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.

Problems Of Energy On Planet Earth

A fundamentally new direction in the theory and practice of quantum nonlinear phenomena in non-ideal and very close to non-degenerate plasma has been developed, for the first time the existence of a new state of matter-imperfect plasma-quantum plasma condensate, combining the properties of ordinary liquid and ionized plasma, has been theoretically predicted and confirmed. The quantum non-ideality of non-degenerate plasma and the exchange interaction of electrons in it, leading to effective energy release in the plasma process under study, were investigated. The directions of use of this energy have been determined: for heating, lighting, conversion by means of photocells or MHD-movements into electrical, for obtaining energy in the ultraviolet range. Particular attention in the work is paid to one of the most popular applications of quantum non-ideal plasma - for heating, at which its plasma combustion occurs, and the generation of electrical energy based on the use of a quantum plasma-MHD generator with plasma delamination. Detection of this kind of phase state of non-ideal non-degenerate plasma and its use in engineering and technology will create a fundamentally new effective energy system corresponding to the Sixth Technological Order on a global scale. This source of energy is the only environmentally friendly, not destroying or polluting our planet, and its use cleanses our ecosphere. The paper shows that the use of existing energy undermines people's health, reduces their immunity and resistance to coronaviruses. Measures have been proposed to end coronavirus pandemics on Earth. Information is provided on the technical capabilities of the proposed fundamentally new structures - Universal Modules of Industrial Disintegrators / Activators, which allow to implement grandiose, payback state projects on the basis of the developed nanotechnologies, representing the work of tens of millions of people

Effect and Mechanism of Modified Si Junzitang Combined with Heat-sensitive Moxibustion on IL-17, IL-22, IL-1α and Cys-C in Serum and Exhale Breath Condensate of Patients with Chronic Obstructive Pulmonary Disease at Stable Stage / 中国实验方剂学杂志

Objective::To observe the effect and mechanism of modified Si Junzitang combined with heat-sensitive moxibustion on interleukin-17(IL-17), interleukin-22(IL-22), interleukin-1α(IL-1α) and serum cystatin C(Cys-C )in serum and exhale breath condensate(EBC) of patients with chronic obstructive pulmonary disease at stable stage(COPD, Qi deficiency of lung and spleen). Method::Totally 120 cases of COPD(Qi deficiency of lung and spleen) treated in pulmonary department and thermal moxibustion department of Affiliated Hospital of Jiangxi University of traditional Chinese medicine from January 2019 to June 2019 were included and randomly divided into traditional Chinese medicine group, heat-sensitive moxibustion group and control group. The patients in traditional Chinese medicine group were treated with Si Junzitang, the patients in heat-sensitive Moxibustion group were treated with heat-sensitive moxibustion in addition to traditional Chinese medicine group, and the patients in control group were treated with placebo. All of the 3 groups were treated with oxygen and bronchodilator according to the guidelines. All groups received 3 consecutive courses of treatment, 20 days per course. After 3 courses of treatment, the clinical efficacy of the three groups, the forced expiratory volume in one second (FEV1), the forced expiratory volume in the estimated value in one second (FEV1%), the forced vital capacity (FVC), and IL-17, IL-22, IL-1α in serum and exhale breath condensate (EBC) were measured. Result::There were no statistically significant difference in general clinical data, lung function levels (FEV1, FEV1%, FVC), serum and EBC levels of IL-17, IL-22, IL-1α and Cys-C in the first three groups. The total clinical effective rate of traditional Chinese medicine group was better than the control group (P<0.05), the heat-sensitive moxibustion group was better than the traditional Chinese medicine group (P<0.05) and significantly better than the control group (P<0.01). Compared with the patients before treatment, the level of lung function was improved, while IL-17, IL-22, IL-1α and Cys-C in serum and EBC were reduced(P<0.05). The traditional Chinese medicine group was superior to that in the control group (P<0.05), the heat-sensitive moxibustion group was superior to that in the traditional Chinese medicine group (P<0.05) and significantly superior to that in the control group (P<0.01). Conclusion::Modified Si Junzitang combined with heat-sensitive moxibustion has an anti-inflammatory effect on COPD by stimulating bullishness of human body, improving body immunity, inhibiting inflammatory cytokines, reducing levels of inflammation cytokines IL-17, IL-22, IL-1α, and chronic inflammation markers serum Cys-C and inflammatory reaction, increasing the lung capacity, improving ventilation function and pulmonary function, so as to effectively relieve chest tightness asthma and other symptoms in COPD patients, and improve the clinical efficacy.

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.

Comparison of volatile organic compounds between cigarette smoke condensate (CSC) and extract (CSE) samples

Cigarette smoke is a major risk factor for several diseases, including chronic obstructive pulmonary and cardiovascular diseases. The toxicity of the cigarette smoke can be determined in vitro. The cytotoxicity test of the cigarette smoke is commonly conducted using the cigarette smoke condensate (CSC) and cigarette smoke extract (CSE). The CSC and CSE methods are well known for sampling of the particles and water-soluble compounds in the cigarette smoke, respectively. In this study, the CSC and CSE were analyzed by using a gas chromatography-mass spectrometry (GC-MS) system equipped with a wax column for separation of the volatile organic compounds. The cytotoxic effect of the CSC and CSE were evaluated thoroughly by comparing the analytical results of the CSC and CSE samples. The total concentration of the volatile organic compounds detected in the CSC sample was similar to that in the CSE sample based on the peak area. Except for the dimethyl sulfoxide solvent, nicotine had the highest concentration in the CSC sample, while acetonitrile had the highest concentration in the CSE sample. The compositions were as follows: (1) CSC sample: 55.8% nicotine, 18.0% nicotyrine, 3.20% 1,2,3-propanetriol, triacetate, 1.28% ethyl chloride, 1.22% phenol, etc. and (2) CSE sample: 18.7% acetonitrile, 18.0% acetone, 12.5% 2-hydroxy-2-methyl-propanenitrile, 8.98% nicotine, 5.86% nicotyrine, etc. In this manner, to accurately examine the cytotoxicity of the cigarette smoke using CSC or CSE, the components and their concentrations in the CSC and CSE samples should be considered.

Progress in Non-invasive Detection of EGFR Mutation in Non-small Cell Lung Cancer / 中国肺癌杂志

Over the past decade, the management model of cancer patients has gradually shifted to individual mode based on molecular mutation detection. Epidermal growth factor receptor (EGFR) gene mutation is an important driving factor in non-small cell lung cancer (NSCLC). Compared with traditional chemotherapy, EGFR-targeted therapy shows significant safety and efficacy. However, not all patients with EGFR mutations are eligible for EGFR-targeted therapy, and different types of mutations often indicate different clinical outcomes, such as the sensitive mutations EGFR 19-Del, L858R, and the resistance mutation. In addition, the third-generation TKI drugs Osimertinib (AZD9291) and Rociletinib (CO-1686) have been developed to further benefit patients with primary TKI resistance caused by T790M mutation of EGFR. Therefore, detection of the EGFR mutation status of patients before treatment, and continuously monitoring the mutation of drug resistance genes during the treatment process is useful for the management of targeted drugs in NSCLC patients. In recent years, the rapid development of "liquid biopsy" technology has made it possible to use non-invasive methods to monitor drug resistance mutations in real time. In this paper, we reviewed the clinical application of various non-invasive detection techniques for EGFR mutations in NSCLC in different liquid samples.
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Comparison of volatile organic compounds between cigarette smoke condensate (CSC) and extract (CSE) samples

Cigarette smoke is a major risk factor for several diseases, including chronic obstructive pulmonary and cardiovascular diseases. The toxicity of the cigarette smoke can be determined in vitro. The cytotoxicity test of the cigarette smoke is commonly conducted using the cigarette smoke condensate (CSC) and cigarette smoke extract (CSE). The CSC and CSE methods are well known for sampling of the particles and water-soluble compounds in the cigarette smoke, respectively. In this study, the CSC and CSE were analyzed by using a gas chromatography-mass spectrometry (GC-MS) system equipped with a wax column for separation of the volatile organic compounds. The cytotoxic effect of the CSC and CSE were evaluated thoroughly by comparing the analytical results of the CSC and CSE samples. The total concentration of the volatile organic compounds detected in the CSC sample was similar to that in the CSE sample based on the peak area. Except for the dimethyl sulfoxide solvent, nicotine had the highest concentration in the CSC sample, while acetonitrile had the highest concentration in the CSE sample. The compositions were as follows: (1) CSC sample: 55.8% nicotine, 18.0% nicotyrine, 3.20% 1,2,3-propanetriol, triacetate, 1.28% ethyl chloride, 1.22% phenol, etc. and (2) CSE sample: 18.7% acetonitrile, 18.0% acetone, 12.5% 2-hydroxy-2-methyl-propanenitrile, 8.98% nicotine, 5.86% nicotyrine, etc. In this manner, to accurately examine the cytotoxicity of the cigarette smoke using CSC or CSE, the components and their concentrations in the CSC and CSE samples should be considered.

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.

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.

Role of Hes1 in malignant transformation of human bronchial epithelial cells induced by tobacco / 中国病理生理杂志

AIM: To investigate the role of transcription factor hairy and enhancer of split 1 (Hes1) in the malignant transformation of human bronchial epithelial cell line BEP2D induced by tobacco.METHODS: The BEP2D cells were chronically exposed to cigarette smoke condensate (CSC) at 1 cigarette per L until the 70th generation.The phenotype of malignant transformation of the cells induced by CSC was detected by soft agar clony formation assay.RT-PCR and Western blot were used to determined the expression of Hes1 at mRNA and protein levels in each generation of the cells.The proliferation and apoptosis of the BEP2D cells exposed to CSC were analyzed with the methods of MTT assay, flow cytometry and cell colony formation assay after treatment with Notch pathway bloker DAPT or liposome transfection with Hes1-siRNA.The expression of Hes1 in the peripheral small airway tissues of the smoking rats was evaluated by immunohistochemical staining.The expression of Hes1 in non-small-cell lung cancer and normal airway tissues was also detected by the methods of immunohistochemistry and RT-PCR.RESULTS: The BEP2D cells in the 70th generation had a malignant transformation phenotype.The expression of Hes1 in the BEP2D cells exposed to CSC for different time showed an increa-sing trend.DAPT and liposome transfection with Hes1-siRNA down-regulated the expression of Hes1, inhibited the cell proliferation and induced cell apoptosis.The expression of Hes1 in the airway mucosa of the rats exposed to cigarette smoke for 1 month and 6 months was significantly higher than that in control group.Cigarette smoking induced the expression of Hes1 in lung cancer and normal airway tissues.CONCLUSION: Hes1 may be involved in smoking-induced lung cancer by promoting the imbalance between apoptosis and proliferation.

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 regression model and correlation analysis between condensate infection level and influencing factors in ventilator pipe / 中国实用护理杂志

Objective To explore the related factors influencing the condensate infection level in order to provide a reference for ventilator pipe care and reducing condensate infections.Methods A total of 80 patients using ventilator in ICU of the First Hospital of Liaoning Medical University was chosen as the research object,and the related factors influencing the condensate infection using correlation and regression analysis method were explored,and the regression model was estabhshed as well.Results Condensate infection were correlated with pipe length (r=0.837,P＜0.01),temperature difference between ward and gas in the pipe (r=0.875,P＜0.01),exhaled gas humidity (r=0.793,P＜0.01) and ventilation (r=0.932,P＜0.01),but the pipe length could not enter the regression equation (t=-0.09,P＞0.05),and the regression equation was y=-168.08 +9.96x1 (temperature difference) +0.33x2 (exhaled gas humidity) +20.98x3 (ventilation).Conclusions Pipe length,temperature difference between ward and gas in the pipe,exhaled gas humidity and ventilation were the influencing factors,and medical personnel can control the infection of condensate considering the influencing factors.

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.

Comparative evaluation of the mutagenicity and genotoxicity of smoke condensate derived from Korean cigarettes

OBJECTIVES: Cigarette smoking is associated with carcinogenesis owing to the mutagenic and genotoxic effects of cigarette smoke. The aim of this study was to evaluate the mutagenic and genotoxic effects of Korean cigarettes using in vitro assays. METHODS: We selected 2 types of cigarettes (TL and TW) as benchmark Korean cigarettes for this study, because they represent the greatest level of nicotine and tar contents among Korean cigarettes. Mutagenic potency was expressed as the number of revertants per μg of cigarette smoke condensate (CSC) total particulate matter whereas genotoxic potency was expressed as a concentration-dependent induction factor. The CSC was prepared by the International Organization for Standardization 3308 smoking method. CHO-K1 cells were used in vitro micronucleus (MNvit) and comet assays. Two strains of Salmonella typhimurium (Salmonella enterica subsp.enterica; TA98 and TA1537) were employed in Ames tests. RESULTS: All CSCs showed mutagenicity in the TA98 and TA1537 strains. In addition, DNA damage and micronuclei formation were observed in the comet and MNvit assays owing to CSC exposure. The CSC from the 3R4F Kentucky reference (3R4F) cigarette produced the most severe mutagenic and genotoxic potencies, followed by the CSC from the TL cigarette, whereas the CSC from the TW cigarette produced the least severe mutagenic and genotoxic potencies. CONCLUSIONS: The results of this study suggest that the mutagenic and genotoxic potencies of the TL and TW cigarettes were weaker than those of the 3R4F cigarette. Further study on standardized concepts of toxic equivalents for cigarettes needs to be conducted for more extensive use of in vitro tests.