Mass Spectrometry-Based Human Breath Analysis:Towards COVID-19 Diagnosis and Research

COVID-19 is a highly contagious respiratory disease that can be infected through human exhaled breath.Human breath analysis is an attractive strategy for rapid diagnosis of COVID-19 in a non-invasive way by monitoring breath biomarkers.Mass spectrometry(MS)-based approaches off er a promising analytical platform for human breath analysis due to their high speed,specificity,sensitivity,reproducibility,and broad coverage,as well as its versatile coupling methods with different chromatographic separation,and thus can lead to a better understanding of the clinical and biochemical processes of COVID-19.Herein,we try to review the developments and applications of MS-based approaches for multidimensional analysis of COVID-19 breath samples,including metabolites,proteins,microorganisms,and elements.New features of breath sampling and analysis are highlighted.Prospects and challenges on MS-based breath analysis related to COVID-19 diagnosis and study are discussed.

Breath-by-breath measurement of exhaled ammonia by acetonemodifier positive photoionization ion mobility spectrometry via online dilution and purging sampling

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.

Association of breastfeeding with tidal breathing analysis in infants with bronchiolitis

BACKGROUND Tidal breathing flow-volume(TBFV)analysis provides important information about lung mechanics in infants.AIM To assess the effects of breastfeeding on the TBFV measurements of infants who recover from acute bronchiolitis.METHODS In this cross-sectional study,TBFV analysis was performed in infants with bronchiolitis prior to hospital discharge.The ratio of time to peak expiratory flow to total expiratory time(tPEF/tE)at baseline and after the administration of 400 mcg salbutamol was evaluated.RESULTS A total of 56 infants(35 boys),aged 7.4±2.8 mo,were included.Of them,12.5%were exposed to tobacco smoke and 41.1%were breastfed less than 2 mo.There were no differences in baseline TBFV measurements between the breastfeeding groups;however,those who breastfed longer than 2 mo had a greater change in tPEF/tE after bronchodilation(12%±10.4%vs 0.9%±7.1%;P<0.001).Moreover,there was a clear dose-response relationship between tPEF/tE reversibility and duration of breastfeeding(P<0.001).In multivariate regression analysis,infants who breastfed less(regression coefficient-0.335,P=0.010)or were exposed to cigarette smoke(regression coefficient 0.353,P=0.007)showed a greater change in tPEF/tE after bronchodilation,independent of sex,prematurity,and family history of asthma or atopy.CONCLUSION Infants who recover from bronchiolitis and have a shorter duration of breastfeeding or are exposed to cigarette smoke,have TBFV measurements indicative of obstructive lung disease.

Modern approaches for detection of volatile organic compounds in metabolic studies focusing on pathogenic bacteria:Current state of the art

Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.

From blood to breath: New horizons for esophageal cancer biomarkers

Esophageal cancer is a lethal cancer encompassing adenocarcinoma and squamous cell carcinoma subtypes. The global incidence of esophageal cancer is increasing world-wide, associated with the increased prevalence of associated risk factors. The asymptomatic nature of disease often leads to late diagnosis and five-year survival rates of less than 15%. Current diagnostic tools are restricted to invasive and costly endoscopy and biopsy for histopathology. Minimally and non-invasive biomarkers of esophageal cancer are needed to facilitate earlier detection and better clinical management of patients. This paper summarises recent insights into the development and clinical validation of esophageal cancer biomarkers, focussing on circulating markers in the blood, and the emerging area of breath and odorant biomarkers.

Breath volatile organic compounds for the gut-fatty liver axis: promise, peril, and path forward

The worldwide interest in the gut microbiome and its impact on the upstream liver highlight a critical upside to breath research: it can uniquely measure otherwise unmeasurable biology. Bacteria make gases [volatile organic compounds(VOCs)] that are directly relevant to pathophysiology of the fatty liver and associated conditions, including obesity. Measurement of these VOCs and their metabolites in the exhaled breath, therefore, present an opportunity to safely and easily evaluate, on both a personal and a population level, some of our most pressing public health threats. This is an opportunity that must be pursued. To date, however, breath analysis remains a slowly evolving field which only occasionally impacts clinical research or patient care. One major obstacle to progress is that breath analysis is inherently and emphatically mutli-disciplinary: it connects engineering, chemistry, breath mechanics, biology and medicine. Unbalanced or incomplete teams may produce inconsistent and often unsatisfactory results. A second impediment is the lack of a well-known stepwise structure for the development of non-invasive diagnostics. As a result, the breath research landscape is replete with orphaned single-center pilot studies. Often, important hypotheses and key observations have not been pursued to maturation. This paper reviews the rationale and requirements for breath VOC research applied to the gut-fatty liver axis and offers some suggestions for future development.

Changes in oral trace gas concentrations following orthognathic surgery and intermaxillary fixation: a case study using selected ion flow tube mass spectrometry

Orthognathic surgery is frequently accompanied by intermaxillary fixation. Intermaxillary fixation impedes the maintenance of effective oral hygiene and prolonged fixation can result in periodontal disease. A potential shorter term effect is the generation of oral malodour. It is unclear, however, as to how the production of malodorous compounds in the oral cavity is altered post-surgery. Oral air concentration of sulphur containing compounds, short chain organic acids, ammonia, isoprene and acetone were measured using selected ion flow tube-mass spectrometry in a patient who had undergone orthognathic surgery with subsequent intermaxillary fixation. Total sulphide levels rose approximately 5-fold during fixation with metal ties, with smaller increases recorded for the other compounds measured with the exception of isoprene which remained close to baseline levels. Organic acid levels declined markedly once elastic ties had replaced metal ties, with a lesser reduction being observed in sulphide levels, with both declining further after the commencement of a chlorhexidinecontaining mouthwash. These data suggest that bacterial generation of a variety of malodorous compounds increases markedly following intermaxillary fixation. This single case also suggests that the use of elastic ties and effective oral hygiene techniques, including the use of chlorhexidine mouthwash, may help ameliorate such post-surgical effects.

Metal oxide semiconductor gas sensing materials for early lung cancer diagnosis

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.

Adsorptive carbon-based materials for biomedical applications

Adsorption or enrichment has been an indispensable and important measure in biomedical engineering since it is promising in diagnosis and treatment of complex diseases.The ongoing development in this arena starves for exploration of outstanding adsorptive materials.As an excellent candidate for adsorption or enrichment carriers,carbon-based material has demonstrated unique superiority in biomedical arena owing to its integrated charac-teristics.Herein,we review the lasted advance in adsorptive carbon-based materials for biomedical application with emphasis on carbon nanotubes(CNTs)-based,graphene-based,and biomass/polymer-based ones.We begin with the classification of different carbon-based materials and elaborate the respective preparation approaches that are utilized to realize optimized microstructure and physicochemical property.Afterwards,we introduce the different applications of carbon-based materials in biomedical arena,including blood purification,enrichment of glycopeptide and phosphopeptide,and breath analysis.Finally,we present a concise summary and give an outlook of this arena.