特发性肺纤维化的药物治疗进展

近年来 ,随着对特发性肺纤维化发病机制和病理生理变化的深入研究和分子生物学技术的应用 ,治疗上有了新的突破。现从免疫抑制剂、抗纤维化、细胞因子、抗氧化、中药等方面作一综述。     

Red Cell Distribution Width Is Independently Associated with Mortality in Sepsis

BackgroundMortality in sepsis remains high. Studies on small cohorts have shown that red cell distribution width (RDW) is associated with mortality. The aim of this study was to validate these findings in a large multicenter cohort.MethodsWe conducted this retrospective analysis of the multicenter eICU Collaborative Research Database in 16,423 septic patients. We split the cohort in patients with low (≤15%; n = 7,129) and high (>15%; n = 9,294) RDW. Univariable and multivariable multilevel logistic regressions were used to fit regression models for the binary primary outcome of hospital mortality and the secondary outcome intensive care unit (ICU) mortality with hospital unit as random effect. Optimal cutoffs were calculated using the Youden index.ResultsPatients with high RDW were more often older than 65 years (57% vs. 50%; p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) IV scores (69 vs. 60 pts.; p < 0.001). Both hospital (adjusted odds ratios [aOR] 1.18; 95% CI: 1.16–1.20; p < 0.001) and ICU mortality (aOR 1.16; 95% CI: 1.14–1.18; p < 0.001) were associated with RDW as a continuous variable. Patients with high RDW had a higher hospital mortality (20 vs. 9%; aOR 2.63; 95% CI: 2.38–2.90; p < 0.001). This finding persisted after multivariable adjustment (aOR 2.14; 95% CI: 1.93–2.37; p < 0.001) in a multilevel logistic regression analysis. The optimal RDW cutoff for the prediction of hospital mortality was 16%.ConclusionWe found an association of RDW with mortality in septic patients and propose an optimal cutoff value for risk stratification. In a combined model with lactate, RDW shows equivalent diagnostic performance to Sequential Organ Failure Assessment (SOFA) score and APACHE IV score.     

维持性血液透析患者红细胞体积分布宽度及相关影响因素研究

目的：了解维持性血液透析患者的红细胞体积分布宽度（redbloodcelldistributionwidth,RDW）及其影响因素。方法：分析2012年1月-3月复旦大学附属中山医院血液净化中心维持性透析患者356例,其中男性226例,女性130例;年龄（59．2±14．5）岁;透析龄（64．3±42．5）个月。收集所有患者的临床病史,并于周中透析前检测血红蛋白（Hb）、RDW、电解质、高敏C反应蛋白（hsCRP）、血清白蛋白、前白蛋白、铁蛋白、转铁蛋白饱和度、甲状旁腺素和N端脑钠肽前体（NT-proBNP）,透析前后检测血肌酐、尿素氮并计算单室尿素清除指数（spKt／V）。结果：整组患者RDW为（15．14±1．22）％（13．0％～20．4％）,中位数14．9％;241例（67．7％）患者RDw水平超过参考值上限。男性患者RDW水平低于女性患者[（15．03±1．11）％比（15．33±1．39）％,P〈0．05]。Spearman相关分析提示,RDw与年龄（r=0．269,P〈0．00I）、透析龄（r=0．116,P=0．033）、每周促红细胞生成素（erythropoietin,EP0）剂量（r=0．250,P〈0．001）、EPo／Hb比值（r=0．214,P〈0．001）、hsCRP（r=0．335,P=d0．001）及NT—proBNP（r=0．133,P=0．027）呈正相关。RDW与血清白蛋白（r=-0．241,P〈0．001）、前白蛋白（r=-0．334,P〈0．001）呈负相关。多元线性逐步回归模型结果提示,RDW与血清白蛋白呈显著负相关（P〈0．01）。结论：血液透析患者中RDW水平异常并不少见,且与年龄、透析龄、营养水平、炎性反应状态、心脏功能、EPO剂量及反应等多项临床指标有关。RDW对透析人群预后的预测作用有待于进一步研究证实。     

胸部高分辨率CT对特发性肺纤维化的诊断价值

目的探讨胸部高分辨率ＣＴ对特发性肺纤维化的诊断价值。方法在常规胸部ＣＴ扫描的基础上对肺部局灶性或弥漫性病变区域再行ＨＲＣＴ扫描。结果ＩＰＦ的ＨＲＣＴ检查的典型表现是二肺弥漫性网织阴影,蜂窝状影,散在肺大泡,常有胸膜肥厚,胸膜下线,肺的外周部呈现多发的直径为１５～３０ｍｍ斑点状高密度影。结论ＨＲＣＴ技术能显著的提高ＩＰＦ的诊断率,是目前诊断ＩＰＦ无创性检查中最精确的方法之一。     

特发性肺纤维化的螺旋CT表现特征与临床病程的相关性

目的 评价特发性肺纤维化(IPF)的螺旋CT表现特征及其合并症与临床病程的关系。方法 收集经临床病理证实的IPF45例，全部行螺旋CT检查，其中25例对兴趣区追加高分辨率CT扫描。观察IPF的CT表现特征及其合并症，并按病程在1年以下、1～2年、2～3年及3年以上进行分组统计，评价各CT征象及其并发症在不同病程中的优势分布。结果 ①磨玻璃样密度影7例，优势地分布于肺的周边部，其中6例(85．7％)病程在1年以下。②小叶内间质增厚18例、小叶间隔增厚19例及支气管血管束增粗20例，其病程在2～3年分别为13例(72．2％)、14例(73．7％)和13例(65％)。③蜂窝肺27例中，21例(77．8％)分布于肺的周边部，其余6例呈弥漫性分布，常伴有牵拉性支气管扩张和、肺动脉高压，22例(81．5％)病程在3年以上。结论 螺旋CT征象能反应IPF的病理变化，并与IPF的病程存在一定的相关性，两者对lPF的诊断及判断其进展和预后具有重要意义。     

Evaluation of Activity Limitation in Patients With Idiopathic Pulmonary Fibrosis Grouped According to Medical Research Council Dyspnea Grade

Objective

To investigate the relations between Medical Research Council (MRC) dyspnea grade and peripheral muscle force, activities of daily living (ADL) performance, health status, lung function, and exercise capacity in subjects with idiopathic pulmonary fibrosis (IPF).

Design

Prospective cross-sectional observational study.

Setting

University hospital.

Participants

Subjects with IPF (N=65, 46 men) in a stable clinical state with a mean age of 68±7 years.

Interventions

Not applicable.

Main Outcome Measures

Right ventricular systolic pressure (RVSP) via transthoracic echocardiography, pulmonary function, isometric quadriceps force (QF) and handgrip force (HF), 6-minute walk distance (6MWD), ADL score, and health status (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]) were assessed and compared between subjects grouped according to MRC grade.

Results

Of the participants, 16 were in MRC grade 2, 17 were in MRC grade 3, 17 were in MRC grade 4, and 15 were in MRC grade 5. RVSP, pulmonary function, QF, HF, 6MWD, ADL, and SF-36 scores decreased with increasing MRC grade (all P<.001). All measures were lower (P<.05) in subjects with grades 4 and 5 than subjects with grades 2 and 3. Strong associations were found between MRC grade and 6MWD (ρ=−.89, P=.001) and ADL score (ρ=−.82, P=.001). MRC grade was also associated with RVSP, pulmonary function, QF, and HF (all ρ≥.56, P=.001).

Conclusions

The MRC dyspnea scale provides a simple and useful method of categorizing individuals with IPF with respect to their activity limitation and may assist in understanding the impact of IPF on an individual.     

胸部高分辨率CT对老年特发性肺纤维化的诊断价值

胸部高分辨率ＣＴ（ｈｉｇｈｒｅｓｏｌｕｔｉｏｎＣＴ，ＨＲＣＴ）的临床应用，显著地提高了特发性肺纤维化（ＩＰＦ）的诊断率。ＩＰＦ的ＨＲＣＴ检查典型表现是两肺弥漫性网织状影，蜂窝状影，散在肺大泡。常有胸膜肥厚，胸膜下线，肺的外周部呈现多发的直径１．５－３．０ｍｍ斑点状高密度影。本组１６例经ＨＲＣＴ扫描结合临床症状、体征、肺功能等项检查得以及时确诊及治疗，我们认为ＨＲＣＴ技术是目前诊断ＩＰＦ无创伤性检查中最精确的方法之一。     

急性心肌梗死患者红细胞分布宽度与N末端脑钠肽前体的关系研究

目的：红细胞分布宽度（RDW）越高,急性心肌梗死（AMI）患者预后越差,本研究探讨AMI患者RDW升高的内在机制。方法：102例确诊AMI患者（AMI组）、与150例稳定性冠心病的患者（CAD组）。所有入选者均检测RDW、高敏C反应蛋白（hsCRP）和N末端脑钠肽前体（NT—proBNP）,比较AMI组与cAD组RDW、hsCRP、NT—proBNP的差异。结果：CAD组的RDW显著低于AMI组（13．0％±0．7％比13．3％±0．9％;P=0．003）,但校正NT—proBNP后,2组间RDW水平的差异无统计学意义（P=0．488）。单变量线性相关及多变量分析提示,NT—proBNP而非hsCRP是RDw的独立预测因子。将入院第7天与入院第1天测得的变量差值进行分析发现,RDw的差值（△RDW）与NT—proBNP的对数差值（△logNT—proBNP）具有相关性。△RDw对NT—proBNP的变化具有中度预测价值（曲线下面积为0．71±0．05;P〈0．01）。结论：NT—proBNp而非hsCRP与AMI患者中RDW呈正相关,即心梗后心功能的恶化可能是导致患者RDw升高的主要原因。     

再生障碍性贫血中红细胞参数和血细胞变化的临床意义

目的：通过分析再生障碍性贫血中红细胞参数和血细胞变化,为再生障碍性贫血临床诊断提供筛选指标。方法：长期观察的7例慢性再生障碍性贫血（SAAⅡ）病儿血红蛋白（Hb）、血小板（PLT）、白细胞（WBC）、平均红细胞体积（MCV）及红细胞分布宽度（RDW）进行回顾性分析。结果：7例慢性再生障碍性贫血病儿标本中除治愈那例外,其他,全部标本MCV大于100fl、RDW小于14.6%。治愈1例在MCV下降前有6个月出现RDW上升,最高15.6%。结论：大MCV和小RDW是再生障碍性贫血较为特异表现,可作为临床筛选SAA指标。     

冠心病患者红细胞体积分布宽度变化及其临床意义

目的观察冠心病患者红细胞体积分布宽度(RDW)的变化,探讨其临床应用价值。方法选择我院2008年1月～2010年10月冠心病515例,随机分为心绞痛组365例,急性心肌梗死(AMI)组103例,急性心力衰竭(AHF)组47例,并选取同期健康体检430例作为对照组。均检测血红蛋白(Hb)、RDW、超敏C反应蛋白(hs-CRP)、B型脑钠肽(BNP)并进行比较。结果 515例冠心病RDW水平较对照组明显增高,差异有统计学意义(P<0.01);AHF组RDW水平较心绞痛组增高,差异有统计学意义(P<0.05);按照RDW四分位数分组,随着RDW的逐级增高,AMI、AHF的发病率逐级增高,冠心病患者病死率也逐级增高;RDW与BNP呈正相关(r=0.415,P<0.01),与hs-CRP亦呈正相关(r=0.234,P<0.01),但相关性较弱。结论 RDW可能为冠心病患者预后的独立预测因子,有助于判断冠心病患者的预后。     

急性特发性肺间质纤维化在影像学上的表现

介绍急性特发性肺间质纤维化的临床表现与影像学特征,以便及早作出诊断和治疗。方法该组6例有完整的临床、实验室结果、胸片、高分辧率CT(HRCT)资料并与病理活检做对照,重点介绍该病在高分辨率CT上的表现。结果6例临床表现为咳嗽、气急、呼吸困难和低氧血征。胸片显示两肺有多发的斑片状影。高分辧率CT上的表现是:磨玻璃样影、网状影以及晚期的蜂窝样影等。病灶以中下肺、胸膜下分布为主。结论临床表现、实验室检查、影像学特征相结合,有助于作出急性特发性肺间质纤维化的诊断,一经病理证实,及时治疗,部分病例可获得好的结果。     

Association Between Red Cell Distribution Width and Hospital Mortality in Patients with Sepsis

ObjectiveSepsis is the leading cause of death in patients admitted to adult intensive care units (ICUs). We aimed to determine the predictive value of red blood cell distribution width (RDW) in patients with sepsis in a large cohort.MethodsThis retrospective observational study used data from the eICU Collaborative Research Database. The prognostic value of RDW was investigated using the receiver operating characteristic (ROC) curve, multiple logistic regression model, integrated discriminatory index (IDI), and net reclassification index (NRI).ResultsIn total, 9743 patients were included. The area under the ROC curve of the RDW for predicting hospital mortality was 0.631 (95% confidence interval [CI]: 0.616–0.645). Based on the multiple logistic regression model, an RDW of ≥14.5% was correlated with hospital mortality, regardless of Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scores (odds ratio [OR]: 1.838, 95% CI: 1.598–2.119). Using SOFA and APACHE IV scores as reference, the IDI and continuous NRI of RDW for hospital mortality was about 0.3 and 0.014, respectively.ConclusionsThe RDW may be useful in predicting hospital mortality in patients with sepsis, offering extra prognostic value beyond SOFA and APACHE IV scores.     

大剂量富露施对特发性肺间质纤维化患者肺功能的影响

目的探讨大剂量富露施对特发性肺间质纤维化患者肺功能的影响。方法将特发性肺间质纤维化患者随机分为两组,A组24例,每天口服强的松0·5mg/kg,4周后减半维持,同时口服富露施600mg/次,每天3次;B组24例,每天口服强的松0·5mg/kg,4周后减半维持。疗程均为3个月。观察临床表现、肺CT、血气、肺功能改变及症状缓解时间。结果A组患者的临床表现如气短、干咳、Velcro罗音经治疗后缓解率为66·7%,B组的缓解率为37·5%(P<0·05);A组缓解时间为(16·7±4·69)d,B组为(23·7±4·87)d(P<0·05);肺CT改善率在A组为62·5%,B组为29·2%(P<0·05)。A组患者治疗前后氧分压(PaO2)、百分肺活量(VC%)、一氧化碳弥散量(DLCO%)提高(P<0·05)。B组患者治疗前后PaO2、VC%、DLCO%有所提高,但与治疗前比较无显著性差异(P>0·05)。两组治疗后比较有显著性差异(P<0·05)。结论大剂量富露施能有效改善特发性肺间质纤维化患者的肺功能。     

急性心肌梗死外周血红细胞分布宽度变化与临床预后的关系研究

目的:探讨外周血红细胞分布宽度(RDW)变化与急性心肌梗死(AMI)患者临床预后的关系。方法:以2012年1月-2014年1月我科收治的AMI患者162例为研究组,同期体检健康者80例为对照组,比较两组RDW及其与AMI临床预后的关系。结果:研究组RDW的水平明显高于对照组[(14.04±1.22)%vs(13.27±1.12)%,P0.05]。研究组中死亡组的RDW水平显著高于存活组[(15.58±1.59)%,vs(13.41±1.00)%,P0.05];研究组中RDW增高组91例与正常组71例的病死率无明显差异(P0.05),而RDW增高组患者心力衰竭、恶性心律失常及再发心肌梗死发生率分别43.96%、38.46%和24.18%,均显著高于RDW值正常组的15.49%、11.27%和7.04%(P0.05)。结论:AMI患者的RDW水平高于健康人,且RDW水平与临床预后具有一定相关性。     

结缔组织生长因子在特发性肺纤维化患者肺组织的表达及意义

目的:研究结缔组织生长因子(CTGF)在特发性肺纤维化(IPF)患者肺组织的表达及意义。方法:IPF组的肺组织标本来自35例IPF患者,对照组的正常肺组织标本来自30例肺叶切除术。用原位杂交结合免疫组化方法检测CTGFmRNA及其蛋白的表达,用免疫组化方法检测纤维连接蛋白(Fn)的表达。结果:IPF组CTGFm-RNA及其蛋白以及Fn的阳性面积百分比均高于对照组(P均<0.001);IPF组CTGFmRNA及其蛋白在增生的Ⅱ型肺泡上皮细胞、肺泡巨嗜细胞和肺间质成纤维细胞中的表达强度均高于对照组(P均<0.001),在细支气管上皮细胞中的表达无差异(P>0.05);IPF组CTGFmRNA及其蛋白的阳性面积百分比与Fn阳性面积百分比之间呈正相关。结论:IPF患者肺组织CTGFmRNA及其蛋白表达增高,并主要定位于Ⅱ型肺泡上皮细胞、肺泡巨嗜细胞和间质成纤维细胞,CTGF可能通过促进Fn的合成而在IPF中发挥作用。     

A Smart-Phrase to Improve Documentation of Supportive Measures for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease of unknown cause occurring in adults and affecting approximately 5 million people worldwide. The American Thoracic Society 2015 guidelines provide recommendations for the treatment of patients with IPF, including supportive care measures such as oxygen therapy, pulmonary rehabilitation, gastric acid therapy, sleep apnea, vaccinations, lung transplant evaluation, and pulmonary hypertension assessment. A smart-phrase was developed that outlines the supportive care measures for the IPF patient, which was then implemented into a new patient clinic note in the electronic medical record. Documentation of the measures improved significantly after implementation of the smart-phrase.     

核心蛋白聚糖在特发性肺纤维化患者血清中的表达及其意义

[目的]探讨核心蛋白聚糖(DCN)在特发性肺纤维化(IPF)患者血清中的表达及其意义.[方法]选取2016年3月至2018年3月在陕西省第四人民医院诊治的87例IPF患者(IPF组)、82例特发性间质性肺炎(idiopathic interstitial pneumonia,IIP)患者(非IPF组)和100例健康体检...     

气泵雾化吸入普米克令舒治疗特发性肺间质纤维化

目的探讨气泵雾化吸入普米克令舒治疗特发性肺间质纤维化（IPF）的临床疗效。方法将72例特发性肺间质纤维化患者随机分为三组,各24例,A组普米克令舒2ml（含布地奈德1mg）气泵雾化吸入,每日2次;B组吸入普通普米克气雾剂,每次4喷,2次/d;C组每天口服强的松1mg/kg,4周后减半量维持,疗程均为3个月。观察三组患者的临床表现、肺CT、血气、肺功能改变及副作用。结果治疗后,临床表现缓解率为A组70.8%、B组25%、C组50%,A组与B组比较差异有显著性意义（P〈0.0125）,A组与C组比较差异无显著性意义（P〉0.0125）;肺CT改善率为A组66.7%、B组29.2%、C组45.8%,A组与B组比较差异有显著性意义（P〈0.0125）,A组与C组比较差异无显著性意义（P〉0.0125）;A组和C组患者PaO2、VC%、DLCO%提高（P〈0.05）,但两组间比较差异无显著性意义（P〉0.05）,B组PaO2、VC%、DLCO%也有提高,与治疗前比较差异无显著性意义（P〉0.05）。副作用发生率为A组8.3%、B组8.3%、C组58.3%,A组与C组比较差异有显著性意义（P〈0.0125）。结论气泵雾化吸入普米克令舒代替口服用药治疗特发性肺间质纤维化副作用少且临床疗效确切。