The prognosis for patients with non-small cell lung cancer (NSCLC) remains poor in spite of better treatments. This relates mainly to the fact that the majority of patients present with advanced disease. There is a ne...The prognosis for patients with non-small cell lung cancer (NSCLC) remains poor in spite of better treatments. This relates mainly to the fact that the majority of patients present with advanced disease. There is a need to identify tools which can improve screening for lung cancer in the at risk patient population. The aim of this study was to compare the breath proteomic profile of NSCLC patients with healthy control subjects to explore the potential of new biomarkers of lung cancer. Comparative proteomic analysis of exhaled breath condensate (EBC) between 14 patients with NSCLC and 13 healthy control subjects were carried out using LTQ FT Ultra mass spectrometry and database searching to determine any unique proteins. In total, 29 unique proteins were identified using multiple protein identification algorithms. A comparison of lung cancer, smoker, and ex-smoker proteomes showed that 18 proteins were shared among the three groups. While one unique protein was found in smokers and lung cancer patients, four proteins were unique to ex-smokers. This data set provides a foundation for evaluation of these proteins from EBC as potential biomarkers for non-invasive lung cancer diagnosis.展开更多
Breath monitoring is a non-invasive, safe, and repeatable approach to determining the respiratory, gastrointestinal, and general health status of humans and other mammals. Breath samples could be detected in two ways...Breath monitoring is a non-invasive, safe, and repeatable approach to determining the respiratory, gastrointestinal, and general health status of humans and other mammals. Breath samples could be detected in two ways—directly sensing exhaled breath (EB) or chilling the EB to obtaining the exhaled breath condensate (EBC). Each has its advantages and disadvantages but they are both affected by different sampling conditions. The dearth of information on how sampling conditions affect the intrinsic properties of biomarkers in breath hinders the use of breath monitoring in clinical use. In this study, ethanol, a potential biomarker of liver function, was chosen as a model biomarker to demonstrate the effect of sampling conditions on different phases and how breath sampling could be standardized by developing predictive models. EB and EBC samples were determined under three simulated breath temperatures, two breath rates, and two condensing temperatures for developing predictive models. Results showed EB samples were affected by breath temperatures and EBC samples were affected by condensing temperatures. Flow rate changes did not have a significant influence on both EB and EBC samples. Final predictive models based on 5 minute sensing time were developed for EB (R2 = 0.8261) and EBC (R2 = 0.9471).展开更多
Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the...Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the inflamed lung. The collection of lung secretions by traditional methods including bronchoalveolar lavage and induced sputum collection are limited by their invasive nature. Exhaled breath condensate (EBC) is a simple and non-invasive technique of collecting fluid samples, which are representative of airway lining fluid. Advances in collection methods and evolving molecular techniques have led to development of more sensitive assays for existing biomarkers and identification of new biomarkers, which can be potentially useful in monitoring lung inflammation. In this review, we present the current understanding of various biomarkers including small molecules (H2O2, pH and nitric oxide related biomarkers), lipid mediators (8-isprostane, leukotrienes and prostaglandins), small proteins (cytokines and chemokines) and nucleic acids (DNA and microRNAs). We also discuss the differential profile of biomarkers in recognizing different patterns of lung inflammation. As the sensitivity of methods of EBC improves, this biofluid will play an increasing role in diagnosis and monitoring of lung diseases.展开更多
Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative...Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.展开更多
Background Pulmonary hypertension （PH） is a common complication of chronic obstructive pulmonary disease （COPD）. Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional cha...Background Pulmonary hypertension （PH） is a common complication of chronic obstructive pulmonary disease （COPD）. Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD. Methods We measured the levels of interleukin-6 （IL-6） and 8-iso-prostaglandin （8-iso-PSG） in exhaled breath condensate （EBC） and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure （PASP） was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg. Results Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH （（8.27±2.14） ng/L vs. （4.95±1.19） ng/L, P 〈0.01）. The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group （（72.8±21.6） ng/L vs. （43.58±13.38） ng/L, P 〈0.01 ）. Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group （EBC： （9.00±2.49） ng/L vs. （5.96±2.31） ng/L, P 〈0.01 and serum： （41.87±9.75） ng/L vs. （27.79±11.09） ng/L, P 〈0.01）. Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum （r=0.477-0.589, P 〈0.05）. Conclusion The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.展开更多
Background： Studies of interleukin （IL）-4 and IL-6 in the exhaled breath condensate （EBC） of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid （ICS） treatment on I...Background： Studies of interleukin （IL）-4 and IL-6 in the exhaled breath condensate （EBC） of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid （ICS） treatment on IL-4 and IL-6 in the EBC ＆asthmatic patients. Methods： In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma （mean age 42.7 years） for 12 weeks. Changes in asthma scores, lung function parameters （forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEFs0], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate） and the concentrations of IL-4 and IL-6 in EBC were measured. Results： Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmolJL after 8 weeks of treatment （P 〈 0.05） and 1.54 ± 0.81 pmol/L after 12 weeks of treatment （P 〈 0.01）. However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEVt, PEF and FEFso values （correlation coefficients -0.468, -0.478, and -0.426, respectively）. Conclusions： The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.展开更多
We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate(EBC).We discuss the fabricatio...We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate(EBC).We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide.The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract,particularly in asthma.We utilized the unique properties of reduced graphene oxide(rGO);specifically,the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes,thus allowing for highly sensitive electrochemical detection with minimal fouling.Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane(PDMS),which was necessary to analyze small EBC sample volumes.The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode.We characterized the performance of the sensors using standard nitrite/buffer solutions,nitrite spiked into EBC,and clinical EBC samples.The sensor demonstrated a sensitivity of 0.21μAμM^(−1) cm^(−2) in the range of 20–100μM and of 0.1μAμM^(−1) cm^(−2) in the range of 100–1000μM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix.To benchmark our platform,we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5μM.This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.展开更多
文摘The prognosis for patients with non-small cell lung cancer (NSCLC) remains poor in spite of better treatments. This relates mainly to the fact that the majority of patients present with advanced disease. There is a need to identify tools which can improve screening for lung cancer in the at risk patient population. The aim of this study was to compare the breath proteomic profile of NSCLC patients with healthy control subjects to explore the potential of new biomarkers of lung cancer. Comparative proteomic analysis of exhaled breath condensate (EBC) between 14 patients with NSCLC and 13 healthy control subjects were carried out using LTQ FT Ultra mass spectrometry and database searching to determine any unique proteins. In total, 29 unique proteins were identified using multiple protein identification algorithms. A comparison of lung cancer, smoker, and ex-smoker proteomes showed that 18 proteins were shared among the three groups. While one unique protein was found in smokers and lung cancer patients, four proteins were unique to ex-smokers. This data set provides a foundation for evaluation of these proteins from EBC as potential biomarkers for non-invasive lung cancer diagnosis.
文摘Breath monitoring is a non-invasive, safe, and repeatable approach to determining the respiratory, gastrointestinal, and general health status of humans and other mammals. Breath samples could be detected in two ways—directly sensing exhaled breath (EB) or chilling the EB to obtaining the exhaled breath condensate (EBC). Each has its advantages and disadvantages but they are both affected by different sampling conditions. The dearth of information on how sampling conditions affect the intrinsic properties of biomarkers in breath hinders the use of breath monitoring in clinical use. In this study, ethanol, a potential biomarker of liver function, was chosen as a model biomarker to demonstrate the effect of sampling conditions on different phases and how breath sampling could be standardized by developing predictive models. EB and EBC samples were determined under three simulated breath temperatures, two breath rates, and two condensing temperatures for developing predictive models. Results showed EB samples were affected by breath temperatures and EBC samples were affected by condensing temperatures. Flow rate changes did not have a significant influence on both EB and EBC samples. Final predictive models based on 5 minute sensing time were developed for EB (R2 = 0.8261) and EBC (R2 = 0.9471).
文摘Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the inflamed lung. The collection of lung secretions by traditional methods including bronchoalveolar lavage and induced sputum collection are limited by their invasive nature. Exhaled breath condensate (EBC) is a simple and non-invasive technique of collecting fluid samples, which are representative of airway lining fluid. Advances in collection methods and evolving molecular techniques have led to development of more sensitive assays for existing biomarkers and identification of new biomarkers, which can be potentially useful in monitoring lung inflammation. In this review, we present the current understanding of various biomarkers including small molecules (H2O2, pH and nitric oxide related biomarkers), lipid mediators (8-isprostane, leukotrienes and prostaglandins), small proteins (cytokines and chemokines) and nucleic acids (DNA and microRNAs). We also discuss the differential profile of biomarkers in recognizing different patterns of lung inflammation. As the sensitivity of methods of EBC improves, this biofluid will play an increasing role in diagnosis and monitoring of lung diseases.
文摘Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.
文摘Background Pulmonary hypertension （PH） is a common complication of chronic obstructive pulmonary disease （COPD）. Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD. Methods We measured the levels of interleukin-6 （IL-6） and 8-iso-prostaglandin （8-iso-PSG） in exhaled breath condensate （EBC） and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure （PASP） was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg. Results Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH （（8.27±2.14） ng/L vs. （4.95±1.19） ng/L, P 〈0.01）. The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group （（72.8±21.6） ng/L vs. （43.58±13.38） ng/L, P 〈0.01 ）. Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group （EBC： （9.00±2.49） ng/L vs. （5.96±2.31） ng/L, P 〈0.01 and serum： （41.87±9.75） ng/L vs. （27.79±11.09） ng/L, P 〈0.01）. Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum （r=0.477-0.589, P 〈0.05）. Conclusion The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.
文摘Background： Studies of interleukin （IL）-4 and IL-6 in the exhaled breath condensate （EBC） of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid （ICS） treatment on IL-4 and IL-6 in the EBC ＆asthmatic patients. Methods： In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma （mean age 42.7 years） for 12 weeks. Changes in asthma scores, lung function parameters （forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEFs0], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate） and the concentrations of IL-4 and IL-6 in EBC were measured. Results： Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmolJL after 8 weeks of treatment （P 〈 0.05） and 1.54 ± 0.81 pmol/L after 12 weeks of treatment （P 〈 0.01）. However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEVt, PEF and FEFso values （correlation coefficients -0.468, -0.478, and -0.426, respectively）. Conclusions： The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.
基金This work was partially funded by the National Institutes of Health NIEHS Center Grant ES005022 and by the Rutgers University Electrical and Computer Engineering Department.
文摘We present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate(EBC).We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide.The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract,particularly in asthma.We utilized the unique properties of reduced graphene oxide(rGO);specifically,the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes,thus allowing for highly sensitive electrochemical detection with minimal fouling.Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane(PDMS),which was necessary to analyze small EBC sample volumes.The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode.We characterized the performance of the sensors using standard nitrite/buffer solutions,nitrite spiked into EBC,and clinical EBC samples.The sensor demonstrated a sensitivity of 0.21μAμM^(−1) cm^(−2) in the range of 20–100μM and of 0.1μAμM^(−1) cm^(−2) in the range of 100–1000μM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix.To benchmark our platform,we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5μM.This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.
