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1.
Shibata A  Katsunuma T  Tomikawa M  Tan A  Yuki K  Akashi K  Eto Y 《Chest》2006,130(6):1718-1722
BACKGROUND: Chronic airway inflammation is a feature of asthma. Increased levels of cysteinyl leukotrienes (cys-LTs; leukotriene [LT]C(4), LTD(4), LTE(4)) have been shown in the exhaled breath condensate (EBC) of children with moderate-to-severe asthma. The aim of this study was to examine the relationship between EBC cys-LTs (LTE(4)) levels and bronchial hyperreactivity in children with mild asthma in order to evaluate the clinical utility of measuring EBC cys-LTs levels. METHODS: We measured LTE(4) levels in the EBC of children aged 8 to 18 years, including healthy nonasthmatic children (n = 6) and children with mild asthma (n = 37). Patients with mild asthma were classified into the following three groups: group 1, participants who had been asymptomatic (no wheezing/symptoms of asthma) for > 6 months prior to examination (n = 12); group 2, participants who were asymptomatic but had had wheezing/symptoms of asthma within 6 months before examination (n = 18); and group 3, patients with current wheeze and/or mild symptoms of asthma exacerbation at the time of examination. RESULTS: Exhaled LTE(4) levels were increased in all children with mild asthma compared with nonasthmatic control subjects (5.69 +/- 9.62 pg/20 min vs 0.74 +/- 0.79 pg/20 min, p < 0.05) [mean +/- SD]. In particular, the EBC LTE(4) levels in group 2 (4.99 +/- 6.70 pg/20 min) and group 3 (14.66 +/- 17.11 pg/20 min) were increased compared with control subjects and group 1 (1.50 +/- 1.69 pg/20 min). The EBC LTE(4) levels negatively correlated with the provocative concentration of methacholine causing a 15% fall in FEV(1) (r = - 0.454, p = 0.012). CONCLUSION: EBC cys-LTs may be useful as a noninvasive marker assessing airway inflammation and hyperreactivity in children with asthma.  相似文献   

2.
Increased leukotrienes in exhaled breath condensate in childhood asthma   总被引:11,自引:0,他引:11  
Cysteinyl leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast cells and eosinophils and induce airway smooth muscle contraction, microvascular leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath condensate from children aged 7-14 years including healthy nonatopic children (n = 11) and children with mild intermittent asthma (steroid naive, n = 11), mild persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled LTB4 levels were increased in patients with mild and moderate to severe persistent asthma compared with patients with mild intermittent asthma (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 52.7 +/- 3.8 pg/ml, p < 0.001 and p < 0.0001) and normal subjects (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 47.9 +/- 4.1 pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients with mild and moderate to severe persistent asthma compared with normal subjects (27.9 +/- 2.8 and 31.5 +/- 4.5 versus 18.5 +/- 0.5 pg/ml, p < 0.01 and p < 0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma.  相似文献   

3.
Chronic neutrophilic airway inflammation is an important feature of cystic fibrosis (CF). Noninvasive inflammatory markers may be useful in monitoring CF. Leukotriene B4 (LTB4) and interleukin (IL)-6 are inflammatory mediators that are increased in chronic neutrophilic inflammation. The aim of this study was to assess whether LTB4 and IL-6 were increased in exhaled breath condensate of CF patients and whether they could be used to monitor inflammation. Twenty patients with CF (13 males, age of 28 +/- 9 years) were recruited together with 15 age-matched healthy subjects (8 males, age 35 +/- 7 years). LTB4 and IL-6 levels were markedly elevated in patients with acute exacerbations (28.8 +/- 4.3 and 8.7 +/- 0.4 pg/ml) compared with control subjects (6.8 +/- 0.7 and 2.6 +/- 0.1 pg/ml, p < 0.0001). We also observed a decrease of exhaled LTB4 and IL-6 concentrations after antibiotic treatment in six patients who were followed until clinically stable (31.1 +/- 4.4 and 9.5 +/- 0.4 pg/ml vs. 18.8 +/- 0.8 and 6.4 +/- 0.2 pg/ml, respectively) and an increase in 15 CF patients infected with Pseudomonas aeruginosa (34.3 +/- 5.0 and 9.3 +/- 0.3 pg/m) compared with those infected with other bacteria (18.3 +/- 0.7 and 6.9 +/- 0.5 pg/ml). These findings suggest that LTB4 and IL-6 levels are increased in exhaled breath condensate of patients with CF during exacerbation and could be used to monitor airway inflammation in these patients.  相似文献   

4.
Oxidative stress is implicated in the pathogenesis of asthma, and clinical studies show an imbalance in the level of oxidants to the level of antioxidants in subjects with asthma. Aldehydes and glutathione are examples of biomarkers of oxidant-induced damage and antioxidant status in asthma, respectively. In the study, we applied analytical techniques based on liquid chromatography for the assessment of aldehydes and glutathione in the exhaled breath condensate of children with asthma and in control subjects without asthma. Twelve subjects with asthma were evaluated at exacerbation and after 5 days of therapy with prednisone. At exacerbation, malondialdehyde levels were higher in patients with asthma (30.2 +/- 2.4 nM) than in control subjects (19.4 +/- 1.9 nM, p = 0.002) and were reduced after steroid therapy (18.5 +/- 1.6 nM, p = 0.001). At exacerbation, glutathione levels were lower in subjects with asthma (5.96 +/- 0.6 nM) than in control subjects (14.1 +/- 0.8 nM, p < 0.0001) and were increased after the therapy (8.44 +/- 1.2 nM, p = 0.04). Malondialdehyde and glutathione both in subjects with asthma and control subjects were negatively correlated (r = -0.5, p = 0.001). The study shows that aldehydes and glutathione are detectable in the exhaled breath condensate of children with asthma and healthy children and that their levels are modified during asthma exacerbation and after a 5-day course of therapy with oral prednisone.  相似文献   

5.
6.
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.  相似文献   

7.
Exhaled breath condensate (EBC) is being used increasingly to sample airway fluid. EBC pH may be a biomarker of airway inflammation in asthma. In this study, we assessed the long-term reproducibility of EBC pH in asthma. We examined 31 asthmatic patients and eight healthy subjects three times over a 1-year period (winter, autumn and summer). EBC pH was measured after argon deaeration. Repeatability of pH measurements was assessed using intraclass correlation coefficients (ICC) and the limits of agreement (LOA) between seasons were calculated according to Bland-Altman method. No significant differences in EBC pH between seasons were detected in healthy subjects and asthmatic patients. EBC pH showed high repeatability either in healthy subjects (ICC=0.94) or in asthmatics (ICC=0.97). Variability between seasons was greater in asthmatics than in healthy subjects: winter-autumn LOA -0.68/+0.52 and -0.31/+0.31, autumn-summer LOA -0.75/+0.67 and -0.24/+0.15, winter-summer LOA -0.92/+0.67 and -0.34/+0.23 in asthmatic and healthy subjects, respectively. In a subgroup of 11 asthmatics who remained in stable conditions during the study, no substantially different LOA were observed in EBC pH compared with the whole group of asthmatics. Asthmatic smokers (n=10) tended to have lower EBC pH (7.57+/-0.46) than asthmatic non-smokers (n=21) (7.74+/-0.21; p=0.063) and wider LOA. In conclusion, we demonstrated that EBC pH exhibits good repeatability in long-term assessment. EBC pH in asthmatics tended to fluctuate more than in healthy subjects. However, EBC pH variability in asthma was not influenced by changes in clinical status. Rather, we suggest that cigarette smoke may be implicated in EBC pH variability.  相似文献   

8.
RATIONALE: Metabolomic analysis provides biochemical profiles of low-molecular-weight endogenous metabolites in biological fluids. OBJECTIVES: The aim of this study was to assess the feasibility of nuclear magnetic resonance (NMR)-based metabolomic analysis applied to exhaled breath condensate ("breathomics"). Information coming from NMR spectra was analyzed with a view to establish the NMR variables that best discriminate between children with asthma and healthy children. METHODS: Twenty-five children with asthma (17 with persistent asthma treated with inhaled corticosteroids, 8 with intermittent asthma inhaled corticosteroid naive; age, 7-15 yr) and 11 healthy age-matched control subjects were enrolled. Every child performed exhaled nitric oxide measurement, spirometry, and condensate collection. Condensate samples were analyzed by means of NMR spectroscopy. Linear and partial least squares discriminant analyses were applied to data obtained from the NMR spectra. MEASUREMENTS AND MAIN RESULTS: The combination of exhaled nitric oxide and FEV(1) discriminates children with asthma and healthy children with a success rate of approximately 81%, whereas selected signals from NMR spectra offer a slightly better discrimination (approximately 86%). The selected NMR variables derive from the region of 3.2 to 3.4 ppm, indicative of oxidized compounds, and from the region of 1.7 to 2.2 ppm, indicative of acetylated compounds. CONCLUSIONS: Metabolomics can be applied to exhaled breath condensate, leading to the characterization of airway biochemical fingerprints. The presence of acetylated compounds suggests new metabolic pathways that may have a role in asthma pathophysiology.  相似文献   

9.
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.  相似文献   

10.
Nitrosothiols (RS-NOs) are formed by interaction of nitric oxide (NO) with glutathione and may limit the detrimental effect of NO. Because NO generation is increased in airway inflammation, we have measured RS-NOs in exhaled breath condensate in patients with asthma, cystic fibrosis, or chronic obstructive pulmonary disease (COPD). We also measured exhaled NO and nitrite (NO(2-)) in the same subjects. RS-NOs were detectable in exhaled breath condensate of all subjects. RS-NOs were higher in subjects with severe asthma (0.81 +/- 0.06 microM) when compared with normal control subjects (0.11 +/- 0.02 microM, p < 0.01) and with subjects with mild asthma (0.08 +/- 0.01 microM, p < 0.01). Elevated RS-NOs values were also found in patients with cystic fibrosis (0.35 +/- 0.07 microM, p < 0.01), in those with COPD (0.24 +/- 0.04 microM, p < 0.01) and in smokers (0.46 +/- 0.09 microM, p < 0.01). In current smokers there was a correlation (r = 0.8, p < 0.05) between RS-NOs values and smoking history (pack/year). We also found elevated concentrations of NO(2-) in patients with severe asthma, cystic fibrosis, or COPD, but not in smokers or patients with mild asthma. This suggests that exhaled NO(2-) is less sensitive than exhaled RS-NOs. This study has shown that RS-NOs are detectable in exhaled breath condensate of healthy subjects and are increased in patients with inflammatory airway diseases. As RS-NOs concentrations in exhaled breath condensate vary in the different airway diseases and increase with the severity of asthma, their measurement may have clinical relevance as a noninvasive biomarker of nitrosative stress.  相似文献   

11.
Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis.   总被引:4,自引:0,他引:4  
Exhaled nitric oxide (ENO), a marker of inflammation in airway diseases is decreased in cystic fibrosis (CF) patients, perhaps because nitric oxide (NO) is metabolized to oxidative end-products. A stable product, 3-nitrotyrosine, may indicate local formation of reactive nitrogen species. Whether NO metabolites in exhaled breath condensate may be increased in CF patients was investigated. The fractional concentration of ENO (Feno), nitrotyrosine and oxides of nitrogen in exhaled breath condensate from 36 stable CF patients were compared to 14 normal subjects using an enzyme immunoassay and fluorescence assay. Nitrotyrosine levels in breath condensate were increased significantly in stable CF patients, compared with normal subjects (25.3 +/- 1.5 versus 6.3 +/- 0.8 ng x mL(-1), p<0.0001). There was an inverse correlation between the levels of nitrotyrosine and the severity of lung disease. Feno levels were significantly lower in CF patients than in normal subjects (4.4 +/- 0.3 versus 5.6 +/- 0.4 (parts per billion), p<0.05). No correlation was found between nitrotyrosine and Feno levels in CF. There was no significant difference in the levels of nitrite and nitrate between CF patients and normals. The elevation in nitrotyrosine may reflect increased formation of reactive nitrogen species such as peroxynitrite or direct nitration by granulocyte peroxidases, indicating increased oxidative stress in airways of cystic fibrosis patients.  相似文献   

12.
Chronic airway inflammation in children with asthma might be present even in the absence of pathological lung function tests and is known to increase the risk of permanent pulmonary damage. Thus, we aimed at investigating to what extent inflammatory markers such as leukotrienes (LTs) in exhaled breath condensate (EBC) or fractional exhaled nitric oxide (FE(NO)) reflect therapeutic effects in these patients. Fifty steroid-naive patients (aged 8.8 +/- 2.7 years) were included in the study. EBC was collected before and 6 months after therapy with inhaled corticosteroids. LTs were determined by using commercially available ELISA. In addition, FE(NO) was measured by means of a chemiluminescence analyzer. Conventional lung function testing was performed revealing vital capacity, forced expiratory volume, maximum expiratory flow, and specific resistance. In EBC, LTE(4) but not LTB(4) levels significantly decreased after steroid therapy from 45.3 +/- 36.0 pg/mL to 17.2 +/- 11.4 pg/mL (p < 0.0001) concomitant with a slight, but significant improvement of lung function parameters. Mean FE(NO) also indicated therapeutic success; however, in 20 of 50 patients, exhaled NO concentrations were higher after therapy. These findings suggest that LTE(4) in breath condensate may be helpful in latent inflammatory activity in the bronchial mucosa in children with asthma.  相似文献   

13.
14.
RANTES has been implicated in the allergic inflammation of asthma by promoting the migration and activation of the inflammatory cells, including eosinophils. The study was undertaken to evaluate RANTES levels in the exhaled breath condensate (EBC) of asthmatics with different degrees of asthma severity. EBC was collected from 33 patients with allergic asthma (11 with steroid-na?ve mild asthma, 10 with ICS-treated, stable mild-to-moderate asthma, 12 with ICS-treated unstable, severe asthma) and seven healthy volunteers. In the three groups of asthmatics, RANTES concentrations in EBC were significantly higher compared with healthy volunteers. RANTES levels were significantly higher in patients with unstable asthma than in the two groups with stable disease. We observed statistically significant correlations between the concentrations of RANTES in EBC and F(ENO) in the three studied groups of asthmatics; notably, the correlation between the parameters described above was strong positive in the group of unstable and steroid-na?ve stable asthmatics. We also discovered a significantly positive correlation between RANTES in EBC and the serum ECP or blood eosinophil count in the groups of asthmatics with severe, unstable asthma and between RANTES and serum ECP in the group of steroid-na?ve stable asthmatics. Measurements of RANTES in EBC may provide another useful diagnostic tool for detecting and monitoring inflammation in patients with asthma.  相似文献   

15.
16.
Both atopy and asthma are claimed to be associated with a Th-2 cytokine pattern. We sought to determine the contribution of atopy and asthma to the observed Th-2/Th-1 imbalance in these conditions. Of 60 children aged 6-16 years that were included in the study, 13 were nonatopic nonasthmatic, 15 atopic nonasthmatic, 14 nonatopic asthmatic, and 18 atopic asthmatic. Atopic children had positive skin prick tests to grass pollens only. All children were studied after an asymptomatic and drug-free period of at least three months. Total IgE was measured in serum. Peripheral blood mononuclear cells were cultured and stimulated in vitro with phytohemagglutinin and interferongamma (IFN-gamma) and interleukin-4 (IL-4) measured in the supernatants. Total IgE was significantly higher in atopic asthmatics compared to nonatopic asthmatics (p = 0.004), and nonatopic nonasthmatics (p = 0.001), but was not different from atopic nonasthmatics (p >0.05). On the other hand, IL-4 was significantly elevated in atopic asthmatics and in nonatopic asthmatics compared to nonatopic nonasthmatics (p = 0.037 and p = 0.009, respectively). Although atopic asthmatics had lower IFN-gamma values than nonatopic asthmatics, the difference did not reach statistical significance. No correlation was detected between any two parameters. Our results suggest that both atopy and asthma contribute to the increased levels of IL-4 and that, whereas nonatopic asthma is associated with increases in both IL-4 and IFN-gamma release by mononuclear cells, only atopic asthma is characterized by a Th-2 type cytokine dominance.  相似文献   

17.
Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides, which play an important role in the development of airway inflammation and remodeling in asthma. The study was undertaken to evaluate the endothelin-1 (ET-1) levels in exhaled breath condensate (EBC) of asthmatics with different degree in asthma severity. EBC was collected from 31 patients with allergic asthma (11 with steroid-na?ve mild asthma, 10 with ICS-treated, stable mild-to-moderate asthma, 10 with ICS-treated unstable, severe asthma) and 7 healthy volunteers. In the three groups of asthmatics, ET-1 concentrations in EBC were significantly higher than in healthy volunteers. ET-1 levels were significantly higher in patients with unstable asthma than in the two groups with stable disease. There was a significant correlation between ET-1 levels and FENO in the three groups of asthmatics and between ET-1 and blood eosinophil counts in the group of patients with unstable asthma. Measurements of ET-1 in EBC may provide another useful diagnostic tool for detecting and monitoring inflammation in patients with asthma.  相似文献   

18.
Persistent airway inflammation may require the use of different markers for monitoring airway inflammation. In this study, the authors investigated whether adenosine, which may be produced in allergic inflammatory conditions, could be measured with good reproducibility in exhaled breath condensate (EBC), and whether its concentration was elevated in patients with asthma. EBC adenosine and exhaled nitric oxide (eNO), a noninvasive marker of asthmatic airway inflammation, were measured in 40 healthy volunteers and 43 patients with allergic bronchial asthma. Repeatability of adenosine measurement was checked in 20 pairs of samples collected from healthy control subjects. Adenosine was detectable in all EBC samples by the applied high-performance liquid chromatographic method. The mean difference between repeated measurements of adenosine was -0.1 nM and all differences were within the coefficient of repeatability. Adenosine concentration was higher in steroid-naive patients (n=23) compared with healthy control subjects and steroid-treated patients (n=20). In patients with worsening symptoms of asthma (n=23), adenosine concentration was elevated compared with those in a stable condition (n=20). Furthermore, adenosine concentrations were related to eNO levels in asthmatic patients. These results, showing good reproducibility of adenosine measurements and increased adenosine concentrations in steroid-naive patients and in patients with worsening of asthmatic symptoms, indicate that adenosine measurement in exhaled breath condensate might be an acceptable novel method to investigate the role of local production of adenosine in the airways.  相似文献   

19.
冼美兰  黄平 《国际呼吸杂志》2007,27(20):1552-1556
收集呼气冷凝液(exhaled breath condensate,EBC)是一种非侵入性、安全、简便、易行的收集气道标本的方法,可用于检测气道炎症程度和氧化应激状态,是目前国外研究的热点。EBC中的氮氧化物及相关产物是氧化、过氧化、硝基化的产物,从而反映了气道氧化、过氧化、硝基化的状况。它们在哮喘的不同时期、不同严重程度时有着不同的变化,对激素的抗炎治疗有不同的反应,有望成为研究哮喘的发病机制、监测哮喘病情变化、抗炎疗效评价以及调整用药的指标。  相似文献   

20.
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.  相似文献   

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