Objective:To evaluate the clinical efficacy of high-throughput real-time mass spectrometry detection technology for exhaled breath in the rapid diagnosis of pulmonary tuberculosis(PTB),providing a novel technological ...Objective:To evaluate the clinical efficacy of high-throughput real-time mass spectrometry detection technology for exhaled breath in the rapid diagnosis of pulmonary tuberculosis(PTB),providing a novel technological support for early screening and diagnosis of PTB.Methods:A total of 120 PTB patients admitted to a hospital from January 2023 to June 2024 were selected as the case group,and 150 healthy individuals and patients with non-tuberculous pulmonary diseases during the same period were selected as the control group.Exhaled breath samples were collected from all study subjects,and the types and concentrations of volatile organic compounds(VOCs)in the samples were detected using a high-throughput real-time mass spectrometer.A diagnostic model was constructed using machine learning algorithms,and core indicators such as diagnostic sensitivity,specificity,and area under the curve(AUC)of this technology were analyzed and compared with the efficacy of traditional sputum smear examination,sputum culture,and GeneXpert MTB/RIF detection.Results:The diagnostic sensitivity of the high-throughput real-time mass spectrometry diagnostic model for exhaled breath in diagnosing PTB was 92.5%,the specificity was 94.0%,and the AUC was 0.978,which were significantly higher than those of sputum smear examination(sensitivity 58.3%,specificity 90.0%,AUC 0.741).Compared with GeneXpert technology,its specificity was comparable(94.0%vs 93.3%),and the detection time was shortened to less than 15 minutes.The model achieved an accuracy of 91.3%in distinguishing PTB from other pulmonary diseases and was not affected by demographic factors such as age and gender.Conclusion:High-throughput real-time mass spectrometry detection technology for exhaled breath has the advantages of being non-invasive,rapid,highly sensitive,and highly specific,and holds significant clinical application value in the rapid diagnosis and large-scale screening of PTB,warranting further promotion.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
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
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
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
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
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
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
The exploitation of the highly reliable gassensing device for exhaled acetone detection possesses momentous and capacious development prospects in the field of an early noninvasive diabetes diagnosis.Considering that ...The exploitation of the highly reliable gassensing device for exhaled acetone detection possesses momentous and capacious development prospects in the field of an early noninvasive diabetes diagnosis.Considering that the characteristics of crystal facets will impact the gas-sensitive performance,herein three different resistive gas sensors were successfully developed by utilizing the stable α-Fe_(2)O_(3)with different crystal facets as the sensitive materials.The gas-sensitive performance testing results reveal that the(110)crystal faceted α-Fe_(2)O_(3)sensor exhibits relatively superior comprehensive gas sensitivity toward acetone.Particularly,it is worth mentioning that the sensor demonstrates reliable sensitivity,rapid response(25 s)/recovery(3 s)speed,and strong anti-interference capability in detecting 2×10^(-6)acetone for the concentration threshold of diabetes,even when exposed to prolonged periods in variable environments.Furthermore,by simply validating the feasibility of the exhalation diagnosis using the as-prepared gas sensor,the(110)faceted α-Fe_(2)O_(3)gas sensor can effectively discriminate the states of healthy human exhalation and the simulated diabetic exhalation.Through integrating the experimental and theoretical analyses,the superior acetone-sensitive performance of the(110)facetedα-Fe_(2)O_(3)gas sensor can principally be interpreted in correlation with crystal facet-dependent gas adsorption capacity and defect-forming ability.These results not only imply a tremendous application perspective in monitoring acetone gas at sub-ppm concentration,but also open up an effective throughway to develop reliable gas-sensing devices for early non-invasive diabetes screening.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
The concentration of the heavy isotope of hydrogen, deuterium (D), is not routinely measured in (human) medical laboratory tests, even though an increasing number of papers prove the pivotal role of D in tumor growth,...The concentration of the heavy isotope of hydrogen, deuterium (D), is not routinely measured in (human) medical laboratory tests, even though an increasing number of papers prove the pivotal role of D in tumor growth, cell cycle regulation, cell metabolism, and aging. Data from a prospective phase 2 clinical study and numerous retrospective clinical studies proved the anticancer effect of deuterium depletion achieved by replacing the regular water intake with deuterium-depleted water (DDW). In previous studies, the changes in serum D concentration of DDW-consuming patients were followed using blood samples and mass spectrometry, which was invasive, costly, and time-consuming. As future clinical trials will also require a follow-up of internal D level and the patient’s compliance, a new sampling device and procedure was developed based on condensing the exhaled breath water vapor and measuring its D content using a liquid water isotope laser analyzer. Test results showed that the device provided accurate, reliable, and reproducible data. According to the data, the internal D level in a person consuming normal water was stable. In contrast, exclusive consumption of DDW for several days resulted in a gradual decrease of D concentration in exhaled breath condensate (EBC), which was proportional to the D concentration of DDW. These data confirm that orally applied DDW equilibrates with the person’s water pool quickly, leading to a reduced internal D level reflected in the D content of EBC.展开更多
The analysis of metabolic waste is a critical method for assessing overall health and metabolic function.The human body eliminates metabolic waste primarily through three pathways:urine from the urinary system,sweat s...The analysis of metabolic waste is a critical method for assessing overall health and metabolic function.The human body eliminates metabolic waste primarily through three pathways:urine from the urinary system,sweat secreted by the skin,and breath expelled via the respiratory system[1,2].展开更多
Face masks are no longer just passive barriers against pathogens.By integrating flexible electronics,biosensors,and fluidic systems,they are becoming intelligent wearable platforms capable of continuous health monitor...Face masks are no longer just passive barriers against pathogens.By integrating flexible electronics,biosensors,and fluidic systems,they are becoming intelligent wearable platforms capable of continuous health monitoring.In a recent study published in Science,Gao et al.introduced“EBCare”,a wearable smart mask that achieves real-time in situ analysis of exhaled breath condensate(EBC).This work presents a comprehensive solution for on-body collection,transport,and detection of multiple breath-derived biomarkers using passive cooling,capillary-driven microfluidics,and multiplexed biosensing,establishing a versatile platform for respiratory diagnostics and personalized medicine.展开更多
Various metals are fundamental elements in the human body.Detection of metals in the human body plays an important role in understanding health and disease but poses a great challenge to analytical science in noninvas...Various metals are fundamental elements in the human body.Detection of metals in the human body plays an important role in understanding health and disease but poses a great challenge to analytical science in noninvasiveness,sensitivity,and detection speed.In this study,a non-invasive handheld sampler was developed to couple to inductively coupled plasma mass spectrometry(ICP-MS)for sensitive detection of metal ions in exhaled breath.Fourteen endogenous exhaled breath metals were simultaneously detected.The limits of detection(LOD)of 14 metals were found to be 0.046–0.134 ngL^(-1).Linear dynamic responses were found to range from 1.0 to 500 ngL^(-1).Satisfactory measurement precision(RSD:1.18%–11.93%)was also obtained.Despite concentrations of metal ions ranging from ng mL^(-1)to mg mL^(-1)levels in breath and blood,it is interesting to find that there is a relatively stable ratio(Rblood/breath:3.55±0.23)by comparing the levels of 9 metal ions in blood and exhaled breath.Furthermore,sensitive detections of 14 breath metal ions from patients with liver cancer and lung cancer were also successfully conducted.A multivariate statistical approach is established for biomarker discovery of breath metals between healthy volunteers and cancer patients,elucidating that cancer progression plays multifaceted roles in affecting the metal ions in exhaled breath.Overall,our data demonstrated that the new method can be not only used for the quantitative detection of trace metal species with high accuracy and high throughput but also for new insights into compositions and changes of metals in exhaled breath.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
基金Science and Technology Plan of Heilongjiang Provincial Health Commission,Study on the Efficacy of High-Throughput Real-Time Mass Spectrometry Detection of Exhaled Breath for Rapid Diagnosis of Pulmonary Tuberculosis(Project No.:20230303110014)。
文摘Objective:To evaluate the clinical efficacy of high-throughput real-time mass spectrometry detection technology for exhaled breath in the rapid diagnosis of pulmonary tuberculosis(PTB),providing a novel technological support for early screening and diagnosis of PTB.Methods:A total of 120 PTB patients admitted to a hospital from January 2023 to June 2024 were selected as the case group,and 150 healthy individuals and patients with non-tuberculous pulmonary diseases during the same period were selected as the control group.Exhaled breath samples were collected from all study subjects,and the types and concentrations of volatile organic compounds(VOCs)in the samples were detected using a high-throughput real-time mass spectrometer.A diagnostic model was constructed using machine learning algorithms,and core indicators such as diagnostic sensitivity,specificity,and area under the curve(AUC)of this technology were analyzed and compared with the efficacy of traditional sputum smear examination,sputum culture,and GeneXpert MTB/RIF detection.Results:The diagnostic sensitivity of the high-throughput real-time mass spectrometry diagnostic model for exhaled breath in diagnosing PTB was 92.5%,the specificity was 94.0%,and the AUC was 0.978,which were significantly higher than those of sputum smear examination(sensitivity 58.3%,specificity 90.0%,AUC 0.741).Compared with GeneXpert technology,its specificity was comparable(94.0%vs 93.3%),and the detection time was shortened to less than 15 minutes.The model achieved an accuracy of 91.3%in distinguishing PTB from other pulmonary diseases and was not affected by demographic factors such as age and gender.Conclusion:High-throughput real-time mass spectrometry detection technology for exhaled breath has the advantages of being non-invasive,rapid,highly sensitive,and highly specific,and holds significant clinical application value in the rapid diagnosis and large-scale screening of PTB,warranting further promotion.
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.
基金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.
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).
基金financially supported by the National Natural Science Foundation of China(Nos.62101477,62071410 and 21802114)the Science and Technology Innovation Program of Hunan Province(No.2023RC3133)the Excellent Youth Scholars of Hunan Provincial Department of Education(No.21B0141)。
文摘The exploitation of the highly reliable gassensing device for exhaled acetone detection possesses momentous and capacious development prospects in the field of an early noninvasive diabetes diagnosis.Considering that the characteristics of crystal facets will impact the gas-sensitive performance,herein three different resistive gas sensors were successfully developed by utilizing the stable α-Fe_(2)O_(3)with different crystal facets as the sensitive materials.The gas-sensitive performance testing results reveal that the(110)crystal faceted α-Fe_(2)O_(3)sensor exhibits relatively superior comprehensive gas sensitivity toward acetone.Particularly,it is worth mentioning that the sensor demonstrates reliable sensitivity,rapid response(25 s)/recovery(3 s)speed,and strong anti-interference capability in detecting 2×10^(-6)acetone for the concentration threshold of diabetes,even when exposed to prolonged periods in variable environments.Furthermore,by simply validating the feasibility of the exhalation diagnosis using the as-prepared gas sensor,the(110)faceted α-Fe_(2)O_(3)gas sensor can effectively discriminate the states of healthy human exhalation and the simulated diabetic exhalation.Through integrating the experimental and theoretical analyses,the superior acetone-sensitive performance of the(110)facetedα-Fe_(2)O_(3)gas sensor can principally be interpreted in correlation with crystal facet-dependent gas adsorption capacity and defect-forming ability.These results not only imply a tremendous application perspective in monitoring acetone gas at sub-ppm concentration,but also open up an effective throughway to develop reliable gas-sensing devices for early non-invasive diabetes screening.
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The concentration of the heavy isotope of hydrogen, deuterium (D), is not routinely measured in (human) medical laboratory tests, even though an increasing number of papers prove the pivotal role of D in tumor growth, cell cycle regulation, cell metabolism, and aging. Data from a prospective phase 2 clinical study and numerous retrospective clinical studies proved the anticancer effect of deuterium depletion achieved by replacing the regular water intake with deuterium-depleted water (DDW). In previous studies, the changes in serum D concentration of DDW-consuming patients were followed using blood samples and mass spectrometry, which was invasive, costly, and time-consuming. As future clinical trials will also require a follow-up of internal D level and the patient’s compliance, a new sampling device and procedure was developed based on condensing the exhaled breath water vapor and measuring its D content using a liquid water isotope laser analyzer. Test results showed that the device provided accurate, reliable, and reproducible data. According to the data, the internal D level in a person consuming normal water was stable. In contrast, exclusive consumption of DDW for several days resulted in a gradual decrease of D concentration in exhaled breath condensate (EBC), which was proportional to the D concentration of DDW. These data confirm that orally applied DDW equilibrates with the person’s water pool quickly, leading to a reduced internal D level reflected in the D content of EBC.
文摘The analysis of metabolic waste is a critical method for assessing overall health and metabolic function.The human body eliminates metabolic waste primarily through three pathways:urine from the urinary system,sweat secreted by the skin,and breath expelled via the respiratory system[1,2].
基金financially supported by the National Natural Science Foundation of China(52275575,52405424,52575458)Science and Technology Programme of Fujian Province(2024J010011,2024H0002).
文摘Face masks are no longer just passive barriers against pathogens.By integrating flexible electronics,biosensors,and fluidic systems,they are becoming intelligent wearable platforms capable of continuous health monitoring.In a recent study published in Science,Gao et al.introduced“EBCare”,a wearable smart mask that achieves real-time in situ analysis of exhaled breath condensate(EBC).This work presents a comprehensive solution for on-body collection,transport,and detection of multiple breath-derived biomarkers using passive cooling,capillary-driven microfluidics,and multiplexed biosensing,establishing a versatile platform for respiratory diagnostics and personalized medicine.
基金supported by the National Key Research and Development Program of China(2022YFF0705300)the National Natural Science Foundation of China(22364002)。
文摘Various metals are fundamental elements in the human body.Detection of metals in the human body plays an important role in understanding health and disease but poses a great challenge to analytical science in noninvasiveness,sensitivity,and detection speed.In this study,a non-invasive handheld sampler was developed to couple to inductively coupled plasma mass spectrometry(ICP-MS)for sensitive detection of metal ions in exhaled breath.Fourteen endogenous exhaled breath metals were simultaneously detected.The limits of detection(LOD)of 14 metals were found to be 0.046–0.134 ngL^(-1).Linear dynamic responses were found to range from 1.0 to 500 ngL^(-1).Satisfactory measurement precision(RSD:1.18%–11.93%)was also obtained.Despite concentrations of metal ions ranging from ng mL^(-1)to mg mL^(-1)levels in breath and blood,it is interesting to find that there is a relatively stable ratio(Rblood/breath:3.55±0.23)by comparing the levels of 9 metal ions in blood and exhaled breath.Furthermore,sensitive detections of 14 breath metal ions from patients with liver cancer and lung cancer were also successfully conducted.A multivariate statistical approach is established for biomarker discovery of breath metals between healthy volunteers and cancer patients,elucidating that cancer progression plays multifaceted roles in affecting the metal ions in exhaled breath.Overall,our data demonstrated that the new method can be not only used for the quantitative detection of trace metal species with high accuracy and high throughput but also for new insights into compositions and changes of metals in exhaled breath.
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.
