Changes and clinical significance of multiple cytokines in exhaled breath condensate in patients with severe inhalation injury / 中华危重病急救医学

Objective:To investigate the changes and clinical significance of multiple cytokine levels in exhaled breath condensate (EBC) in patients undergoing tracheotomy with severe inhalation injury.Methods:A prospective study was conducted. A total of 32 patients with severe burn combined with severe inhalation injury admitted to the department of burns and plastic surgery of Affiliated Suzhou Hospital of Nanjing Medical University from May 2021 to August 2022 were enrolled. Twenty healthy volunteers from the same period were served as controls. EBC of patients at 12 hours after burn and the samples of healthy controls were collected. The levels of 27 cytokines in EBC, including tumor necrosis factor-α (TNF-α) and interleukins (IL-1β, IL-6, IL-8, IL-10, and IL-17), were determined by liquid phase chip technology. Meanwhile, plasma of patients at 12 hours after burn and the plasma of volunteers were collected, and the levels of inflammatory cytokines were detected by liquid chip technology, and the differences between the levels in plasma and those in EBC were analyzed. Plasma and EBC of patients with aspiration injury were collected at 12 hours and 3, 7, 14 and 21 days after burn, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA).Results:Finally, 32 patients were enrolled, and the total burned area was (40±16)% of total body surface area (TBSA). The time of admission was (4.2±2.3) hours after injury. ① Twenty-seven cytokines in EBC: 18 kinds of cytokines including macrophage inflammatory protein-1β (MIP-1β), IL-6, IL-5, IL-2, IL-1β, IL-8, IL-10, IL-15, IL-9, interferon-γ (IFN-γ), IL-1 receptor antagonist (IL-1ra), TNF-α, chemotactic factor for eosinophil (Eotaxin), basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), interferon-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF) were significantly increased in patients with severe aspiration injury compared with health controls. Eotaxin was not detected in EBC of healthy controls. Five cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine ligand 5 (CCL5/RANTES), IL-13, IL-4 and MIP-1α, were not detected in EBC of severe inhalation injury patients and healthy controls. Vascular endothelial growth factor (VEGF) and IL-12 p70 in EBC of severe aspiration injury patients were slightly decreased as compared with healthy controls, while IL-7 and IL-17 were slightly increased, but the differences were not statistically significant. ② Six inflammatory cytokines in plasma: the levels of IL-6 and IL-8 in the severe aspiration injury group were significantly increased as compared with healthy controls [IL-6 (ng/L): 18.51 (10.87, 26.21) vs. 0.22 (0.10, 0.36), IL-8 (ng/L): 10.75 (8.58, 18.79) vs. 1.06 (0.81, 2.14), both P < 0.01]. The plasma levels of TNF-α, IL-1β and IL-10 were slightly increased in patients with severe aspiration injury as compared with healthy controls, and IL-17 was slightly decreased, but the difference was not statistically significant. In the EBC collected during the same period, five inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8 and IL-10, in patients with severe inhalation injury were significantly increased as compared with healthy controls [TNF-α (ng/L): 16.42 (12.57, 19.21) vs. 7.34 (6.11, 8.69), IL-1β (ng/L): 15.57 (10.53, 20.25) vs. 0.99 (0.67, 1.41), IL-6 (ng/L): 13.36 (9.76, 16.54) vs. 0.70 (0.42, 0.85), IL-8 (ng/L): 1 059.29 (906.91, 1 462.37) vs. 10.36 (8.40, 12.37), IL-10 (ng/L): 2.69 (1.54, 3.33) vs. 1.54 (1.18, 2.06), all P < 0.05]. ③ Dynamic changes of TNF-α in plasma and EBC: the level of TNF-α in EBC of patients with severe aspiration injury was lower than that in plasma. Plasma TNF-α level was increased gradually with the extension of time after injury, and was significantly higher than that of healthy controls on day 3 [ng/L: 30.38 (24.32, 39.19) vs. 22.94 (17.15, 30.74), P < 0.05], and reached the peak on day 14, then fell back. The level of TNF-α in EBC at 12 hours after injury was significantly higher than that in healthy controls [ng/L: 15.34 (11.75, 18.14) vs. 6.99 (6.53, 7.84), P < 0.01], and reached the peak on 3 days after injury, and then gradually decreased. Conclusion:There are changes in the expression of multiple cytokines in EBC of patients with severe inhalation injury, and the changes of many inflammatory cytokines including TNF-α are more sensitive than those in plasma, which can be used to monitor and evaluate the condition of patients with inhalation injury.

Correlation between tumor necrosis factor-α and interleukin-1β in exhaled breath condensate and pulmonary function in chronic obstructive pulmonary disease / 中国热带医学

@#Abstract: Objective To explore the correlation between lung function in patients with chronic obstructive pulmonary disease (COPD) and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels in exhaled breath condensate (EBC), and to provide a convenient methodological basis for the diagnosis and treatment of COPD and the determination of its efficacy. Methods A total of 81 COPD patients and 40 healthy controls were selected from the respiratory department of the Fourth Affiliated Hospital of Guangzhou Medical University from August 2020 to February 2022 as the research subjects. The COPD patients were divided into 41 cases in the acute exacerbation group and 40 cases in the remission group according to their status. All participants underwent lung function detection, venous blood and EBC collection, and the levels of TNF-α and IL-1β in EBC and venous blood were analyzed by enzyme-linked immunosorbent assay (ELISA), and correlation analysis was performed by Pearson correlation analysis method. Results The levels of TNF-α and IL-1β in EBC of in the acute exacerbation group, the healthy control group, the remission group were (5.16±0.18) pg/μL and (7.75±0.27) pg/μL, (2.66±0.31) pg/μL and (2.41±0.24） pg/μL, (3.61±0.29) pg/μL and (3.17±0.38) pg/μL, respectively. Compared with the healthy control group, the levels of TNF-α and IL-1β in EBC in the COPD acute exacerbation group were significantly higher than those in the healthy control group and the COPD remission group (F=9.451, 8.217, P<0.001). Serum tests were consistent with this result. Correlation analysis showed that the levels of TNF-α and IL-1β in EBC were significantly positively correlated with the level of serum inflammation levels (P<0.001), while significantly negatively correlated with lung function (P<0.001).  Conclusions TNF-α and IL-1β in EBC are potential biomarkers of inflammation in patients with COPD, and their detection can be used to effectively assess lung function in patients with COPD. 

Accuracy of IL-6 and IL-8 concentrations in exhaled breath condensate in predicting postoperative ARDS in patients undergoing cardiac surgery under cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the accuracy of interleukin-6 (IL-6) and IL-8 concentrations in exhaled breath condensate (EBC) in predicting postoperative acute respiratory distress syndrome (ARDS) in the patients undergoing cardiac surgery under cardiopulmonary bypass (CPB).Methods Forty-two American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes,aged 18-64 yr,scheduled for elective cardiac valve replacement under CPB,were selected.EBC samples were collected for determination of the concentrations of IL-6 and IL-8 by enzyme-linked immunosorbent assay.The patients were divided into either ARDS group or non-ARDS group according to whether the patients developed ARDS after surgery.The receiver operating characteristic curve for IL-6 and IL-8 concentrations in EBC in diagnosing postoperative ARDS was plotted,and the area under the curve and 95％ confidence interval (CI) were calculated.The critical value,sensitivity and specificity were calculated according to the corresponding concentrations of IL-6 and IL-8 in EBC when Youden index reached the maximal value.Results Twenty-two patients developed postoperative ARDS,and the incidence was 52％.The concentrations of IL-6 and IL-8 in EBC were significantly higher at T2-4 than at T1 in two groups (P＜0.05).Compared with group nonARDS,the concentrations of IL-6 and IL-8 in EBC were significantly increased at T2-4 in group ARDS (P＜0.05).The area under the curve (95％ CI) of IL-6 concentrations in EBC measured at T2-4 in predicting postoperative ARDS was 0.822 (0.673-0.922),0.850 (0.706-0.941) and 0.906 (0.775-0.974),respectively,the critical value was 2.92,5.04 and 2.64 pg/ml,respectively,the sensitivity was 95.5％,68.2％ and 77.3％,respectively,and the specificity was 70.0％,90.0％ and 90.0％,respectively.The area under the curve (95％ CI) of IL-8 concentrations in EBC measured at Y24 in predicting postoperative ARDS was 0.700 (0.539-0.831),0.851 (0.707-0.942) and 0.737 (0.579-0.861),respectively,the critical value was 26.75,42.73 and 21.86 pg/ml,respectively,the sensitivity was 68.2％,77.3％ and 72.7％,respectively,and the specificity was 65.0％,80.0％ and 70.0％,respectively.Conclusion The concentrations of IL-6 and IL-8 in EBC can accurately predict the occurrence of postoperative ARDS in the patients undergoing cardiac surgery under CPB.

Metabolomics Study of Exhaled Breath Condensate in Childhood Asthma by Gas Chromatography-Mass Spectrometry / 分析化学

Exhaled breath condensate (EBC) was analyzed by gas chromatography-mass spectrometry (GC-MS / MS) in childhood asthma and healthy control, aiming to find the potential markers of EBC in children with asthma, and provide a scientific reference for its pathogenesis and early screening. EBC samples were collected from 21 asthmatic children (age (8. 2 ±1. 6) years) and 17 healthy children ( age (8. 1 ±1. 3) years). GC-MS / MS was used to obtain the full scan data of chemical components. Cluster analysis was performed on the two groups of metabolites by principal component analysis (PCA), and potential biomarkers were found using Metaboanalyst 3. 0 attributable metabolic pathways. The results showed that the EBC metabolic maps of asthmatic group and normal group were very different, and eight endogenous potential biomarkers were identified, suggesting that starch and sucrose metabolism, lysine degradation, aminoglycan nucleoside metabolism, phenylalanine metabolism may play important roles in the development of asthma in children.

Influence of Lipo PGE1 on ET-1 and IL-6 in exhaled breath condensate of patients with chronic obstructive pulmonary disease and pulmonary hypertension / 安徽医科大学学报

Objective To explore the influence of Lipo PGE1 on endothelin (ET-1) and interleukin (IL-6) in exhaled breath condensate(EBC) of patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension(PH) and its clinical significance.Methods A total of 40 cases of patients with COPD and PH were randomly divided into thecontrol group and the treatment group,20 cases in each group.The control group was administered with the conventional treatments such as anti-infection,bronchodilator,antiasthma,expectorant and oxygen therapy;the treatment group was administered with Lipo PGE1 (10 μg/d,iv,for 10 days) besides the conventional treatments.ET-1 and IL-6 in EBC,pulmonary artery systolic pressure(PASP),arterial blood PaO2 and PaCO2,lung function FEV1/FVC,FEV1%pred in both groups were assayedbefore and after the treatment.Results There were no statistical difference between the two groups in the ET-1 and IL-6 in EBC,PASP,arterial blood PaO2 and PaCO2,FEV1/FVC,FEV1% pred before the treatment.After the treatment,the ET-1,IL-6 in EBC,PASP and arterial blood PaCO2 of the treatment group were lower than thoseof the control group (P<0.05);the arterial blood PaO2,FEV1/FVC,FEV1% pred of the treatment group were higher than those of the control group (P<0.05);The levels of ET-1 and IL-6 in EBC wereboth positivelycorrelated with PASP in the two groups.Conclusion Lipo PGE1 can reduce the levels of ET-1 and IL-6 in EBC of patients with COPD and PH.ET-1 and IL-6 may become a curative effect judgment index of COPD and PH,which has a certain clinical significance.

The effect of preoperative pulmonary protection on surfactant protein A content in lung tissue / 天津医药

Objective To explore the effect of preoperative pulmonary protection therapy on surfactant protein A(SP–A) content in lung tissue and postoperative complications. Methods Sixty patients with non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease(COPD) who underwent surgical treatment in Tianjin Chest Hospital from January 2015 to June 2016 were enrolled in this study. Thirty patients were included in the control group and 30 patients in the pulmonary protection group. The control group was given routine preoperative preparation, while the pulmonary protection group was given 1 week pulmonary protection therapy on the basis of routine preoperative preparation. The exhaled breath condensate (EBC) was collected and pulmonary function was re-checked after admission and before surgery. The content of SP-A in EBC was detected by ELISA. The lung tissue samples were collected during surgery, and the SP-A level was measured by Western blotting. Results The SP-A level of the pulmonary protection group was significantly higher than that of the control group (1.05±0.21 vs. 0.93±0.16, P0.05). The average postoperative hospital stay was statistically significant shorter in the pulmonary protection group than that in the control group[(9.2 ± 3.1) d vs. (11.6 ± 4.8) d, P<0.05]. Conclusion Preoperative pulmonary protection therapy can not only improve pulmonary function and shorten postoperative hospital stay, but also improve SP-A content in lung tissue.

Soluble triggering receptor expressed on myeloid cells-1 as a diagnostic marker of ventilator-associated pneumonia in patients with acute ischemic stroke / 中国医师进修杂志

Objective To investigate the potential role of soluble triggering receptor expressed on ayeloid cells-1(sTREM-1) expression in serum,endotracheal aspiration (ETA),bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) as early biomarkers for the diagnosis of ventilator-associated pneumonia (VAP) in patients with acute ischemic stroke.Methods One hundred and thirty-two patients with clinically suspected VAP were prospectively included in this multicenter study.The levels of sTREM-1 in serum,ETA,BALF and EBC were analyzed for diagnostic evaluation at the time of VAP clinically suspected.The bacterial count over 104/CFU as a gold standard for VAP,and the receiver operating characteristic curves were used to identify the ideal cutoff values.Results VAP was confirmed in 76 patients (57.58％).In VAP patients (VAP group) and non-VAP patients (non-VAP group),the level of sTREM-1 in BALF was 32.35 (30.08-41.72) and 18.92(11.89-31.72) ng/L,and the level of sTREM-1 in EBC was 1.57 (1.02-2.61) and 0.41(0.19-1.61)ng/L respectively.The level of sTREM-1 in BALF and in EBC in VAP group was significantly higher than that in non-VAP group (P ＜0.05).The optimum cutoff value for sTREM-1 in BALF according to the maximum Youden index was 23.61 ng/L.This cutoff value had 85.5％ sensitivity and 73.1％ specificity,with 0.813 area under the curve.sTREM-1 in BALF had excellent correlation with that in EBC (R2 =0.78,P ＜ 0.05).Conclusions The results of this prospective study suggest that sTREM-1 levels in BALF and EBC have better roles in facilitating the diagnosis of VAP and thus may be practically recommended to guide the administration of antibiotics when VAP is suspected.

Assessment of leukotriene E4 in exhaled breath condensate as a marker of inflammation and therapeutic effect in allergic rhinitis children

PURPOSE: Recent studies have shown that the cysteinyl leukotriene (cysLT) of exhaled breath condensate (EBC) could be predictive of inflammatory status and effectiveness of treatment in allergic disease. The aim of this study was to evaluate the inflammation and therapeutic effectiveness of cysLT in EBC in pediatric patients with allergic rhinitis (AR). METHODS: We enrolled 34 healthy children (median age, 4 years 10 months) and 67 AR children (median age, 5 years 1 month). All of the AR patients received intranasal steroid (fluticasone furoate) once daily for 2 weeks. After 2 week of fluticasone furoate treatment, they were classified into 2 groups: the fluticasone furoate (F) and montelukast (M) groups. We treated each group for another 8 weeks. To evaluate the therapeutic effectiveness, we used symptom score (SS) and EBC leukotriene E4 (LTE4). EBC samples were collected with RTube. Each parameter was checked at 0, 2, and 10 weeks of therapy. RESULTS: Most of the AR patients showed clinical improvement with 2- and 10-week fluticasone therapy (F group: 0-week SS, 5.6; 2-week SS, 3.6; 10-week SS, 2.1; P<0.01; M group: 0-week SS, 4.8; 2-week SS, 3.2; 10-week SS, 1.9: P<0.01). LTE4 levels were higher in AR patients than in control subjects (0 week: 87 pg/mL vs. 18 pg/mL) and were reduced after 2 weeks of fluticasone treatment (F group: 90→51.6 pg/mL, P<0.01; M group: 84→46.1 pg/mL, P<0.01). After 10 weeks of treatment, there was no significant difference in the LTE4 level between the F and M groups. CONCLUSION: LTE4 in EBC may be useful for evaluating inflammation and therapeutic effectiveness in patients with allergic rhinitis.

Periostin in Exhaled Breath Condensate and in Serum of Asthmatic Patients: Relationship to Upper and Lower Airway Disease

PURPOSE: Periostin is considered a biomarker for eosinophilic airway inflammation and have been associated with NSAID-Exacerbated Respiratory Disease (NERD) and chronic rhinosinusitis (CRS). In this study, we aimed to evaluate periostin in exhaled breath condensate (EBC) and in serum of patients with various asthma phenotypes. METHODS: The study included 40 asthmatic patients (22 with NERD) and 17 healthy controls. All the procedures (questionnaire, spirometry, FeNO, nasal swabs, EBC collecting, and blood sampling) were performed on the same day. Periostin concentrations were measured using an ELISA kit. RESULTS: Periostin was detected in EBC from 37 of 40 asthmatics and in 16 from 17 of controls. The concentration of periostin in EBC did not differ between the study groups and was not associated with NERD or asthma severity. However, the EBC periostin was significantly higher in asthmatics with CRS as compared to those without (3.1 vs 2 ng/mL, P=0.046). Patients with positive bacterial culture from nasal swabs had higher EBC periostin concentrations than those without (3.2 vs 2.1 ng/mL; P=0.046). The mean serum periostin level was higher in asthmatics with a 1-year history of exacerbation than in those without (3.2 vs 2.3 ng/mL, P=0.045). Asthmatics with skin manifestation of NSAIDs hypersensitivity had higher serum periostin levels as compared to those without (3.5 vs 2.3 ng/mL; P=0.03). CONCLUSIONS: EBC periostin levels seem to reflect intensity of upper airway disease in asthmatics, while serum levels of periostin are associated with asthma activity (exacerbations or FeNO) or NERD subphenotypes.

The effects of smoking and smoking cessation on nasal mucociliary clearance, mucus properties and inflammation

OBJECTIVE: The aim of the present study was to assess nasal mucociliary clearance, mucus properties and inflammation in smokers and subjects enrolled in a Smoking Cessation Program (referred to as quitters). METHOD: A total of 33 subjects with a median (IQR) smoking history of 34 (20-58) pack years were examined for nasal mucociliary clearance using a saccharine transit test, mucus properties using contact angle and sneeze clearability tests, and quantification of inflammatory and epithelial cells, IL-6 and IL-8 concentrations in nasal lavage fluid. Twenty quitters (mean age: 51 years, 9 male) were assessed at baseline, 1 month, 3 months and 12 months after smoking cessation, and 13 smokers (mean age: 52 years, 6 male) were assessed at baseline and after 12 months. Clinicaltrials.gov: NCT02136550. RESULTS: Smokers and quitters showed similar demographic characteristics and morbidities. At baseline, all subjects showed impaired nasal mucociliary clearance (mean 17.6 min), although 63% and 85% of the quitters demonstrated significant nasal mucociliary clearance improvement at 1 month and 12 months, respectively. At 12 months, quitters also showed mucus sneeze clearability improvement (∼26%), an increased number of macrophages (2-fold) and no changes in mucus contact angle or cytokine concentrations. CONCLUSION: This study showed that smoking cessation induced early improvements in nasal mucociliary clearance independent of mucus properties and inflammation. Changes in mucus properties were observed after only 12 months of smoking cessation.

Cysteinyl leukotriene and 8-isoprostane in exhaled breath condensate of asthmatic children / 国际儿科学杂志

Objective To analyze the change of cysteinyl leukotriene ( Cys-LTs) levels and 8-Isopros-tane (8-iso-PG) levels in the exhaled breath condensate (EBC) of asthmatic children from acute exacerbation to clinical remission, and investigate the role of the detection of Cys-LTs and 8-iso-PG in EBC in its severity and pathogenesis , and explore the relationship between the Cys-LTs and 8-iso-PG through measuring Cys-LTs levels and 8-iso-PG levels in the EBC of asthmatic children. Methods The outpatient or inpatient asthmatic children of the pediatrics and a group of healthy children were studied. All subjects′ EBC were collected by the R-Tube produced by American Respiratory Research. The concentration of Cys-LTs and 8-iso-PG in EBC were measured by enzyme-linked immunosorbent assay (ELISA), and compared among children in asthmatic exacerbation, asthmatic remission, and healthy condition. The relevance of their change would be explored at the same time. Results (1) Cys-LTs levels in EBC were higher in asthma exacerbation, compared to healthy controls (P0. 05 ) . ( 2 ) 8-iso-PG levels was higher in asthmatic exacerbation compared to asth-matic remission ( P<0. 05 ) . Moreover, the 8-iso-PG levels were significantly higher in asthmatic remission than in healthy controls (P<0. 05). (3) Through the relevance analysis of the Cys-LTs and 8-iso-PG levels in EBC among the three groups, Cys-LTs levels in EBC of asthmatic exacerbation significantly were correlated with 8-iso-PG levels (n1 =35, r1 =0. 61, P<0. 05), while there was no significant correlation between 8-iso-PG levels and Cys-LTs levels in asthmatic remission. Conclusion The increase of 8-iso-PG levels in EBC of bronchial asthmatic patients correlates with the disease and its control. Therefore, 8-iso-PG can be an objective indicator for asthmatic diagnosis and healing efficacy. Cy-LTs levels increase in the EBC of bronchial asthmatic according to disease severity. The two levels correlate during asthmatic exacerbation, indicating that a link be-tween airway oxidative stress and inflammation among asthmatics.

The Immune Paradox of Sarcoidosis: A Review of Literature.

This review briefly summarises the literature concerning our current understanding of the aetiology and immunopathogenesis of sarcoidosis, and the identification of novel markers of this disease. Although the immune paradox is a key part of sarcoid immunology, the mechanisms underlying this remarkable phenomenon are not well understood. Biomarkers may further the current understanding of the granulomatous inflammation seen in sarcoidosis. Exhaled breath condensate (EBC) is a novel, minimally invasive tool to sample the fluid lining the respiratory tract. EBC can be used to identify sarcoid specific biomarkers, which may shed light on the sarcoid immune paradox.

Effects of Qingfeitang on ET-1 and PGE2 in exhaled breath condensate and serum of patients with ARDS / 实用医学杂志

Objective To observe the changes of endothelin-1 (ET-1) and prostaglandin E2 (PGE2) in exhaled breath condensate (EBC) and serum of patients with acute respiratory distress syndrome (ARDS) after treated by Qingfeitang and investigate its clinical value. Methods 52 ARDS patients receiving mechanical ventilation at intensive care unit (ICU) were divided into the Qingfeitang treatment group and the control group, with 26 cases in each group. The EBC were collected by Ecoscreen condenser within 24 h after diagnosis of ARDS and on the 5th day of medication, and the venous blood were collected at the same time. The levels of ET-1 and PGE2 in the EBC and serum of different period were measured by EIA. Results (1) After treatment, The levels of ET-1 in EBC and serum of the Qingfeitang treatment group were significantly lower than those of the control group. (2) After treatment, the levels of PGE2 in serum of the Qingfeitang treatment group were significantly lower than that of the control group. (3) The oxygenation index difference before and after treatment of Qingfeitang in the treatment group was higher than in the control group. (4) The duration of mechanical ventilation of the Qingfeitang treatment group was significantly less than that of the control group. Conclusions Qingfeitang could be an effective method for alleviating acute respiratory distress syndrome.

The clinical significance of nitric oxide and endothelin-1 in exhaled breath condensate and serum of patients with acute lung injury/acute respiratory distress syndrome / 实用医学杂志

Objective To observe the level of the nitric oxide (NO) and endothelin-1 (ET-1) in the exhaled breath condensate(EBC)and serum of the patients with ALI /ARDS, and investigate its clinical significance. Methods The study group included 52 mechanical ventilation patients with ALI/ARDS in ICU , which were divided into the survival and death group, while 30 healthy volunteers were recruited as healthy control. EBC samples of the healthy control and the study group on the 1st day and 5st day were collected by EcoScreen condenser with the synchronous collection of the venous blood. The concentrations of NO and ET-1 in the EBC and serum were measured by EIA. Results The levels of NO and ET-1 in EBC and serum of the patients with ALI /ARDS were all significantly higher than those of the healthy control. After treatment , the levels of NO and ET-1 in EBC and serum of the patients all decreased significantly compared with before treatment. After treatment , The levels of NO in EBC and serum of the survival group were significantly lower than those of the death group. After treatment , the levels of ET-1 in serum of the survival group was significantly lower than that of the death group. Conclusions Detecting the levels of NO and ET-1 in the EBC and serum can reflect oxidative stress , inflammatory reaction and endothelial injury in lung of patients with ALI/ARDS.

Malondialdehyde and 3-Nitrotyrosine in Exhaled Breath Condensate in Retired Elderly Coal Miners with Chronic Obstructive Pulmonary Disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important cause of occupational mortality in miners exposed to coal mine dust. Although the inflammatory mediators involved in COPD have not been defined, many studies have shown that inflammatory mediators such as reactive oxygen and nitrogen species are involved in orchestrating the complex inflammatory process in COPD. METHODS: To investigate the relevance of exhaled biomarkers of oxidative and nitrosative stress in participants with COPD, we determined the levels of hydrogen peroxide, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) in exhaled breath condensate (EBC) in 90 retired elderly coal miners (53 non-COPD and 37 COPD participants). RESULTS: Mean levels of MDA (4.64 nM vs. 6.46 nM, p = 0.005) and 3-NT (3.51 nM vs. 5.50 nM, p = 0.039) in EBC were significantly higher in participants with COPD. The median level of MDA did show statistical difference among the COPD severities (p = 0.017), and the area under the receiver operating characteristic curve for MDA (0.67) for the diagnostic discrimination of COPD indicated the biomarker. The optimal cutoff values were 5.34 nM (64.9% sensitivity and 64.2% specificity) and 5.58 nM (62.2% sensitivity and 62.3% specificity) for MDA and 3-NT, respectively. The results suggest that high levels of MDA and 3-NT in EBC are associated with COPD in retired elderly miners. CONCLUSION: These results showed that the elevated levels of EBC MDA and EBC 3-NT in individuals with COPD are biomarkers of oxidative or nitrosative stress.

Increased inflammatory mediator in exhaled breath condensate from asthmatic children

PURPOSE: There has recently been increasing interest in the use of exhaled breath condensate (EBC) as a simple noninvasive means for understanding the physiology of asthma. The aim of this study was to evaluate the levels of leukotriene B4 (LTB4) and eosinophil cationic protein (ECP) in the EBC of asthmatic children. METHODS: We measured LTB4 and ECP levels in EBC from children aged 6-14 years, including healthy children (n=25) and asthmatic children (n=25). We also measured serum LTB4 and serum ECP. Pulmonary function tests and methacholine challenge tests were performed on all subjects. RESULTS: Exhaled LTB4 levels were increased significantly in patients with asthma compared to normal subjects (7.1+/-3.7 pg/mL vs. 2.2+/-1.7 pg/mL, P<0.05). Serum LTB4 levels were not significantly different in patients with asthma compared to normal subjects (674.7+/-484.1 pg/mL vs. 487.1+/-272.0 pg/mL, P=0.156,) and no significant correlations were found between exhaled and serum LTB4 concentrations in children with asthma (r=0.052, P=0.758). Exhaled ECP levels were not significantly different in patients with asthma compared to normal subjects (P=0.419). Serum ECP levels were significantly increased in patients with asthma compared to normal subjects (44.37+/-32.14 microg/L vs. 16.40+/-13.23 microg/L, P=0.001). CONCLUSION: We found significantly elevated LTB4 levels in the EBC of asthmatic children. Our results suggest that EBC may be one of the supportive tools to measure airway inflammation in children with asthma.

pH in exhaled breath condensate and nasal lavage as a biomarker of air pollution-related inflammation in street traffic-controllers and office-workers

OBJECTIVE: To utilize low-cost and simple methods to assess airway and lung inflammation biomarkers related to air pollution. METHODS: A total of 87 male, non-smoking, healthy subjects working as street traffic-controllers or office-workers were examined to determine carbon monoxide in exhaled breath and to measure the pH in nasal lavage fluid and exhaled breath condensate. Air pollution exposure was measured by particulate matter concentration, and data were obtained from fixed monitoring stations (8-h work intervals per day, during the 5 consecutive days prior to the study). RESULTS: Exhaled carbon monoxide was two-fold greater in traffic-controllers than in office-workers. The mean pH values were 8.12 in exhaled breath condensate and 7.99 in nasal lavage fluid in office-workers; these values were lower in traffic-controllers (7.80 and 7.30, respectively). Both groups presented similar cytokines concentrations in both substrates, however, IL-1β and IL-8 were elevated in nasal lavage fluid compared with exhaled breath condensate. The particulate matter concentration was greater at the workplace of traffic-controllers compared with that of office-workers. CONCLUSION: The pH values of nasal lavage fluid and exhaled breath condensate are important, robust, easy to measure and reproducible biomarkers that can be used to monitor occupational exposure to air pollution. Additionally, traffic-controllers are at an increased risk of airway and lung inflammation during their occupational activities compared with office-workers. .

Exhaled breath condensate analysis in chronic obstructive pulmonary disease.

The increasing focus on airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) has led to development and evolution of tools to measure it. Direct assessment of airway inflammation requires invasive procedures, and hence, has obvious limitations. Non-invasive methods to sample airway secretions and fluids offer exciting prospects. Analysis of exhaled breath condensate (EBC) is rapidly emerging as a novel non-invasive approach for sampling airway epithelial lining fluid and offers a convenient tool to provide biomarkers of inflammation. It has definite advantages that make it an attractive and a feasible option. It is a source of mediators and molecules that are the causes or consequences of the inflammatory process. Measurement of such markers is increasingly being explored for studying airway inflammation qualitatively and quantitatively in research studies and for potential clinical applications. These biomarkers also have the potential to develop into powerful research tools in COPD for identifying various pathways of pathogenesis of COPD that may ultimately provide specific targets for therapeutic intervention. The EBC analysis is still an evolving noninvasive method for monitoring of inflammation and oxidative stress in the airways. The limited number of studies available on EBC analysis in COPD have provided useful information although definite clinical uses are yet to be defined. Evolving technologies of genomics, proteomics, and metabonomics may provide deeper and newer insights into the molecular mechanisms underlying the pathogenesis of COPD.

Avaliação do grau de controle clínico, espirométrico e da intensidade do processo inflamatório na asma / Assessing clinical and spirometric control and the intensity of the inflammatory process in asthma

OBJETIVOS: Revisar o papel da avaliação clínica, da qualidade de vida, da espirometria, do teste de broncoprovocação e dos marcadores inflamatórios na avaliação da asma. FONTES DOS DADOS: Pesquisa nas bases MEDLINE e LILACS. SÍNTESE DOS DADOS: A avaliação clínica auxilia na avaliação do controle da asma e é amplamente preconizada. No entanto, os pacientes podem apresentar obstrução e inflamação das vias aéreas a despeito da normalidade clínica. A espirometria quantifica o grau de obstrução das vias aéreas e auxilia no diagnóstico, enquanto a broncoprovocação pode ser indicada na suspeita de asma com espirometria normal. Já os marcadores inflamatórios do condensado do ar exalado, do escarro induzido e do lavado broncoalveolar, além dos fragmentos da biópsia brônquica, encontram-se alterados na asma e são métodos complexos, quase sempre restritos às pesquisas. A fração exalada de óxido nítrico (FeNO) é elevada nos pacientes com asma, reprodutível e não invasiva, reduzindo-se com o tratamento. O uso da FeNO como auxiliar no ajuste de doses do corticoide inalatório tem sido estudado, mas as vantagens ainda não estão claras. CONCLUSÕES: Vários métodos são necessários para avaliar de forma acurada o controle da asma, e todos têm vantagens e limitações. A avaliação clínico-funcional é útil para o diagnóstico de asma, porém limitada para avaliar de forma precisa a intensidade do processo inflamatório nas vias aéreas. É necessário que mais estudos controlados, randomizados, com adequado poder estatístico sobre a utilidade dos marcadores inflamatórios não invasivos, especialmente a FeNO, no manejo da asma, sejam realizados para determinar sua utilidade clínica.

OBJECTIVES: To review the role of clinical assessment, quality of life assessment, spirometry, bronchial responsiveness test and inflammatory markers for asthma assessment. SOURCES: Search run on MEDLINE and LILACS. SUMMARY OF THE FINDINGS: Clinical assessment aids with assessing asthma control and is widely recommended. However, patients may have airway inflammation and obstruction despite normal clinical findings. Spirometry quantifies the degree of airway obstruction and helps with diagnosis, while the bronchial responsiveness test may be indicated for when asthma is suspected but spirometry is normal. The results of assaying the inflammatory markers in exhaled breath condensate, induced sputum, bronchoalveolar lavage and bronchial biopsy specimens are abnormal in asthma patients, but these are complex techniques almost always restricted to research. Fractional exhaled nitric oxide (FeNO) is elevated in patients with asthma, is reproducible and noninvasive and reduces with treatment. Studies have investigated using FeNO to help with adjusting inhaled corticoid dosages, but the benefits are not clear. CONCLUSIONS: A range of different methods are needed to accurately assess disease control, all with their advantages and limitations. Clinical and functional assessment is useful for diagnosing asthma, but is of limited use for precisely evaluating the intensity of the inflammatory process in the airways. More randomized and controlled studies with adequate statistical power should be carried out to investigate the true utility of noninvasive inflammatory markers, especially FeNO, for asthma management.

Correlation Between the Levels of NO2/NO3 in Exhaled Breath Condensate and Pulmonary Infection in Mechanically Ventilated Patients / 中国呼吸与危重监护杂志

Objective To explore the correlation between the levels of nitrite/nitrate(NO2/NO3) in exhaled breath condensate (EBC) and pulmonary infection in mechanically ventilated patients.Methods The clinical data from ventilated patients in critical care units of Peking University People' s Hospital from November 2006 to August 2007 were collected and analyzed.The patients' clinical pulmonary index score (CPIS) were calculated.EBC of those patients were collected via endotracheal tube or tracheostomy cannula, and the concentrations of NO2/NO3 were assayed.The level of NO2/NO3 in different CPIS patients in 24 hours' ventilation,weaning proportion in 3 days and mortality in different NO2/NO3 level patients were compared.The correlation of the CPIS and level of NO2/NO3 were explored between survival and non-survival patients.Results A total of 76 patients were enroled.The NO2/NO3 levels in patients of CPIS≤3 ,CPIS 3-6 and CPIS >6 in 24 hours of ventilation were (23.31±5.79), (28.72±9.10) and (35.42±12.10) μmoL/L respectively, with significantly differences between each other (P < 0.01).The lower the patients' concentration of NO2/NO3 was, the earlier the weaning and the lower the mortality were.The NO2/NO3 levels on 4th and 7th day were detected in 24 survival patients and 23 non-survival patients.The difference of NO2/ NO3 levels between the survival patients and non-survival patients became significant on 7th day [(29.32±9.52) μmol/L vs.(37.22±12.03) μmol/L, P < 0.01].Linear correlation analysis showed that the NO2/ NO3 level was positively correlated with CPIS (r = 0.76, P < 0.01).Condusions The NO2/NO3 level of EBC in ventilated patients is positively correlated to the severity of pulmonary infection, thus may be used as a new predictor for weaning and prognosis.