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Treatment of COPD: a matrix perspective.

ABSTRACT: Fundamental physical properties, such as the intrinsic recoil of the lung, are governed by the extracellular matrix. The prototypical roles of the matrix proteins, collagen and elastin, in pulmonary fibrosis and emphysema have long been recognized, and much research effort has been devoted to understanding mechanisms of extracellular matrix synthesis and turnover in the lung. Yet, despite extensive knowledge of the biochemical properties of collagen and elastin, none of the present clinical strategies for treating COPD directly target the extracellular matrix. From a matrix perspective, therapeutic interventions that limit elastic fiber destruction and/or restore function to damaged alveolar units merit particular consideration as clinical strategies for treating the emphysema component of COPD. Effective treatment of the bronchiolar component of COPD requires a better understanding of the relationship between airway fibrosis and airflow obstruction. Translating basic knowledge of extracellular matrix biology into the clinical venue will be essential in the development of new approaches to COPD treatment.

SUBMITTER: Dunsmore SE

PROVIDER: S-EPMC2528213 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Treatment of COPD: a matrix perspective.

Dunsmore Sarah E SE

International journal of chronic obstructive pulmonary disease 20080101 1

Fundamental physical properties, such as the intrinsic recoil of the lung, are governed by the extracellular matrix. The prototypical roles of the matrix proteins, collagen and elastin, in pulmonary fibrosis and emphysema have long been recognized, and much research effort has been devoted to understanding mechanisms of extracellular matrix synthesis and turnover in the lung. Yet, despite extensive knowledge of the biochemical properties of collagen and elastin, none of the present clinical stra ...[more]

PMID: 18488434

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Project description:Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-?, interferon-?, interleukin (IL)-1?, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-?. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD. The two largest studies that have been reported in the literature involve the use of blocking antibody to TNF? and CXCL8 (IL-8), and neither has provided benefit. Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either. Studies of antibodies against IL-17, IL-18, IL-1?, and TSLP are currently either being undertaken or planned. There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target. Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond.

Dataset Information

Treatment of COPD: a matrix perspective.

Publications

Treatment of COPD: a matrix perspective.

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