Chambers Rachel C, Mercer Paul F
Centre for Inflammation and Tissue Repair, University College London, London, United Kingdom.
Ann Am Thorac Soc. 2015 Mar;12 Suppl 1(Suppl 1):S16-20. doi: 10.1513/AnnalsATS.201410-448MG.
The challenge facing many fibrotic lung diseases is that these conditions usually present late, often after several decades of repetitive alveolar epithelial injury, during which functional alveolar units are gradually obliterated and replaced with nonfunctional connective tissue. The resulting fibrosis is often progressive and, in the case of idiopathic pulmonary fibrosis (IPF), invariably leads to respiratory insufficiency and, ultimately, the premature death of affected individuals. Recent years have seen a greater appreciation of the relative importance of chronic inflammation as a driver of fibrotic responses. Current evidence suggests that IPF arises as a result of repetitive epithelial injury and a highly aberrant wound healing response in genetically susceptible and aged individuals. Nonspecific anti-inflammatory agents offer no clinical benefit, but the potential contribution of maladaptive immune responses in determining outcome is gaining increasing recognition. The importance of key differences in the tissue-regenerative potential in young versus aged individuals is also beginning to be more fully appreciated. Moreover, there is considerable overlap in the mechanisms underlying tissue repair and cancer, and patients with IPF are at heightened risk of developing lung cancer. Progressive fibrosis and cancer may therefore represent the extremes of a highly dysregulated tissue injury response. This brief review focuses on some of this evidence and on our current understanding of abnormal tissue repair responses after chronic epithelial injury in the specific context of IPF.
许多肺纤维化疾病面临的挑战在于，这些病症通常在疾病晚期才出现，往往是在经历数十年反复的肺泡上皮损伤之后，在此期间功能性肺泡单位逐渐被破坏，并被无功能的结缔组织所取代。由此产生的纤维化通常呈进行性发展，就特发性肺纤维化（IPF）而言，最终会导致呼吸功能不全，并最终导致受影响个体过早死亡。近年来，人们越来越认识到慢性炎症作为纤维化反应驱动因素的相对重要性。目前的证据表明，IPF是由基因易感性和老年个体中反复的上皮损伤以及高度异常的伤口愈合反应引起的。非特异性抗炎药并无临床益处，但适应不良的免疫反应在决定疾病转归方面的潜在作用正日益受到认可。年轻个体与老年个体在组织再生潜力方面的关键差异的重要性也开始得到更充分的认识。此外，组织修复和癌症的潜在机制存在相当大的重叠，IPF患者患肺癌的风险更高。因此，进行性纤维化和癌症可能代表了高度失调的组织损伤反应的两个极端情况。本简要综述重点关注其中一些证据，以及我们目前对IPF特定背景下慢性上皮损伤后异常组织修复反应的理解。
