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Idiopathic interstitial pneumonias最新文献

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Matrix metalloproteinases, as markers of the severity of idiopathic pulmonary fibrosis 基质金属蛋白酶,作为特发性肺纤维化严重程度的标志
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa4706
K. Gashynova, V. Rodionova, O. Karasyova, O. Shaulska, O. Khmel
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引用次数: 1
Late Breaking Abstract - BBT-877, a Potent Autotaxin Inhibitor in Clinical Development to Treat Idiopathic Pulmonary Fibrosis 摘要:BBT-877,一种治疗特发性肺纤维化的强效自taxin抑制剂
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1293
Gwanghee Lee, Sang-Uk Kang, Jeong-Hyun Ryou, Jongwon Lim, Yong-Hee Lee
Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible and fatal lung disease with unmet medical needs. Autotaxin (ATX) is an extracellular enzyme involved in the generation of lysophosphatidic acid (LPA). Preclinical and clinical data have suggested the ATX – LPA – LPA receptor (LPAR) axis plays a pivotal role in the pathogenesis and the progression of IPF. BBT-877 is an orally available small molecule inhibitor against ATX. In ex vivo enzymatic assays using human plasma, IC50 of BBT-877 was measured 6.5 – 6.9 nM (LPA 18:2) whereas that of GLPG1690 was measured 75 – 132 nM. To determine in vivo anti-fibrotic efficacy of BBT-877, bleomycin was intranasally administrated in mice at day 0, and BBT-877 was administrated orally twice a day from day 7 to 21. The BBT-877 treatment showed anti-fibrotic efficacy as revealed by significantly reduced body weight loss, lung weight and Ashcroft score as well as collagen content compared to the vehicle-treated group. During phase 1 clinical trial with 80 healthy volunteers, in which 50 – 800 mg (SAD) and 200 – 800 mg QD or 100 – 200 mg BID for two weeks (MAD) doses were administrated, only mild adverse events were noted. Pharmacokinetic analysis revealed the dose-proportional increase in systemic exposure with elimination half-life of 12hr. The decrease of plasma LPA level was maintained at 80% or higher for 24hr when 400 mg BBT-877 was administrated. Taken together, nonclinical data suggest BBT-877 is a potent, selective, and potentially best-in-class ATX inhibitor. Phase 1 clinical data demonstrate BBT-877 is a safe and well-tolerated drug with excellent pharmacokinetic-pharmacodynamic profiles.
特发性肺纤维化(IPF)是一种进行性、不可逆和致命的肺部疾病,医疗需求未得到满足。Autotaxin (ATX)是一种参与溶血磷脂酸(LPA)生成的细胞外酶。临床前和临床数据表明,ATX - LPA - LPA受体(LPAR)轴在IPF的发病和进展中起关键作用。BBT-877是一种口服的抗ATX小分子抑制剂。在人血浆离体酶促实验中,BBT-877的IC50为6.5 - 6.9 nM (LPA 18:2), GLPG1690的IC50为75 - 132 nM。为了确定BBT-877的体内抗纤维化效果,在第0天小鼠鼻内给药博来霉素,在第7天至第21天每天口服两次。与载体治疗组相比,BBT-877治疗组的体重减轻、肺重量、Ashcroft评分以及胶原蛋白含量均显著降低,显示出抗纤维化疗效。在80名健康志愿者的1期临床试验中,他们给药50 - 800毫克(SAD)、200 - 800毫克QD或100 - 200毫克BID,持续两周(MAD),只发现轻微的不良事件。药代动力学分析显示,全身暴露剂量正比增加,消除半衰期为12小时。给药400mg BBT-877后24小时血浆LPA水平下降维持在80%以上。综上所述,非临床数据表明,BBT-877是一种有效的、选择性的、可能是同类最佳的ATX抑制剂。1期临床数据表明,BBT-877是一种安全且耐受性良好的药物,具有良好的药代动力学-药效学特征。
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引用次数: 7
Pulmonary fibrosis modulation by mesenchymal stem cells and conditioned medium 间充质干细胞和条件培养基对肺纤维化的调节作用
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1284
R. Felix, A. L. C. Bovolato, P. D. Leão, M. Golim, W. Teodoro, A. Fabro, E. Deffune, V. Capelozzi
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引用次数: 2
Interstitial lung disease related surfactant protein-C mutations alter the transcriptome and progenitor cell function of alveolar epithelial cells in mice 肺间质性疾病相关表面活性剂蛋白- c突变改变小鼠肺泡上皮细胞的转录组和祖细胞功能
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1291
J. Katzen, A. Venosa, Y. Tomer, Meghan C. Kopp, Michael Morely, A. Diwadkar, E. Morrisey, B. Himes, S. Mulugeta, M. Beers
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引用次数: 1
Predictive value of 18F-FDG PET/CT for chemotherapy-related acute exacerbation of interstitial lung disease in lung cancer patients with interstitial lung disease 18F-FDG PET/CT对肺癌间质性肺病患者化疗相关急性加重的预测价值
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1313
K. Akaike, K. Saruwatari, S. Oda, S. Hamada, Y. Tomita, S. Saeki, H. Ichiyasu, K. Fujii, S. Shiraishi, T. Sakagami
Background: Acute exacerbation (AE) of interstitial pneumonia disease (ILD) in lung cancer (LC) patients with ILD could be one of the lethal adverse effect related to chemotherapy. The purpose of this study was to determine if the result of 18F-FDG PET/CT before chemotherapy could predict onset of chemotherapy-related AE-ILD in LC patients with ILD. Methods: Between April 2006 and March 2018, 33 patients with LC and ILD performed 18F-FDG PET/CT and treated with chemotherapy in Kumamoto University Hospital. The SUVmax of interstitial lesion was measured to quantify the background ILD activity. A prediction model chemotherapy-related AE of ILD was developed using a logistic regression and ROC curve analysis. Results: Among 33 patients, 7 experienced AE of ILD (AE group) and 26 did not (non-AE group), the SUVmax of contralateral interstitial lesion in AE group was significantly higher than that in non-AE group (median SUVmax 2.22 vs. 1.80, P = 0.041). An univariable logistic regression analysis showed that the SUVmax of contralateral interstitial lesion had potential to be associated with chemotherapy-related AE of ILD (odds ratio, 8.683; 95% confidence interval [CI], 0.88–85.83; P = 0.064). The AUC of the SUVmax for predicting chemotherapy-related AE of ILD was 0.780 (95% CI: 0.579-0.982, P = 0.025). The optimal cut-off value for SUVmax was 2.005. Sensitivity and specificity value for this cut-off point were 0.857 and 0.769, respectively. Conclusions: The SUVmax of contralateral interstitial lesion in 18F-FDG PET/CT might be useful to predict chemotherapy-related AE of ILD in LC with ILD.
背景:肺癌(LC)间质性肺炎(ILD)患者急性加重(AE)可能是化疗相关的致死性不良反应之一。本研究的目的是确定化疗前18F-FDG PET/CT结果是否可以预测LC合并ILD患者化疗相关AE-ILD的发病。方法:2006年4月至2018年3月,33例LC和ILD患者在熊本大学医院进行了18F-FDG PET/CT检查并接受了化疗。测量间质病变的SUVmax以量化背景ILD活性。采用logistic回归和ROC曲线分析建立了化疗相关AE的预测模型。结果:33例患者中,有7例发生了ILD的AE (AE组),26例未发生AE(非AE组),AE组对侧间质病变SUVmax显著高于非AE组(中位SUVmax 2.22 vs. 1.80, P = 0.041)。单变量logistic回归分析显示,对侧间质病变SUVmax可能与化疗相关的ILD AE相关(优势比8.683;95%置信区间[CI], 0.88-85.83;P = 0.064)。SUVmax预测ILD化疗相关AE的AUC为0.780 (95% CI: 0.579 ~ 0.982, P = 0.025)。SUVmax的最佳临界值为2.005。该分界点的敏感性和特异性分别为0.857和0.769。结论:18F-FDG PET/CT对侧间质病变SUVmax可用于预测LC合并ILD患者化疗相关AE。
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引用次数: 0
STARMAP: an observational study to assess disease-relevant outcomes using home-monitoring devices in patients with idiopathic pulmonary fibrosis (IPF) STARMAP:一项观察性研究,评估特发性肺纤维化(IPF)患者使用家庭监测设备的疾病相关结果
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1333
J. Swigris, S. Nathan, R. Tighe, Sunny Nagra, C. Rabe, Douglas O. Kelkhoff, Thomas Switzer, N. Kolatkar, P. Belloni, J. Golden
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引用次数: 5
Late Breaking Abstract - Transbronchial lung cryobiopsy for interstitial lung disease diagnosis: results of the COLDICE Study 经支气管肺低温活检诊断间质性肺疾病:COLDICE研究的结果
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.rct1886
L. Troy, C. Grainge, T. Corte, J. Williamson, M. Vallely, W. Cooper, A. Mahar, J. Myers, Simon Lai, Ellie Mulyadi, P. Torzillo, M. Phillips, H. Jo, Susanne E Webster, Qi Lin, J. Rhodes, M. Salamonsen, J. Wrobel, B. Harris, G. Don, P. Wu, B. Ng, C. Oldmeadow, G. Raghu, E. Lau, Coldice Investigators
Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease (ILD) diagnosis. Despite increasing use, the diagnostic accuracy of TBLC compared to surgical lung biopsy (SLB) remains unclear. Methods: We conducted a prospective, multicenter study investigating agreement between TBLC and SLB. ILD patients referred for lung biopsy after central screening underwent sequential TLBC and SLB, under one anesthetic. Blinded analysis of samples was conducted by 3 pathologists, individually and by consensus. At multidisciplinary discussion (MDD), deidentified cases were discussed twice with either TBLC or SLB along with clinical and radiology data, in random non-consecutive order. Primary endpoints were agreement of TBLC and SLB for 1) “definite/probable usual interstitial pneumonia (UIP)”, “indeterminate for UIP” and “alternative diagnosis” histopathologic patterns; and for 2) MDD diagnoses. Concordance and kappa values were calculated. Results: 65 patients (30 males; age 66±9yrs; FVC 84±14%; DLCO 63±13%) were enrolled. TBLC (7.1±1.9mm) and SLB samples (47±15mm) were taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70.8%, weighted κ 0.70 (95%CI 0.55-0.86); agreement at MDD was 76.9%, κ 0.62 (95%CI 0.47-0.78). For TBLC with high/definite diagnostic confidence at MDD (39/65, 60% cases), 94.9% were concordant with SLB diagnoses. In the 26 with low-confidence/unclassifiable TBLC diagnoses, SLB reclassified only 6 to alternative high/definite MDD diagnoses. Conclusion: High agreement between TBLC and SLB for pathologic and MDD diagnoses support the clinical utility of TBLC in ILD diagnostic algorithms.
经支气管肺低温活检(TBLC)是一种新的肺组织取样技术,用于诊断间质性肺疾病(ILD)。尽管TBLC的使用越来越多,但与外科肺活检(SLB)相比,TBLC的诊断准确性仍不清楚。方法:我们进行了一项前瞻性、多中心研究,调查TBLC和SLB之间的一致性。ILD患者在中心筛查后行序贯TLBC和SLB,在一种麻醉下进行肺活检。3名病理学家分别和一致对样本进行盲法分析。在多学科讨论(MDD)中,以随机、非连续的顺序,对未确诊病例与TBLC或SLB以及临床和放射学数据进行了两次讨论。主要终点是TBLC和SLB的一致性:1)“明确/可能的通常间质性肺炎(UIP)”,“UIP不确定”和“替代诊断”的组织病理学模式;2)重度抑郁症诊断。计算一致性和kappa值。结果:65例患者(男性30例;年龄66±9岁;FVC 84±14%;DLCO为63±13%)。TBLC(7.1±1.9mm)和SLB(47±15mm)分别取自两个同侧叶。TBLC和SLB的组织病理学一致性为70.8%,加权κ 0.70 (95%CI 0.55 ~ 0.86);MDD的一致性为76.9%,κ 0.62 (95%CI 0.47-0.78)。对于重度抑郁症高/明确诊断置信度的TBLC(39/65, 60%), 94.9%与SLB诊断一致。在26例低可信度/无法分类的TBLC诊断中,SLB仅将6例重新分类为替代性高/明确MDD诊断。结论:TBLC和SLB在病理和重度抑郁症诊断上的高度一致性支持TBLC在ILD诊断算法中的临床应用。
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引用次数: 3
Risk factors for diagnostic delay in a prospective IPF-cohort 在一个前瞻性ipf队列中诊断延迟的危险因素
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1724
N. Hoyer, T. Prior, E. Bendstrup, T. Wilcke, S. Shaker
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引用次数: 0
Efficacy of switching antifibrotic therapy in idiopathic pulmonary fibrosis: real life data 转换抗纤维化治疗在特发性肺纤维化中的疗效:真实生活数据
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1727
Ivonne M. Raats ten Cate, C. V. Moorsel, A. Meer, P. Zanen, J. Grutters
{"title":"Efficacy of switching antifibrotic therapy in idiopathic pulmonary fibrosis: real life data","authors":"Ivonne M. Raats ten Cate, C. V. Moorsel, A. Meer, P. Zanen, J. Grutters","doi":"10.1183/13993003.congress-2019.pa1727","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1727","url":null,"abstract":"","PeriodicalId":13242,"journal":{"name":"Idiopathic interstitial pneumonias","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78947618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Change in serum surfactant protein (SP)-A, SP-D and KL-6 predict the therapeutic effect of antifibrotic drugs in IPF 血清表面活性蛋白(SP)-A、SP- d和KL-6的变化预测抗纤维化药物对IPF的治疗效果
Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa4704
Takumi Yoshikawa, M. Otsuka, Kimiyuki Ikeda, Yuki Mori, Yasuaki Umeda, Hirotaka Nishikiori, Satsuki Miyajima, Mamoru Takahashi, K. Kuronuma, H. Chiba, Hiroki Takahashi
Background: Serum surfactant protein (SP)-A, SP-D, and KL-6 are prognostic biomarkers of patients with idiopathic pulmonary fibrosis (IPF), however, the relationship with the therapeutic effect of antifibrotic drugs has not been investigated. Aim: To clarify whether serum SP-A, SP-D and KL-6 are therapeutic predictive markers of pirfenidone and nintedanib in patients with IPF. Methods: We retrospectively investigated patients with IPF who started pirfenidone or nintedanib between January 2014 and June 2018 at our hospital. The change in clinical parameters and serum SP-A, SP-D and KL-6 levels were evaluated. Patients with a > 10% decline in forced vital capacity (FVC) or a > 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as a deterioration group and the other was classified as an effective group. Results: Forty-nine patients were included (pirfenidone; 23, nintedanib; 26). Thirty-two patients were the effective group and 17 patients were the deterioration group. In the effective group, the change in serum SP-A, SP-D, and KL-6 from baseline to 3 and/or 6 months significantly decreased compared with the deterioration group. The change in serum SP-A and SP-D showed significant negative correlations with the change in %FVC and %DLCO. According to the logistic regression analysis, the decrease in SP-A from baseline to 3 months was a predictor of the effect at 6 months (odd’ ratio 0.88). Conclusions: Change in SP-A, SP-D and KL-6 represent the therapeutic effect of antifibrotic drugs. These may be therapeutic predictive biomarkers of antifibrotic drugs.
背景:血清表面活性蛋白(SP)-A、SP- d和KL-6是特发性肺纤维化(IPF)患者的预后生物标志物,但其与抗纤维化药物治疗效果的关系尚未研究。目的:阐明血清SP-A、SP-D和KL-6是否为IPF患者吡非尼酮和尼达尼布治疗的预测指标。方法:回顾性调查2014年1月至2018年6月在我院开始使用吡非尼酮或尼达尼布的IPF患者。观察两组临床指标及血清SP-A、SP-D、KL-6水平的变化。从基线到6个月,用力肺活量(FVC)下降> 10%或肺一氧化碳弥散量(DLco)下降> 15%的患者归为恶化组,另一组归为有效组。结果:纳入49例患者(吡非尼酮;23日,nintedanib;26)。有效组32例,恶化组17例。与恶化组相比,有效组血清SP-A、SP-D和KL-6从基线到3和/或6个月的变化显著降低。血清SP-A、SP-D的变化与FVC %、DLCO %的变化呈显著负相关。根据logistic回归分析,SP-A从基线到3个月的下降是6个月效果的预测因子(奇数比0.88)。结论:SP-A、SP-D和KL-6的变化反映了抗纤维化药物的治疗效果。这些可能是抗纤维化药物的治疗预测性生物标志物。
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引用次数: 0
期刊
Idiopathic interstitial pneumonias
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