Novel therapeutic approaches for pulmonary fibrosis.
Novel therapeutic approaches for pulmonary fibrosis.
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DOI：
10.1111/j.1476-5381.2011.01247.x
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发表时间：
2011-05
影响因子：
7.3
通讯作者：
Chambers RC
中科院分区：
文献类型：
--
作者：
Datta A;Scotton CJ;Chambers RC
肺纤维化代表了许多异质性疾病的终末阶段，并且或多或少地是间质性肺病的标志。其特征在于细胞外基质蛋白在肺内的过度沉积，导致功能性肺泡单位的闭塞，并且在许多情况下，导致呼吸衰竭。虽然少数间质性肺病的病因已知，但大多数是特发性的，其中特发性肺纤维化是最常见的，预后令人震惊-诊断后的中位生存期不到3年。这反映了缺乏任何有效的治疗方法来改变疾病的进程，这反过来又表明我们对这种疾病的发病机制的理解不完全。目前流行的假说集中在失调的上皮-间充质相互作用，促进持续的上皮细胞损伤和成纤维细胞活化的循环，导致进行性纤维化。然而，很可能在影响炎症和伤口修复的无数生物学途径中的多种异常-包括基质调节、上皮重建、凝血级联、新血管形成和抗氧化剂途径-调节这种有缺陷的串扰并促进纤维形成。本综述旨在提供当前治疗背后的发病机理，简要概述以前和正在进行的临床试验，但将重点放在我们对特发性肺纤维化发病机制的理解方面的最新和令人兴奋的进展，这可能最终导致这种破坏性疾病的新型有效治疗干预措施的发展。这篇文章是呼吸药理学主题问题的一部分。要查看本期的其他文章，请访问http://dx.doi.org/10.1111/bph.2011.163.issue-1
Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of functional alveolar units and in many cases, respiratory failure. While a small number of interstitial lung diseases have known aetiologies, most are idiopathic in nature, and of these, idiopathic pulmonary fibrosis is the most common and carries with it an appalling prognosis – median survival from the time of diagnosis is less than 3 years. This reflects the lack of any effective therapy to modify the course of the disease, which in turn is indicative of our incomplete understanding of the pathogenesis of this condition. Current prevailing hypotheses focus on dysregulated epithelial–mesenchymal interactions promoting a cycle of continued epithelial cell injury and fibroblast activation leading to progressive fibrosis. However, it is likely that multiple abnormalities in a myriad of biological pathways affecting inflammation and wound repair – including matrix regulation, epithelial reconstitution, the coagulation cascade, neovascularization and antioxidant pathways – modulate this defective crosstalk and promote fibrogenesis. This review aims to offer a pathogenetic rationale behind current therapies, briefly outlining previous and ongoing clinical trials, but will focus on recent and exciting advancements in our understanding of the pathogenesis of idiopathic pulmonary fibrosis, which may ultimately lead to the development of novel and effective therapeutic interventions for this devastating condition. This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1
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DOI：
10.1165/rcmb.2002-0009oc
发表时间：
2002-10-01
影响因子：
6.4
作者：
Belperio, JA;Dy, M;Keane, MP
通讯作者：
Keane, MP
影响因子：
24.3
作者：
Beeh, KM;Beier, J;Buhl, R
通讯作者：
Buhl, R
影响因子：
24.3
作者：
Behr, J;Degenkolb, B;Vogelmeier, C
通讯作者：
Vogelmeier, C
DOI：
10.1164/ajrccm/144.5.1080
发表时间：
1991-11-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
BOROK, Z;GILLISSEN, A;CRYSTAL, RG
通讯作者：
CRYSTAL, RG
影响因子：
24.3
作者：
BEHR, J;DEGENKOLB, B;FRUHMANN, G
通讯作者：
FRUHMANN, G