Exhaled ammonia(NH_(3))is an essential noninvasive biomarker for disease diagnosis.In this study,an acetone-modifier positive photoionization ion mobility spectrometry(AM-PIMS)method was developed for accurate qualita...Exhaled ammonia(NH_(3))is an essential noninvasive biomarker for disease diagnosis.In this study,an acetone-modifier positive photoionization ion mobility spectrometry(AM-PIMS)method was developed for accurate qualitative and quantitative analysis of exhaled NH_(3)with high selectivity and sensitivity.Acetone was introduced into the drift tube along with the drift gas as a modifier,and the characteristic NH_(3)product ion peak of(C_(3)H_(6)O)_(4)NH_(4)^(+)(K_(0)=1.45 cm^(2)/V·s)was obtained through the ion-molecule reaction with acetone reactant ions(C_(3)H_(6)O)_(2)H^(+)(K_(0)=1.87 cm^(2)/V·s),which significantly increased the peak-to-peak resolution and improved the accuracy of exhaled NH_(3)qualitative identification.Moreover,the interference of high humidity and the memory effect of NH_(3)molecules were significantly reduced via online dilution and purging sampling,thus realizing breath-by-breath measurement.As a result,a wide quantitative range of 5.87-140.92μmol/L with a response time of 40 ms was achieved,and the exhaled NH_(3)profile could be synchronized with the concentration curve of exhaled CO_(2).Finally,the analytical capacity of AM-PIMS was demonstrated by measuring the exhaled NH_(3)of healthy subjects,demonstrating its great potential for clinical disease diagnosis.展开更多
BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is bei...BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.展开更多
The lungs are the main fundamental part of the human respiratory system and are among the major organs of the human body.Lung disorders,including Coronavirus(Covid-19),are among the world’s deadliest and most life-th...The lungs are the main fundamental part of the human respiratory system and are among the major organs of the human body.Lung disorders,including Coronavirus(Covid-19),are among the world’s deadliest and most life-threatening diseases.Early and social distance-based detection and treatment can save lives as well as protect the rest of humanity.Even though X-rays or Computed Tomography(CT)scans are the imaging techniques to analyze lung-related disorders,medical practitioners still find it challenging to analyze and identify lung cancer from scanned images.unless COVID-19 reaches the lungs,it is unable to be diagnosed.through these modalities.So,the Internet of Medical Things(IoMT)and machine learning-based computer-assisted approaches have been developed and applied to automate these diagnostic procedures.This study also aims at investigating an automated approach for the detection of COVID-19 and lung disorders other than COVID-19 infection in a non-invasive manner at their early stages through the analysis of human breath.Human breath contains several volatile organic compounds,i.e.,water vapor(5.0%–6.3%),nitrogen(79%),oxygen(13.6%–16.0%),carbon dioxide(4.0%–5.3%),argon(1%),hydro-gen(1 ppm)(parts per million),carbon monoxide(1%),proteins(1%),isoprene(1%),acetone(1%),and ammonia(1%).Beyond these limits,the presence of a certain volatile organic compound(VOC)may indicate a disease.The proposed research not only aims to increase the accuracy of lung disorder detection from breath analysis but also to deploy the model in a real-time environment as a home appliance.Different sensors detect VOC;microcontrollers and machine learning models have been used to detect these lung disorders.Overall,the suggested methodology is accurate,efficient,and non-invasive.The proposed method obtained an accuracy of 93.59%,a sensitivity of 89.59%,a specificity of 94.87%,and an AUC-Value of 0.96.展开更多
Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying ...Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying the onset of acute elderly asthma as soon as possible and giving the effective treatment is crucial to improve the prognosis. This study was to investigate the significance of fractional exhaled nitric oxide （FeNO） combined with serum procalcitonin （PCT） and C-reactive protein （CRP） in the evaluation of elderly asthma. A total of 120 elderly patients with an acute attack of asthma from July, 2010 to May, 2012 were studied. On presentation, FeNO, serum PCT and CRP concentrations were measured and sputum culture was also performed. The elderly patients were re-evaluated when they had returned to their stable clinical state. The elderly patients were classified into two groups： positive bac- terial culture group （A） and negative bacterial culture group （B）. The results showed that： （1） In patients with an acute exacerbation of asthma, 48 （40%） patients had positive sputum bacterial culture and 72 （60%） had negative sputum bacterial culture. （2） The levels of FeNO in patients with acute exacerbation of asthma were significantly higher than in those with no acute exacerbation state （63.8±24.6 vs. 19±6.5 ppb, P〈0.05）. There was no significant difference in FeNO between group A and group B （P〉0.05）. （3） The levels of PCT and CRP in group A patients with an acute exacerbation of asthma were significantly higher （P〈0.05） than in group B （for PCT： 27.46±9.32 vs. 7.85±3.52 ng/mL; for CRP： 51.25±11.46 vs. 17.11±5.87 mg/L, respectively）. When they had returned to stable clinical state, the levels of PCT and CRP in group A were decreased significantly （P〈0.05）, and those in group B had no significant change （P〉0.05） when compared with the exacerbation group. There were no significant differences in the levels of PCT and CRP between the two groups in non-acute exacerbation state （/9〉0.05）. These results suggest that the increase in FeNO indicates the acute exacerbation of asthma, and the elevation of serum PCT and CRP levels may be associated with bacterial infection.展开更多
Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained incre...Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of medicine.After the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical application.Specific VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing scores.Preliminary results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver disease.However,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained results.Given the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.展开更多
Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled...Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.展开更多
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
Introduction: Tuberculosis still characterizes till now a major respiratory insult with concurrent pulmonary manifestations and later disability. Aim of Work: To evaluate the level of exhaled fraction of nitric oxide ...Introduction: Tuberculosis still characterizes till now a major respiratory insult with concurrent pulmonary manifestations and later disability. Aim of Work: To evaluate the level of exhaled fraction of nitric oxide (FENO) and fraction of exhaled carbon monoxide (FECO) as markers of pulmonary tuberculosis TB activity in patients under chemotherapy in comparison to healthy negative patients and latent TB patients. Patients and Methods: This cross-sectional study was conducted on 130 patients recruited from the outpatient clinic of Mansoura Chest hospital during the period from May 2019 to December 2019. They were categorized into the three groups: 1) Pulmonary tuberculous patients PTB (group1) which included 48 cases with positive sputum for TB bacilli in the initiation phase after 1 month of starting anti-tuberculous chemotherapy;2) Latent patients (group 2): included 40 patients with positive tuberculin skin test (Mantoux test) > 10 mm. 3) Control patients (group 3) which included 42 healthy volunteers with negative sputum for TB bacilli. They were subjected to portable spirogram as well as exhaled fractional NO and CO measurement. Results: FECO and FENO levels prevailed in pulmonary TB patients followed by Latent TB patients and lastly healthy volunteers (42 ± 12.32/5 ± 0.16 & 38 ± 8.25/6 ± 2.25 and 23 ± 3.25/2 ± 0.40 respectively). Conclusion: Measurement of CO and NO level in expired air may correlate with active pulmonary TB infection in comparison to healthy negative tuberculous patients and latent tuberculous patients.展开更多
Aim: The goal of this study was to compare asthma treatment guidance based on bronchial hyper-responsiveness to mannitol, spirometry or exhaled nitric oxide (FeNO) in stable asthmatic children. Methods: 60 stable alle...Aim: The goal of this study was to compare asthma treatment guidance based on bronchial hyper-responsiveness to mannitol, spirometry or exhaled nitric oxide (FeNO) in stable asthmatic children. Methods: 60 stable allergic asthmatic children aged 7 to 16 years on a low to medium dose treatment with inhaled corticosteroids (ICS) were recruited to a double blind randomised controlled trial. At study entry (visit 1), the following was assessed: FeNO, spirometry, bronchial hyper-responsiveness to mannitol (MDP-?test), quality of life (paediatric asthma quality-of-life questionnaire;PAQLQ) and asthma control (asthma control test;ACT). Subjects were randomly assigned to one of three groups and treatment was modified by a blinded respiratory physician according to the test results of visit 1: ICS dose was doubled when FeNO was >22 ppb (group 1), in case of a positive MDP-test (group 2) or when FEV1 was <80% of a predicted one (group 3), respectively, or remained unchanged for the remaining subjects. After 3 months (visit 2), the subjects were reassessed and all tests were repeated. Results: 48 children successfully completed the study. At the first visit, 8 out of 16 (50%) children in group 1 showed a FeNO > 22 ppb, 8 children out of 16 (50%) in group 2 showed a positive MDP-test and 3 children out of 16 (18.7%) in group 3 had a FEV1 < 80% of that predicted and had their ICS-dose doubled. In group 1, FeNO decreased significantly after the intervention (p = 0.005), whereas the self-administered and the interviewer-administered PAQLQ (p = 0.02 resp. p = 0.033) as well as the ACT (p = 0.031) increased. Neither the number of children with a positive mannitol challenge nor spirometric results changed significantly. In group 2 and group 3, there were no significant changes in none of the assessed parameters. Conclusion: In this small pragmatic double blind randomised controlled study, we showed that ICS dose modification based on FeNO led to increased quality of life and enhanced asthma control, and to a reduction in airway inflammation and was superior to treatment modifications based on bronchial hyper-responsiveness to mannitol or on FEV1.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 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 The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide （FENO） for th...Background The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide （FENO） for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter （forced expiratory volume in one second （FEV1））. Methods Sixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide. Results Sixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV1 value of the 63 subjects was （2.75±0.54） L at baseline, （2.97±0.56） L and （3.07±0.52） L at month 3 and month 6, respectively, and maintained as （3.14±0.51） L in the following six months. Mean FENO decreased from （61±25） parts per billion （ppb） at baseline to （32±19） ppb at month 3 （P 〈0.05）, and continued to decrease to （22±12） ppb at month 6, the difference being significant when compared to both baseline and control group （（13±8） ppb）. Mean eosinophil counts decreased to （0.032±0.011） ×106/ml at month 3, which was significantly different from baseline （（0.093±_0.023） xl06/ml） and the control group （（0.005±0.003）×l06/ml （both P 〈0.05）. The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months （all P 〈0.05）. The concentration of FENO had a significant negative correlation with FEV1 value （all P 〈0.05） in any time point in the follow-up period. The Asthma Control Test scores were 18±5, 19±7, 23±-2, 24±1 and 24±1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline （14±3） （P 〈0.05 ）. The most rapid clinical effect was observed at the second month after treatment. Conclusion Eosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.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
Small-scale measurements of the radon exhalation rate using the flow-through and closed-loop methods were conducted on the surface of a uranium tailing pond to better understand the differences between the two methods...Small-scale measurements of the radon exhalation rate using the flow-through and closed-loop methods were conducted on the surface of a uranium tailing pond to better understand the differences between the two methods.An abnormal radon exhalation behavior was observed,leading to computational fluid dynamics(CFD)-based simulations in which dynamic radon migration in a porous medium and accumulation chamber was considered.Based on the in-situ experimental and numerical simulation results,variations in the radon exhalation rate subject to permeability,flow rate,and insertion depth were quantified and analyzed.The in-situ radon exhalation rates measured using the flow-through method were higher than those measured using the closed-loop method,which could be explained by the negative pressure difference between the inside and outside of the chamber during the measurements.The consistency of the variations in the radon exhalation rate between the experiments and simulations suggests the reliability of CFD-based techniques in obtaining the dynamic evolution of transient radon exhalation rates for diffusion and convection at the porous medium-air interface.The synergistic effects of the three factors(insertion depth,flow rate,and permeability)on the negative pressure difference and measured exhalation rate were quantified,and multivariate regression models were established,with positive correlations in most cases;the exhalation rate decreased with increasing insertion depth at a permeability of 1×10^(−11) m^(2).CFD-based simulations can provide theoretical guidance for improving the flow-through method and thus achieve accurate measurements.展开更多
Accurate measurements of the radon exhalation rate help identify and evaluate radon risk regions in the environment.Among these measurement methods,the closed-loop method is frequently used.However,traditional experim...Accurate measurements of the radon exhalation rate help identify and evaluate radon risk regions in the environment.Among these measurement methods,the closed-loop method is frequently used.However,traditional experiments are insufficient or cannot analyze the radon migration and exhalation patterns at the gas–solid interface in the accumulation chamber.The CFD-based technique was applied to predict the radon concentration distribution in a limited space,allowing radon accumulation and exhalation inside the chamber intuitively and visually.In this study,three radon exhalation rates were defined,and two structural ventilation tubes were designed for the chamber.The consistency of the simulated results with the variation in the radon exhalation rate in a previous experiment or analytical solution was verified.The effects of the vent tube structure and flow rate on the radon uniformity in the chamber;permeability,insertion depth,and flow rate on the radon exhalation rate and the effective diffusion coefficient on back-diffusion were investigated.Based on the results,increasing the inser-tion depth from 1 to 5 cm decreased the effective decay constant by 19.55%,whereas the curve-fitted radon exhalation rate decreased(lower than the initial value)as the deviation from the initial value increased by approximately 7%.Increasing the effective diffusion coefficient from 2.77×10^(-7) to 7.77×10^(-6) m^(2) s^(-1) made the deviation expand from 2.14 to 15.96%.The conclusion is that an increased insertion depth helps reduce leakage in the chamber,subject to notable back-diffusion,and that the closed-loop method is reasonably used for porous media with a low effective diffusion coefficient in view of the back-diffusion effect.The CFD-based simulation is expected to provide guidance for the optimization of the radon exhalation rate measurement method and,thus,the accurate measurement of the radon exhalation rate.展开更多
Accurate diagnosis of different bronchopul- monary diseases is important in clinical practice. This study involved 20 healthy volunteers and 77 patients with bronchopulmonary diseases, including chronic obstructive pu...Accurate diagnosis of different bronchopul- monary diseases is important in clinical practice. This study involved 20 healthy volunteers and 77 patients with bronchopulmonary diseases, including chronic obstructive pulmonary disease （COPD）, bronchial asthma, pulmonary tuberculosis, and community-acquired pneumonia. The absorption spectrum of exhaled air samples was recorded on an intra-cavity photo-acoustic gas analyzer （ILPA-1, Special Technologies, Ltd., Russia） with photo-acoustic detectors and CO2 laser with a tuning range from 9.2 to 10.8μm. In conclusion, analysis of the Mahalanobis distance-based absorption spectral profiles of breath air from bronchopulmonary patients and healthy volunteers allows the formulation of a preliminary diagnosis.展开更多
Direct determination of the oxidative potential in exhaled air(OPEA)as a biological indicator of the redox balance status in airways requires an extremely sensitive sensing approach to counterbalance the high dilution...Direct determination of the oxidative potential in exhaled air(OPEA)as a biological indicator of the redox balance status in airways requires an extremely sensitive sensing approach to counterbalance the high dilution of the exhaled air matrix.In opposite to standard colorimetric assays based on Beer-Lambert Law,the use of simple multiscattering-enhanced absorbance(MEA)strategy results in an improved photonic sensing system.Based on this strategy and using the ferrous-xylenol orange assay,analytical performances allowing the detection of 3 pmol of H_(2)O_(2) could be obtained.The comparative analysis of photometric configurations–standard vs MEA–highlights the large absorbance gain obtained for tiny H_(2)O_(2) amounts–from 0 to 30 pmol–whereas similar sensing trends are observed at higher concentration range.The automated introduction of exhaled air sample into the reaction compartment via needle-impinger coupled with the MEA-based photonic cell enables ultrasensitive determination of OPEA in short time(<5 min).A pilot study conducted on healthy subjects(n=22)and chronic obstructive pulmonary disease(COPD)patients(n=23)volunteers shows a significant increase of the OPEA for COPD versus controls and strong negative correlation between OPEA and spirometry parameters(Tiffeneau index:FEV1/FVC)for ex-/non-smokers.Application perspectives to assess inflammatory episodes in obstructive lung diseases are thus made possible using this sensing approach.展开更多
Environmental radon emanates from the exhalation and release of soil,rocks,and building materials.Environmental radon contamination tracing and radon pollution prevention and control require the measurement of the rad...Environmental radon emanates from the exhalation and release of soil,rocks,and building materials.Environmental radon contamination tracing and radon pollution prevention and control require the measurement of the radon exhalation rate on media surfaces.Reliable measurements of the radon exhalation rate cannot be achieved without regular calibration of the measuring instrument with a high-performance reference device.In this study,a reference device for the calibration of radon exhalation rate measuring instruments was developed using a diffusion solid radon source with a high and stable radon emanation coefficient,an integrated diffusion component composed of a plasterboard and a high-density wooden board,an air pressure balance device,a radon accumulation chamber,and a support structure.The uniformity and stability of the reference device were evaluated using the activated carbon-γspectrum and open-loop method,respectively,to measure the radon exhalation rate.The reference device achieved different radon exhalation rates by using different activities of diffusion solid radon sources.Nineteen measurement points were regularly selected on the radon exhalation surface of the reference device,and the uniformity of the radon exhalation rate exceeded 5%.The short-term stability of the reference device was better than 5%under different environmental conditions and was almost unaffected by the ambient air pressure,environmental temperature,and relative humidity.展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.:22027804,21974141,and 21904125)Natural Science Foundation of Liaoning Province(Grant Nos.:2022-MS-019 and 2022-MS-016)+2 种基金Science and Technology Innovation Foundation of Dalian(Grant No.:2022JJ13SN096)Dalian Institute of Chemical Physics(Grant Nos.:DICP I202141 and DICP I202144)1+X Program for Large Cohort Study-Clinical Research Incubation Project,The Second Hospital of Dalian Medical University(Project No.:2022DXDL01).
文摘Exhaled ammonia(NH_(3))is an essential noninvasive biomarker for disease diagnosis.In this study,an acetone-modifier positive photoionization ion mobility spectrometry(AM-PIMS)method was developed for accurate qualitative and quantitative analysis of exhaled NH_(3)with high selectivity and sensitivity.Acetone was introduced into the drift tube along with the drift gas as a modifier,and the characteristic NH_(3)product ion peak of(C_(3)H_(6)O)_(4)NH_(4)^(+)(K_(0)=1.45 cm^(2)/V·s)was obtained through the ion-molecule reaction with acetone reactant ions(C_(3)H_(6)O)_(2)H^(+)(K_(0)=1.87 cm^(2)/V·s),which significantly increased the peak-to-peak resolution and improved the accuracy of exhaled NH_(3)qualitative identification.Moreover,the interference of high humidity and the memory effect of NH_(3)molecules were significantly reduced via online dilution and purging sampling,thus realizing breath-by-breath measurement.As a result,a wide quantitative range of 5.87-140.92μmol/L with a response time of 40 ms was achieved,and the exhaled NH_(3)profile could be synchronized with the concentration curve of exhaled CO_(2).Finally,the analytical capacity of AM-PIMS was demonstrated by measuring the exhaled NH_(3)of healthy subjects,demonstrating its great potential for clinical disease diagnosis.
文摘BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.
文摘The lungs are the main fundamental part of the human respiratory system and are among the major organs of the human body.Lung disorders,including Coronavirus(Covid-19),are among the world’s deadliest and most life-threatening diseases.Early and social distance-based detection and treatment can save lives as well as protect the rest of humanity.Even though X-rays or Computed Tomography(CT)scans are the imaging techniques to analyze lung-related disorders,medical practitioners still find it challenging to analyze and identify lung cancer from scanned images.unless COVID-19 reaches the lungs,it is unable to be diagnosed.through these modalities.So,the Internet of Medical Things(IoMT)and machine learning-based computer-assisted approaches have been developed and applied to automate these diagnostic procedures.This study also aims at investigating an automated approach for the detection of COVID-19 and lung disorders other than COVID-19 infection in a non-invasive manner at their early stages through the analysis of human breath.Human breath contains several volatile organic compounds,i.e.,water vapor(5.0%–6.3%),nitrogen(79%),oxygen(13.6%–16.0%),carbon dioxide(4.0%–5.3%),argon(1%),hydro-gen(1 ppm)(parts per million),carbon monoxide(1%),proteins(1%),isoprene(1%),acetone(1%),and ammonia(1%).Beyond these limits,the presence of a certain volatile organic compound(VOC)may indicate a disease.The proposed research not only aims to increase the accuracy of lung disorder detection from breath analysis but also to deploy the model in a real-time environment as a home appliance.Different sensors detect VOC;microcontrollers and machine learning models have been used to detect these lung disorders.Overall,the suggested methodology is accurate,efficient,and non-invasive.The proposed method obtained an accuracy of 93.59%,a sensitivity of 89.59%,a specificity of 94.87%,and an AUC-Value of 0.96.
基金supported by Fundation of Henan Provincial Medical Science and Technology Research(No.201003098)
文摘Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying the onset of acute elderly asthma as soon as possible and giving the effective treatment is crucial to improve the prognosis. This study was to investigate the significance of fractional exhaled nitric oxide （FeNO） combined with serum procalcitonin （PCT） and C-reactive protein （CRP） in the evaluation of elderly asthma. A total of 120 elderly patients with an acute attack of asthma from July, 2010 to May, 2012 were studied. On presentation, FeNO, serum PCT and CRP concentrations were measured and sputum culture was also performed. The elderly patients were re-evaluated when they had returned to their stable clinical state. The elderly patients were classified into two groups： positive bac- terial culture group （A） and negative bacterial culture group （B）. The results showed that： （1） In patients with an acute exacerbation of asthma, 48 （40%） patients had positive sputum bacterial culture and 72 （60%） had negative sputum bacterial culture. （2） The levels of FeNO in patients with acute exacerbation of asthma were significantly higher than in those with no acute exacerbation state （63.8±24.6 vs. 19±6.5 ppb, P〈0.05）. There was no significant difference in FeNO between group A and group B （P〉0.05）. （3） The levels of PCT and CRP in group A patients with an acute exacerbation of asthma were significantly higher （P〈0.05） than in group B （for PCT： 27.46±9.32 vs. 7.85±3.52 ng/mL; for CRP： 51.25±11.46 vs. 17.11±5.87 mg/L, respectively）. When they had returned to stable clinical state, the levels of PCT and CRP in group A were decreased significantly （P〈0.05）, and those in group B had no significant change （P〉0.05） when compared with the exacerbation group. There were no significant differences in the levels of PCT and CRP between the two groups in non-acute exacerbation state （/9〉0.05）. These results suggest that the increase in FeNO indicates the acute exacerbation of asthma, and the elevation of serum PCT and CRP levels may be associated with bacterial infection.
文摘Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of medicine.After the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical application.Specific VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing scores.Preliminary results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver disease.However,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained results.Given the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.
文摘Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.
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Introduction: Tuberculosis still characterizes till now a major respiratory insult with concurrent pulmonary manifestations and later disability. Aim of Work: To evaluate the level of exhaled fraction of nitric oxide (FENO) and fraction of exhaled carbon monoxide (FECO) as markers of pulmonary tuberculosis TB activity in patients under chemotherapy in comparison to healthy negative patients and latent TB patients. Patients and Methods: This cross-sectional study was conducted on 130 patients recruited from the outpatient clinic of Mansoura Chest hospital during the period from May 2019 to December 2019. They were categorized into the three groups: 1) Pulmonary tuberculous patients PTB (group1) which included 48 cases with positive sputum for TB bacilli in the initiation phase after 1 month of starting anti-tuberculous chemotherapy;2) Latent patients (group 2): included 40 patients with positive tuberculin skin test (Mantoux test) > 10 mm. 3) Control patients (group 3) which included 42 healthy volunteers with negative sputum for TB bacilli. They were subjected to portable spirogram as well as exhaled fractional NO and CO measurement. Results: FECO and FENO levels prevailed in pulmonary TB patients followed by Latent TB patients and lastly healthy volunteers (42 ± 12.32/5 ± 0.16 & 38 ± 8.25/6 ± 2.25 and 23 ± 3.25/2 ± 0.40 respectively). Conclusion: Measurement of CO and NO level in expired air may correlate with active pulmonary TB infection in comparison to healthy negative tuberculous patients and latent tuberculous patients.
文摘Aim: The goal of this study was to compare asthma treatment guidance based on bronchial hyper-responsiveness to mannitol, spirometry or exhaled nitric oxide (FeNO) in stable asthmatic children. Methods: 60 stable allergic asthmatic children aged 7 to 16 years on a low to medium dose treatment with inhaled corticosteroids (ICS) were recruited to a double blind randomised controlled trial. At study entry (visit 1), the following was assessed: FeNO, spirometry, bronchial hyper-responsiveness to mannitol (MDP-?test), quality of life (paediatric asthma quality-of-life questionnaire;PAQLQ) and asthma control (asthma control test;ACT). Subjects were randomly assigned to one of three groups and treatment was modified by a blinded respiratory physician according to the test results of visit 1: ICS dose was doubled when FeNO was >22 ppb (group 1), in case of a positive MDP-test (group 2) or when FEV1 was <80% of a predicted one (group 3), respectively, or remained unchanged for the remaining subjects. After 3 months (visit 2), the subjects were reassessed and all tests were repeated. Results: 48 children successfully completed the study. At the first visit, 8 out of 16 (50%) children in group 1 showed a FeNO > 22 ppb, 8 children out of 16 (50%) in group 2 showed a positive MDP-test and 3 children out of 16 (18.7%) in group 3 had a FEV1 < 80% of that predicted and had their ICS-dose doubled. In group 1, FeNO decreased significantly after the intervention (p = 0.005), whereas the self-administered and the interviewer-administered PAQLQ (p = 0.02 resp. p = 0.033) as well as the ACT (p = 0.031) increased. Neither the number of children with a positive mannitol challenge nor spirometric results changed significantly. In group 2 and group 3, there were no significant changes in none of the assessed parameters. Conclusion: In this small pragmatic double blind randomised controlled study, we showed that ICS dose modification based on FeNO led to increased quality of life and enhanced asthma control, and to a reduction in airway inflammation and was superior to treatment modifications based on bronchial hyper-responsiveness to mannitol or on FEV1.
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 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 The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide （FENO） for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter （forced expiratory volume in one second （FEV1））. Methods Sixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide. Results Sixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV1 value of the 63 subjects was （2.75±0.54） L at baseline, （2.97±0.56） L and （3.07±0.52） L at month 3 and month 6, respectively, and maintained as （3.14±0.51） L in the following six months. Mean FENO decreased from （61±25） parts per billion （ppb） at baseline to （32±19） ppb at month 3 （P 〈0.05）, and continued to decrease to （22±12） ppb at month 6, the difference being significant when compared to both baseline and control group （（13±8） ppb）. Mean eosinophil counts decreased to （0.032±0.011） ×106/ml at month 3, which was significantly different from baseline （（0.093±_0.023） xl06/ml） and the control group （（0.005±0.003）×l06/ml （both P 〈0.05）. The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months （all P 〈0.05）. The concentration of FENO had a significant negative correlation with FEV1 value （all P 〈0.05） in any time point in the follow-up period. The Asthma Control Test scores were 18±5, 19±7, 23±-2, 24±1 and 24±1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline （14±3） （P 〈0.05 ）. The most rapid clinical effect was observed at the second month after treatment. Conclusion Eosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.
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.
基金National Natural Science Foundation of China(No.11575080)Hunan Provincial Natural Science Foundation of China(No.2022JJ30482)Hunan Provincial Innovation Foundation for Postgraduate(No.QL20220206).
文摘Small-scale measurements of the radon exhalation rate using the flow-through and closed-loop methods were conducted on the surface of a uranium tailing pond to better understand the differences between the two methods.An abnormal radon exhalation behavior was observed,leading to computational fluid dynamics(CFD)-based simulations in which dynamic radon migration in a porous medium and accumulation chamber was considered.Based on the in-situ experimental and numerical simulation results,variations in the radon exhalation rate subject to permeability,flow rate,and insertion depth were quantified and analyzed.The in-situ radon exhalation rates measured using the flow-through method were higher than those measured using the closed-loop method,which could be explained by the negative pressure difference between the inside and outside of the chamber during the measurements.The consistency of the variations in the radon exhalation rate between the experiments and simulations suggests the reliability of CFD-based techniques in obtaining the dynamic evolution of transient radon exhalation rates for diffusion and convection at the porous medium-air interface.The synergistic effects of the three factors(insertion depth,flow rate,and permeability)on the negative pressure difference and measured exhalation rate were quantified,and multivariate regression models were established,with positive correlations in most cases;the exhalation rate decreased with increasing insertion depth at a permeability of 1×10^(−11) m^(2).CFD-based simulations can provide theoretical guidance for improving the flow-through method and thus achieve accurate measurements.
基金This work was supported by the National Natural Science Foundation of China(No.11575080)the National Natural Science Foundation of Hunan Province,China(No.2022JJ30482)the Hunan Provincial Innovation Foundation for Postgraduates(No.QL20220206).
文摘Accurate measurements of the radon exhalation rate help identify and evaluate radon risk regions in the environment.Among these measurement methods,the closed-loop method is frequently used.However,traditional experiments are insufficient or cannot analyze the radon migration and exhalation patterns at the gas–solid interface in the accumulation chamber.The CFD-based technique was applied to predict the radon concentration distribution in a limited space,allowing radon accumulation and exhalation inside the chamber intuitively and visually.In this study,three radon exhalation rates were defined,and two structural ventilation tubes were designed for the chamber.The consistency of the simulated results with the variation in the radon exhalation rate in a previous experiment or analytical solution was verified.The effects of the vent tube structure and flow rate on the radon uniformity in the chamber;permeability,insertion depth,and flow rate on the radon exhalation rate and the effective diffusion coefficient on back-diffusion were investigated.Based on the results,increasing the inser-tion depth from 1 to 5 cm decreased the effective decay constant by 19.55%,whereas the curve-fitted radon exhalation rate decreased(lower than the initial value)as the deviation from the initial value increased by approximately 7%.Increasing the effective diffusion coefficient from 2.77×10^(-7) to 7.77×10^(-6) m^(2) s^(-1) made the deviation expand from 2.14 to 15.96%.The conclusion is that an increased insertion depth helps reduce leakage in the chamber,subject to notable back-diffusion,and that the closed-loop method is reasonably used for porous media with a low effective diffusion coefficient in view of the back-diffusion effect.The CFD-based simulation is expected to provide guidance for the optimization of the radon exhalation rate measurement method and,thus,the accurate measurement of the radon exhalation rate.
文摘Accurate diagnosis of different bronchopul- monary diseases is important in clinical practice. This study involved 20 healthy volunteers and 77 patients with bronchopulmonary diseases, including chronic obstructive pulmonary disease （COPD）, bronchial asthma, pulmonary tuberculosis, and community-acquired pneumonia. The absorption spectrum of exhaled air samples was recorded on an intra-cavity photo-acoustic gas analyzer （ILPA-1, Special Technologies, Ltd., Russia） with photo-acoustic detectors and CO2 laser with a tuning range from 9.2 to 10.8μm. In conclusion, analysis of the Mahalanobis distance-based absorption spectral profiles of breath air from bronchopulmonary patients and healthy volunteers allows the formulation of a preliminary diagnosis.
基金This study was supported in the frame of the project OxAirDirect(Grant EST2015-1-151)funded by the French Agency for Food,Environmental and Occupational Health&Safety(ANSES)the project ROBoCoP(Grant IZCOZ0-177,067)funded by the Swiss National Science Foundation(SNSF)the framework of CliniMARK COST Action(CA16113).
文摘Direct determination of the oxidative potential in exhaled air(OPEA)as a biological indicator of the redox balance status in airways requires an extremely sensitive sensing approach to counterbalance the high dilution of the exhaled air matrix.In opposite to standard colorimetric assays based on Beer-Lambert Law,the use of simple multiscattering-enhanced absorbance(MEA)strategy results in an improved photonic sensing system.Based on this strategy and using the ferrous-xylenol orange assay,analytical performances allowing the detection of 3 pmol of H_(2)O_(2) could be obtained.The comparative analysis of photometric configurations–standard vs MEA–highlights the large absorbance gain obtained for tiny H_(2)O_(2) amounts–from 0 to 30 pmol–whereas similar sensing trends are observed at higher concentration range.The automated introduction of exhaled air sample into the reaction compartment via needle-impinger coupled with the MEA-based photonic cell enables ultrasensitive determination of OPEA in short time(<5 min).A pilot study conducted on healthy subjects(n=22)and chronic obstructive pulmonary disease(COPD)patients(n=23)volunteers shows a significant increase of the OPEA for COPD versus controls and strong negative correlation between OPEA and spirometry parameters(Tiffeneau index:FEV1/FVC)for ex-/non-smokers.Application perspectives to assess inflammatory episodes in obstructive lung diseases are thus made possible using this sensing approach.
基金supported by the National Natural Science Foundation of China(No.11875165).
文摘Environmental radon emanates from the exhalation and release of soil,rocks,and building materials.Environmental radon contamination tracing and radon pollution prevention and control require the measurement of the radon exhalation rate on media surfaces.Reliable measurements of the radon exhalation rate cannot be achieved without regular calibration of the measuring instrument with a high-performance reference device.In this study,a reference device for the calibration of radon exhalation rate measuring instruments was developed using a diffusion solid radon source with a high and stable radon emanation coefficient,an integrated diffusion component composed of a plasterboard and a high-density wooden board,an air pressure balance device,a radon accumulation chamber,and a support structure.The uniformity and stability of the reference device were evaluated using the activated carbon-γspectrum and open-loop method,respectively,to measure the radon exhalation rate.The reference device achieved different radon exhalation rates by using different activities of diffusion solid radon sources.Nineteen measurement points were regularly selected on the radon exhalation surface of the reference device,and the uniformity of the radon exhalation rate exceeded 5%.The short-term stability of the reference device was better than 5%under different environmental conditions and was almost unaffected by the ambient air pressure,environmental temperature,and relative humidity.
