Airway Remodeling in Asthma: Therapeutic Implications of Mechanisms

Homer, Robert J.; Elias, Jack A.

doi:10.1152/physiol.00035.2004

Cited by 108 publications

(105 citation statements)

References 104 publications

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“…In addition, chronic inflammation can cause tissue injury and structural changes, collectively referred to as remodeling. Airway remodeling is characterized by increased wall thickness, subepithelial fibrosis, smooth muscle hypertrophy and hyperplasia, epithelial mucus metaplasia, increased vascularity, and abnormalities in extracellular matrix composition (40). These structural changes may account for some characteristics of asthmatic physiology that are poorly addressed by current anti-inflammatory treatment (41).…”

Section: Airway Inflammationmentioning

confidence: 99%

“…These structural changes may account for some characteristics of asthmatic physiology that are poorly addressed by current anti-inflammatory treatment (41). Airway wall thickness correlates with disease severity and length of time with disease, while smooth muscle thickness correlates with fatal versus nonfatal asthma (40). Airway remodeling has been proposed to explain aspects of asthma severity, such as airway hyperresponsiveness and fixed airway obstruction (41).…”

Section: Airway Inflammationmentioning

confidence: 99%

“…A cycle beginning with Th2 inflammation and culminating in remodeling has been described. ASM cells are directly involved in this cycle, perpetuating lung inflammation (40). In addition, human ASM cells in culture can also produce several compounds implicated in remodeling, including fibronectin, laminin, percelan, chondroitin, and vascular endothelial growth factor (42,43,45,46).…”

Section: Airway Inflammationmentioning

confidence: 99%

“…Data exist suggesting that epithelial damage participates in the pro-inflammatory process by releasing cytokines, growth factors, and mediators (40,52). Epithelial damage induces up-regulation of receptors, specifically members of the EGFR family that drive proliferation and repair.…”

Section: Epithelial-mesenchymal Unitmentioning

confidence: 99%

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Asthma: where is it going?

Faffe¹

2008

Braz J Med Biol Res

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Asthma is characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. Although our understanding of its pathophysiological mechanisms continues to evolve, the relative contributions of airway hyperresponsiveness and inflammation are still debated. The first mechanism identified as important for asthma was bronchial hyperresponsiveness. In a second step, asthma was recognized also as an inflammatory disease, with chronic inflammation inducing structural changes or remodeling. However, persistence of airway dysfunction despite inflammatory control is observed in chronic severe asthma of both adults and children. More recently, a potential role for epithelial-mesenchymal communication or transition is emerging, with epithelial injury often resulting in a self-sustaining phenotype of wound repair modulation by activation/ reactivation of the epithelial-mesenchymal trophic unit, suggesting that chronic asthma can be more than an inflammatory disease. It is noteworthy that the gene-environmental interactions critical for the development of a full asthma phenotype involve processes similar to those occurring in branching morphogenesis. In addition, a central role for airway smooth muscle in the pathogenesis of the disease has been explored, highlighting its secretory function as well as different intrinsic properties compared to normal subjects. These new concepts can potentially shed light on the mechanisms underlying some asthma phenotypes and improve our understanding of the disease in terms of the therapeutic strategies to be applied. How we understand asthma and its mechanisms along time will be the focus of this overview.

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Section: Airway Inflammationmentioning

confidence: 99%

Section: Airway Inflammationmentioning

confidence: 99%

Section: Airway Inflammationmentioning

confidence: 99%

Section: Epithelial-mesenchymal Unitmentioning

confidence: 99%

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Asthma: where is it going?

Faffe¹

2008

Braz J Med Biol Res

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“…Recent reports in mutant eosinophil-deleted mice established that these mice did not exhibit signs of airway remodeling, even after continuous antigen challenge (Lee et al 2004;Humbles et al 2004). Airway remodeling in asthma involves well-defined chronic structural airway changes, including glandular increases within the airways, enhanced collagen deposition within the lamina propria, and an increase in the airway vasculature in conjunction with airway smooth muscle hypertrophy and hyperplasia (Holgate 2002;Homer and Elias 2005;Pascual and Peters 2005). While the above pathology is characteristic of asthma, diagnostic approaches to airway remodeling are now developing, for example using high-resolution CT scanning (Jaffuel et al 2001).…”

Section: Strategies Used To Develop Anti-allergic Drugs Active At Nr4mentioning

confidence: 99%

The NR4A nuclear receptor family in eosinophils

Hashida¹,

Ohkura²,

Saito

et al. 2006

J Hum Genet

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It is well-known that many members of the family of nuclear receptors have been implicated in human diseases, and metabolic disorders in particular. The NR4A nuclear receptor family consists of three members, Nur77, Nurr1, and NOR1. All of these are orphan receptors, and Nur77 and NOR1 exert possible pathological roles in immune diseases through the modulation of leukocyte functions. CD30 stimulation, which induces eosinophil-specific apoptosis, markedly enhances expression of Nur77 and NOR1 in eosinophils. This suggests the possibility of pharmacological modulation of Nur77-or NOR1-specific apoptotic pathways via receptor-dependent transactivation. In this review, we discuss treatment of allergic diseases by low molecular weight compounds acting through the NR4A receptor family to cause eosinophil apoptosis. NR4A nuclear receptor genes were selected following comprehensive analysis of differentially expressed genes in eosinophils of atopic dermatitis patients compared with healthy volunteers.

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Profibrotic and Angiogenic Factors in Asthma

Berkman

Levi‐Schaffer

2011

Inflammation and Allergy Drug Design

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Airway Remodeling in Asthma: Therapeutic Implications of Mechanisms

Cited by 108 publications

References 104 publications

Asthma: where is it going?

Asthma: where is it going?

The NR4A nuclear receptor family in eosinophils

Profibrotic and Angiogenic Factors in Asthma

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