contribute to the airway remodeling and fibrosis observed in chronic asthma.

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confidence: 98%

mentioning

confidence: 99%

Airway remodeling in murine asthma correlates with a defect in PGE₂synthesis by lung fibroblasts

Stumm

Wettlaufer

Jancar

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Airway remodeling (5)(6)(7)(8) , airway inflammation (9) , epithelial-mesenchymal interactions (10;11) , severe asthma (12) , and longitudinal changes of lung function (13) , have also been reviewed elsewhere. In this review, evidence that an irreversible component develops as asthma evolves or progresses, potential mechanisms underlying disease progression, and limitations to existing models will be discussed.…”

Section: Introductionmentioning

confidence: 99%

The irreversible component of persistent asthma

2009

Journal of Allergy and Clinical Immunology

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Irreversible airflow obstruction or limitation occurs in some patients with asthma, may develop early in life and becomes more common as asthma becomes more severe. Efforts to understand irreversible airflow obstruction or limitation have been hampered by the lack of a standardized definition of the phenotype and by the lack of appropriate research models. Unfortunately, it appears that currently available asthma treatments do not prevent this important asthma complication. Herein, the evidence of an irreversible component of asthma, its underlying pathology and the limitations of current asthma treatments are reviewed.

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“…Genetic disposition, atopic state, and interactions with many external stimuli may play roles, however. The principle of remodeling mainly consists of changes in bronchial epithelium properties, which include multiplication of goblet cells (GC), thickening of the basement membrane [BM; predominantly in the reticular lamina (RL) area], differentiation and activation of myofibroblasts, smooth muscle cell proliferation in the airway walls, growth of submucosal glands, deposition of extracellular proteins into the lamina propria mucosae, and vascularization changes [3,4,5]. …”

Section: Introductionmentioning

confidence: 99%

Airway Wall Remodeling in Young and Adult Rats with Experimentally Provoked Bronchial Asthma

Uhlı́k¹,

Šimůnková²,

Žaloudíková

et al. 2014

Int Arch Allergy Immunol

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Background: Airway wall remodeling is a typical finding in patients suffering from bronchial asthma. While morphological changes have been thoroughly described in adults, less is known about such changes in children because of the limited accessibility of relevant material. To overcome this constraint, animal asthma models may be used instead of human specimens. This study examined rats with artificially stimulated chronic asthma-like symptoms. Methods: Brown Norway rats of two age categories (young and adult) were sensitized by ovalbumin (OA), and their intrapulmonary airways (IA) were studied using morphometric and histochemical methods. Results: OA administration induced a significant increase in lung resistance in young animals but not in adults. The total IA wall area was significantly increased in both young and adult OA rats. In young animals, thickening of the adventitia played a more crucial role in this increase than it did in adults, in which the mucosa and the submucosa participated to a higher degree. The IA walls of young OA rats had significantly higher levels of infiltrating eosinophils than those of adult OA animals. The multiplication of goblet cells was more pronounced in adult rats, which was associated with a tendency to produce a higher proportion of acidic glycoconjugates. Conclusions: OA stimulation affected the IA of young rats differently than those of adult animals. Changes in the outer IA layer of young rats can be triggered by activated eosinophils; however, stimulated airway epithelium can be a source of factors that influence the inner IA layers in adult rats.

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Airway remodelling: the future

Cited by 35 publications

References 48 publications

Airway remodeling in murine asthma correlates with a defect in PGE₂synthesis by lung fibroblasts

Airway remodeling in murine asthma correlates with a defect in PGE₂synthesis by lung fibroblasts

The irreversible component of persistent asthma

Airway Wall Remodeling in Young and Adult Rats with Experimentally Provoked Bronchial Asthma

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Airway remodelling: the future

Cited by 35 publications

References 48 publications

Airway remodeling in murine asthma correlates with a defect in PGE2synthesis by lung fibroblasts

Airway remodeling in murine asthma correlates with a defect in PGE2synthesis by lung fibroblasts

The irreversible component of persistent asthma

Airway Wall Remodeling in Young and Adult Rats with Experimentally Provoked Bronchial Asthma

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Product

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Airway remodeling in murine asthma correlates with a defect in PGE₂synthesis by lung fibroblasts

Airway remodeling in murine asthma correlates with a defect in PGE₂synthesis by lung fibroblasts