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
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
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
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： 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
The novel coronavirus pneumonia,a global pandemic disease named as coronavirus disease 2019,has caused enormous losses on the health and economies of people all over the world,while there is still a lack of quick and ...The novel coronavirus pneumonia,a global pandemic disease named as coronavirus disease 2019,has caused enormous losses on the health and economies of people all over the world,while there is still a lack of quick and sensitive diagnostic method and effective therapy.Developing rapid diagnostic method for coronavirus disease 2019 has become exceptional urgent.Herein we report a rapid diagnostic method for the novel coronavirus through monitoring the volatile biomarkers in human exhaled breath.The breath volatile biomarkers are derived from the metabolism of novel coronavirus,including acetoin,2,4,6-trimethylpyridine,3-methyl tridecane,tetradecane,isooctyl alcohol,pentadecane,hexadecane,1-methylene-1H-indene.By comparing the types and concentrations of the volatile biomarkers in human exhaled breath combined with SERS sensor,we could distinguish between the healthy person and the patients with coronavirus disease 2019.This work confirms that various volatile organic compounds metabolized by novel coronavirus can be employed for rapidly screening of patients with coronavirus disease 2019,and has broad application prospects in the prevention and control of the epidemic.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
Aerosol transmission plays an important role in airborne-spread diseases.The transmission variations across language-usage regions were observed during COVID-19,however the potential differences from languages on aero...Aerosol transmission plays an important role in airborne-spread diseases.The transmission variations across language-usage regions were observed during COVID-19,however the potential differences from languages on aerosol transmission are poorly understood.Here,fifty-one multilingual volunteers were recruited to speak same-semantic dialogues in three languages selected from eight different languages studied to investigate the emission characteristics of exhaled aerosol across languages.The findings revealed that the size of exhaled aerosol particles generated by speaking was predominantly concentrated below 1μm.The emission loads of exhaled aerosols during speaking and the associated potential risk of aerosol transmission across languages showed notable discrepancies.Additionally,the individual physiological factors such as age,gender and body mass index(BMI)also jointly influenced the exhaled aerosols during speaking.The machine learning model of random forest regression further revealed that language differences had a considerably greater impact on size-resolved exhaled aerosol emission concentrations than gender,but not than BMI.Thus,different language usages can influence the emission concentrations of exhaled aerosol during speaking,thereby impacting the potential for aerosol transmission across languages.This linguistic-induced diversity of transmission potentials could have played a non-negligible role in the disparate global dissemination patterns observed in aerosol-transmitted pandemics including COVID-19.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
Breath analysis can be used to diagnose diseases non-invasively.Accurate measurement of volatolomics is critical for breath analysis to be a gold standard.Tedlar bags(TB)are often used to collect breath samples,but th...Breath analysis can be used to diagnose diseases non-invasively.Accurate measurement of volatolomics is critical for breath analysis to be a gold standard.Tedlar bags(TB)are often used to collect breath samples,but they emit contaminants that affect accuracy.This issue was overlooked in previous studies.We found contamination issues with TB(e.g.,siloxanes and aromatic impurities)that affect the identification of volatile organic compounds(VOCs)due to impurities.Then,home-designed equipment(HD)made with poly-tetrafluoride(PTFE)and quartz glass for breath collection was developed and employed in clinical trials.15 healthy individuals and 32 non-small cell lung cancer(NSCLC)patients at IA stage participated in this study.610 VOCs can be collected through TB,which is less than HD(1109 VOCs),demonstrating that the inner wall of the TB easily adsorbs VOCs,leading to decreased detection concentrations.Otherwise,utilizing orthogonal partial least squares discriminant analysis(OPLS-DA),we identified chemical markers with significant discriminatory power(VIP>1.5,P<0.05).The HD method identified 12 target VOCs,surpassing the 3 target VOCs discerned by the TB method.A model combined with a machine learning algorithm for distinguishing early-stage lung cancer patients was established based on biomarkers,which were selected based on OPLS-DA.The results showed strong predictive capabilities for the HD-based model.It indicated that 12 biomarkers derived from the HD model were more effective in distinguishing NSCLC patients,with an AUC value of 0.92,compared to the AUC value of 0.5 from 3 markers obtained from the TB model.The sensitivity and specificity in the confusion matrix reached 100%and 80%for the HD test,but TB test reached only 40%and 60%.This work demonstrated that optimizing and standardizing VOCs collection methodology from breath of lung cancer patients is essential to identify actual volatiles,which could promote disease volatolomics worldwide.展开更多
Background： The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway...Background： The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. Methods： We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing 〈100 m, 100-200 m, and 〉200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate （EBC） pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. Results： Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s （FEV1% -1.54, 95% confidence interval [CI]： -0.20 to -2.89）. The odds ratio for chronic cough was 2.54 （95% CI： 1.57-4.10） for category 1 and 1.97 （95% CI： 1.16-3.37） for category 2, compared with category 3. EBC pH was positively correlated with road distance （rank correlation coefficient of Spearman [rs] = 0.176, P 〈 0.001 ）. Conclusions： Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.展开更多
The urgency of early lung cancer(LC)diagnosis and treatment has been more and more significant.Exhaled breath analysis using gas sensors is a promising way to find out if someone has LC due to its low-cost,non-invasiv...The urgency of early lung cancer(LC)diagnosis and treatment has been more and more significant.Exhaled breath analysis using gas sensors is a promising way to find out if someone has LC due to its low-cost,non-invasive,and real-time monitoring compared with traditional invasive diagnostic techniques.Among sensor-based gas detection techniques,metal oxide semiconductor’s gas sensors are one of the most important types.This review presents the-state-of-art in metal oxide gas sensors for the diagnosis of early LC.First,the exhaled breath biomarkers are described with emphasis on the concentration of abnormal volatile organic compounds(VOCs)caused by the metabolic process of LC cells.Then,the research status of metal oxide gas sensors in LC diagnosis is summarized.The sensing performance and enhancement strategy of biomarkers provided by metal oxide semiconductor materials are reviewed.Another effective way to improve VOC detection performance is to build a gas sensor array.At the same time,various gas sensors combined with self-powered techniques are mentioned to display a broad development prospect in breath diagnosis.Finally,metal oxide gas sensor-based LC diagnosis is prospected.展开更多
Aerosol transmission has been officially recognized by the world health authority resulting from its overwhelming experimental and epidemiological evidences.Despite substantial progress,few additional actions were tak...Aerosol transmission has been officially recognized by the world health authority resulting from its overwhelming experimental and epidemiological evidences.Despite substantial progress,few additional actions were taken to prevent aerosol transmission,and many key scientific questions still await urgent investigations.The grand challenge,the effective control of aerosol transmission of COVID-19,remains unsolved.A better understanding of the viral shedding into the air has been developed,but its temporal pattern is largely unknown.Sampling tools,as one of the critical elements for studying SARS-CoV-2 aerosol,are not readily available around the world.Many of them are less capable of preserving the viability of SARS-CoV-2,thus offering no clues about viral aerosol infectivity.As evidenced,the viability of SARS-CoV-2 is also directly impacted by temperature,humidity,sunlight,and air pollutants.For SARS-CoV-2 aerosol detection,liquid samplers,together with real-time polymerase chain reaction(RT-PCR),are currently used in certain enclosed or semi-enclosed environments.Sensitive and rapid COVID-19 screening technologies are in great need.Among others,the breath-borne-based method emerges with global attention due to its advantages in sample collection and early disease detection.To collectively confront these challenges,scientists from different fields around the world need to fight together for the welfare of mankind.This review summarized the current understanding of the aerosol transmission of SARS-CoV-2 and identified the key knowledge gaps with a to-do list.This review also serves as a call for efforts to develop technologies to better protect the people in a forthcoming reopening world.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.
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： 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supported by Key Basic Research Program of China(No.2017YFA0205304 and 2015CB931802)Innovative Team Project of Nature Scientific Foundation of China(No.81921002)Medical Engineering Cross Project of Shanghai Jiao Tong University(YG2017ZD12).
文摘The novel coronavirus pneumonia,a global pandemic disease named as coronavirus disease 2019,has caused enormous losses on the health and economies of people all over the world,while there is still a lack of quick and sensitive diagnostic method and effective therapy.Developing rapid diagnostic method for coronavirus disease 2019 has become exceptional urgent.Herein we report a rapid diagnostic method for the novel coronavirus through monitoring the volatile biomarkers in human exhaled breath.The breath volatile biomarkers are derived from the metabolism of novel coronavirus,including acetoin,2,4,6-trimethylpyridine,3-methyl tridecane,tetradecane,isooctyl alcohol,pentadecane,hexadecane,1-methylene-1H-indene.By comparing the types and concentrations of the volatile biomarkers in human exhaled breath combined with SERS sensor,we could distinguish between the healthy person and the patients with coronavirus disease 2019.This work confirms that various volatile organic compounds metabolized by novel coronavirus can be employed for rapidly screening of patients with coronavirus disease 2019,and has broad application prospects in the prevention and control of the epidemic.
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.
基金supported by the National Natural Science Foundation of China(NSFC)Creative Research Group Funds(22221004)Guangzhou National Lab Grant(SRPG22-007)+1 种基金National Key Research&Development Program of China(2022YFC3702801 and 2023YFC3708200)the Young Scientists Fund of the National Natural Science Foundation of China(No.22406008).
文摘Aerosol transmission plays an important role in airborne-spread diseases.The transmission variations across language-usage regions were observed during COVID-19,however the potential differences from languages on aerosol transmission are poorly understood.Here,fifty-one multilingual volunteers were recruited to speak same-semantic dialogues in three languages selected from eight different languages studied to investigate the emission characteristics of exhaled aerosol across languages.The findings revealed that the size of exhaled aerosol particles generated by speaking was predominantly concentrated below 1μm.The emission loads of exhaled aerosols during speaking and the associated potential risk of aerosol transmission across languages showed notable discrepancies.Additionally,the individual physiological factors such as age,gender and body mass index(BMI)also jointly influenced the exhaled aerosols during speaking.The machine learning model of random forest regression further revealed that language differences had a considerably greater impact on size-resolved exhaled aerosol emission concentrations than gender,but not than BMI.Thus,different language usages can influence the emission concentrations of exhaled aerosol during speaking,thereby impacting the potential for aerosol transmission across languages.This linguistic-induced diversity of transmission potentials could have played a non-negligible role in the disparate global dissemination patterns observed in aerosol-transmitted pandemics including COVID-19.
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 Key Research and Development Program of Shaanxi(No.2022ZDLSF01-04)National Natural Science Foundation of China(No.22104117)The First Affiliated Hospital of Xi’an Jiaotong University’s Medical"Basic-Clinical"Integration Innovation(No.YXJLRH2022033)。
文摘Breath analysis can be used to diagnose diseases non-invasively.Accurate measurement of volatolomics is critical for breath analysis to be a gold standard.Tedlar bags(TB)are often used to collect breath samples,but they emit contaminants that affect accuracy.This issue was overlooked in previous studies.We found contamination issues with TB(e.g.,siloxanes and aromatic impurities)that affect the identification of volatile organic compounds(VOCs)due to impurities.Then,home-designed equipment(HD)made with poly-tetrafluoride(PTFE)and quartz glass for breath collection was developed and employed in clinical trials.15 healthy individuals and 32 non-small cell lung cancer(NSCLC)patients at IA stage participated in this study.610 VOCs can be collected through TB,which is less than HD(1109 VOCs),demonstrating that the inner wall of the TB easily adsorbs VOCs,leading to decreased detection concentrations.Otherwise,utilizing orthogonal partial least squares discriminant analysis(OPLS-DA),we identified chemical markers with significant discriminatory power(VIP>1.5,P<0.05).The HD method identified 12 target VOCs,surpassing the 3 target VOCs discerned by the TB method.A model combined with a machine learning algorithm for distinguishing early-stage lung cancer patients was established based on biomarkers,which were selected based on OPLS-DA.The results showed strong predictive capabilities for the HD-based model.It indicated that 12 biomarkers derived from the HD model were more effective in distinguishing NSCLC patients,with an AUC value of 0.92,compared to the AUC value of 0.5 from 3 markers obtained from the TB model.The sensitivity and specificity in the confusion matrix reached 100%and 80%for the HD test,but TB test reached only 40%and 60%.This work demonstrated that optimizing and standardizing VOCs collection methodology from breath of lung cancer patients is essential to identify actual volatiles,which could promote disease volatolomics worldwide.
文摘Background： The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. Methods： We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing 〈100 m, 100-200 m, and 〉200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate （EBC） pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. Results： Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s （FEV1% -1.54, 95% confidence interval [CI]： -0.20 to -2.89）. The odds ratio for chronic cough was 2.54 （95% CI： 1.57-4.10） for category 1 and 1.97 （95% CI： 1.16-3.37） for category 2, compared with category 3. EBC pH was positively correlated with road distance （rank correlation coefficient of Spearman [rs] = 0.176, P 〈 0.001 ）. Conclusions： Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.
基金supported by the Outstanding Youth Foundation of Jiangsu Province of China under Grant No.BK20211548the National Natural Science Foundation of China under Grant No.51872254+1 种基金the Yangzhou City-Yangzhou University Cooperation Foundation under Grant No.YZ2021153the Walloon Region of Belgium through the Interreg V France-Wallonie-Vlaanderen program under PATHACOV project(Grant No.1.1.297).
文摘The urgency of early lung cancer(LC)diagnosis and treatment has been more and more significant.Exhaled breath analysis using gas sensors is a promising way to find out if someone has LC due to its low-cost,non-invasive,and real-time monitoring compared with traditional invasive diagnostic techniques.Among sensor-based gas detection techniques,metal oxide semiconductor’s gas sensors are one of the most important types.This review presents the-state-of-art in metal oxide gas sensors for the diagnosis of early LC.First,the exhaled breath biomarkers are described with emphasis on the concentration of abnormal volatile organic compounds(VOCs)caused by the metabolic process of LC cells.Then,the research status of metal oxide gas sensors in LC diagnosis is summarized.The sensing performance and enhancement strategy of biomarkers provided by metal oxide semiconductor materials are reviewed.Another effective way to improve VOC detection performance is to build a gas sensor array.At the same time,various gas sensors combined with self-powered techniques are mentioned to display a broad development prospect in breath diagnosis.Finally,metal oxide gas sensor-based LC diagnosis is prospected.
基金supported by the National Natural Science Foundation of China(NSFC)Distinguished Young Scholars Fund Awarded to M.Yao(21725701)NSFC grants(22040101,92043302)by a grant(EKPG21-02)from Guangzhou Laboratory.
文摘Aerosol transmission has been officially recognized by the world health authority resulting from its overwhelming experimental and epidemiological evidences.Despite substantial progress,few additional actions were taken to prevent aerosol transmission,and many key scientific questions still await urgent investigations.The grand challenge,the effective control of aerosol transmission of COVID-19,remains unsolved.A better understanding of the viral shedding into the air has been developed,but its temporal pattern is largely unknown.Sampling tools,as one of the critical elements for studying SARS-CoV-2 aerosol,are not readily available around the world.Many of them are less capable of preserving the viability of SARS-CoV-2,thus offering no clues about viral aerosol infectivity.As evidenced,the viability of SARS-CoV-2 is also directly impacted by temperature,humidity,sunlight,and air pollutants.For SARS-CoV-2 aerosol detection,liquid samplers,together with real-time polymerase chain reaction(RT-PCR),are currently used in certain enclosed or semi-enclosed environments.Sensitive and rapid COVID-19 screening technologies are in great need.Among others,the breath-borne-based method emerges with global attention due to its advantages in sample collection and early disease detection.To collectively confront these challenges,scientists from different fields around the world need to fight together for the welfare of mankind.This review summarized the current understanding of the aerosol transmission of SARS-CoV-2 and identified the key knowledge gaps with a to-do list.This review also serves as a call for efforts to develop technologies to better protect the people in a forthcoming reopening world.
