肺力咳合剂联合布地奈德福莫特罗治疗慢性阻塞性肺疾病急性加重期的临床研究

目的 探讨肺力咳合剂联合布地奈德福莫特罗治疗慢性阻塞性肺疾病急性加重期（AECOPD）的临床效果。方法 选取2018年10月—2020年9月天津医科大学宝坻临床学院收治的102例AECOPD患者,随机分为对照组（51例）和治疗组（51例）。对照组吸入布地奈德福莫特罗吸入剂,2吸/次,2次/d。治疗组口服肺力咳合剂,20 mL/次,3次/d。两组连续治疗2周。观察两组患者临床疗效,比较治疗前后两组患者肺部哮鸣音、呼吸症状缓解时间,肺功能参数第1秒用力呼气容积与用力肺活量比值（FEV1/FVC）、深吸气量与肺总量比值（IC/TLC）、一氧化碳弥散量与肺泡通气量比值（DLCO/VA）和FEV1占预计值%,咳痰的评估问卷（CASA-Q）总分,中性粒细胞与淋巴细胞比值（NLR）和呼出气一氧化氮（FeNO）浓度及血清白细胞介素-17（IL-17）、淀粉样蛋白A（SAA）和肺表面活性蛋白D（SP-D）水平。结果 治疗后,治疗组临床有效率为96.1%,显著高于对照组的84.3%（P<0.05）。治疗后,治疗组肺部哮鸣音和呼吸症状缓解时间均显著短于对照组（P<0.05）。治疗后,两组肺功能参数FEV1/FVC、IC/TLC、DLCO/VA、FEV1占预计值%和CASA-Q总分均显著升高（P<0.05）,并均以治疗组改善更显著（P<0.05）。治疗后,两组患者NLR和FeNO浓度及血清IL-17、SAA、SP-D水平均显著低于治疗前（P<0.05）,且治疗组对NLR和FeNO浓度及血清IL-17、SAA、SP-D水平的降低作用较对照组更显著（P<0.05）。结论 肺力咳合剂联合布地奈德福莫特罗治疗AECOPD的整体疗效确切,可安全、有效且迅速地缓解患者症状,改善气流受限,抑制体内炎症反应。     

无创正压机械通气配合参芪扶正注射液治疗对重症肺炎呼吸衰竭患者血气指标及血清sTREM-1、SP-D水平的影响

目的观察无创正压机械通气配合参芪扶正注射液治疗对重症肺炎呼吸衰竭患者血气指标及血清可溶性髓系细胞触发受体-1(sTREM-1)、肺表面活性蛋白(SP-A)水平的影响。方法选取重症肺炎呼吸衰竭患者98例,根据治疗方案不同分为联合组与对照组各49例。常规治疗基础上,对照组予以无创正压机械通气,联合组予无创正压机械通气配合参芪扶正注射液,治疗疗程10 d。对比两组病死率、预后转归情况[住院时间、呼吸机相关性肺炎(VAP)发生率]、不同时间节点患者临床体征评分、血气情况及血清sTREM-1、SP-D水平。结果联合组病死率低于对照组(P<0.05);治疗3、7、10 d后联合组临床体征评分低于对照组(P<0.05);治疗10d后联合组二氧化碳分压(PaLCO2)低于对照组,氧分压(PaO2)、血氧饱和度(SaO2)高于对照组(P<0.05);治疗10 d后联合组血清sTREM-1、SP-D水平低于对照组(P<0.05);联合组住院时间短于对照组,VAP发生率低于对照组(P<0.05)。结论无创正压机械通气配合参芪扶正注射液治疗重症肺炎呼吸衰竭,能有效降低病死率,改善患者临床体征及血气情况,调节血清sTREM-1、SP-D水平,促进预后恢复。     

慢性阻塞性肺疾病高分辨率CT分型与气道炎症之间的关系

目的 探讨慢性阻塞性肺病（COPD）患者的高分辨率CT（HRCT）表型与气道炎症和临床特征的关系。方法 收集2015年11月至2017年4月于大连医科大学附属第二医院住院的COPD患者87例,按照HRCT影像特点分为3种类型,其中A型：无或轻微有肺气肿（LAA ≤ 1级）,合并或不合并支气管管壁增厚;E型：LAA ≥ 2级肺气肿,但无支气管管壁增厚;M型：LAA ≥ 2级的肺气肿同时有支气管管壁增厚。比较3型间吸烟指数、过去1年内急性加重次数、肺功能及血清肺泡表面活性蛋白-D（SP-D）、超敏C反应蛋白（hs-CRP）和血浆纤维蛋白原（Fig）水平。结果 A型患者吸烟指数为（21.41±23.28）包年,明显低于E型（38.71±41.28）包年和M型（38.07±33.84）包年（P<0.05）。A型过去1年内急性加重≥ 2次的患者比例为21.3%,明显少于E型（42.9%）和M型（89.5%）,差异有统计学意义（P<0.05）。A型患者FEV1/FVC（59.82±11.17）%,优于E型和M型[（50.65±9.26）%、（51.75±8.89）%]（P<0.05）;A型患者的RV/TLC为（50.66±9.8）%,明显低于E型和M型[（74.71±13.75）%、（77.20±10.56）%]（P<0.05）。M型患者的血浆Fig和血清hs-CRP水平分别为（5.23±1.67）g/L和（37.81±40.8）mg/L,明显高于A型[（4.26±1.37）g/L、（9.57±13.66）mg/L]和E型[（3.86±1.48）g/L、（6.28±4.35）mg/L]（P<0.05）,而血清SP-D水平3组之间无差异。LAA ≥ 2级患者的吸烟指数、RV/TLC和血清hs-CRP水平明显高于LAA ≤ l级的患者（P<0.05）;支气管管壁增厚≥ 2级患者的RV/TLC和血浆Fig和血清hs-CRP水平均高于支气管管壁增厚≤ l级患者（P<0.05）。结论 HRCT不同表型的COPD患者的临床特征和气道炎症水平不同,其中M型吸烟指数和炎症指标更高,急性加重更频繁。     

Comparative evaluation of KL-6 and surfactant protein D as serum markers for interstitial pneumonia associated with collagen diseases

We evaluated the usefulness of serum levels of KL-6 and surfactant protein D (SP-D) as markers of interstitial pneumonia (IP) associated with collagen diseases in 115 patients. KL-6 and SP-D levels in patients with IP (n = 38) were significantly higher than those in patients without IP (n = 77). Moreover, KL-6 and SP-D levels in patients with active IP (n = 8) were significantly higher than those in patients with inactive IP (n = 30). Both KL-6 and SP-D proved useful for the diagnosis of IP associated with collagen diseases and for the evaluation of disease activity. We classified IP into three groups according to the extent of the lesion on computed tomographs of the chest. There was a significant difference among three groups in serum levels of KL-6, but not in serum levels of SP-D. KL-6 proved to be useful as an indicator of the extent of the IP lesions. We monitored changes in KL-6 and SP-D levels in seven of eight patients with active IP. Chronological changes of serum KL-6 and SP-D in patients with active IP were different. In fatal cases in particular, serum levels of SP-D decreased at the terminal stage of IP while levels of KL-6 continued to increase. Received: April 11, 2000 / Accepted: November 27, 2000     

二陈汤加味对COPD急性期患者CC16，SP-D及HAT/HDAC的影响

目的:观察二陈汤加味对COPD急性期加重期(acute exacerbation period of COPD,AECOPD)患者血浆、呼气冷凝液(exhale breath condensat,EBC)中克拉拉细胞蛋白(Clara cell protein,CC16),肺表面活性蛋白-D(pulmonary surfactant associated protein-D,SP-D)含量及外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中组蛋白乙酰基转移酶(histone acetyl transferase,HAT)及组蛋白去乙酰基酶(histone deacetylase,HDAC)活性的影响,评价二陈汤加味对AECOPD的作用及机制。方法:选取符合纳入标准AECOPD患者200例,随机分成对照组和治疗组,每组100例。两组均在西医常规治疗的基础上,对照组给予安慰剂,治疗组接受二陈汤加味治疗,疗程14 d。检测肺功能,酶联免疫吸附试验(ELISA)法测定血浆,EBC中白细胞介素-17(interleukin-17,IL-17),C反应蛋白(C-reactive protein,CRP),CC16,SP-D及PBMC中HDAC1,HDAC2浓度。酶联免疫荧光法测定PBMC中HAT及HDAC活性。结果:与对照组治疗后比较,治疗组血浆及EBC中CRP,IL-17,CC16和SP-D水平均明显降低(P0.05,P0.01),PBMC中HAT活性明显降低(P0.05),HDAC活性,HDAC2含量均明显增高(P0.05)。结论:二陈汤加味可能调整HAT/HDAC的平衡,发挥抗炎作用,保护气道和肺的结构与功能。     

矽肺早期诊断的生物标志物CC16和SP-D

矽肺是由于在生产过程中长期吸入含有游离二氧化硅粉尘而引起以肺组织纤维化为主的全身性疾病,是尘肺中危害最严重的职业病之一。其病理演化过程为与炎性有关的纤维化反应。近几年一些学者在研究矽肺的致病机制过程中发现CC16、SP-D的抗炎及抗纤维化等作用在矽肺发生发展过程中起到重要作用,并可能成为矽肺早期诊断的生物标志物。本文就它们在矽肺诊断中的价值作一简单介绍。     

Simultaneous measurements of KL-6 and SP-D in patients undergoing thoracic radiotherapy

Purpose Radiation pneumonitis (RP) is a serious complication in patients undergoing thoracic radiotherapy (TRT). Serum KL-6 and SP-D have been shown to increase in several kinds of interstitial pneumonia. To evaluate their clinical usefulness in detecting RP, we serially measured them in patients receiving TRT. Materials and Methods Thirty-nine patients, who received TRT for lung cancer between July 1999 and April 2004, were prospectively studied. Serum levels of KL-6 and SP-D were measured using enzyme-linked immunosorbent assays. Patients were followed up until August 2004 or their deaths. Results During the period, RP occurred in 19 patients. In five patients with diffust RP extended outside the radiation field, serum KL-6 levels increased, reaching more than 1000 U/mL. Serum KL-6 levels at 40 gy in patients who developed RP were higher than those without it (p=0.0363, Mann-Whitney U test). In addition, serum KL-6 levels at 40 Gy in patients who developed RP were higher than those of pretreatment (p=0.0126, Wilcoxon signed rank test). On the other hand, there were no statistical differences between SP-D at 40 Gy and those before TRT (p=0.1165). Conclusions Increased KL-6 at 40 Gy compared with those before treatment in patients undergoing TRT may be of clinical significance. KL-6 proved to be a useful indicator for estimating RP, while usefulness of SP-D was not confirmed in this study.     

Novel, non-radioactive, simple and multiplex PCR-cRFLP methods for genotyping human SP-A and SP-D marker alleles

We have previously identified an allele of the human SP-A2 gene that occurs with greater frequency in an RDS population [12]. Because of the importance of SP-A in normal lung function and its newly emerging role in innate host defense and regulation of inflammatory processes, we wish to better characterize genotypes of both SP-A1 and SP-A2 genes. It has been determined that SP-D shares similar roles in immune response. Therefore, in this report we 1) describe a novel, non radioactive PCR based-cRFLP method for genotyping both SP-A and SP-D; 2) describe two previously unpublished biallelic polymorphisms within the SP-D gene; 3) present the partial sequence of one new SP-A1 allele (6A14) and describe other new SP-A1 and SP-A2 alleles; and 4) describe additional methodologies for SP-A genotype assessment. The ability to more accurately and efficiently genotype samples from individuals with various pulmonary diseases will facilitate population and family based association studies. Genetic polymorphisms may be identified that partially explain individual disease susceptibility and/or treatment effectiveness.     

硫酸镁联合甲泼尼龙治疗小儿毛细支气管炎的临床研究

目的探讨硫酸镁联合甲泼尼龙治疗小儿毛细支气管炎的临床效果。方法选取2015年10月—2017年10月朝阳市第二医院收治的118例毛细支气管炎患儿,随机分为对照组和治疗组,每组各59例。对照组静脉滴注注射用甲泼尼龙琥珀酸钠,2 mg/kg加入5%葡萄糖溶液100 m L充分稀释后给药,1次/d。治疗组在对照组治疗基础上静脉滴注硫酸镁注射液,25 mg/kg用5%葡萄糖溶液均匀稀释至浓度为1.25%后给药,滴注时间约2 h/次,2次/d。两组均连续治疗5 d。观察两组的临床疗效和一般临床症状消失时间,比较两组治疗前后酸碱度(p H)、血氧饱和度(Sa O_2)、二氧化碳分压(p CO_2)、肺表面活性蛋白A、D(SP-A、SP-D)、嗜酸粒细胞阳离子蛋白(ECP)、纤维蛋白原(FIB)、红细胞聚集指数(RCAI)、血浆黏度(PV)的变化情况。结果治疗后,对照组和治疗组的总有效率分别为76.27%、91.53%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组喘憋、咳嗽、哮鸣音及湿罗音消失时间均显著短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组p H值、Sa O_2均明显增加,但p CO_2、SP-A、SP-D、ECP、FIB、RCAI、PV显著降低,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组p H值、Sa O_2高于对照组,p CO_2、SP-A、SP-D、ECP、FIB、RCAI、PV低于对照组,两组比较差异有统计学意义(P0.05)。对照组和治疗组的不良反应发生率分别为3.4%、5.1%,两组不良反应发生率比较差异无统计学意义。结论硫酸镁联合甲泼尼龙治疗小儿毛细支气管炎具有较好的临床疗效,可较快消除患儿症状,改善血气状况,调节血流变状态,具有一定的临床推广应用价值。     

Inflammatory effects of inhaled sulfur mustard in rat lung

Inhalation of sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating its cytotoxic effects are unknown and were investigated in the present studies. Male rats Crl:CD(SD) were anesthetized, and then intratracheally intubated and exposed to 0.7-1.4 mg/kg SM by vapor inhalation. Animals were euthanized 6, 24, 48 h or 7 days post-exposure and bronchoalveolar lavage fluid (BAL) and lung tissue collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including focal ulceration and detachment of the trachea and bronchial epithelia from underlying mucosa, thickening of alveolar septal walls and increased numbers of inflammatory cells in the tissue. There was also evidence of autophagy and apoptosis in the tissue. This was correlated with increased BAL protein content, a marker of injury to the alveolar epithelial lining. SM exposure also resulted in increased expression of markers of inflammation including cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNFα), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9), each of which has been implicated in pulmonary toxicity. Whereas COX-2, TNFα and iNOS were mainly localized in alveolar regions, MMP-9 was prominent in bronchial epithelium. In contrast, expression of the anti-oxidant hemeoxygenase, and the anti-inflammatory collectin, surfactant protein-D, decreased in the lung after SM exposure. These data demonstrate that SM-induced oxidative stress and injury are associated with the generation of cytotoxic inflammatory proteins which may contribute to the pathogenic response to this vesicant.