高氧致早产鼠BALF及肺组织中MDA、SOD的变化

目的观察丙二醛(MDA)、超氧化物歧化酶(SOD)在高氧致(CLD)早产鼠支气管肺泡灌洗液(BALF)及肺组织中的变化.方法用高浓度氧致早产鼠CLD为研究对象,应用生化方法同步检测肺组织和BALF中MDA含量及SOD的活性.结果实验组肺组织中SOD的活性呈升高趋势,但与对照组比较,肺组织和BALF中SOD的活性均无差异(P>0.05、P>0.05),实验组肺组织和BALF中MDA的水平呈同相变化,自吸入高氧的第3d开始升高,(P<0.05),7d达高峰并持续至14d(P<0.01),21d时虽有下降,但仍高于对照组(P<0.05).结论 SOD、MDA的动态变化,可间接反应肺部疾病的变化,对慢性肺疾病的诊断、鉴别诊断、活动性判断及预后均有一定的价值.同时也证实机体的氧化与抗氧化失衡是高氧所致早产儿慢性肺疾病的发病原因之一.     

肺泡巨噬细胞在慢性肺疾病中作用的研究进展

肺泡巨噬细胞（AMs）作为呼吸树的前哨细胞，也是构成稳定状态下的优势免疫细胞，在防御病原体和耐受无害刺激之间的平衡中发挥重要作用。AMs的不同特征影响着肺部感染、慢性炎症疾病以及肺癌的预后。因此，本文主要通过查阅国内外文献，对AMs与不同慢性肺部疾病中的相关性进行综述，以期为慢性肺病的临床防治提供更多的理论依据。     

腺苷和抗IgE抗体对哮喘患者BALF中肥大细胞分泌组胺的影响

目的 :研究支气管哮喘 (哮喘 )患者支气管肺泡灌洗液 (BALF)中肥大细胞的功能特性。方法 :2 9例轻度哮喘患者BALF中的细胞经冲洗后 ,加入含抗IgE抗体、腺苷、缓冲液或腺苷 +抗IgE抗体的LP4试管中进行激发试验。检测BALF肥大细胞中的组胺释放量。结果 :腺苷浓度达 10 0 μmol/L时 ,仍无明显刺激组胺释放的作用 ,仅在浓度高达 10 0 0 μmol/L时 ,方可诱导哮喘患者BALF中肥大细胞释放约 17%的组胺。抗IgE抗体的浓度大于 1× 10 -4g/L时对哮喘患者BALF中肥大细胞的释放组胺有明显的促进作用 ;仅 3× 10 -5g/L的抗IgE抗体与腺苷联合应用的实测值 ,明显高于对应的单独作用组的相加值。结论 :哮喘患者BALF中的肥大细胞对腺苷的刺激反应较差 ,但对抗IgE抗体刺激的反应性明显增强。仅低浓度的抗IgE抗体和腺苷具有协同作用。     

角化生长因子在慢性肺疾病早产大鼠的表达

目的探讨高氧致CLD早产大鼠KGF表达的变化规律.方法 60只新生早产大鼠随机分为2组,每组30只:A组-对照组;B组-高氧组(吸入95%O2).分别采用Western Blotting及RT-PCR检测肺组织KGF及其mRNA表达.结果高氧组肺内KGF及其mRNA表达高于对照组.结论高氧引起新生早产大鼠肺内KGF及其mRNA的表达随时间发生变化.     

BALF中ET、CGRP变化与原发性支气管肺癌的相关性研究（摘要）

本文报道经纤维支气管镜(FOB)活检、刷片、灌洗等,并获得病理组织学及细胞学诊断的12例肺癌患者,并同步检测支气管肺泡灌洗液(BALF)ET、CGRP,结果:男性10例、女性2例,年龄30～63岁,平均51.7±11.7,鳞癌6例,小细胞未分化癌4例,腺癌2例,ET高表达6例占50％,CGRP升高7例占58.0％,以CGRP升高显著,P<0.001,且CGP的高表达与小细胞未分化癌有明显相关性,ET和CGRP的高表达与临床分期呈正相关、并随癌细胞扩散和转移逐渐增加,以CGRP明显。     

IL-6在慢性阻塞性肺疾病合并糖尿病大鼠肺组织中水平变化的实验研究

目的探讨白细胞介素6(IL-6)在慢性阻塞性肺疾病(COPD)大鼠、糖尿病大鼠、慢性阻塞性肺疾病合并糖尿病大鼠肺组织中的浓度水平变化及其意义。方法清洁级雄性SD大鼠80只,随机分为4组即COPD组、糖尿病组、COPD合并糖尿病组和正常对照组,各组均为20只。采用每日熏香烟法制造COPD组模型,饲以高脂饲料并注射小剂量链脲佐菌素法制造糖尿病组模型,合并上述方法制造COPD合并糖尿病组模型。造模后提取各大鼠肺组织,通过病理形态学检测证明造模成功,并采用免疫组织化学方法检测4组大鼠肺组织中IL-6的浓度水平。结果 1.COPD组和COPD合并糖尿病组大鼠支气管鳞状上皮化生、呼吸道壁纤维化及肺泡壁的破坏和纤维化上皮明显增生增厚,壁有大量淋巴细胞、巨噬细胞为主的炎细胞浸润,较多中性粒细胞浸润,肺泡腔扩大,肺泡壁断裂融合形成肺泡气肿,COPD合并糖尿病组较COPD组、糖尿病组病理表现更为显著。2.免疫组化结果显示:正常组IL-6浓度为(4.27±0.89)%,COPD组IL-6浓度为(13.13±1..28)%,糖尿病组IL-6浓度为(8.26±0.92)%,COPD合并糖尿病组IL-6浓度为(20.86±2.73)%。与正常组比较,COPD组、糖尿病组和COPD合并糖尿病组IL-6水平均升高(P0.01);与COPD组比较,糖尿病组IL-6降低(P0.01),COPD合并糖尿病组IL-6升高(P0.01);与糖尿病组比较,COPD合并糖尿病组IL-6升高(P0.01)。结论大鼠肺组织中IL-6水平的增高与COPD及高血糖的炎性反应有叠加作用。     

肺泡巨噬细胞免疫代谢与慢性阻塞性肺疾病关系的研究进展

肺泡巨噬细胞（AMs）在慢性阻塞性肺疾病（COPD）的发病中起着重要作用，代谢途径和代谢产物的改变是AMs功能和相关疾病进展的关键因素之一。本文就影响AMs代谢变化的因素，以及代谢变化如何影响AMs的功能作了阐述，并进一步总结了AMs的免疫代谢变化在COPD中的研究进展，以期为COPD的防治提供新的思路和途径。     

支气管肺泡灌洗液在鉴别肺良恶性肿瘤中的价值

本文对54例肺疾病患者的肺泡灌洗液及血清进行了CYFRA21-1、CEA水平检测,其中肺良性疾病21例,肺癌33例,同时检测健康人血清41例并加以比较,发现它对早期鉴别肺恶性肿瘤可提供有价值的依据,现报道如下. 1 对象和方法 1.1 对象 `1.1.1 对照组 41例(男31,女10),年龄(31～59)岁,为我院体检中心确认的健康者,各项指标正常,无呼吸、肝、肾、肺等重要器官疾病. 1.1.2 疾病组 54例(男33,女21),年龄(45～71)岁,为我院及另一医院呼吸科住院病人,经临床病理学、细胞学及影像学检查确诊肺癌32例,其中鳞癌17例、腺癌14例、小细胞癌1例.肺良性疾病22例(男14,女8),年龄(32～66)岁.     

Assessment of local cellular immunity in lung cancer by bronchoalveolar lavage

Summary Small cell lung cancer (SCLC) is the most malignant of the pulmonary neoplasms and is associated with a poor local cellular immune response. 16 patients with non small cell lung cancer (NSCLC) and 11 patients with SCLC underwent bronchoalveolar lavage (BAL) in the lung which harbored the tumor in order to investigate the lymphocyte surface antigens utilizing the immunoperoxidase technique. Analysis of blood lymphocytes was performed in parallel. 8 patients with previous sarcoidosis in complete remission who underwent BAL and 10 normal blood donors served as controls.Among blood lymphocytes the CD3⁺, CD4⁺ and CD16⁺ cell populations were elevated significantly and the T4/T8 ratio was elevated in NSCLC patients, but only CD16⁺ were augmented in SCLC. Cell populations expressing the activation markers transferrin (TF) receptor, interleukin-2 (IL-2) receptor and the very late antigen VAL-1 were also increased in NSCLC, while SCLC was associated with antigen distributions similar to controls. No differences between the cohorts were seen in the expression of human leukocyte antigen (HLA)-DR. In BAL the population of CD3⁺ and CD4⁺ cells were reduced in SCLC and the T4/T8 ratio was diminished in contrast to controls and NSCLC patients, whereas these two latter groups did not differ from each other. The distribution pattern of CD16, TF receptor and IL-2 receptor in the study groups resembled that of cells of the blood stream, but CD16⁺ natural killer cells were additionally down regulated to control values in SCLC. No differences were seen in the distribution of VLA-1. HLA-DR⁺ cells were clearly elevated in both cancer groups.In general NSCLC was associated with a shift to higher relative numbers of immunocompetent and activated cells. This was most probably attributable to an immune response to neoplastic growth. This shift was largely lacking in SCLC. The analysis of lymphocytes from the periphery of the target organ emerged as a sensitive tool for the study of cellular immunity in lung cancer and showed many similarities to circulating blood cells. However, the analysis of natural killer cells and HLA-DR suggested a dissection of cellular immune response between blood and lung in pulmonary cancer. A depressive interaction between the tumor and the cellular host immune response may contribute to the exceptional malignancy of SCLC.Abbreviations BAL bronchoalveolar lavage - HLA-DR human leukocyte antigen-DR - IL-2 interleukin-2 - NSCLC non small cell lung cancer - SCLC small cell lung cancer - TF transferrin - VLA-1 very late antigen-1     

The effect of netilmicin and vancomycin on lipid peroxidation processes in cerebrospinal fluid in children with hydrocephalus

In biological systems, it is difficult to determine free radicals because of their reactivity and their very short time of existence. On the basis of markers, which come into being as a result of radical processes, one might believe that there exist reactive oxygen species. One of the determinants of free radical activity of oxygen is the presence of malondialdehyde (MDA), a final product of lipid peroxidation. This study aimed at finding the answer to the question whether the concentration of netylmicin and vancomycin influences the amount of substances reacting with thiobarbituric acid (TBA) in cerebrospinal fluid (CSF) in children with hydrocephalus. Applying the TBA test for examinations with antibiotics added both in vivo and in vitro, we could demonstrate that increased concentration of the examined antibiotics in cerebrospinal fluid reduces the amount of MDA. The results obtained demonstrate that products of lipid peroxidation are present in the CSF samples analyzed. In this study, we found that the concentration of vancomycin and netilmicin influenced the lipid peroxidation process in cerebrospinal fluid in children with hydrocephalus, thus confirming anti-inflammatory properties of the antibiotics applied.     

Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses

Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALF) of patients with different stages of RA-ILD. 9/21 RA-derived BALF specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALF and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment—further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALF and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD.     

右美托咪定在支气管肺泡灌洗过程中作用的研究

目的 考察右美托咪定在未建立人工气道的颅脑疾病患者支气管肺泡灌洗过程中的作用.方法 对46例颅脑疾病后无人工气道的肺部感染患者行支气管肺泡灌洗治疗,年龄17～82岁,平均年龄（56.6±9.2）岁,其中男性26例,女性20例.随机分为2组,其中对照组23例,支气管肺泡灌洗过程中接受咪达唑仑镇静;实验组23例,支气管肺泡灌洗过程中接受右美托咪定镇静.观察2组患者在支气管肺泡灌洗前和灌洗过程中的心率、平均动脉压及指脉氧等指标的变化.结果 支气管肺泡灌洗过程中最低指脉氧实验组高于对照组,最快心率实验组低于对照组,最低平均动脉压实验组高于对照组,差异均具有统计学意义（P＜0.05）.支气管肺泡灌洗过程中与灌洗前比较,2组心率均有增快,平均动脉压下降,指脉氧下降,但实验组各指标的幅度变化较小（P＜0.05）.结论 右美托咪定对患者呼吸和血压抑制较小,用于无人工气道的颅脑疾病患者的支气管肺泡灌洗过程相对安全有效.     

Comparison of cysteinyl leukotriene concentrations between exhaled breath condensate and bronchoalveolar lavage fluid

Background Collection of exhaled breath condensate (EBC) is a simple, non‐invasive method of obtaining samples from the airways and it can be repeated in short intervals without side effects; therefore, it provides an opportunity to monitor the changes in concentration of inflammatory mediators in the airways. However, EBC analysis still has several unresolved issues. Objective To better understand the characteristics of EBC, we compared cysteinyl leukotriene (CysLT) concentrations between bronchoalveolar lavage fluid (BALF) and EBC. We also attempted to correct CysLT concentrations in BALF and EBC diluted with saline and water vapour using biological markers. Methods EBC was collected from 14 patients with idiopathic pulmonary fibrosis before bronchoscopy. We measured CysLT concentrations and also quantified tyrosine, urea and total protein as possible biomarkers for correcting dilution. Results (1) We have validated the quantification of CysLTs in EBC. (2) Although a significant correlation was observed among tyrosine and urea concentrations in BALF, urea and total protein concentrations were below the detection limit in EBC. (3) CysLT concentrations were higher in BALF than in EBC (median, 15.96 pg/mL vs. 5.5 pg/mL; P=0.001) and there was no correlation of CysLT concentrations in BALF with those in EBC. A significant correlation of the ratio of total CysLT concentration to tyrosine concentration (CysLT/Y) in EBC with that in BALF was observed (r=0.547, P=0.043). (4) CysLT/Y in EBC correlated with serum KL‐6 concentration and total cell count in BALF, and CysLT/Y in BALF also correlated with exhaled NO concentration and %VC. Conclusions CysLT/Y in EBC significantly correlated with that in BALF and some clinical parameters correlated with CysLT/Y. Tyrosine concentration may be used to correct the dilution error for CysLT concentrations, and CysLT/Y in EBC can be a surrogate marker for CysLT concentrations in BALF.     

IL-9 and IL-9 receptor expression in lymphocytes from bronchoalveolar lavage fluid of patients with interstitial lung disease

IntroductionIL-9, mainly produced by T helper 9 (Th9) cells, promotes allergic airway inflammation and remodeling through the interaction with its receptor (IL-9R). Th9 cells and IL-9 have also been implicated in tissue fibrosis and autoimmunity pathways. However, the role of IL-9/IL-9R in the pathogenesis of interstitial lung disease (ILD) is unknown.AimTo evaluate IL-9/IL-9R expression in bronchoalveolar lavage fluid (BALF) lymphocytes of patients with various ILDs.MethodsConsecutive patients with ILD, who underwent BAL for diagnostic purposes, were studied. As control group, consecutive patients without evidence of ILD were included. Immunocytochemical staining of BALF lymphocytes for IL-9 and IL-9R was performed and evaluated by two independent readers.Results45 patients, of them 8 had idiopathic pulmonary fibrosis (IPF), 12 nonspecific interstitial pneumonia (NSIP), 10 sarcoidosis, 9 hypersensitivity pneumonitis (HP), 6 cryptogenic organizing pneumonia (COP), and 24 controls were studied. In the ILD group, the highest BALF lymphocyte count was seen in HP followed by NSIP, COP, sarcoidosis, and IPF (p < 0.05 for HP vs IPF). The highest percentages of IL-9 and IL-9R positive lymphocytes were seen in COP. Conversely, NSIP showed the lowest rate of IL-9, and sarcoidosis the lowest rate of IL-9R positive lymphocytes. Only in NSIP, a direct correlation between IL and 9 and IL-9R positive lymphocytes was seen (r = 0.639, p = 0.025).ConclusionBALF lymphocytes IL-9 and IL-9R expression differs between various ILDs and could reflect different pathogenetic mechanisms.     

Bronchoalveolar lavage improves diagnostic accuracy in patients with diffuse lung disease

Bronchoalveolar lavage (BAL) is an established diagnostic tool in diffuse parenchyma lung disease. The objective of the present study was designed to investigate whether immunophenotyping affects BAL results and improves diagnostic accuracy. BAL from 61 patients was included in the study. The patients were also submitted to transbronchial biopsy, with a final diagnosis of granulomatous disease [tuberculosis (TB), n = 20; sarcoidosis (SARC), n = 3; and hypersensitivity pneumonitis (HP), n = 4]; idiopathic interstitial pneumonias (IIPs) [idiopathic pulmonary fibrosis (IPF), n = 9; organizing pneumonia (OP), n = 17]; and lung cancer (LC), n = 8. Immunohistochemistry and histomorphometry were used to identify and quantify type 1 and type 2 alveolar epithelial cells, macrophages, CD3+T‐cells, CD4+T‐cells, CD8+T‐cells, and CD20+B‐cells in BAL. These markers were correlated with a database and pulmonary function tests. The cellular, inflammatory, and immune components of BAL varied among the diagnostic groups and were negatively correlated with age and smoking history. An increased quantity of lymphocyte surface markers CD3 (P < 0.05) and CD20 (P = 0.01) was seen in IIPs. Patients with a pattern of OP had a higher proportion of type 2 alveolar epithelial cells; patients with SARC had a higher density of CD20+B‐cells and CD4+T‐helper cells; and patients with HP had a higher proportion of CD8+T‐cytotoxic cells. A positive association was found between the density of type I alveolar epithelial cells and forced vital capacity. The immunophenotyping affects the cellular, inflammatory, or immune constituents of BAL and improved the diagnostic accuracy in diffuse parenchymal lung disease. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Pneumocystis jirovecii colonisation in patients with interstitial lung disease

A prospective study was conducted to determine the prevalence of colonisation by Pneumocystis jirovecii in 80 consecutive patients who required bronchoscopy and bronchoalveolar lavage (BAL) following suspicion of interstitial lung disease (ILD). The mtLSU rRNA gene of P. jirovecii was identified by nested PCR in BAL samples. Patients with ILDs were divided into three groups: group A comprised those with idiopathic interstitial pneumonias; group B comprised those with sarcoidosis; and group C comprised those with other ILDs. The overall prevalence of P. jirovecii carriage was 33.8%, with colonisation rates of 37.8%, 18.8% and 37% in groups A, B and C, respectively (p not significant). There were more smokers among the carriers, but there were no other significant differences between carriers and non-carriers. The high prevalence of P. jirovecii carriers found among immunocompetent patients with ILDs in Spain suggests a possible role of P. jirovecii in the natural history of these diseases.