Magnini Daniele, Montemurro Giuliano, Iovene Bruno, Tagliaboschi Linda, Gerardi Rafael Emanuele, Lo Greco Erminia, Bruni Teresa, Fabbrizzi Alessio, Lombardi Francesco, Richeldi Luca
Division of Respiratory Medicine, A. Gemelli University Hospital, Catholic University of the Sacred Heart, Rome, Italy.
Respiration. 2017;93(6):379-395. doi: 10.1159/000475780. Epub 2017 May 5.
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown causes. Current diagnostic criteria are based on radiological, clinical, and histopathological features but, unfortunately, still many patients remain undiagnosed. Two currently approved therapies, pirfenidone and nintedanib, slow down disease progression but failed to block or revert it. On the other hand, many of the therapeutic agents tested in several clinical trials have not given satisfactory answers, probably due to the pathological heterogeneity of the disease. A growing number of studies show that IPF phenotype is the common clinical outcome of a variety of different pathophysiological mechanisms that identify disease subgroups characterised by specific genetic and molecular biomarkers (endotypes). The precision medicine approach is identifying and analysing the complex system of genetic, molecular, environmental, and behavioural variables underlying the development of the disease and the response to therapy. These molecular pathways are potential targets for novel agents and useful diagnostic, prognostic, and theragnostic biomarkers. We outline the status of knowledge in this field by discussing the complex pathogenetic pathways underlying different disease subgroups and assessing a stratification approach to novel therapeutic agents based on these endotypes.
特发性肺纤维化（IPF）是一种病因不明的慢性进行性纤维化间质性肺炎的特殊形式。目前的诊断标准基于影像学、临床和组织病理学特征，但遗憾的是，仍有许多患者未被诊断出来。目前两种获批的疗法，吡非尼酮和尼达尼布，可减缓疾病进展，但未能阻止或逆转疾病进程。另一方面，在多项临床试验中测试的许多治疗药物并未给出令人满意的结果，这可能是由于该疾病的病理异质性所致。越来越多的研究表明，IPF表型是多种不同病理生理机制的常见临床结果，这些机制确定了以特定基因和分子生物标志物（内型）为特征的疾病亚组。精准医学方法正在识别和分析疾病发生发展及对治疗反应背后的复杂的基因、分子、环境和行为变量系统。这些分子途径是新型药物的潜在靶点以及有用的诊断、预后和诊疗生物标志物。我们通过讨论不同疾病亚组背后的复杂发病机制，并评估基于这些内型的新型治疗药物分层方法，概述该领域的知识现状。
