细胞因子网络与特发性肺纤维化

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是特发性间质性肺炎中最常见的一种类型,也是一种进展性的不可逆的快速致死性问质性肺疾病.关于IPF发病机制及治疗的研究已经有50余年,目前还没有有效的治疗方案能逆转肺纤维化.IPF的发病机制复杂,细胞因子网络是其重要机制.现已知生长因子、细胞因子、化学因子以及凋亡调节因子在肺纤维化发病机制中起重要作用.目前认为转化生长因子β是细胞因子网络的关键环节,与之相关的各种细胞因子是纤维化进程中的重要介质.本综述总结了IPF发病机制相关的细胞因子及其交互作用,通过对这些与异常损伤修复相关介质的阐述,为IPF靶向治疗提供理论依据.     

特发性肺纤维化急性加重的最新研究进展

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种病因不明的慢性进展性纤维化型间质性肺炎,组织学表现为普通型间质性肺炎.IPF通常是缓慢进展,但部分IPF患者可以出现急剧、原因不明的临床明显恶化,称之为IPF急性加重.IPF急性加重难以预测、病死率高、缺乏有效的治疗措施.本文就近年来IPF急性加重的发病率、危险因素、病理生理、发病机制、诊断和治疗等方面的研究进展进行综述.     

特发性肺间质纤维化发病机制及治疗进展

特发性肺间质纤维化（idiopathic pulmonary fibrosis,IPF）是特发性间质性肺炎（idiopathic interstitial pneumonia,IIP）中最常见的一种,由于其发病机制复杂,目前尚无有效治疗措施,预后极差,成为目前国内外的诊治难点及研究热点。近年来,在IPF发病机制及药物治疗方面的认识取得了一些进展。     

特发性肺纤维化发病机制和治疗的研究进展

目前,国内外关于特发性肺纤维化的研究报道较多,但其发病机制尚不明确,其治疗仍是临床一大难题。IPF发病分为肺间质炎症改变及随后的肺纤维化两个阶段,很多细胞因子参与其中。IPF治疗方法仍很有限,尚未找到有效的治疗方案。因此,在更深层次上研究其发病的分子机制,延缓纤维化进程,探寻安全可靠的治疗方法,具有深远的临床意义。     

特发性肺纤维化相关性肺高压的诊断与治疗

肺高压(pulmonary hypertension,PH)作为特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的严重并发症,预后极差.其发病机制目前尚未完全阐明,PH的发生、发展严重降低了IPF患者的生活质量并缩短了患者的生存期.但早期诊断及合理治疗可提高该病患者的生存率并改善患者的生存质量.近年,对IPF相关性PH的认识不断深入,现将研究的最新进展作一综述.     

结缔组织生长因子在特发性肺纤维化患者肺泡上皮细胞中的表达

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是最常见的一种间质性肺疾病,发病机制仍不明确.目前国内外关于结缔组织生长因子(connective tissue factor,CTGF)与肺纤维化之间关系的研究明显增加,但多以动物模型或体外研究为主,来自人类IPF肺组织的研究较少.本研究旨在探讨CTGF在IPF发病机制中的作用,为制定新的IPF治疗方案提供理论依据.     

特发性肺纤维化的发病机制及抗凝治疗研究进展

特发性肺纤维化（IPF）是指原因不明、以普通型间质性肺炎为特征性病理改变的慢性炎症性间质性肺病，其病理生理特点是肺组织进行性损伤、炎症和纤维化。目前，IPF的发病机制尚不清楚，无有效治疗方法，患者中位生存期仅4～5a。为此，本文结合文献对IPF的发病机制及抗凝治疗研究进展综述如下。     

肺泡损伤修复障碍与特发性肺纤维化

IPF是一种病因不明的渐进性致死性肺部纤维化疾病。美国胸科协会(ATS)和欧洲呼吸学会(ERS)最近发表的共识意见中，将IPF定义为原因不明并以普通型间质性肺炎(UIP)为特征性病理改变的一种慢性纤维化性间质性肺疾病。流行病学资料显示，IPF患者存活率很低，确诊后平均存活时间为2～4年。传统治疗主要是基于抑制炎症可阻止肺纤维化进展这一观念，一般采用激素治疗，但IPF患者通常对激素反应较差，应用免疫抑制剂或细胞毒药物也大多不能降低IPF死亡率。为了显著提高IPF患者的生存率，明确IPF发病的始动因素，制定新的治疗策略，势必成为必然。如今，已有研究向传统观念(即炎症是促使IPF发展的始动因素)提出了挑战，认为IPF主要是一种肺泡受损后异常修复及重构的疾病。因此，有必要对IPF的发病机制重新评价，希望对未来的治疗策略产生有益的影响。     

特发性肺纤维化的治疗进展

特发性肺间质纤维化是间质性肺疾病的一种特殊类型.至今为止,其病因、发病机制尚不明确,病死率高,传统药物治疗效果欠佳且毒副作用明显.本文参考国内外文献,对当前IPF的研究进展与治疗现状作一概述.     

特发性肺纤维化的治疗现状

特发性肺纤维化（IPF）是一种病因不明的进展性纤维化肺泡炎,以炎症和纤维化为病理特点。流行病学资料显示,IPF发病率呈不断上升趋势,由于发病机制不清,病死率高,至今尚无确切有效的治疗方法,因此,积极寻找新的治疗方法已成为改善IPF患者预后,提高生存率的迫切需要。     

Idiopathic pulmonary fibrosis: phenotypes and comorbidities

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease of the lung with an unknown etiology and limited treatment options. Three distinct phenotypes of IPF have been proposed: combined pulmonary fibrosis and emphysema, disproportionate pulmonary hypertension in IPF, and rapidly progressive IPF. Although treatment options for IPF are limited, much can be done to identify and alleviate symptoms from comorbidities, potentially improving the overall quality of life and well-being of these patients. This article describes emerging evidence to support the hypothesis that there is more than one phenotype for IPF and describes the common comorbidities seen in this disease.     

What parameters can be used to identify early idiopathic pulmonary fibrosis?

Elucidating the disease process of early idiopathic pulmonary fibrosis (IPF) will help clinicians in addressing the contentious issues of when and in which patients, therapeutic intervention should be initiated. Here, we discuss several possible parameters for diagnosing early IPF and their clinical impacts. Physiologically, early IPF can be considered as IPF with normal or mild impairment in pulmonary function. Radiologically, early IPF can be considered as IPF with a small extent and/or early features of fibrosis. Symptomatically, early IPF can be considered as asymptomatic or less symptomatic IPF. IPF at Gender-Age-Physiology index stage I can be considered early IPF. Interstitial lung abnormalities are defined as parenchymal abnormalities in more than 5% of the lung in patients with no prior history of interstitial lung disease, and in some cases, this seems to be equivalent to early IPF. Previous clinical trials showed the effect of antifibrotic therapies in early IPF, but the effects of therapy are uncertain in early IPF outside of clinical trials, such as in cases of IPF with normal pulmonary function, IPF without honeycombing or traction bronchiectasis, and asymptomatic IPF. Moreover, little has been reported on disease progression in such conditions. Because the conceptual framework of early IPF may vary depending on its definition, not only is a diagnosis of early IPF important but prediction of disease progression is also crucial. Further investigations are needed to identify biomarkers that can detect patients who may experience greater degrees of disease progression and require treatment even with those forms of early IPF.     

Pirfenidone: significant treatment effects in idiopathic pulmonary fibrosis

Pirfenidone has been shown in three recently published trials to slow down the progression of the devastating interstitial lung disease, idiopathic pulmonary fibrosis (IPF). The precise mechanisms that initiate and perpetuate the histopathological process leading to lung fibrosis in IPF are still uncertain, but increased concentrations of reactive oxidative species and fibrogenetic factors have been observed in the pulmonary tissue of patients. Although the exact mechanisms of its action are unknown, pirfenidone is a small molecule with antifibrotic and some hydroxyl scavenger properties that has recently been approved in Europe and elsewhere for the treatment of IPF. Along with the new ATS/ERS/JRS/ALAT 2011 statement for 'Evidence Based Guidelines for Diagnosis and Management', there is now a more profound basis for offering IPF patients an evidence-based evaluation and treatment. This review summarizes the background to the recommended use of pirfenidone for the treatment of IPF.     

How useful is traditional herbal medicine for pulmonary fibrosis?

IPF, despite considerable advances in clinical management and understanding of its complex pathophysiology, is still a fatal disease without effective treatment. Herbal medicine has been used for more than 5000 years and is the central component of medical practice in many parts of Asia. Not surprisingly, traditional and herbal medicine is also widely applied for treatment of IPF. This review describes the most important herbal medicines that are used for IPF treatment. The relevant experimental studies investigating potential mechanisms of these drugs are discussed. The best conducted clinical studies which have reported beneficial effects of some herbal medications in the management of IPF are also evaluated. Overall, there is considerable experimental support from preclinical studies for some of these herbal medicines, but the translation into clinical practice appears difficult. The clinical trials evaluating their anti-fibrotic potential are not fulfilling the standards expected from 'Western' medicines. Systematic clinical research in this field is still in its infancy, and as such, the routine use of traditional and herbal medicine cannot be recommended for patients suffering from IPF.     

Polymyxin B-immobilized fiber columns: A column to breathe new life into the treatment of interstitial lung disease?

Acute exacerbations of idiopathic pulmonary fibrosis (IPF) is a severe respiratory condition with high mortality rate. Direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX-DHP) was originally introduced for the treatment of septic shock. Application of PMX-DHP to the treatment of acute exacerbations of IPF may improve oxygenation and survival of the patients with the disease. In addition to acute exacerbations of IPF, PMX-DHP has been applied to acute respiratory failure from various causes; an amyopathic dermatomyositis patient who developed rapidly progressive interstitial lung disease (ILD) with elevated anti-CADM-140/MDA5 autoantibody and a patient with severe amiodarone pulmonary toxicity. It is also demonstrated that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive ILDs in a case-control setting. PMX treatment decreases not only various circulating molecules but also inflammatory cells, in particular activated monocytes, producing such mediators. Although the incidence of acute exacerbations of IPF is too low for proper randomization, in order to test the effects of PMX-DHP on the disease, a cohort or case-control analytic study needs to be conducted, preferably from more than one center or research group.     

Idiopathic pulmonary fibrosis: pathobiology of novel approaches to treatment

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown cause that conveys a dismal prognosis. In the United States there are currently no licensed therapies for treatment of IPF. The development of effective IPF clinical trials networks across the United States and Europe, however, has led to key developments in the treatment of IPF. Advances in understanding of the pathogenetic processes involved in the development of pulmonary fibrosis have led to novel therapeutic targets. These developments offer hope that there may, in the near future, be therapeutic options available for treatment of this devastating disease.     

Treatment of idiopathic pulmonary fibrosis: a position paper from a Nordic expert group

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients. In this review, past and present management is discussed based on a comprehensive literature search. A treatment algorithm is presented based on available evidence and our overall clinical experience. In addition, unmet needs with regard to treatment are highlighted and discussed. We describe the development of various treatment options for IPF from the first consensus to recent guidelines based on evidence from large‐scale, multinational, randomized clinical trials, which have led to registration of the first drugs for IPF.     

Management of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a deadly progressive lung disease without an effective standard treatment approach. Because of the complexity and uncertainties of IPF treatment, therapeutic decisions need to be tailored to the individual patient, after discussing the potential benefits and pitfalls. Pirfenidone has been approved for the treatment of IPF in many countries, but is not recommended as a first-choice therapy by current guidelines because of the lack of a definite efficacy. Randomized controlled trials represent a valid choice for patients with IPF, and their completion is important in improving both survival and quality of life.     

Review series: Aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from IPF? How should the clinical approach differ?

The lung is frequently involved in connective tissue diseases (CTDs), although the frequency of lung manifestations varies according to the type of CTD. Interstitial lung diseases (ILD) are frequently seen in CTDs, particularly systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA), accounting for a significant proportion of deaths. A large percentage of patients with CTD-associated ILD has limited and stable disease, not requiring treatment. However, a significant minority has severe and/or progressive disease, necessitating prompt initiation of treatment. CTD-ILD histological patterns include non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP). NSIP is the most common pattern in all CTDs, except for RA, characterized by a higher frequency of UIP. ILD can present acutely or chronically, with acute presentations being more common in systemic lupus erythematosus and PM/DM. Idiopathic pulmonary fibrosis (IPF) is a progressively worsening ILD characterized by inflammation and fibrosis. The characteristic histological pattern of IPF is UIP. Interestingly, a UIP pattern is associated with a significantly better survival in CTD-related disease compared to the idiopathic variety. Prognosis in IPF is dismal, with a median survival since diagnosis of 2-3 years. No treatment regimen has been shown to improve survival in IPF. By contrast, although there have been only two randomized placebo-controlled trials investigating the effect of immunosuppressive treatment in SSc-associated ILD, clinical experience suggests that immunosuppressive drugs in CTD-related ILDs are capable of benefiting a significant proportion of patients, particularly those with certain histological patterns of disease. This review will essentially focus on CTD-associated ILD and will compare aspects of clinical presentation and management to those of IPF.