特发性肺纤维化患者血硫化氢水平下降

目的探讨特发性肺纤维化(IPF)患者疾病过程中内源性硫化氢(H2S)的变化和意义,及其与IPF疾病严重程度的关系。方法将研究对象分为IPF组和对照组,检测各组血浆H2S含量。对IPF组行动脉血氧分压、红细胞沉降率(ESR)、C反应蛋白(CRP)、乳酸脱氢酶(LDH)、肺功能及高分辨CT(HRCT)检查;测定IPF组患者在症状急性加重和缓解时血浆H2S含量。结果(1)IPF组血浆H2S含量明显低于对照组(P<0.01);(2)IPF组血浆H2S含量在急性加重时明显高于症状缓解时(P<0.01);(3)随影像学病变进展,IPF组患者血浆H2S含量无明显下降。结论内源性H2S可能参与了IPF的疾病过程,可能与疾病的严重程度相关。     

60例特发性肺纤维化患者中医治疗临床体会

目的：探讨中医治疗特发性肺纤维化的临床疗效。方法选取我院2011年1月~2013年6月收治的60例特发性肺纤维化患者作为观察对象,将患者随机分为观察组和对照组,每组各30例。对对照组进行常规治疗,对观察组给予中医的治疗方法,比较两组患者治疗后的临床疗效。结果观察组成功治疗29例,成功率为96%;对照组成功治疗23例,成功率为74%,两组比较差异具有统计学意义(P<0.05)。结论在临床应用,中医治疗特发性肺纤维化临床疗效的成功率更高,能够有效减少患者的痛苦且见效快,具有推广价值。     

特发性肺纤维化的生物力学特性

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)是常见的慢性间质性纤维化疾病。纤维化进程中,肌成纤维细胞异常活化,胶原蛋白大量沉积,肺组织生物力学特征发生显著变化。研究表明,生物力学因素在IPF疾病发生发展中发挥重要作用。本文对IPF进程中肺组织、细胞生物力学特性的变化以及生物力学信号的转导进行系统综述,并总结IPF生物力学特征的体外再现及靶向生物力学的治疗策略,为IPF临床防治提供参考。     

特发性肺纤维化/普通型间质性肺炎

1969年Liebow首次提出间质性肺炎的5种病理分类,分别是普通型间质性肺炎(UIP)、脱屑性间质性肺炎(DIP)、闭塞性细支气管炎间质性肺炎(BIP)、淋巴性间质性肺炎(LIP)、巨细胞性间质性肺炎(GIP)。近年来国际上对特发性间质性肺炎(IIP)的研究和认识进展很快,1998年Katzenstein和Myers剔除LIP、GIP和BIP,提出从病因学角     

特发性肺纤维化与代谢失调的研究进展

<正>特发性肺纤维化（idiopathic pulmonary fibrosis,IPF）是一种病因不明的慢性间质性肺病（interstitiallung disease,ILD）,该病在放射学和病理组织学上表现为间质性肺炎,并伴有实质纤维化和过度胶原沉积。IPF多发于65岁以上的吸烟者,常伴进行性呼吸困难和肺功能恶化,如不积极治疗,确诊后平均预期寿命仅有3～5年。随着全球人口老龄化,     

特发性肺纤维化（IPF）的CT诊断

目的评价CT对特发性肺纤维化(IPF)的诊断及鉴别诊断的价值.方法经临床证实的30例IPF患者行CT扫描后,对感兴趣区(ROI)行后重建薄层处理观察病变的分布及CT表现.结果 30例中磨玻璃样密度影19例,小叶间隔增厚10例,小叶内间质增厚14例,蜂窝肺25例,小叶结构变形21例交界面不规则19例,胸膜增厚13例,上述症状均有者5例.结论 CT能较细致、准确地反映IPF的大体病理变化.但各种征象均可见于其他各种间质性疾病,小叶间隔增厚及小叶间质增厚伴有肺结构变形和病变的周围型分布对诊断和鉴别诊断较有意义.诊断须结合临床并除外其他原因引起的肺纤维化.     

内源性气体信号分子和调节肽在特发性肺纤维化发病中的作用

特发性肺纤维化是一种病因不明的慢性进行性肺疾病,以纤维增殖、肺实质的破坏及细胞外基质的沉积为特征,其发病机制尚不明确。近几年的研究发现内源性气体信号分子(一氧化氮、一氧化碳和硫化氢)及调节肽(血管紧张素II、松弛素和尾加压素等)在调节肺纤维化,参与特发性肺纤维化的发病中发挥重要的作用。     

PAI-1基因4G/5G多态性与特发性肺纤维化的相关性研究

目的探讨纤溶酶原激活剂抑制物-1（plasminogen activator inhibitor-1,PAI-1）基因启动子区4G/5G多态性与特发性肺纤维化（IPF）的相关性。方法应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析,检测42例IPF患者和164例正常对照组人群PAI-1基因4G/5G多态性。结果PAI-1基因4G/4G、4G/5G、5G/5G基因型频率分布,IPF组分别为31.0%、50.0%、19.0%,对照组分别为17.1%、54.9%、28.0%;4G和5G等位基因频率,IPF组分别为0.560和0.440,对照组分别为0.445和0.555;4G/4G基因型频率IPF组显著高于对照组（P〈0.05）。与4G/5G和5G/5G基因型比较,携带4G/4G型个体发生IPF的风险增加2.18倍,95%CI：1.02～4.68（P〈0.05）。结论PAI-1基因4G/5G多态性与IPF的发病相关,纯合子4G/4G基因型可能是IPF发病的重要危险因素之一。     

24例特发性肺纤维化合并糖尿病病人诊治体会

特发性肺间质纤维化（IPF）是下呼吸道的间质性疾病,累及终末气道、肺泡上皮细胞、肺毛细血管内皮细胞和肺动静脉,使肺间质纤维组织大量增生,气体交换发生障碍。其发病率逐年增加,已成为呼吸科常见病之一,而特发性肺间质纤维化合并糖尿病在临床也显著增加,现将本科自2000年至今诊断的24例临床资料总结如下：     

特发性肺纤维化的16层螺旋CT表现特征及其解剖、病理基础

为明确特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的16层螺旋CT表现特征、合并症及其解剖的优势分布。对临床病理证实的IPF38例行16层螺旋CT检查,其中26例追加薄层CT扫描。观察IPF的CT征像和合并症,评价其CT征像在解剖中优势分布。其中蜂窝肺14例(36.8%),10例(71.4%)主要分布于中下肺的外带、以双肺下叶基底段显著,4例(28.6%)呈弥漫性分布,11例(78.6%)病程在3年以上。小叶内间质增厚16例(42.1%)、小叶间隔增厚20例(52.6%)及支气管血管束增粗9例(23.7%),分别优势分布于中下肺的外带、双肺下叶基底段,双肺下叶及右肺中叶中内带。磨玻璃样密度影15例(39.5%),优势分布于肺的外带,主要以双肺下叶基底段显著;其中10例(66.7%)病程在1年以下。结果表明IPF的16层螺旋CT征象能反映其病理变化,在解剖分布上有明显特点。     

Sputum eosinophilia in idiopathic pulmonary fibrosis

Objectives and Design: Cough is a common symptom in idiopathic pulmonary fibrosis that is difficult to treat and has a major impact on quality of life. We tested the hypothesis that the cough and increased cough reflex sensitivity seen in patients with idiopathic pulmonary fibrosis may be due to airway inflammation in a prospective, cross-sectional study.Subjects and Methods: We measured the induced sputum inflammatory cell profile and cell-free supernatant inflammatory mediator concentrations in 15 patients with idiopathic pulmonary fibrosis, 17 healthy controls and 15 patients with chronic obstructive pulmonary disease.Results: Both the geometric mean sputum differential eosinophil cell count and median eosinophilic-cationic-protein concentration were significantly higher in patients with idiopathic pulmonary fibrosis than controls (2.1% vs 0.3%; p < 0.001 and 1.1 mg/ml versus 0.2 mg/ml; p = 0.03 respectively). There were no significant differences in sputum eosinophil counts and eosinophilic-cationic-protein concentrations between patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Sputum leukotriene-B4 concentrations were significantly lower in patients with idiopathic pulmonary fibrosis (p = 0.03) and chronic obstructive pulmonary disease (p = 0.008) compared to controls.Conclusions: Idiopathic pulmonary fibrosis is characterised by the presence of active eosinophilic airway inflammation raising the possibility that airway inflammation may contribute to symptoms such as cough.Received 11 June 2004; returned for revision 20 August 2004; accepted by N. Boughton-Smith 24 September 2004Supported by a grant from the British Lung Foundation and University Hospitals of Leicester NHS Trust. S.S.B. is a British Lung Foundation clinical research fellow.     

Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1) and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP) using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF). Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci), severe (mural) fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.     

Increase in both angiogenic and angiostatic mediators in patients with idiopathic pulmonary fibrosis

Background

Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease.

Methods and results

Sixty-four subjects with IPF and 10 healthy control subjects (60–70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DL_CO < 40% or > 40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both < 55% or > 55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P = 0.0008) as well as those of TSP-1 (P = 0.008), irrespective of the severity of the disease as reflected by DL_CO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls.

Conclusions

Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.     

Reviews and prospectives of signaling pathway analysis in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing disease with disappointing survival rate, and uneffective therapeutic progress has been made in the last few years, forcing the urgent need to improve research to this disease. The commonly accepted pathogenic hypothesis of IPF is the trigger from continuous alveolar epithelium microinjuries and in the following series events, many signaling pathways were reported to lead to abnormal tissue repair and lung structure derangement in IPF, such as TGF-β, wnt, VEGF and PI3K–Akt signaling pathways. Traditional research of IPF related signaling pathway always focus on the independent function of pathway and disease signals, but the crosstalks and interactions among them were rarely valued. In this review, we summarize the signaling pathways which were reported to play important roles in the pathologic changes of IPF and the synergistic effect among those pathways. Next we discuss the application of genomics research and bioinformatics tools on IPF related pathway analysis, and give a systems biology perspective by integrating multi-level disease related data. The novel prospective of pathway analysis could tease out the complex pathway interaction profiles of IPF, and is powerful to detect IPF related biomarkers for early diagnose and potential therapeutic targets.     

Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis

Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis‐associated lung cancer (IPF‐LC). This study was performed to investigate the genomic profiles of IPF‐LC and to explore the possibility of defining potential therapeutic targets in IPF‐LC. We assessed genomic profiles of IPF‐LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice‐site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC‐related mutagenesis and the development of IPF‐LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF‐LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK–STAT signalling pathway were significantly amplified in IPF‐LC (P = 0.012). This study demonstrates that IPF‐LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Pulmonary vascular lesions in end-stage idiopathic pulmonary fibrosis: Histopathologic study on lung explant specimens and correlations with pulmonary hemodynamics

In patients presenting with idiopathic pulmonary fibrosis (IPF), modifications of pulmonary vessels are well defined in fibrotic areas but have not been accurately assessed in the intervening patches of preserved lung. Moreover, the relation between pulmonary vessel lesions and pulmonary hemodynamics is not well known. We therefore designed a retrospective study on lung explant specimens from 26 patients with a firm diagnosis of IPF who had undergone lung transplantation. Our aim was to (1) describe the vascular lesions, especially in preserved lung areas, and (2) correlate them with pulmonary hemodynamics. In dense fibrotic zones, thickening of the arterial and venous wall with severe luminal narrowing was present in each patient. In architecturally preserved lung zones, occlusion of venules and small pulmonary veins was observed in 65% of the patients, although there were only mild changes of muscular pulmonary arteries. We found a significant positive correlation between the macroscopic extent of lung fibrosis and mean pulmonary artery pressure, but we failed to find a relation between mean pulmonary artery pressure and venous/venular lesions in nonfibrotic areas. Our study points out that in many patients with IPF, nonfibrotic lung areas demonstrate an occlusive venopathy, the signification of which remains undetermined.