病因不明性肺纖維化診斷與治療新知

Recent Advances in the Diagnosis and Treatment of the Idiopathic Pulmonary Fibrosis

林承志(Cheng-Chih Lin)

《內科學誌》 24卷6期 (2013/12) Pp. 446-452

https://doi.org/10.6314/JIMT.2013.24(6).02

摘要

病因不明性肺纖維化（idiopathic pulmonary fibrosis，IPF），是一種特殊的原因不明之慢性進行性纖維化間質性肺炎，主要發生在老年人，病灶局限於肺部。它的特點是呼吸困難和肺功能漸進性惡化，且預後很差。在過去十年，研究人員陸續發現一些與IPF發病機制有關之新的細胞和分子機轉和訊號傳遞路徑，包括了β型轉化生長因子（TGF－β1）之誘導機轉、肺泡上皮細胞與纖維母細胞之異常、端粒體（telomere）縮短與榖胱甘肽（glutathione）缺乏在纖維化的角色等等，未來可能成為新的治療標的。美國、歐洲、拉丁美洲及日本胸腔科醫學會根據現有的最佳證據，在2011年出版IPF診治共識，最重要的是確認IPF為具有獨特的臨床症狀與病理學表現之尋常性間質性肺炎，並提供臨床醫師診斷和處置之具體建議。早期的研究發現，許多治療方式可能改善某些病程指標，但總結近年來較大型研究的結果顯示，發現單用類固醇（corticosteroid）或秋水仙素或環孢菌素（cyclosporine A）、合併類固醇及免疫抑制劑、干擾素（INF－γ1B）、血管內皮素接受器拮抗劑（bosentan）、腫瘤壞死因子抑制劑（etanercept）等治療方式都讓人失望。合併NAC（N－acetylcysteine）加上prednisolone及免疫抑制劑azathioprine這種治療方式，現在也不建議使用。不過，最近歐盟已批准pirfenidone可用來治療IPF。此外，仍有許多治療方式的臨床研究在進行，相信在未來IPF可能會有更多更新的治療選擇。

關鍵字

病因不明性肺纖維化（Idiopathic pulmonary fibrosis） ； 尋常性間質性肺炎（Usual interstitial pneumonia） ； 間質性肺炎（Interstitial pneumonia）

並列摘要

Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause and characterized by progressive and chronic fibrotic change of pulmonary interstitial tissue. IPF occur mainly in older adults, show progressive worsening of dyspnea and lung function, and are associated with poor prognosis. During the past decade, researchers have found several novel cellular and molecular mechanisms, and related signalling pathways, implicated in the pathogenesis of IPF, including the roles of transforming growth factor-β pathway; the abnormal behavior of alveolar epithelial cells and fibroblasts; the shortening of telomere, the deficiency of extracellular glutathione and excessive oxidative stress, these findings may contribute to the identification of new therapeutic targets. An international consensus on the diagnosis and management of IPF was published in 2011 and based on the best available evidence. Meaningfully, the statement defines IPF as a distinct clinical entity associated with the histological appearance of usual interstitial pneumonia, and provides specific recommendations for its diagnosis and management. To date, available evidence against the use of the following monotherapy of IPF: corticosteroid, colchicine, cyclosporine A, wafarin, interferon-γ1b, bosentan and etanercept. The combined regimen of acetylcysteine, azathioprine and prednisone is also not recommended. With the recent approval of pirfenidone in Europe for use in IPF, and a rich pipeline of experimental therapies in various stages of clinical development, the future looks bright for new treatment options.