MicroRNA 与特发性肺纤维化

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种不明原因引起的以肺间质纤维化和肺功能损害为特点的进行性发展的肺部疾病,目前的治疗效果十分有限,存活期大概为诊断后的2.5~3.5年。虽然国内外有关肺纤维化的研究在不断取得新的进展,但迄今为止,IPF 的发病机制仍不得而知。微小 RNA (microRNA,miRNA)是一类由17~24个核苷酸构成的功能性非编码小分子 RNA。近年来,miRNA 因其对诸多生命活动的重要调控作用而备受关注,已经有部分 miRNA被证明与肺纤维化的发病机制存在着密切的关系。本文将对 miRNA 与 IPF 的关系的研究进展作一综述。     

体外循环下单肺移植治疗特发性肺纤维化合并肺动脉高压

在体外循环下为1例终末期特发性肺纤维化合并肺动脉高压患者施行右侧单肺移植术,供肺采用改良LPD液灌洗,冷缺血205min,管道吻合55min,体外循环120min。术后采用环孢素A、激素及骁悉三联免疫抑制治疗。移植肺术后即刻发挥功能,术后第4天因胸腔内渗血多再次开胸止血并清除血块,次日撤呼吸机,恢复良好．第37天康复出院。认为特发性肺纤维化合并肺动脉高压是肺移植的适应证之一,术中是否应用体外循环应慎重评估,术后尤应注重出血的监测和控制。     

特发性肺动脉高压的诊断与治疗

特发性肺动脉高压(Idiopathic Pulmonary ArterialHypertension,IPAH)是指没有明确原因呈单克隆细胞增生和致丛性病变的肺动脉高压.早期诊断和及时治疗有助于改善IPAH患者的预后,因此综合分析患者的个人史、家族史、临床表现、体格检查和实验室检查,进行规范的IPAH诊断评估,进而明确诊断和规范治疗,对于提高IPAH患者的生存期和改善生活质量具有十分重要的意义.     

特发性肺纤维化的血管病变

目前对特发性肺纤维化的血管病变的研究主要集中在肺部毛细血管的血管发生和血管重分布、微血管损伤及合并肺动脉高压等方面.对特发性肺纤维化的血管病变的相关文献进行复习和整理,可能为将来进一步研究特发性肺纤维化的发病机制、寻找新的治疗靶点和判断预后提供参考和理论依据.     

Thy-1在特发性肺纤维化发病机制中的作用

特发性肺纤维化(IPF)是指病因不明、局限于肺部的弥漫性肺间质纤维化.近年研究表明,Thy-1在IPF发生发展中起重要作用.现结合文献对Thy-1在IPF发病机制中的作用综述如下.     

从特发性肺纤维化到特发性间质性肺炎:概念上的变迁

在过去四年中，特发性肺纤维化(idiopathic pulmonary fibrosis，IPF)的概念发生了一系列的变化，反映了对疾病认识的进步。只有了解了从IPF到特发性间质性肺炎(idiopathic interstitial pneumonia，IIP)在概念上的变化过程，才不会对IPF和IIP所包含的种种名词及不同内涵感到困惑。而2002年美国胸科协会(ATS)和欧洲呼吸协会(ERS)对IIP的分类发表的共识意见对疾病名称和诊断标准进行了规范化的界定^[1]。     

特发性肺动脉高压一例临床分析

特发性肺动脉高压（idiopathic pulmonary arterial hypertension,IPAH）是一种罕见的、进行性加重、原因不明的肺动脉血管硬化病变,诊断往往比较困难,预后险恶。至今全世界约有1000多例报道,我国尚无精确统计,但也有散在报道。2010年我院收治1名患者,现将其临床资料进行回顾性分析。     

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.     

肺动脉高压血管收缩与重塑的研究

肺动脉高压（PH）可以出现在原发于肺动脉的疾病（如特发性肺动脉高压，IPAH）或者继发于心肺疾病同时伴有肺动脉高压的疾病（如继发性肺动脉高压，SPH）。由于肺动脉高压发病机制复杂且有许多机制不明，治疗效果不理想。特别是IPAH，一经确诊，平均存活时间只有2．5年，有学者认为其预后比恶性肿瘤还差。诸多致病因素参与了肺动脉高压的发生与发展并最终引起血管收缩，导致血管重塑。     

特发性肺动脉高压的药物治疗进展

特发性肺动脉高压(IPAH)是指原因不明的肺血管阻力增加引起持续性肺动脉压力升高,其病理改变为肺血管的收缩和重塑、原位血栓形成和血管内皮损伤。由于缺乏有效的治疗措施,病死率极高,预后差,明确诊断后平均存活时间为2~3年。近年来随着对IPAH的分子生物学水平研究的深入,一些新的治疗方法如前列环素及其衍生物、内皮素受体拮抗剂等不断应用于临床,使IPAH的生存率明显提高,生活质量明显改善。而一些被证明对IPAH具有潜在治疗意义的药物如肾上腺髓质素、西地那非、他汀类药物等仍在临床研究中,在不久的将来可能成为治疗IPAH的一线用药。     

Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots

Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and a course that is unpredictable. Pulmonary hypertension may complicate the course of IPF and potentially impact prognosis. There are multiple factors that might influence the onset and severity of pulmonary hypertension in IPF. The relationship between the physiologic and pathobiologic manifestations of the progressive fibrotic process and interceding pulmonary hypertension has not been well defined. This article serves to explore these relationships and to hypothesize about the possible linkage between these entities. From a prognostic standpoint, recent evidence suggests this to be important to assess for pulmonary hypertension in patients with IPF. The appropriate triggers for evaluating for pulmonary hypertension and the best method of detection require further study. Despite the relative ease of noninvasive methods, such as echocardiography, right-heart catheterization remains the best diagnostic test. The appeal of pulmonary hypertension in IPF is that it may be an enticing therapeutic target in a disease that otherwise does not have any proven effective therapies. Which agent(s) might be useful and when they should be implemented mandate the appropriate studies being performed. Some of the data presented in this article have previously been reported in abstract form only.     

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a devastating, age-related lung disease of unknown cause that has few treatment options. This disease was once thought to be a chronic inflammatory process, but current evidence indicates that the fibrotic response is driven by abnormally activated alveolar epithelial cells (AECs). These cells produce mediators that induce the formation of fibroblast and myofibroblast foci through the proliferation of resident mesenchymal cells, attraction of circulating fibrocytes, and stimulation of the epithelial to mesenchymal transition. The fibroblast and myofibroblast foci secrete excessive amounts of extracellular matrix, mainly collagens, resulting in scarring and destruction of the lung architecture. The mechanisms that link idiopathic pulmonary fibrosis with ageing and aberrant epithelial activation are unknown; evidence suggests that the abnormal recapitulation of developmental pathways and epigenetic changes have a role. In this Seminar, we review recent data on the clinical course, therapeutic options, and underlying mechanisms thought to be involved in the pathogenesis of idiopathic pulmonary fibrosis.     

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF), known in Europe as cryptogenic fibrosing alveolitis, is a rare, progressive and usually fatal form of idiopathic interstitial pneumonia. IPF is characterized by failure of alveolar re-epithelization, persistence of fibroblasts, deposition of extracellular matrix, and distortion of lung architecture which ultimately results in respiratory failure. Current consensus statements reserve the term IPF to refer to a specific clinical entity associated with the histopatological pattern of usual interstitial pneumonia (UIP). UIP is characterized by temporal heterogeneity, with alternating areas of interstitial fibrosis, fibroblastic foci (areas of proliferating fibroblasts and myofibroblasts), inflammation, honeycomb lung, and normal parenchyma. Fibroblastic foci are associated with progressive disease. Treatment of IPF remains clinical problem. Currently, there is no conservative therapy improving the survival of patients. Lung transplantation, however, improves survival. Identification of pathways crucial to fibrogenesis might offer potentially novel therapeutic targets to slow or halt progression of IPF.     

Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis

STUDY OBJECTIVES: The development of pulmonary arterial hypertension (PAH) can complicate many interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). We sought to characterize the prevalence of PAH and its impact on survival in patients with advanced IPF. DESIGN: Retrospective analysis of consecutive IPF patients undergoing pretransplantation right heart catheterization. SETTING: Lung transplant and IPF referral center. METHODS: PAH was defined as a mean pulmonary artery pressure (mPAP) of > 25 mm Hg. We compared demographic, spirometric, 6-min walk test (6MWT) results, and survival outcomes between those with PAH and those without PAH. MEASUREMENTS AND RESULTS: Seventy-nine patients were included in the study. PAH was present in 31.6% of patients (mean [+/- SD] mPAP, 29.5 +/- 3.3 vs 19.1 +/- 3.7 mm Hg, respectively). Those patients with PAH had a lower mean diffusing capacity of the lung for carbon monoxide (Dlco) (37.6 +/- 11.3% vs 31.1 +/- 10.1%, respectively; p = 0.04) and were more likely to require supplemental oxygen (66.7% vs 17.6%, respectively; p < 0.0001). Mean distance walked (143.5 +/- 65.5 vs 365.9 +/- 81.8 m, respectively; p < 0.001) and mean pulse oximetric saturation nadir (80.1 +/- 3.7% vs 88.0 +/- 3.5%, respectively; p < 0.001) during the 6MWT were also lower among those with PAH. PAH was associated with a greater risk of death during the study period (mortality rate, 60.0% vs 29.9%, respectively; odds ratio, 2.6; 95% confidence interval [CI], 2.3 to 3.1; p = 0.001). One-year mortality rates were higher in those with PAH (28.0% vs 5.5%, respectively; p = 0.002). As a predictor of mortality, PAH had a sensitivity, specificity, and accuracy of 57.1%, 79.3%, and 73.4%, respectively. There was a linear correlation between mPAP and outcomes with higher pressures associated with a greater risk of mortality (hazard ratio, 1.09; 95% CI, 1.02 to 1.16). FVC and Dlco did not predict outcomes. CONCLUSIONS: PAH is common in advanced cases of IPF and significantly impacts survival. A reduced Dlco, supplemental oxygen requirement, or poor 6-min walk performance should raise suspicion of the presence of underlying PAH. Identifying PAH might be an important adjunct in monitoring disease progression, triaging for transplantation, and guiding therapy.     

Idiopathic pulmonary fibrosis and malignancy

The reported frequency of lung cancer in the setting of diffuse pulmonary fibrosis varies greatly, depending on the country of origin and the type of study. Most recent reports regarding diffuse pulmonary fibrosis in general and idiopathic pulmonary fibrosis in particular and lung cancers come from Japan; only a few clinical studies of this issue are available from other countries of the world, including the United States. The reported frequency ranges from 4.8% in the United States to 48.2% in Japan. The most frequent type of cancer is adenocarcinoma. Risk factors may include cigarette smoking, exposure to metal dusts, onset of idiopathic pulmonary fibrosis at an older age, and male predominance. Possible pathologic mechanisms are summarized. Given the very poor prognosis of idiopathic pulmonary fibrosis itself, with a mean survival of only 2.8 years, and that different diagnostic criteria were used in each study, it is likely that many of these studies are flawed because they evaluate lesions other than idiopathic pulmonary fibrosis. Thus, the frequency of lung cancer in idiopathic pulmonary fibrosis is still uncertain, and clearly requires follow-up of cohorts of clinically well-characterized patients, using standard diagnostic criteria for idiopathic pulmonary fibrosis. Finally, if the association between idiopathic pulmonary fibrosis and lung cancer is reconfirmed in these studies, the molecular and genetic mechanisms governing the development of lung cancer in this setting require additional study.