成纤维细胞在特发性肺纤维化发病机制及治疗中的研究进展

目前治疗特发性肺纤维化(IPF)的主要药物为糖皮质激素和免疫抑制剂,但其疗效尚未获得明确的临床证据.IPF中的主要效应细胞为成纤维细胞,干扰成纤维细胞的增殖对抑制IPF的进展有重要的临床意义.本文重点论述IPF的诊断标准并综述成纤维细胞在IPF发病机制及治疗中的研究进展.     

从指南看特发性肺纤维化治疗药物的选择

自1892年首次报道慢性间质性肺病的组织病理学以来,相关研究不断深入,其中特发性肺纤维化(IPF)发病机制的研究也取得了一定进展,但仅个别药物可能对IPF具有潜在益处.依据2011年《特发性肺纤维化诊治循证指南》,本文简要综述指南提出的4种IPF药物治疗方案的研究现状.     

博莱霉素诱导的肺纤维化动物模型评价及应用研究进展

特发性肺纤维化(IPF)是一种发病原因不明的严重损伤性肺部疾病,缺乏理想的治疗药物。在临床上肿瘤患者使用博莱霉素治疗后,少数患者出现肺纤维化病变。目前博莱霉素已被广泛用于制备IPF动物模型。本文对博莱霉素诱导肺纤维化动物模型的研究现状进行总结,并与临床IPF的作用机制、病理变化等进行对比评价,以期对IPF发病机制研究和药物研发有所帮助。     

特发性肺纤维化的药物治疗

特发性肺纤维化(IPF)是最难治的慢性纤维化肺部疾病,其死亡率甚至超过许多癌症.尽管过去十年间IPF临床治疗有了很大的进步,但2011年《特发性肺纤维化诊治循证指南》依然宣布到目前为止IPF尚无特效治疗药物.本文综述最近几年国内外有关IPF治疗的研究成果,展望未来IPF治疗药物的研发前景,探索新的治疗靶点及其研究策略的制定.     

特发性肺纤维化药物治疗的研究进展

特发性肺纤维化(IPF)是一种慢性、渐进性的细胞间质病,病因和发病机制尚不明确。2种或2种以上药物联合使用可减少药物使用剂量,减轻不良反应,增加治疗靶通路,是目前IPF研究的关注热点。吡非尼酮和尼达尼布是FDA首次批准治疗IPF的多靶点治疗药物,其联合用药正处于临床试验阶段。本文对IPF的多靶点治疗进展进行综述,进一步讨论联合用药的利弊,浅谈中医在治疗IPF中的优势。     

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。     

治疗特发性肺纤维化新药尼达尼布的研究进展

目的:介绍尼达尼布在特发性肺纤维化(IPF)治疗中的研究进展,为其临床应用提供参考。方法:查阅近年来国内外相关文献,对尼达尼布应用于IPF的药理机制、临床研究、安全性评价等方面的资料进行归纳和总结。结果与结论:尼达尼布在IPF治疗中能够减缓肺纤维化的进展,延缓肺功能下降,降低轻/中度肺纤维化的急性加重发生率,提高患者的生存质量,且临床使用相对安全。     

自噬调节与特发性肺纤维化药物治疗研究进展

特发性肺纤维化（idiopathic pulmonary fibrosis，IPF）是一种病因复杂、与年龄相关的肺纤维化疾病，其发病过程表现出进行性与不可逆性，最终导致患者呼吸系统衰竭而死亡。近些年的研究证实自噬参与了IPF的发生发展。本文回顾总结了自噬和IPF相关的临床研究、动物和细胞模型研究以及基于自噬的药物治疗研究，希望对阐明IPF的病理机制和药物研发有所帮助。     

特发性肺纤维化的炎症机制与潜在药物靶标

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)是一种进行性的、治愈难度大的慢性间充质性肺疾病。导致肺纤维化的因素有很多,例如：吸烟、外界环境污染、药物、病毒感染等。肺泡上皮损伤,肌成纤维细胞增多和胶原纤维沉积是特发性肺纤维化的特征,进而导致功能性气体交换障碍,呼吸衰竭甚至死亡。IPF发病原因不明且缺乏治愈的特效药,所以,探究肺纤维化的发病机制,寻找新的治疗策略十分迫切。在这篇综述中,我们总结了巨噬细胞介导肺纤维化的炎症机制,成纤维细胞在特发性肺纤维化中的作用,以及可能存在的潜在药物靶标。     

中药对特发性肺纤维化抑制作用的研究

特发性肺纤维化(IPF)目前其发病原因不明确,现代医学主要用糖皮质激素治疗、免疫抑制剂治疗、抗氧化剂治疗、细胞因子拮抗剂治疗等,长期使用对肝肾损害非常大,还会危害其他器官,使人体免疫力下降。中医药则通过辨证分析对IPF进行综合治疗,其中以益气养阴、活血化瘀为基本大法,对特发性肺纤维化进行试验研究取得了明显的进展。     

Precision medicine in idiopathic pulmonary fibrosis therapy: From translational research to patient-centered care

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible fibrotic chronic lung disease affecting predominantly older adults, with a history of smoking. The current model of disease natural course is that recurrent injury of the alveolar epithelium in the context of advanced aging/cellular senescence is followed by defective re-epithelialization and scar tissue formation. Currently, two drugs, nintedanib and pirfenidone, that modify disease progression have been approved worldwide for the treatment of IPF. However, despite treatment, patients with IPF are not cured, and eventually, disease advances in most treated patients. Enhancing biogenomic and metabolic research output, its translation into clinical precision and optimal service delivery through patient-centeredness are key elements to support effective IPF care. In this review, we summarize therapeutic options currently investigated for IPF based on the major pathogenetic pathways and molecular targets that drive pulmonary fibrosis.     

The role of urokinase in idiopathic pulmonary fibrosis and implication for therapy

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and frequently fatal form of interstitial lung disease for which there are no proven drug therapies. The pathogenesis of IPF is complex and the urokinase-type plasminogen activator (uPA)/plasminogen system participates in the repair process. The balance between the activating enzyme uPA, and its inhibitor PAI-1, is a critical determinant of the amount of scar development that follows. Objective: To address the role of urokinase in the pathogenesis of pulmonary fibrosis and its implications for therapy. Methods: We reviewed a spectrum of therapeutic strategies and focused on fibrinolytic and anticoagulant drugs for IPF patients. Results/conclusion: There is currently a search for new pharmacotherapeutic agents that may modulate the fibrogenic pathways in IPF. Either blocking PAI-1 or using uPA itself may be a promising new therapeutic strategy.     

Pirfenidone for the treatment of idiopathic pulmonary fibrosis: therapeutic potential prompts further investigation

Idiopathic pulmonary fibrosis (IPF) is a rare, progressive disease of the lungs with unknown aetiology. Currently, there is no therapy that is specifically approved to be used for IPF treatment and the efficacy of ‘conventional therapy’, recommended by the existing therapeutic guidelines and consisting of a combination of corticosteroids with immunosuppressives, is not sufficiently substantiated. Based on the current pathogenetic hypothesis advocating the major role of fibrosis in IPF, novel antifibrotic agents are being developed for the treatment of this disease. Among them, IFN-γ and N-acetylcysteine are at later stages of clinical development. Pirfenidone is another antifibrotic agent that has also demonstrated preclinical anti-inflammatory and antioxidant effects. Earlier clinical studies showed that prifenidone could be efficacious for IPF treatment. Pirfenidone acquired orphan drug status in both Europe and the US for the treatment of IPF. The current randomised, placebo-controlled study authored by Azuma et al. further assesses its efficacy in IPF patients and searches for new potential efficacy end points in this setting.     

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.     

Emerging drugs for idiopathic pulmonary fibrosis

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal lung disorder of unknown etiology. The disease is characterized by alveolar epithelial cell injury, formation of activated fibroblasts/myofibroblasts foci and finally by the exaggerated accumulation of extracellular matrix with the subsequent destruction of the lung architecture. The long-term survival is distinctly poor, with only a 20-30% survival 5 years after the time of diagnosis. Actually, regardless of extensive research, no current therapy has been shown to either reverse or stop the progression of this disease. AREAS COVERED: The authors searched the Medline database from January 1990 to December 2010 using search terms 'pulmonary fibrosis', 'fibrosing alveolitis' and 'usual interstitial pneumonia'. Several subsets were included: definition and epidemiology, risk factors, clinical behavior, pathogenesis and therapy. For the section of IPF treatment, the authors examined all relevant studies including randomized controlled trials, cohort studies, case-control studies and cross-sectional studies. In this review, the authors describe the current therapeutic approaches, the ongoing clinical trials and some future options based on stem cells, lung bioengineering and microRNAs. EXPERT OPINION: The treatment of IPF represents one of the greatest challenges confronting respiratory medicine and, currently, there is no effective therapeutic option for IPF. Perhaps some of the drugs that are under evaluation in clinical trials will slow the decline of the pulmonary function tests or hopefully stabilize some patients. Nonetheless, it appears clear that new therapeutic approaches are urgently needed.     

Update on models of pulmonary fibrosis therapy for preclinical drug research

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with high morbidity and mortality for which current medications are not effective. Therefore, identification of potential therapies is of paramount importance. The preclinical evaluation of novel compounds in animal models represents a critical step in drug development. Objective: To describe features and limitations of common animal models of pulmonary fibrosis and discuss relevant preclinical and clinical data on novel potential IPF therapies. Methods: Review of the existing literature on such models with a special focus on the bleomycin model and its usefulness for the IPF preclinical drug testing. Conclusions: The model of bleomycin-induced pulmonary fibrosis has the advantages of being well established, reproducible and both time- and cost-efficient. However, it has major limitations as it only mimics some features of human IPF. Most importantly, it is initiated by acute lung injury and is at least partially reversible, which is strikingly different from IPF. The failure in establishing effective IPF therapies despite strong efforts in the last decade is partly attributable to our uncritical trust in the models of lung fibrosis and the false belief that they truly reflect what is going on in human disease.     

特发性肺间质纤维化的CT临床诊断回顾性队列追踪研究

目的探讨特发性肺间质纤维化CT临床诊断。方法采用流行病学回顾性队列追踪研究方法,进行个体化问卷调查表。结果 CT可见病变累及上叶和下叶,中下野明显较多,背侧更为明显,呈清晰的外周分布,重者或涉及肺中带。101例均出现清晰可见网状结节影,结节直径2～3mm,边缘模糊,网络相连。28例有明显蜂窝改变占27.72%,11例有磨玻璃改变占10.89%,13例有局限性胸膜增厚占12.87%。结论特发性肺间质纤维化（IPF）临床CT临床诊断非常重要,其肺部CT表现及病理改变为为深入和全面了解患者的治疗与转归工作提供一线临床基础资料。     

Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF) is a serious and fatal pulmonary inflammatory disease with an increasing incidence worldwide. The drugs nintedanib and pirfenidone, are listed as conditionally recommended drugs in the “Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”. However, these two drugs have many adverse reactions in clinical application. Salvianolic acid B(Sal B), a water-soluble component of Salvia miltiorrhiza, could alleviate bleomycin-induc...     

Emerging drugs for idiopathic pulmonary fibrosis

Pulmonary fibrosis is often the end stage of chronic, persistent, low-level lung injury, either of known or unknown cause. The most severe form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF), a disease process of unknown aetiology and one that often leads to respiratory failure and death. At present there are no proven or effective drug therapies for IPF. Recent advances in understanding of disease pathogenesis have focused attention on drug targeting of fibrogenic pathways, as opposed to traditional anti-inflammatory approaches. In this report, the present status of drug development of a number of emerging antifibrotic strategies and agents that may prove more effective in the therapy of this progressive, debilitating and fatal disease are reviewed.