Determination of 27 volatile organic compounds in exhaled breath by thermal desorption-gas chromatography-mass spectrometry / 环境与职业医学

Background Volatile organic compounds (VOCs) in exhaled breath are closely associated with respiratory diseases and are linked to various metabolic reactions in the human body. A quantitative analytical method can provide technical support for studying VOCs related to various diseases. Objective To establish a thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) method for the determination of 27 VOCs in exhaled breath. Methods VOCs in exhaled breath were collected using a Bio-VOC sampler and enriched with Tenax TA thermal desorption tubes before TD-GC-MS analysis. Standards were collected using thermal desorption tubes and optimized for thermal desorption conditions as well as chromatographic and mass spectrometric conditions: The separation of the 27 VOCs was achieved by an optimized temperature program, the improvement of sensitivity by optimizing quantitative ions, and the increase of VOCs desorption efficiency by optimizing thermal desorption time and temperature. Limit of detection, limit of quantification, accuracy, precision, and stability of the proposed method were investigated by spiking with a blank gas bag, and exhaled breath samples from 20 healthy individuals were collected for an application study of the proposed method. Results The thermal desorption temperature was 280 ℃, and desorption time was 6 min. A VF-624ms chromatographic column was selected for the separation of target substances. The initial temperature of heating program was 35 ℃, maintained for 1 min, and then increased to 100 ℃ at a heating rate of 3 ℃·min−1 for 1 min, followed by increasing to 210 ℃ at a heating rate of 28 ℃·min−1 for 5 min. A quantitative analysis was conducted with a single ion monitoring (SIM) mode. Under these conditions, the 27 VOCs showed good linear relationships in their respective concentration ranges and the correlation coefficients were higher than 0.9990. The limits of detection of the method were in the range of 0.01-0.13 nmol·mol−1, the limits of quantification were in the range of 0.02-0.44 nmol·mol−1, and the spiked recoveries were in the range of 80.1%-120.5%, with intra-batch and inter-batch precision ≤ 18.8% and 17.9% respectively. All substances can be stored at room temperature (23-28 °C) for 7 d and at 4 °C for 14 d. The proposed method was applied to exhaled breath samples from 20 subjects with detection rates≥ 80% (except for trans-2-pentene and decane) and a concentration range of 0.00-465.50 nmol·mol−1. Conclusion The established TD-GC-MS method for quantification of VOCs in exhaled breath is characterized by high sensitivity and good accuracy, and is suitable for quantitative determination of VOCs in exhaled breath, which can provide technical support for the study of exhaled breath VOCs.

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. 

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.

Exhaled breath detection is expected to become a new method for non-invasive screening of lung cancer— Project initiation of "research on the application of human exhaled breath detection technology based on quantum cascade laser in the diagnosis of lung cancer and other diseases" / 中国胸心血管外科临床杂志

@#Being a non-invasive diagnostic technique for molecular biological markers, exhaled breath detection has the most latent capacity and future in the diagnosis and treatment of tumors. The National Key Research and Development Plan named "Strategic Advanced Electronic Materials" in 2020 has laid out the application of exhaled breath detection technology in the medical field, and the scientific research project led by Sichuan Cancer Hospital has been successfully launched. For the moment, as a novel strategy for early detection of lung cancer, exhaled breath detection is being perfected further and popularized or put in clinical practice step by step to reduce the mortality of lung cancer patients.

Identification and diagnostic value of characteristic volatile organic compounds in exhaled breath of patients with early stage lung cancer / 中国胸心血管外科临床杂志

@#Objective    To investigate the characteristic volatile organic compounds (VOCs) in exhaled breath and their diagnostic value in patients with early stage lung cancer. Methods    Solid-phase micro-extraction combined with gas chromatography mass spectrometry was used to analyze exhaled breath VOCs of 117 patients with early stage lung cancer (54 males and 63 females, with an average age of 61.9±6.8 years) and 130 healthy subjects (79 males and 51 females, with an average age of 63.3±6.6 years. The characteristic VOCs of early stage lung cancer were identified, and a diagnostic model was established. Results    Ten characteristic VOCs of early stage lung cancer were identified, including acetic acid, n-butanol, dimethylsilanol, toluene, 2,3,4-trimethylheptane, 3,4-dimethylbenzoic acid, 5-methyl-3-hexene-2-ketone, n-hexanol, methyl 2-oxoglutarate and 4-methoxyphenol. Gender and the 10 characteristic VOCs were included in the diagnostic model, with a sensitivity of 83.8% and a specificity of 96.2%. Conclusion    Analysis of exhaled breath VOCs is expected to be one of the potential methods used for early stage lung cancer diagnosis.

Predictive value of volatile organic compounds in exhaled breath on pulmonary nodule in people aged less than 50 years / 中国胸心血管外科临床杂志

@#Objective    To investigate the predictive value of volatile organic compounds (VOCs) on pulmonary nodules in people aged less than 50 years. Methods    The 147 patients with pulmonary nodules and aged less than 50 years who were treated in the Department of Thoracic Surgery of Sichuan Cancer Hospital from August 1, 2019 to January 15, 2020 were divided into a lung cancer group and a lung benign disease group. The lung cancer group included 36 males and 68 females, with the age of 27-49 (43.54±5.73) years. The benign lung disease group included 23 males and 20 females, with the age of 22-49 (42.49±6.83) years. Clinical data and exhaled breath samples were collected prospectively from the two groups. Exhaled breath VOCs were analyzed by gas chromatography mass spectrometry. Binary logistic regression analysis was used to select variables and establish a prediction model. The sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve of the prediction model were calculated. Results    There were statistically significant differences in sex (P=0.034), smoking history (P=0.047), cyclopentane (P=0.002), 3-methyl pentane (P=0.043) and ethylbenzene (P=0.009) between the two groups. The sensitivity, specificity and area under the ROC curve of the prediction model with gender, cyclopentane, 3-methyl pentane, ethylbenzene and N,N-dimethylformamide as variables were 80.8%, 60.5% and 0.781, respectively. Conclusion    The combination of VOCs and clinical characteristics has a certain predictive value for the benign and malignant pulmonary nodules in people aged less than 50 years.

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.

In vivo Breath Analysis by Extractive Electrospray Ionization-Mass Spectrometry for Investigation of Metabolic Responses to Traditional Chinese Medicine Massages / 分析化学

Traditional Chinese Medicine massage is a kind of physiotherapy which affects on specific parts of the body surface by means of training to regulate the function of the body to achieve the therapeutic effect. In this work,under positive detection model, the chemical fingerprint of exhaled breath from volunteers before and after receiving Traditional Chinese Medicine massage within m/z 50-1000 were detected by extractive electrospray ionization-mass spectrometry (EESI-MS). And through high resolution mass spectrometry analysis, the metabolites such as epinephrine (m/z 184. 0889), 3-(3-hydroxyphenyl) propionic acid (m/z 167.0615) and L-tryptophan (m/z 205. 0933) were successfully identified. Besides, chemical fingerprints of volunteers before and after receiving Traditional Chinese Medicine massage under different health condition were clearly differentiated via partial least squares discrimination analysis (PLS-DA). The results showed that Traditional Chinese Medicine massage could significantly change the metabolic process of volunteers. Moreover, it further indicated that the established method could provide a real time fashion to follow metabolic changes caused by Traditional Chinese Medicine massage.

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.

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.

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.

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.

Clinical implication of exhaled breath temperature measurement in pediatric asthma

PURPOSE: Exhaled breath temperature (EBT) has been suggested as a noninvasive marker of airway inflammation in asthma. The aim of this study was to determine its clinical implication in children with asthma. METHODS: A total of 233 children were enrolled in this study. Among them, 116 were asthmatic children and 117 were healthy children. Spirometry, bronchodilator response (BDR) test, methacholine challenge test, and skin prick test were performed. EBT, fractional exhaled nitric oxide (FeNO), blood eosinophils, and total IgE levels were measured. EBT was measured by using X-halo. RESULTS: EBT was significantly higher in the asthma group than in the control group (median [interquartile range], 32.1℃ [30.0℃–33.9℃] vs. 29.7℃ [29.0℃–31.3℃], P<0.001). EBT was significantly higher in poorly or partly controlled asthmatic children than well-controlled asthmatic children (33.5℃ [31.0℃–34.4℃] vs. 30.3℃ [29.3℃–32.9℃], P<0.0001). Among total subjects, EBT was significantly higher in the atopic group than in the nonatopic group (32.4℃ [30.3℃–34.0℃] vs. 29.8℃ [29.0℃–30.3℃], P<0.001). There were neither significant associations between EBT and BDR (r=0.109, P=0.241) nor between EBT and PC20 (provocation concentration causing a 20% fall in FEV1) in total subjects (r=0.127, P=0.316). EBT did not show any association with FeNO (r=0.353, P=0.071). CONCLUSION: Our study suggests that EBT might play a role as an ancillary marker for allergic airway inflammation and the degree of control in pediatric asthma patients. Additional studies are required to explore the value of EBT in detail.

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.

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.

Slower Rise of Exhaled Breath Temperature in Cystic Fibrosis.

Objective: To measure exhaled breath temperature in patients with cystic fibrosis. Methods: 17 patients (6-18 years) with cystic fibrosis and 15 age- and gender-matched healthy controls were recruited in this cross sectional study. Exhaled breath temperature was measured in subjects recruited in both the groups with a device X-halo and analyzed as plateau temperature achieved and rate of temperature rise. Results: Patients with cystic fibrosis showed no significant difference in plateau temperature [34.4(32.3-34.6) versus 33.9 (33.0- 34.4)oC; P=0.35] while mean (SEM.) rate of temperature rise was significantly less in patients [0.09 (0.01) versus 0.14 (0.02) ΔºC/s ; P=0.04] as compared to controls. Conclusion: There was a slower rise of exhaled breath temperature in patients with cystic fibrosis whereas plateau temperature was not significantly different from controls.

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.

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 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.