COPD患者呼出气冷凝液中8-异前列腺素的检测及其意义

目的研究COPD患者呼出气冷凝液（EBC）中8-异前列腺素（8-isoPG）浓度的改变及临床意义。方法收集COPD患者（39例）急性发作期和缓解期以及正常对照组（32例）的EBC,用酶标记法检测EBC中8-isoPG,同时检测AECOPD患者的第一秒呼气容量（FEV1）、最大呼气流速（PEF）、pH值、PaCO2、PaO2及血白细胞总数。结果①COPD患者急性发作期8-isoPG为6.44±3.68 ng/L,高于缓解期（4.04±1.25 ng/L）及正常对照组（3.31±0.91 ng/L）,P〈0.05;②COPD患者8-isoPG浓度与痰量呈正相关,r=0.217,P〈0.05。结论 COPD的急性发作期,8-isoPG升高反映了氧化应激增强。     

呼出气冷凝液中8-异前列腺素水平检测对咳嗽变异性哮喘的临床意义

目的探讨8-异前列腺素检测对诊治咳嗽变异性哮喘(CVA)的临床意义。方法选取50例CVA患者和30例健康对照纳入研究,所有受试者测定呼出气冷凝液中8-异前列腺素水平并进行肺功能检测。结果与健康人群相比,CVA患者EBV中8-iso-PG水平显著升高(P0.01);治疗前后比较,CVA患者EBV中8-iso-PG水平明显降低(P0.01),而FEV1%检测差异无统计学意义。EBV中8-iso-PG水平与FEV1%检测值之间无相关性(r=-0.17,P0.05)。结论 EBC中8-iso-PG检测可直观反映CVA患者存在的气道氧化应激状态,并能较好的预测治疗敏感性,从而有助于CVA患者的早期诊断和疗效预判。     

慢性阻塞性肺疾病患者呼出气冷凝液中检测一氧化氮、8-异前列腺素的临床意义

目的观察慢性阻塞性肺疾病（COPD）患者呼出气冷凝液（EBC）中一氧化氮（NO）、8-异前列腺素（8-isoPG）的变化及其临床意义。方法收集COPD急性发作期（AECOPD）、缓解期患者和正常对照组的EBC,用硝酸还原法检测NO的浓度,酶免疫法检测8-isoPG的浓度。结果①AECOPD组（19例）患者EBC中NO和8-isoPG的浓度显著高于正常对照组（12例）,NO测定值分别为（80．83±40．15）μmol／L和（36．95±22．47）μmol／L,8-isoPG测定值分别为（13．56±11．11）ng／L和（5．87±3．39）ng／L,P〈0．05;②10例COPD急性发作期患者EBC中NO和8-isoPG的浓度显著高于缓解期,NO测定值分别为（91．09±34．30）μmol／L和（29．65±11．76）μmol／L,8-isoPG测定值分别为（17．60±12．44）ng／L和（5．23±6．20）ng／L,P〈0．05;③AECOPD组NO测定值与FEV1呈负相关（r=0．565,P〈0．05）,与血白细胞计数呈正相关（r=0．746,P〈0．01）。结论COPD患者急性发作期气道炎症反应和氧化应激增强。     

COPD治疗期间呼出气冷凝液中细胞因子的变化及意义

目的探讨COPD患者治疗期间呼出气冷凝液(EBC)细胞因子水平的变化及与肺功能相关性。方法入选稳定期COPD组24例,健康对照组18例。治疗前及治疗2周、4周、12周收集EBC并检测其LTB4、TNF-α、IL-13水平,并行肺功能检查。结果治疗前COPD组EBC中LTB4、TNF-α、IL-13水平高于对照组,治疗2周后均下降,治疗4周LTB4进一步下降(P0.05),且至12周保持低水平;而TNF-α、IL-13在治疗后2周至12周水平未见明显变化;治疗前后肺功能比较差异有统计学意义(P0.05);治疗前FEV1%与LTB4呈负相关关系(r=-0.574,P=0.003)。结论 LTB4、TNF-α可能参与COPD发病机制,可作为治疗期间观察疗效及监测病情指标。     

呼出气冷凝液中8-异前列腺素F2α的检测及其临床意义

8-异前列腺素F2α是目前研究比较多的一种呼出气中的标志物，反映了呼吸系统疾病炎症反应及氧化应激变化，有较好特异性及灵敏度。本文就呼出气冷凝液中8-异前列腺素F2α的来源、代谢、检测方法、影响呼出气中8-异前列腺素F2α水平的因素和临床意义等进行综述。     

Detection of microorganisms in exhaled breath condensate during acute exacerbations of COPD

Background and objective: One hallmark of COPD is colonization and infection of the lung. Acute exacerbations of COPD (AECOPD) are acute deteriorations of the chronic disease and are associated with a change of the pulmonary microbial balance. The collection of exhaled breath condensate (EBC) can be used to non‐invasively determine markers of lung disease. The aim of the present study was to compare the results of assays based on the detection of microbial nucleic acids from EBC and from spontaneous sputum in patients with AECOPD. Methods: EBC and sputa of 29 adults with AECOPD were obtained. Isolated DNA or RNA were used as starting material for the PCR assays to detect Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, influenza viruses (AH 1, AH 3) and respiratory syncytial virus. Results: Bacterial or viral nucleic acids were identified in 14 EBC and 21 sputa from 29 patients. Results from EBC did not correlate well with those from sputum. Viral and S. pneumoniae nucleic acids were detected only in sputum, whereas L. pneumophila DNA was only found in EBC. In three EBC and 10 sputa nucleic acids of more than one microorganism was detected. Conclusions: Bacterial nucleic acids can be identified in EBC of COPD patients with exacerbations. The results obtained from EBC and sputum did not correlate well.     

阻塞性睡眠呼吸暂停低通气综合征呼出气冷凝液8-异前列烷的昼夜变化及其意义

目的 探讨阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)患者呼出气冷凝液(exhaled breath condensate,EBC)8-异前列烷(8-isoprostane,8-isoPG)的昼夜变化及其意义.方法 采用德国JAEGER公司的呼出气收集器.收集40例OSAHS患者和30名正常对照者睡眠监测前后的EBC,同时采集睡眠监测后的血清,采用酶联免疫技术测定EBC及血清中8-isoPG的含量,并与睡眠监测指标进行相关性分析.结果 OSAHS组EBC中8-isoPG睡眠监测前为(13.08±1.42)ng/L、睡眠临测后为(14.93±1.39)ng/L(P<0.01).正常对照组EBC中8-isoPG睡眠监测前为(11.06±0.72)ng/L、睡眠监测后为(10.97±0.70)ng/L(P>0.05).OSAHS组睡眠监测后EBC及血清中8-isoPG比正常对照组升高,P<0.01.OSAHS患者睡眠监测后EBC 8-isoPG与血清8-isoPG呈正相关(r=0.685,P<0.01),与AHI呈正相关(r=0.650,P<0.05),与睡眠中最低血氧饱和度、基础血氧饱和度和平均血氧饱和度呈负相关(r=-0.406,-0.439,-0.454,P值均<0.05).结论 OSAHS患者存在夜间氧化应激反应增强,OSAHS患者早晨EBC中8-isoPG可以作为评价患者氧化应激状态和估计病情严重程度的较好指标.     

慢性阻塞性肺疾病患者呼出气冷凝液中髓过氧化物酶的检测及其意义

目的 检测COPD患者呼出气冷凝液（EBC）中髓过氧化物酶（MPO）浓度,探讨MPO与COPD发病发展的关系.方法 纳入49例COPD患者、18例健康体检者作为研究对象,采用EcoscrecnEBC收集仪采集标本,以酶免疫法测定EBC中MPO浓度.结果 COPD组EBC中MPO浓度显著高于健康对照组[（35.68±0.32）μg/L vs （11.72±0.34）μg/L,P＜0.05];COPD组EBC中MPO浓度与患者FEV1％ pred、呼气流量峰值呈正相关（相关系数r分别为0.418、0.327,P值均＜0.05）.结论 EBC中的MPO浓度能监测肺组织局部的炎症和氧化应激程度,能反映COPD患者病情严重程度,有助于发现COPD的病情变化,是一种较好的评价COPD病情的生物学指标.     

AECOPD患者呼出气冷凝液中分泌性白细胞蛋白酶抑制剂的检测及其临床意义

目的分析慢性阻塞性肺疾病急性加重期(AECOPD)患者治疗前后呼出气冷凝液(EBC)中分泌性白细胞蛋白酶抑制剂(SLPI)浓度的变化,及其与AECOPD各临床指标的相关性。方法随机选择AECOPD患者30例,正常健康者18例,采用ELISA方法检测AECOPD组治疗前后及健康对照组EBC中SLPI浓度,应用Pearson直线相关分析AECOPD组治疗前EBC中SLPI浓度与COPD临床特征、肺功能(PEF、FEV1%预计值)、血气分析、血WBC计数等指标的相关性。结果经抗感染、氧疗、解痉、激素等常规治疗7天后,AECOPD组EBC中SLPI浓度明显高于治疗前(P0.05);AECOPD组治疗前EBC中SLPI浓度与患者FEV1%预计值、痰量、呼吸困难症状密切相关(P0.05),与患者PEF、血白细胞(WBC)计数、动脉血pH值、PaO2/FiO2、PaCO2无相关性(P均0.05)。结论 AECOPD患者EBC中SLPI浓度可作为反映病情的严重程度和临床转归的指标。     

COPD患者血清中8-异前列腺素的检测及其意义

目的研究慢性阻塞性肺疾病（COPD）患者血清中8-异前列腺素（8-isoPG）浓度的改变及临床意义。方法收集COPD患者（40例）急性发作期和缓解期以及正常对照组（30例）的血清,用酶标记法检测血清中8-isoPG,同时检测AECOPD患者的第一秒呼气容量（FEV1）、最大呼气流速（PEF）、pH值、PaCO2、PaO2及血白细胞总数。结果①COPD患者急性发作期8-isoPG为35.43±7.29ng/L,高于缓解期（24.71±8.25ng/L）及正常对照组（13.31±6.19ng/L）,P〈0.05;②COPD患者8-isoPG浓度与痰量呈正相关,r=0.217,P〈0.05。结论 COPD的急性发作期,8-isoPG升高反映了氧化应激增强。     

阻塞性睡眠呼吸暂停低通气综合征患者治疗前后呼出气冷凝液中8-异前列腺素水平的变化

目的探讨阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者治疗前后氧化应激标记物的变化以及这些变化与病情严重程度的关系。方法68例OSAHS患者中40例接受治疗2个月,其中33例使用持续气道正压通气治疗（CPAP）、5例行外科手术、2例使用口矫器,28例未经任何治疗,随访2个月。所有患者分别于治疗前和治疗后2个月,于晨起空腹时收集呼出气冷凝液（EBC）,同时抽取静脉血5ml,应用酶联免疫吸附法（ELISA）测定EBC和血清中8．异前列腺素的含量,并进行统计学的处理。结果治疗后EBC和血清中8-异前列腺素的水平较治疗前明显降低,差异具有显著性[EBC：（19．9±2．9）pg／ml,（14．4±3．1）pg/ml,P〈0．001;血清：（29．9±5．7）pg／ml,（20．4±3．9）pg／ml,P〈0．001];EBC和血清中8-异前列腺素水平的绝对变化（治疗后．治疗前）与呼吸暂停低通气指数（AHI）和最长窒息时间的绝对变化呈正相关（EBC：r=0．69,r=0．50,P〈0．001;血清：r=0．72,r=0．46,P〈0．001）,与夜间最低SaO2的绝对变化呈负相关（EBC：r=-0．58,P〈0．001;血清：r=-0．53,P〈0．001）。结论EBC和血清中8-异前列腺素的水平能通过治疗有效降低,治疗前后的水平变化与病情的严重程度有关,可作为随访病情和反映治疗效果的指标。     

High levels of interleukin-6 in the exhaled breath condensate of patients with COPD

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the respiratory tract. METHODS: We investigated the presence of interleukin-6 (IL-6: a cytokine secreted by monocytes/macrophages, T cells, B cells, fibroblasts, bone marrow stromal cells, keratinocytes and endothelial cells) in the exhaled breath condensate of 16 exsmokers with moderate COPD, 12 healthy non-smokers. IL-6 was measured by means of a specific enzyme immunoassay. RESULTS: IL-6 levels were detectable in all of the subjects, but were higher in the COPD patients (8.0 +/- 0.1 pg/ml; P < 0.0001) than in the healthy non-smokers (4.9 +/- 0.2 pg/ml) with a correlation in this group between age and IL-6 levels (r = 0.597; P < 0.05). CONCLUSIONS: The increased IL-6 levels in exhaled breath condensate may reflect airway inflammation in patients with COPD.     

Exercise increases exhaled breath condensate cysteinyl leukotriene concentration in asthmatic patients

Background. Although the importance of cysteinyl leukotrienes (Cys-LTs) in exercise-induced bronchoconstriction (EIB) is supported by various sources of evidence, how the concentration of these mediators change during the development of EIB has not been investigated. Objectives. Our goal was to determine the effect of exercise on the concentration of airway Cys-LT in asthmatic patients by measuring Cys-LT in exhaled breath condensate (EBC). Methods. Seventeen atopic asthmatic patients with a previous history of EIB and six healthy volunteers were studied. Before and two times within 10 minutes after exercise challenge, FEV₁ was measured and EBC was collected for Cys-LT measurement. Exhaled nitric oxide level, a marker of airway inflammation, was also determined at baseline. Results. Baseline Cys-LT level was higher in the asthmatic group versus healthy subjects (168 pg/mL /112–223/ vs. 77 pg/mL /36–119/, p = .03). EBC Cys-LT concentration increased in all asthmatic patients post-exercise (n = 17, p = .03), with the increase significantly greater in patients developing exercise-induced bronchospasm (n = 7, p = .03), whereas no change was observed in healthy controls (p = .59). The exercise-induced fall in FEV₁ in asthmatics was related to the increase in EBC Cys-LT concentration (r = ?0.40, p = .03). Conclusions. Our study shows that Cys-LT concentration of EBC is elevated minutes after physical exercise in asthmatic patients and strongly supports the concept that the release of this mediator is involved in the development of EIB.     

COPD无创通气患者呼出气冷凝液亚硝酸盐/硝酸盐检测意义

目的探讨AECOPD患者呼出气冷凝液(EBC)中亚硝酸盐/硝酸盐(NO 2-/NO 3-)的临床价值。方法随机选择AECOPD无创正压通气(NPPV)治疗患者40例,比较NPPV治疗前及治疗后2 h、24 h、72 h三个时间点EBC中NO 2-、NO 3-的变化。结果治疗有效组(A组)AECOPD患者三个时间点EBC中NO 2-均较治疗前明显降低(P0.05);而治疗失败组(B组)治疗前后均无统计学差异(P0.05)。两组NO 3-的治疗前后未见变化(P0.05)。A组治疗前NO 2-与FEV1呈负相关。结论 AECOPD患者EBC中NO 2-与病情程度相关,NO 2-有望成为监测AECOPD治疗及预后的有效指标。     

Clinical and technical factors affecting pH and other biomarkers in exhaled breath condensate

Exhaled breath condensate (EBC) pH appears to be a robust measure of asthma. However, the association between EBC pH and clinical factors and airway inflammatory markers remains unclear. The objectives of this study were to investigate the factors determining EBC pH in asthmatic children, and the reproducibility and effects of collection devices on EBC pH in nine healthy, nonsmoking adults. EBC was collected once from asthmatic children using EcoScreen, and from adults over 3 consecutive days using both RTubes and EcoScreen. EBC pH was measured immediately in non-deaerated samples by microelectrode pH meter. Concentrations of 8-isoprostane, cysteinyl leukotrienes (cys-LT), and leukotriene B4 (LTB4) were measured using enzyme immunoassay. Exhaled nitric oxide concentration (FeNO) was measured by chemiluminescence. Fifty-eight asthmatics (16 intermittent, 12 mild persistent, and 30 moderate-to-severe persistent) were recruited. EBC pH was lower among patients with moderate-to-severe persistent than intermittent asthma (P = 0.046). This marker correlated inversely with disease severity score (rho = -0.276, P = 0.036), but not FeNO or other EBC biomarkers. Bland-Altman analyses found pH but not other EBC biomarkers to be reproducible, which were confirmed by its low coefficient of variation (2.7%; range, 0.4-5.2%). There was poor correlation between pH in EBC collected by RTube and EcoScreen (rho = 0.059, P = 0.784). Factor analysis selected four factors that explained 67.5% of the total variance, and EBC pH clustered with both cys-LT and LTB4. In conclusion, our results suggest that pH in non-deaerated EBC is influenced by asthma severity in children. EBC pH measurement is reproducible, but is dependent on the collection devices used.     

呼出气冷凝液中生物标记物在COPD的意义

COPD是全球范围内发病率和病死率最高的疾病之一,目前发病机制尚未明确,主要认为其与气道、肺实质及肺血管的慢性炎症、氧化应激及蛋白酶-抗蛋白酶的失衡有关.呼出气冷凝液可有效收集呼吸过程中气道表面形成的气溶胶和挥发性分子,是检测呼吸道炎症因子的重要标本来源,可反映氧化损伤、炎症以及治疗等导致的气道内环境的变化.应用呼出气冷凝液可对COPD的发生发展及急性加重过程实现无创、简单的监测.     

OSAHS患者呼出气冷凝液中MMP-9的变化

目的观察阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者呼出气冷凝液(EBC)中基质金属蛋白酶9(MMP-9)的变化。方法选取男性40例OSAHS患者为实验组,30例年龄、体重指数等均相匹配的健康查体者为对照组,用ELISA检测EBC中MMP-9水平。结果和对照组比较,OSAHS组EBC中MMP-9明显升高,有显著统计学意义(P0.05)。MMP-9与AHI呈正相关,与最低SaO2负相关(P均0.05)。结论OSAHS患者EBC中MMP-9水平可反映OSAHS病情的严重程度。     

慢性阻塞性肺疾病呼出气冷凝液中的生物标记物及其意义

呼出气冷凝液(exhaled breath condensate,EBC)是一种无创研究气道内衬液成分的方法,也为评估肺部炎症提供可能.目前普遍认为,慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是以气道、肺实质和肺血管的慢性炎症为特征的疾病.通过对COPD患者EBC的收集和检测,可实现对气道炎症的实时、无创、简单、重复的监测.     

Leukotriene B4 in exhaled breath condensate and sputum supernatant in patients with COPD and asthma

STUDY OBJECTIVES: Some patients with COPD present with significant reversibility of airflow limitation after receiving bronchodilation therapy. Leukotriene B(4) (LTB(4)) has been implicated in the pathophysiology of both COPD and asthma. We tested the hypothesis that COPD patients with airflow reversibility and asthmatic patients who smoke might have similar levels of LTB(4) in exhaled breath condensate (EBC) and sputum supernatant. The repeatability and stability of LTB(4) measurements were additionally studied. DESIGN: Prospective, cross-sectional study. PATIENTS OR PARTICIPANTS: We studied 30 patients with COPD (15 smokers [FEV(1), 56% predicted; SD, 6% predicted]; 15 patients with significant reversibility in airway obstruction after bronchodilation [FEV(1), 14% predicted; SD, 2% predicted]). Fifteen asthmatic patients who smoked, with similar FEV(1) and reversibility were also studied. Ten healthy smokers served as control subjects. SETTING: A hospital research laboratory. INTERVENTIONS: Spirometry and reversibility testing were performed on the first visit. On the following day, EBC was collected for the measurement of LTB(4), and induced sputum was collected for differential cell counts and LTB(4) measurement in the sputum supernatant. MEASUREMENTS AND RESULTS: LTB(4) levels in EBC [mean (SD)] were increased in COPD patients (mean, 86.7 pg/mL; SD, 19 pg/mL) and asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL) compared to control subjects (mean, 32.3 pg/mL; SD, 10 pg/mL; p < 0.0001 for both groups). COPD patients with airflow reversibility (mean, 99.8 pg/mL; SD, 12 pg/mL) had values similar to those of asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL; p = 0.2) and higher than those of COPD patients without airflow reversibility (mean, 73.7 pg/mL; SD, 17 pg/mL; p = 0.002). Similar results were observed in the sputum supernatant. Measurements of LTB(4) in EBC and sputum were repeatable on two consecutive days, but measurements in the frozen samples of EBC and sputum were not stable after 3 weeks. CONCLUSIONS: Patients with asthma and reversible COPD presented with higher LTB(4) values compared to patients with nonreversible COPD and healthy smokers. This difference may be mainly attributed to the presence of reversibility in airway obstruction, probably as part of a common underlying inflammatory process.     

慢性阻塞性肺疾病呼出气冷凝液中生物标记物的研究进展

呼出气冷凝液(exhaled breath condensate,EBC)检测作为一种新的研究肺部疾病的方法,具有无创、简便易行、实时监测、重复性好、患者易耐受等优点.对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者EBC中反映气道炎症、氧化应激状态的生物标...