特发性肺纤维化的发病机制及药物治疗研究进展

特发性肺纤维化是一种以两肺间质纤维化伴蜂窝状改变为特征的疾病,其发病率及死亡率逐年增高,且生存期较短,愈后极差,几乎与恶性肿瘤无异。因此,特发性肺纤维化发病机制和治疗也成为国际医学界的研究热点。本文就其病发机制和药物治疗研究进展进行了综述,为今后的进一步研究提供参考。     

特发性肺纤维化发病机制研究进展

<正>特发性肺纤维化(Idiopathic pulmonary fibrosis,IPF)是一种病因不明的以寻常型间质型肺炎(UIP)为特征性病理改变的慢性炎症性间质性肺疾病。世界各地均有报道,近年来其发病率呈不断上升趋势,无明显地理和种族差别。多为中     

免疫细胞在特发性肺纤维化中的研究进展

特发性肺纤维化（idiopathic pulmonary fibrosis,IPF）是慢性进展性肺间质疾病,其发病率呈逐年上升趋势,且预后差、病死率高。现有指南仅推荐尼达尼布和吡非尼酮用于IPF治疗,但二者均因价格昂贵导致临床应用受限。虽然IPF发病机制至今未完全阐明,但是免疫细胞及其相互作用在IPF发病中起着重要作用。本文结合近年来研究热点,通过总结分析IPF相关的免疫细胞作用机制及相关药物研究,为进一步探索免疫治疗提供参考。     

特发性肺纤维化治疗靶点及药物研究进展

近年来,对特发性肺纤维化(IPF)发病机制和治疗靶点的研究成为热点。一些细胞因子与IPF关系密切,其中转化生长因子-β(TGF-β)引导成纤维细胞和巨噬细胞至损伤处,直接诱发成纤维细胞转化为肌成纤维细胞并促进胶原合成;血小板源生长因子(PDGF)和碱性纤维母细胞生长因子(b FGF)与成纤维细胞增殖有关。此外,相关蛋白如赖氨酰氧化酶相关蛋白2(LOXL2)、ανβ6整合蛋白和溶血磷脂酸1受体(LPA1)等均为新的IPF治疗靶点。目前针对IPF治疗靶点的药物相继进入临床试验,吡非尼酮(Pirfenidone)为转化生长因子-β(TGF-β)抑制剂;尼达尼布(Nintedanib)为三重酪氨酸激酶抑制剂,作用于PDGF、VEGF和FGF受体;Simtuzumab是一种人源化单克隆抗体,作用于赖氨酰氧化酶相关蛋白2(LOXL2),阻断胶原交联,正处于IPFⅡ期临床试验。STX-100是一种人源化ανβ6特异性单克隆抗体,与ανβ6整合蛋白结合,阻止后者激活TGF-β。     

mTOR信号通路在特发性肺纤维化中的作用研究进展

特发性肺纤维化(IPF)是一种病因不明的纤维化性间充质性肺疾病,多发于中老年人,且死亡率高。哺乳动物西罗莫司(雷帕霉素)靶点蛋白(mTOR)信号通路在机体生长、代谢和存活方面起着核心调控作用。在IPF疾病进程中,mTOR信号通过调控多种细胞功能缓解肺纤维化。抑制mTOR信号可诱导肺泡上皮自噬,抑制上皮细胞损伤、凋亡和炎症反应以保护上皮细胞;同时抑制成纤维细胞增殖和活化,促进成纤维细胞凋亡,抑制胶原合成和分泌;抑制mTOR信号还可抑制上皮间充质转化和肺部纤维化因子的释放,抑制纤维化进程。以mTOR为靶点治疗IPF在临床上也具有一定可行性,目前以mTOR为靶点的临床在研药物有西罗莫司、奥米帕西(omipalisib)和HEC-68498。本文综述mTOR信号通路在IPF中的研究进展,为进一步研究mTOR在肺纤维化发病机制和治疗中的作用提供支持。     

药物治疗特发性肺纤维化的研究进展

特发性肺纤维化属于慢性的肺部纤维化疾病,具有进展性、不可逆性等特点,且患者的死亡率较高,需要得到及时的治疗和干预。随着临床研究的不断深入,针对特发性肺纤维化的有效的治疗药物不断出现。本文将对药物治疗特发性肺纤维化的研究进展作一综述。     

特发性肺纤维化的研究进展及其治疗

特发性肺纤维化(IPF)是一种进行性加重且目前尚无有效治疗药物的疾病,相关病因尚未明确.近期研究发现了IPF新的治疗靶点.本文综述IPF的发病机制、诊断的最新研究,以及其治疗的研究进展.     

特发性肺纤维化治疗药物的研究进展

特发性肺纤维化(IPF)是一种不可逆、进展性、致死性的慢性肺纤维化疾病,其进展较快,存活率较低,缺乏有效诊疗手段和治疗药物。近年来随着对其发病机制的了解,IPF治疗药物的开发也取得了一定进展。全球新批准并上市的治疗药物有吡非尼酮和尼达尼布,处于研发I、II期的有10多种,另外也有一些曾经有希望但已经不推荐用于IPF治疗的药物。     

特发性肺纤维化治疗药物研究进展

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是最常见、致命性、病因不明的间质性肺病,目前认为是反复的肺泡上皮细胞损伤引起的异常修复导致肺功能丧失的过程.目前全球范围内仅有吡非尼酮和尼达尼布被批准用于治疗IPF,抗肺纤维化药物治疗手段仍亟待开发.由于已上市药物的药动学以及安全性资料...     

特发性肺纤维化的药物治疗

特发性肺纤维化是特发性间质性肺炎中的最常见类型,肺脏病理表现为寻常型间质性肺炎;病因和发病机制不明,尚无有效的治疗药物。对初治患者可试用糖皮质激素联合免疫抑制药和抗氧化治疗方案,并密切随诊疗效决定进一步治疗方案。吡菲尼酮是目前经临床试验证实,对特发性肺纤维化可能有效的抗纤维化药物;有多种分子靶向药物正处在临床试验阶段。     

特发性肺纤维化药物治疗进展

目的:介绍治疗特发性肺纤维化的药物及进展。方法:查询近几年国内外关于特发性肺纤维化药物治疗文献并进行分析。结果和结论:治疗特发性肺纤维化的药物有糖皮质激素+N-乙酰半胱氨酸+硫唑嘌呤、单用N-乙酰半胱氨酸、抗凝药物等,但均被随机临床对照试验(RCT)所否定,近年出现的新药吡非尼酮、尼达尼布可以改善患者肺功能下降速度,延缓疾病进展,但仍不能阻止疾病进展。     

Pirfenidone for the treatment of idiopathic pulmonary fibrosis

Although multidrug therapy is required in order to achieve good blood pressure control in many hypertensives, there are no studies directly comparing fixed-dose combinations as initial therapy. The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial compares regimens of benazepril plus amlodipine versus benazepril plus hydrochlorothiazide, force-titrated to 40/10 and 40/25mg, respectively. A total of 12,600 high-risk hypertensives have been randomised and will be followed for 3 – 5years, during which cardiovascular events will be monitored. The investigators hypothesise that the benazepril plus amlodipine regimen will decrease cardiovascular events by 15% compared with benazepril plus hydrochlorothiazide. Recruitment began in 2003, and the trial is expected to end in 2008. The ACCOMPLISH trial shares important limitations with many other recent trials that will make it difficult to apply the results in clinical practice. These include the focus on high-risk hypertensive patients, in whom significant reductions in relative risk will translate into meaningful reductions in absolute risk: in lower-risk hypertensives with a low absolute risk, similar relative risk reductions may not be of great impact on the population disease burden. In ACCOMPLISH, as in most industry-sponsored clinical trials, the main goal appears to be market-driven: doses of drugs tested are not those available for clinical practice. The question asked, whether the combination of benazepril with either diuretic or dihydropyridine calcium channel blocker is more efficacious, is not a clinically compelling one. Finally, the univariate subgroup analyses proposed are unlikely to lead to an understanding of whether either combination has specific advantages for patients encountered clinically, most of whom have multiple risk factors. Thus, it appears that ACCOMPLISH, as with many recent pharmacological trials, will not greatly impact the treatment of hypertension.     

Nintedanib for the treatment of idiopathic pulmonary fibrosis

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by the progressive loss of pulmonary function, ultimately leading to respiratory failure and death. Two novel compounds, nintedanib and pirfenidone, have shown efficacy in reducing the rate of decline of lung function in IPF patients. The multiple tyrosine kinase inhibitor nintedanib has extensively being studied as a potential angiogenesis inhibitor in clinical against various neoplastic disorders. Afterwards, this compound was successfully tested in IPF.

Areas covered: Herein, the authors review the working mechanisms of nintedanib, its pharmacological profile, and its efficacy and safety for patients with IPF.

Expert opinion: Nintedanib has shown to be safe and effective in patients with IPF, with a favorable long-term safety profile. There is a lack of comparative trials of pirfenidone and nintedanib, and the choice of treatment is left to the physicians’ judgement. Future directions of nintedanib use are represented by the treatment of progressive fibrosing interstitial lung disease other than IPF, IPF with advanced functional impairment, and lung fibrosis secondary to connective tissue diseases. A promising safety profile for the combinational use of nintedanib and pirfenidone in IPF has also recently emerged.     

Advances in the treatment of idiopathic pulmonary fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a lung limited, progressive fibrotic disease with a poor prognosis. The cause is unknown, and currently there is no treatment that reverses the disease or stops progression. This combination of a poor prognosis and the absence of curative therapy has prompted a sustained investigative effort to identify beneficial treatments. Recently released trial results suggest progress.

Areas covered: Although the mechanism of disease is poorly understood, a number of compounds that influence pathways thought to play a mechanistic role have been studied for use in IPF. This article discusses a number of these landmark trials.

Expert opinion: From these studies we conclude that the future treatment of IPF will include expanding pharmacological options. Recent studies have identified two agents that appear to slow disease progression and may offer a window into pathogenesis and future drug targets.     

间充质干细胞治疗特发性肺纤维化药理机制研究进展

间充质干细胞（MSCs）具有多种分化能力,可以直接迁移到损伤组织中并分化为肺泡上皮细胞,还可以分泌并释放多种细胞因子和外泌体,调节炎症和免疫反应。特发性肺纤维化（IPF）是与年龄相关、发病机制尚不明确的慢性进行性肺部疾病,临床上使用的吡非尼酮和尼达尼布仅能缓解症状。MSCs在治疗IPF方面具有广阔的应用前景,就目前关于MSCs治疗特发性肺纤维化的药理机制以及该疗法所存在的局限性进行综述和探讨。     

吡非尼酮联合乙酰半胱氨酸治疗特发性肺间质纤维化的疗效观察

目的观察吡非尼酮胶囊联合乙酰半胱氨酸颗粒治疗特发性肺间质纤维化的临床疗效。方法选取2016年1月—2018年3月成都市中西医结合医院收治的特发性肺间质纤维化患者67例为研究对象,根据随机数字表法随机分为对照组(32例)和治疗组(35例)。对照组饭后口服乙酰半胱氨酸颗粒,0.2 g/次,3次/d。治疗组在对照组的基础上口服吡非尼酮胶囊,初始用量200 mg/次,两周后调整为400 mg/次,3周后调整为600 mg/次,3次/d。两组均持续治疗4个月。观察两组临床疗效,比较治疗前后高分辨率CT(HRCT)改变阳性率,肺功能指标和肺纤维化指标。结果治疗后,对照组和治疗组的总有效率分别为71.88%、88.57%,两组比较差异具有统计学意义(P0.05)。治疗后,对照组网格影阳性率显著降低,治疗组网格影、斑片影阳性率均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组网格影、斑片影阳性率显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者最大呼气流量(PEF)、用力肺活量(FVC)、一秒用力呼气容积(FEV1)水平均显著升高,同组治疗前后比较差异具有统计学意义(P0.05),且治疗后治疗组肺功能指标显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者Ⅲ型胶原(Ⅲ-C)、IV型胶原(Ⅳ-C)、透明质酸(HA)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组肺功能指标显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论吡非尼酮胶囊联合乙酰半胱氨酸颗粒治疗特发性肺间质纤维化疗效显著,能明显改善肺功能和肺纤维化指标,安全性高,具有一定的临床推广应用价值。     

Targeting the endothelin pathway in the idiopathic pulmonary fibrosis: the role of bosentan

Background: Idiopathic pulmonary fibrosis (IPF) is a rapidly lethal disease characterized by anarchic, progressive fibrosis. Pulmonary fibrosis is the result of interactions between many effector cells and cytokines and better understanding of this can help with identification of novel therapeutic targets. Objective: To evaluate the role of the endothelin-1 (ET-1) pathway in IPF pathogenesis and the effects of therapeutic targeting with bosentan, an ET-1 antagonist. Methods: Data on ET-1's pathogenic involvement in IPF and the preclinical and clinical data on bosentan in this context are discussed and analyzed. A parallel overview of existing and upcoming therapies for IPF is presented. Conclusions: Bosentan is a promising antifibrotic therapy for IPF and clinical data on its long-term efficacy support its use.