支气管哮喘患者呼出气冷凝液和诱导痰中炎性指标检测的临床意义

目的 通过测定支气管哮喘(以下简称哮喘)患者呼出气冷凝液(EBC)和诱导痰中炎性指标的浓度,分析其与临床指标的关系,探讨炎性指标用于病情和疗效评估的价值.方法 选四川大学华西医院呼吸内科门诊接受吸入糖皮质激素联合长效β2受体激动剂治疗的中重度慢性持续期哮喘患者,记录治疗前和治疗1个月后哮喘症状积分,测定第1秒钟用力呼气容积(FEV1)占预计值百分比,采集诱导痰和EBC标本,测定标本中过氧化氧(H2O2)、硝酸盐/哑硝酸盐(NO3-/N2-)和半胱氨酰白三烯E4(LTE4)浓度.结果 共有25例中重度哮喘患者按研究方案完成治疗和随访.哮喘患者经联合治疗1个月后临床症状积分和FEV1占预计值百分比明显改善(P<0.01);EBC和诱导痰中H2O2、NO3-/NO2-和LTE4浓度均降低,但仍高于健康对照者;H2O2和NO3-/NO2-的下降比LTE4明显;哮喘患者EBC中的H2O2和NO3-/NO2-;浓度与FEV1呈负相关(P<0.01),与症状积分呈正相关(P<0.01),LTE4与症状积分和FEV1均无相关性.诱导痰中H2O2浓度与FEV1占预计值百分比呈负相关(P<0.01),与症状积分呈正相关(P<0.01);NO3-/NO2-浓度与FEV1占预计值百分比呈负相关(P<0.01),与症状积分无相关性;LTE4浓度与症状积分和FEV1占预计值百分比均无相关性.治疗后FEV1占预计值百分比增高程度与EBC和诱导痰中H2O3、NO3-/NO2-浓度降低水平呈正相关(P<0.01).诱导痰和EBC对应的炎性指标之间有相关性(P值均小于0.01).EBC和诱导痰中H2O2浓度与NO3-/NO2-浓度呈正相关(P<0.01),与LIE4之间无相关性.结论 中重度哮喘患者联合治疗后在临床症状和肺功能改善的同时,气道炎症显著减轻.EBC的安全性和可重复性优于诱导痰,H2O2和NO3-/NO2-的敏感性优于LTE4.     

支气管哮喘患者呼出气冷凝液标志物研究进展

呼出气冷凝液（exhaled breath condensate,EBC）是近年来出现的用于评价气道炎症及氧化应激程度的新型手段。相比传统的评价气道炎症的采样方法如：支气管肺泡灌洗液、诱导痰等,EBC具有安全无创、简便易行及可多次重复的优点。     

舒利迭对支气管哮喘患者呼出气一氧化氮浓度及超敏C-反应蛋白的影响

目的探讨支气管哮喘患者使用舒利迭前后呼出气一氧化氮浓度及超敏C-反应蛋白(hs-CRP)的变化。方法选择59例支气管哮喘患者,随机分组,30例使用舒利迭,29例使用万托林,治疗前后测定患者呼出气一氧化氮浓度及血中hs-CRP数值的变化。结果舒利迭组(试验组)与万托林组(对照组)比较,在治疗前后,呼出气一氧化氮浓度及血中hs-CRP有显著性差异(P<0.05)。结论舒利迭较万托林可显著降低气道炎症及复发,可显著降低患者呼出气一氧化氮浓度及血中hs-CRP浓度。     

支气管哮喘患者呼出气一氧化氮及诱导痰的相关性研究

目的 分析诱导痰嗜酸粒细胞计数与呼出气一氧化氮水平的相关性,并探讨其对治疗方案调整的意义.方法 收集门诊疑似支气管哮喘(简称哮喘)患者138例(哮喘60例,非哮喘78例),测定呼出气一氧化氮水平;哮喘组查诱导痰嗜酸细胞计数.结果 哮喘组呼出气一氧化氮为(49.73±24.99) ppb,与非哮喘组(31.51±27.43) ppb比较,差异有统计学意义(t=4.19,P＜0.001).诱导痰中EOS计数与呼出气一氧化氮水平呈正相关(P＜0.01).结论 哮喘患者诱导痰嗜酸粒细胞计数和呼出气一氧化氮测定值升高,且两者之间呈正相关.     

呼出气冷凝液检测在呼吸系统疾病中的应用

呼出气冷凝液（ exhaled breath condensate, EBC） 分析是一种新兴的呼吸系统疾病检测手段,通过检测冷凝水中的生化标记物以评价气道炎症或氧化应激水平,由于其具有无创、方便、可重复等特点．被认为具有良好的发展前景。目前EBC检测在慢性阻塞性肺疾病、支气管哮喘、肺癌、间质性肺疾病等多种呼吸系统疾病的诊断、监测及疗效评价中均有相关的研究报道,本文拟对近年来的研究进展作一简要综述。     

支气管哮喘患者呼出气冷凝液中LTB4和TNF-α检测的研究

目的:了解支气管哮喘患者呼出气冷凝液(EBC)中白三烯B4(LTB_4)和肿瘤坏死因子(TNF-α)的水平及其临床意义。方法:收集42例哮喘患者急性发作期和缓解期以及40例正常对照组的EBC,检测EBC中LTB_4和TNF-α水平,同时检测患者第1秒呼气容量(FEV_1)、最大呼气流速(PEF)、动脉血二氧化碳分压(PaCO_2)、动脉血氧分压(PaO_2)、血IgE及血嗜酸性粒细胞计数。结果:1哮喘患者急性发作期LTB_4为(36.71±15.23)ng/L,缓解期为(26.65±12.71)ng/L,与正常对照组(13.82±7.80)ng/L比较,差异有显著性(均P0.05);2哮喘患者急性发作期TNF-α水平为(16.07±7.60)ng/L,缓解期为(9.72±4.36)ng/L,与正常对照组(4.88±3.31)ng/L比较,差异有显著性(均P0.05);3哮喘患者急性发作期EBC中LTB_4和TNF-α水平与血清IgE水平呈正相关,LTB_4水平与PEF、FEV_1占预计值的百分比呈负相关。结论:EBC中LTB_4和TNF-α水平可作为评价哮喘急性发作、判断病情严重程度和观察疗效的重要指标。     

呼出气冷凝液检测在呼吸系统疾病中的应用

呼出气冷凝液 (exhaledbreathcondensate,EBC)检查为新的呼吸道炎症状态检测方法。气道内衬液体中抗氧化物、可溶性标记物等多种生化分子 ,平静呼吸时可随气体呼出 ,遇冷则随水蒸气凝结而进入EBC。EBC中某些成分的显著异常 ,可反映哮喘、慢性阻塞性肺疾病、急性呼吸窘迫综合征、肺间质疾病等肺内及气道内氧化应激、炎症状态的变化及程度。EBC与传统方法如诱导痰、支气管镜肺泡灌洗液等相比 ,具有实时、无创、简单、可多次重复等特点 ,结果也有可比性。目前EBC检测尚属探索阶段 ,但随着检测技术的提高和了解的深入 ,EBC检测在未来会有广泛的前景     

呼出气冷凝液癌胚抗原测定对肺癌的诊断价值

为了寻找诊断肺癌的无创检查方法，我们探索呼出气冷凝液(EBC)检测癌胚抗原(CEA)对肺癌的诊断价值。     

呼出气冷凝液检测在肺癌中的研究与应用

早期发现、早期治疗是降低肺癌发病率和病死率的有效措施.传统的胸片、痰细胞学检查、低剂量CT等手段在肺癌筛查和诊断中具有一定的应用价值,但是否有助于降低肺癌病死率还有待进一步观察.呼出气冷凝液收集是一种新型、无创、简易、安全的技术,众多研究表明呼出气冷凝液检测可用来筛选灵敏性和特异性比较可靠的生物标记物,在分子水平辅助肺癌早期诊断,且在病情评估、疗效评价、预后估计等方面也起重要作用.     

呼出气冷凝液在监测支气管哮喘气道炎症中的应用

支气管哮喘（以下简称哮喘）是一种由多种细胞如嗜酸性粒细胞、肥大细胞、T淋巴细胞、中性粒细胞、气道上皮细胞和细胞组分参与的气道慢性炎症性疾病，目前评价哮喘病情的常用指标为肺功能，但肺功能仅能反映气流受限的严重程度，不能直接反映气道炎症的严重程度。呼出气冷凝液（exhaled breath condensate，EBC）检测是近10余年来新出现的一种检测方法，在气道炎症方面的研究中越来越受到重视。本文就EBC在监测哮喘气道炎症中的应用作一综述。     

Exhaled nitric oxide and exhaled breath condensate pH as predictors of sputum cell counts in optimally treated asthmatic smokers

Background and objective: Smoking is thought to modify the pattern of airway inflammation. Induced sputum provides useful information on cellular phenotype in inflammatory airways disorders; however, it is time‐consuming and difficult to implement in everyday clinical practice. The aim of this study was to determine whether exhaled NO (FeNO) and exhaled breath condensate (EBC) pH differed in asthmatic smokers compared with asthmatic non‐smokers and healthy subjects, and to evaluate the performance of FeNO and EBC pH for predicting the cellular phenotype of induced sputum. Methods: Asthmatic smokers (n = 40) and non‐smoking asthmatic patients (n = 43) were recruited for the study. Healthy smoking (n = 30) or non‐smoking (n = 30) subjects served as controls. FeNO and EBC pH were measured and all subjects underwent sputum induction for assessment of cell counts. Results: EBC pH was significantly lower in asthmatic smokers compared with non‐smokers (P < 0.01). FeNO levels were also significantly lower in asthmatic smokers compared with non‐smokers (P < 0.001). EBC pH was inversely associated with sputum eosinophils in both asthmatic smokers and non‐smokers (P < 0.001), whereas it was inversely associated with sputum neutrophils only in asthmatic smokers (P < 0.001). FeNO was positively associated with sputum eosinophils both in asthmatic smokers and non‐smokers (P < 0.001) but was not associated with sputum neutrophils. In asthmatic smokers, FeNO was a better predictor of sputum eosinophilia, whereas EBC pH was a better predictor of sputum neutrophilia. A combination of FeNO ≤ 14 ppb together with EBC pH > 7.20 predicted the paucigranulocytic induced sputum phenotype. Conclusions: EBC pH and FeNO levels were significantly lower in asthmatic smokers compared with non‐smokers. Combined specific cut‐off levels for FeNO and EBC pH may predict the paucigranulocytic phenotype in asthmatic smokers.     

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.     

Inflammatory markers in exhaled breath condensate from patients with asthma

Background and objective:   Evaluation of airway inflammation is important for the diagnosis and treatment of asthma. Exhaled breath condensate (EBC) is a minimally invasive method for assessing inflammation and may be useful for monitoring airway inflammation in asthma. The aims of this study were to establish an EBC collection method, to assess biomarkers reflecting asthmatic airway inflammation, and to determine the relationship of these biomarkers with asthma severity and lung function.
Methods:   Fifty-eight non-smoking healthy subjects, seven asymptomatic smokers, nine subjects with common cold and 55 asthmatics with disease severity ranging from mild intermittent to severe persistent were studied. The efficacy of a pipette method was compared with that of a commercial collecting device. pH, CRP, albumin, hydrogen peroxide (H₂O₂) and nitrite/nitrate levels were measured in EBC.
Results:   Except for the quantity of EBC collected and albumin levels, there were no differences between the commercial method and the pipette method in levels of biomarkers measured. Levels of CRP, H₂O₂ and nitrite/nitrate were significantly higher in the asthma group than that in the control group. In terms of asthma severity, pH and levels of CRP, H₂O₂ and nitrate were significantly higher in the mild persistent group than that in the other groups. In addition, H₂O₂ levels in EBC correlated significantly with the level of nitrite/nitrate. FEV₁ and PEF showed significant negative correlations with H₂O₂ and nitrite/nitrate levels.
Conclusion:   Measurement of EBC biomarkers is a non-invasive and useful way to evaluate airway inflammation in patients with asthma.     

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。     

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.     

Exhaled breath condensate nitrite/nitrate and pH in relation to pediatric asthma control and exhaled nitric oxide

BACKGROUND: Combining exhaled breath condensate (EBC) and exhaled nitric oxide (eNO) may be a useful, non-invasive method to assess airway inflammation in pediatric asthma. This cross-sectional study evaluated the relationship of both EBC nitrite/nitrate (NOx) and EBC pH with asthma control and eNO in asthmatic, normal, and atopic children. METHODS: A total of 92 children were recruited, comprising 62 with asthma, 14 with atopy only, and 16 who were normal and non-atopic. All completed a questionnaire for asthma symptoms and control. Variables measured were spirometry, EBC NOx, pH, and eNO. RESULTS: EBC NOx in those with asthma (mean 8.4 microM, CI 7.5-9.4) was significantly elevated when compared with normal (4.8 microM, CI 3.4-6.2, P = 0.0007) and atopic children (6.5 microM, CI 4.0-9.1, P = 0.02). The mean level of eNO was significantly higher in those with asthma (43.7 ppb, CI 34.7-51.1, P < 0.001) and atopy (24 ppb, CI 16.7-31.2, P < 0.05) when compared with normal children (11.5 ppb, CI 6.7-16.2). There was a significantly lower pH in those with asthma and a FEV(1) < 80% predicted (P = 0.03), but no significant overall differences in EBC pH between the three groups of children. There was a significant correlation between eNO and EBC NOx in the group as a whole, but not between eNO and EBC pH. CONCLUSIONS: Mean EBC NOx levels differ between children with asthma, atopy, and those who are normal, but it is not interchangeable with eNO. EBC pH may be an additional marker of asthma control.     

Reduced exhaled breath condensate pH in asthmatic smokers using inhaled corticosteroids

Background and objectives:   Exhaled breath condensate (EBC) pH has been proposed as a biomarker of airway inflammation and oxidative stress in asthma. Cigarette smoking reduces EBC pH in mild asthma. The effects of smoking on EBC pH in more symptomatic asthmatic patients using inhaled corticosteroids (ICS) are unknown. We aimed to compare EBC pH in asthmatic smokers (AS) and non-smokers (ANS) with moderate to severe disease, who were taking ICS. We also investigated the relationship between EBC pH and biomarkers of airway inflammation and oxidative stress.
Methods:   AS ( n  = 18) and ANS ( n  = 17), who were using ICS, were recruited and EBC pH, sputum inflammatory cell counts and sputum supernatant 8-isoprostane concentrations were measured. Full lung function testing was performed.
Results:   EBC pH was significantly lower in AS than in ANS (6.91 vs 7.41). In AS there was a significant inverse correlation between EBC pH and 8-isoprostane levels ( r  = −0.54, P  = 0.03). There was no correlation between EBC pH and sputum neutrophil counts.
Conclusions:   EBC pH appears to be a biomarker of the level of oxidative stress in smokers with moderate to severe asthma. EBC pH may have applications for the longitudinal monitoring of the effects of smoking on the airways of asthmatic patients.     

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.