Article

GC-MS analysis of breath odor compounds in liver patients

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Abstract

Liver diseases can cause a sweet, musty aroma of the breath, called fetor hepaticus. Even in a stage of cirrhosis, the disease can be asymptomatic for many years. Breath analysis might be helpful to detect occult liver pathology. This study examined whether specific breath odor compounds can be found in liver patients, suffering from cirrhosis, which might be useful for diagnosis. Fifty-two liver patients and 50 healthy volunteers were enrolled. Alveolar air was analyzed by gas chromatography-mass spectrometry. Using discriminant analysis a model for liver disease was built. Dimethyl sulfide, acetone, 2-butanone and 2-pentanone were increased in breath of liver patients, while indole and dimethyl selenide were decreased. Sensitivity and specificity of the model were respectively 100% and 70%. Fetor hepaticus is caused by dimethyl sulfide and to a lower extent by ketones in alveolar air. Breath analysis by GC-MS makes it possible to discriminate patients with breath malodor related to hepatic pathologies.

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... In recent years, several studies have explored the use of volatile organic compounds (VOCs) in exhaled breath as a non-invasive diagnostic tool in chronic liver disease [3][4][5][6][7][8]. The underpinning concept is that perturbed metabolic pathways can alter the pattern of breath VOC composition. ...
... These compounds have been previously shown to be associated with cirrhosis [6] , [8]. Within the samples we identified these compounds based on the mass spectra and an identifiable peak at consistent retention time. ...
... Of the 19 VOCs studied in the exhaled breath samples, seven compounds (styrene, acetone, isoprene, DMS, D-limonene, acetophenone and terpinene) were significantly different between the groups (Figure 1). There was no correlation between age and VOCs in line with previous findings [7,8,26]. However, acetone, isoprene, DMS and D-limonene were correlated with BMI. ...
Article
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Background Analysis of volatile organic compounds (VOCs) in exhaled breath, ‘volatomics’, provides opportunities for non-invasive biomarker discovery and novel mechanistic insights into a variety of diseases. Aim The purpose of this pilot study was to compare breath VOCs in an initial cohort of non-alcoholic fatty liver disease (NAFLD) patients and healthy controls. Methods Breath samples were collected from 15 participants with Child-Pugh Class A NAFLD cirrhosis, 14 with non-cirrhotic NAFLD and 14 healthy volunteers. Exhaled breath samples were collected using an established methodology and VOC profiles were analysed by gas chromatography-mass spectrometry. The levels of 19 VOCs previously associated with cirrhosis were assessed. Peaks of the VOCs were confirmed and integrated using Xcalibur® software, normalized to an internal standard. Receiver Operating Characteristic (ROC) curves were used to determine the diagnostic accuracy of candidate VOCs. Results Terpinene, dimethyl sulfide (DMS) and D-limonene provided the highest predictive accuracy to discriminate between study groups. Combining DMS with D-limonene led to even better discrimination of NAFLD cirrhosis from healthy volunteers (AUROC 0.98, 95% confidence interval (CI) 0.93 -1.00, p<0.001) and NAFLD cirrhosis from non-cirrhotic NAFLD (AUROC 0.91, 95% CI 0.82 – 1.00, p<0.001). Breath terpinene concentrations discriminated between non-cirrhotic NAFLD and healthy volunteers (AUROC 0.84, 95% CI 0.68 – 0.99, p=0.002). Conclusion Breath terpinene, dimethyl sulfide and D-limonene are potentially useful volatomic markers for stratifying NAFLD; and a two-stage approach allows differentiation of non-cirrhotic and cirrhotic patients. These observations require validation in a larger NAFLD population. (ClinicalTrials.gov Identifier: NCT02950610)
... These VOCs arise from body chemical reaction cascades in diseased individuals due to cellular damage [32]; they are released in the bloodstream and spread among the body excretions. In particular, liver diseases alter VOC abundances in the blood [33,34], leading to different amounts of VOCs present in body excretions. ...
... Many studies have explored different approaches to quantifiably detect VOCs in liver disease patients [22,[33][34][35]. The vast majority of these studies examined breath as the means of discovering discriminatory VOCs, whereas only a handful of studies used body excretions other than breath [24,36,37]. ...
... Van den Velde et al. [33] and Dadamio et al. [45] also analysed liver cirrhosis patients' and healthy controls' breath to identify VOCs related to liver cirrhosis by using GC-MS. Van den Velde et al. found that acetone, dimethyl-sulphide, 2-butanone, and 2-pentanone were elevated, while indole and dimethyl-selenide were reduced in the patients compared to controls. ...
Article
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Liver diseases are currently diagnosed through liver biopsy. Its invasiveness, costs, and relatively low diagnostic accuracy require new techniques to be sought. Analysis of volatile organic compounds (VOCs) in human bio-matrices has received a lot of attention. It is known that a musty odour characterises liver impairment, resulting in the elucidation of volatile chemicals in the breath and other body fluids such as urine and stool, which may serve as biomarkers of a disease. Aims: This study aims to review all the studies found in the literature regarding VOCs in liver diseases, and to summarise all the identified compounds that could be used as diagnostic or prognostic biomarkers. The literature search was conducted on ScienceDirect and PubMed, and each eligible publication was qualitatively assessed by two independent evaluators using the SANRA critical appraisal tool. Results: In the search, 58 publications were found, and 28 were kept for inclusion: 23 were about VOCs in the breath, one in the bile, three in urine, and one in faeces. Each publication was graded from zero to ten. A graphical summary of the metabolic pathways showcasing the known liver disease-related VOCs and suggestions on how VOC analysis on liver impairment could be applied in clinical practice are given.
... [7] These compounds give a distinctive odour in the breath of cirrhotic patients. [11,12] So sulfur compounds can be suggested as major markers of liver failure. The breath of patients with hepatocellular failure has a sweet, musty, or slightly faecal aroma, termed fetor hepaticus and is mostly attributed to sulfur compounds. ...
... Impairment of liver function increases the level of these compounds, which have a characteristic smell, such as that of rotten cabbage. [11] Bacteria and fungi related to lung infections, such as Haemophilus influenza and Streptococcus pneumoniae) also generate dimethyl sulfide. Normally, human blood and breath shows very low (a few parts per billion) concentrations of sulfur-containing compounds. ...
Article
A comprehensive analysis of volatile organic compounds (VOCs) from the exhaled breath sample is termed as breathomics. Breath samples are a complex mixture composed of a multitude of VOCs and other molecules. The analysis of total VOCs in exhaled breath provides a promising tool for the diagnosis of many diseases because it enables the observation of biochemical processes in the body in a non-invasive way. VOCs are produced in various physiological and pathophysiological conditions thus making it a potential biomarker for several diseases.
... According to these two concerns, what is the philosophy of research methodology to answer these questions in such an interdisciplinary research field? Some critical review articles had been published [28][29][30][31][32], in which these concerns were partly considered. However, a systematical summary and elaboration is still necessary. ...
... Theoretically, blood volatolomics could reveal full information of all diseases in the human body. The blood-related VOCs metabolic processes can be classified into two categories as follow: • Damage to the cells by reactive oxygen species through direct oxidative stress processes generates a major source of VOCs that partially exchange into blood (Path ①) [32]. ...
Article
Various diseases increasingly challenge the health status and life quality of human beings. Volatolome emitted from patients has been considered as a potential family of markers, volatolomics, for diagnosis/screening. There are two fundamental issues of volatolomics in healthcare. On one hand, the solid relationship between the volatolome and specific diseases needs to be clarified and verified. On the other hand, effective methods should be explored for the precise detection of volatolome. Several comprehensive review articles had been published in this field. However, a timely and systematical summary and elaboration is still desired. In this review article, the research methodology of volatolomics in healthcare is critically considered and given out, at first. Then, the sets of volatolome according to specific diseases through different body sources and the analytical instruments for their identifications are systematically summarized. Thirdly, the advanced electronic nose and photonic nose technologies for volatile organic compounds (VOCs) detection are well introduced. The existed obstacles and future perspectives are deeply thought and discussed. This article could give a good guidance to researchers in this interdisciplinary field, not only understanding the cutting-edge detection technologies for doctors (medicinal background), but also making reference to clarify the choice of aimed VOCs during the sensor research for chemists, materials scientists, electronics engineers, etc.
... There is a possibility that a liver with progressed stage of dysfunction may cause change in the concentration of exhaled sulphur compounds. DMS is found significantly different in concentration between healthy and liver cirrhosis patients 25 . Liver patients exhaled breath carries a higher amount of DMS than healthy individuals. ...
... The mean limonene concentration of the healthy group is less compared to the liver patient group as shown in figure 4 and support a previous study 18 . The same trend also observed with DMS concentration in the breath 22,25 . DMS concentration in the breath is supposed to be higher in liver patients than a healthy people. ...
Preprint
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Liver function test is the first step to diagnose various liver diseases by measuring certain proteins and liver enzymes from the blood sample. After getting the required data of the clinical parameters from the blood test it is possible to calculate Child-Pugh (CTP), AST to PLT ratio (APRI) and Model for end-stage liver disease (MELD) clinical scores that help the doctors about the severity of the disease progression. Volatile organic compounds (VOCs) found in-breath and monitoring their concentration may be a prevailing method for disease diagnosis. In this work, Isoprene, Limonene, and Dimethyl sulphide (DMS) are considered as a potential breath biomarker related to liver disease. A dataset is designed, that includes the biomarkers concentration analysed from the breath sample before and after study subjects performed an exercise. Four regression methods are performed to predict the clinical scores using breath biomarkers data as features set by the machine learning techniques. Regression methods on the dataset for prediction are evaluated by mean absolute error and root mean square error. A significant difference observed for isoprene concentration (p<0.01) and for DMS concentration (p<0.0001) between liver patients and healthy subjects breath sample. Ensemble regression methods are found best suited for the dataset. The mean absolute error for CTP score is 0.07, for APRI score 0.1 and for MELD score 0.7. The R-square value between actual clinical score and predicted clinical score is found to be 0.78, 0.95, and 0.85 for CTP score, APRI score, and MELD score, respectively. These results suggest that breath biomarkers hold a promising approach for non-invasive test and mass screening related to liver disease.
... It occurs as a late symptom of diseases leading to liver failure caused, for instance, by toxins (including alcohol), viral hepatitis, and autoimmune diseases (AIH, PBC, PSC). VSCs, in particular, methyl mercaptan, and nitrogenous substances (including ammonia), and volatile organic compounds (acetone, 2-butanone and isopropyl alcohol) are responsible for bad breath [19,20] (Table I). Because of the phenomenon of portal hypertension and collateral circulation, substances causing halitosis can enter the systemic circulation through the connection between the inferior vena cava and the portal vein bypassing the liver, and directly enter the lungs from which they diffuse [15]. ...
... Examples of volatile organic compounds (VOCs) in diseases of the gastrointestinal tract and liver[19,20] ...
Article
Full-text available
Bad breath is a clinical symptom encountered by doctors of various specialties in their daily practice. The symptom causes lower self-esteem and a negative perception of the patient by society, and consequently personal and social isolation. Bad breath can be an early manifestation of many systemic diseases. Because its causes are numerous, it is important to properly diagnose the condition and apply the appropriate treatment. The aim of the study was to present the gastroenterological aspect of halitosis on the basis of available literature reports.
... When liver function is reduced, waste products are eliminated through the lungs, causing 'fetor hepticus': a sweet, excremental odor (the breath of death) [55]. Liver failure inhibits detoxification throughout the body, causing unpleasant odors, called Fetor hepticus [56]. In addition, some hereditary disorders can influence breathing: tyrosinemia is the most important example (cabbage odor). ...
Article
Full-text available
Halitosis, or bad breath, is an oral health problem characterized by an unpleasant malodor emanating from the oral cavity. This condition can have different origins and causes a negative burden in social interactions, communication and quality of life, and can in uncommon cases be indicative of underlying non-oral non-communicable diseases. Most cases of halitosis are due to inadequate oral hygiene, periodontitis and tongue coating, yet the remaining proportion of cases are due to ear–nose–throat-associated (10%) or gastrointestinal/endocrine (5%) disorders. For this reason, the diagnosis, treatment and clinical management of halitosis often require a multidisciplinary team approach. This comprehensive review revisits the etiology of halitosis as well as standard and novel treatment that may contribute to higher clinical success.
... Ammonia is clinically important as it is a potential breath biomarker for liver disease. [2][3][4] Ammonia is produced during protein metabolism. The liver converts the nitrogen compound from protein metabolism to less toxic urea. ...
Article
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Breath ammonia is an important biomarker linked to liver malfunction. Acetone is the most abundant compound in the breath, acts as major interference for selective detection of ammonia gas. Here, a novel method based on viscosity modulation of the silicone oil absorbent is reported for selectivity improvement of ammonia over acetone gas. ATD-GC-MS and T201 ammonia analyzer are used to measure the absorption of acetone and ammonia respectively into the silicone oil. The absorption of ammonia and acetone gas is measured in different absorbent viscosities at a constant flow rate (50 cc min-1). Absorption results of ammonia are 7.37%, 16.3%, and 17.1% and acetone absorption results are 35%, 68%, and 78% respectively into 500 cSt, 100 cSt, and 20 cSt viscous silicone oil at room temperature. More bubbles of smaller diameter are formed at a lower viscosity, increases the contact time of the gas with absorbent. Consequently, the absorption of acetone into silicone oil at lower viscosity increases as compared to ammonia. The absorption of acetone is about 4.6-fold higher than the ammonia. Hence, it proves to be an effective technique for enhancing selectivity. This novel concept can be incorporated with any sensor for portable breath ammonia sensing in the detection of liver dysfunction. © 2020 The Author(s). Published on behalf of The Electrochemical Society by IOP Publishing Limited.
... LC-MS is commonly used for analyzing organic and biological compounds and protein digestion from EBC [65,66]. Various key factors may significantly affect the results of EBC sampling, as listed in Table 3. Unlike collecting VOCs and nonvolatiles in EBA sampling under normal-temperature [17,55,[67][68][69][70][71][72][73][74][75][76], the main factor of EBC sampling is that water vapor, metabolites, and bioparticles from exhaled samples were condensed into a cold collector under a low temperature (below zero degrees centigrade) [77][78][79][80][81][82][83][84][85][86]. Numerous special metabolites have been studied based on LC-MS approaches. ...
Article
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 offer 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.
... Nowadays, scientists have identifi ed many compounds by breath analysis which plays signifi cant roles in development of symptoms in clinically active patients. For example, higher concentrations of acetone is present in diabetic patients; dimethylamine and triethyl-amine in patients with renal insuffi ciency [53,54], and hydrogen sulphide in liver disease [55][56][57][58][59][60][61]. So far, biomarkers have been recognized for a variety of diseases such as breast cancer, liver cirrhosis, lung cancer, pulmonary tuberculosis, asthma and diabetes [62][63][64][65][66]. ...
Article
Abstract Our exhaled breath is known to contain several volatile organic compounds (VOCs) at very low concentration (ppm-ppv) including hydrocarbons, alcohols, aldehydes, ketones, esters etc. and other nonvolatile compounds. These VOCs have been correlated with various types of diseases though the concentration level of VOCs in exhaled breath varies depending upon individual’s health status. Analysis of breath VOCs concentrations with a satisfactory precision can give an indicator of metabolic condition, allowing a diff erence between healthy and diseased states. Breath prints of VOCs provide fi ngerprints of diseases in discriminating healthy persons from patients and it is necessary to establish specifi c methods of sampling, sample preparation, and sample identifi cation for every disease to get accurate information. Therefore identifi cation of VOCs as a biomarker in exhaled breath could be useful method for assessing, diagnosing, and monitoring of diff erent types of diseases including Covid-19. This Review presents an update on biomarkers of specifi c diseases with the systematic studies of biochemical synthesis of VOCs and also describes conventional and advance techniques of breath analysis as well as breath collection techniques for future prosperity in non-invasive biomedical perspectives. Keyword: Biomarker; Breath prints; Exhaled breath; Metabolomics; VOCs
... While research on the exhaled breath dates from the time of Hippocrates, who described in his treatise on breath aroma and disease, its development has recently begun to accelerate (3,4). Since the 1970s, 250-280 different volatile organic compounds (VOCs) have been identified in human urine and exhaled breath (5). ...
Article
Full-text available
Background Screening endoscopy is considered to be the most accurate tool for early detection of gastric cancer, but it is both invasive and costly. It is therefore essential to develop cost-effective and non-invasive diagnostic tools for gastric cancer. The aim of this study is to investigate the presence of certain volatile organic compounds (VOCs) associated with gastric cancer and to survey the usefulness of VOCs as screening tools of gastric cancer. Methods The present study was conducted prospectively to identify the relationship between gastric cancer and specific VOCs quantified by mass spectrometry. Exhaled breath samples from a total of 43 participants were analysed. This study was approved by the Institutional Review Board of the College of Medicine, Catholic University of Korea (KC16TISI0598), and registered to clinical research information service (KCT0004356). Results Nine VOCs differed significantly between the control and cancer patient groups. When participants were divided into control, early gastric cancer (EGC), and advanced gastric cancer (AGC) groups, seven VOCs remained significantly different. Of these, four (propanal, aceticamide, isoprene and 1,3 propanediol) showed gradual increases as cancer advanced, from normal control to EGC to AGC. In receiver operating characteristic curves for these four VOCs, the area under the curve for gastric cancer prediction was highest (0.842) when more than two VOCs were present. Conclusions The present study offers potential directions for non-invasive gastric cancer screening, and may inspire advanced diagnostic technologies in the era of smart home healthcare. However, despite the high accuracy, cancer-specific VOCs from several studies on different populations, and analytic methods show inconsistency, it is necessary to establish standards for each analytical method, and to validate on each population.
... Анализ альвеолярного воздуха анализировался с помощью газовой хроматографии с масс-спектроскопическим разделением. Было обнаружено увеличенное содержание диметилсульфида, ацетона, 2-бутанона и 2-пентанона в выдыхаемом воздухе у пациентов с заболеваниями печени, в то время как индол и диметил селенид были снижены у тех же пациентов по сравнению с нормой [32]. По мнению авторов, специфический «печеночный запах» у пациентов с заболеваниями печени обусловлен именно повышенным содержанием диметилсульфида в выдыхаемом воздухе и в меньшей степени -кетонами. ...
... Some of the discriminatory VOCs, identified in this study, have been suggested as potential biomarkers in breath or stool for other disease. For example, 2-pentanone has been found to be associated with several diseases, such as non-alcoholic fatty liver disease [30], inflammatory bowel disease (ulcerative colitis and Crohn's disease) [31,32] and lung cancer [33]. Nonanal is a saturated fatty aldehyde formally arising from reduction of the carboxy group of nonanoic acid. ...
Article
Pancreatic ductal adenocarcinoma (PDAC) is a particularly challenging cancer, with very low 5-year survival rates. This low survival rate is linked to late stage diagnosis, associated with the lack of approved biomarkers. One approach that is receiving considerable attention is the use of volatile organic compounds (VOCs) that emanate from biological waste as biomarkers for disease. In this study, we used urine as our biological matrix and two VOC analysis platforms: gas chromatography – ion mobility spectrometry (GC-IMS) and GC time-of-flight mass spectrometry (GC-TOF-MS). We measured the urinary headspace of samples from patients with PDAC, chronic pancreatitis (CP) and healthy controls. In total, 123 samples were tested from these groups. Results indicate that both GC-IMS and GC-TOF-MS were able to discriminate PDAC from healthy controls with high confidence and an AUC (area under the curve) in excess of 0.85. However, both methods struggled to separate CP from PDAC, with the best result of AUC 0.58. This indicates that both conditions produce similar biomarkers in the urinary headspace. Chemical identification suggests that 2,6-dimethyl-octane, nonanal, 4-ethyl-1,2-dimethyl-benzene and 2-pentanone play an important role in separating between groups. Therefore, both techniques validate this approach in identifying subjects for further investigation in a clinical setting.
... Increased concentrations of dimethyl sulfide in the breath of patients with cirrhosis has been reported previously in multiple studies. (39)(40)(41) Interestingly, a previous study using the same SIFT-MS device found that sulfur-containing compounds were decreased in childhood chronic liver disease compared with healthy controls. (42) In the same study, (E)-2-nonene was significantly decreased in children with chronic liver disease compared with healthy controls. ...
Article
Full-text available
Hepatocellular carcinoma (HCC) and secondary liver tumors, such as colorectal cancer liver metastases are significant contributors to the overall burden of cancer‐related morality. Current biomarkers, such as alpha‐fetoprotein (AFP) for HCC, result in too many false negatives, necessitating noninvasive approaches with improved sensitivity. Volatile organic compounds (VOCs) detected in the breath of patients can provide valuable insight into disease processes and can differentiate patients by disease status. Here, we investigate whether 22 VOCs from the breath of 296 patients can distinguish those with no liver disease (n = 54), cirrhosis (n = 30), HCC (n = 112), pulmonary hypertension (n = 49), or colorectal cancer liver metastases (n = 51). This work extends previous studies by evaluating the ability for VOC signatures to differentiate multiple diseases in a large cohort of patients. Pairwise disease comparisons demonstrated that most of the VOCs tested are present in significantly different relative abundances (false discovery rate P
... Indole and skatole, along with volatile sulfur compounds, are major components of breath odor [125] and halitosis [126] and may be used as clinical markers for the diagnosis of halitosis and underlying etiologies, including metabolic diseases and oral inflammations [127]. Patients with bowel cancer have higher fecal skatole content than healthy individuals [128], suggesting that skatole may be a valuable biomedical marker in this context as well. ...
Article
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The olfactory receptor neurons of insects and vertebrates are gated by odorant receptor (OR) proteins of which several members have been shown to exhibit remarkable sensitivity and selectivity towards volatile organic compounds of significant importance in the fields of medicine, agriculture and public health. Insect ORs offer intrinsic amplification where a single binding event is transduced into a measurable ionic current. Consequently, insect ORs have great potential as biorecognition elements in many sensor configurations. However, integrating these sensing components onto electronic transducers for the development of biosensors has been marginal due to several drawbacks, including their lipophilic nature, signal transduction mechanism and the limited number of known cognate receptor-ligand pairs. We review the current state of research in this emerging field and highlight the use of a group of indole-sensitive ORs (indolORs) from unexpected sources for the development of biosensors.
... There are few studies on patients with chronic liver disease with e-nose [13], [14]. A large number of methods which were developed for measuring ammonia in human breath and discriminating between healthy and cirrhotic subjects, involve ion flow tube mass spectrometry (SIFT-MS), or photoacustic laser spectrometry (PALS), [15], [16], or gas chromatographymass spectrometry (GC-MS) [17], or proton transfer reaction time-of-flight mass spectrometry (PTR-MS) [18]; although very accurate and excellent laboratory tools, such systems are not portable, very expensive, and far from being translated into daily applications in biomedical diagnostics, where the major goal is to provide easy-to-use point-of-care systems. ...
... Many of the VOCs in EBC samples are linked to airway disease or lung cancer diagnosis. This is expected, considering that VOCs are transported from organs to the lungs through the circulatory system and exchanged in exhaled breath (6). For example, Phillips et al. (7) analyzed breath VOCs in a noninvasive approach to distinguish hospitalized patients from healthy controls, and reported that benzene derivatives and alkanes such as styrene and decane are associated with tuberculosis, both in mycobacterial in vitro culture and in the fuzzy logic breath discriminators. ...
Article
Full-text available
Breathomics is a special branch of metabolomics that quantifies volatile organic compounds (VOCs) from collected exhaled breath samples. Understanding how breath molecules are related to diseases, mechanisms and pathways identified from experimental analytical measurements is challenging due to the lack of an organized resource describing breath molecules, related references and biomedical information embedded in the literature. To provide breath VOCs, related references and biomedical information, we aim to organize a database composed of manually curated information and automatically extracted biomedical information. First, VOCs-related disease information was manually organized from 207 literature linked to 99 VOCs and known Medical Subject Headings (MeSH) terms. Then an automated text mining algorithm was used to extract biomedical information from this literature. In the end, the manually curated information and auto-extracted biomedical information was combined to form a breath molecule database-the Human Breathomics Database (HBDB). We first manually curated and organized disease information including MeSH term from 207 literatures associated with 99 VOCs. Then, an automatic pipeline of text mining approach was used to collect 2766 literatures and extract biomedical information from breath researches. We combined curated information with automatically extracted biomedical information to assemble a breath molecule database, the HBDB. The HBDB is a database that includes references, VOCs and diseases associated with human breathomics. Most of these VOCs were detected in human breath samples or exhaled breath condensate samples. So far, the database contains a total of 913 VOCs in relation to human exhaled breath researches reported in 2766 publications. The HBDB is the most comprehensive HBDB of VOCs in human exhaled breath to date. It is a useful and organized resource for researchers and clinicians to identify and further investigate potential biomarkers from the breath of patients. Database URL: https://hbdb.cmdm.tw.
... Nowadays, scientists have identifi ed many compounds by breath analysis which plays signifi cant roles in development of symptoms in clinically active patients. For example, higher concentrations of acetone is present in diabetic patients; dimethylamine and triethyl amine in patients with renal insuffi ciency [53,54]; and hydrogen sulphide in liver disease [55][56][57][58][59][60][61]. So far, biomarkers have been recognized for a variety of diseases such as breast can cer, liver cirrhosis, lung cancer, pulmonary tuberculosis, asthma and diabetes [62][63][64][65][66]. ...
... In breath studies looking into cirrhotic and non-cirrhotic liver patients, serum bilirubin showed a positive correlation with 2-butanone. The 2-butanone in the breath also distinguished different classes of liver cirrhosis, demonstrated by Child-Turcotte-Pugh (CTP) scores of A, B and C [34,35]. ...
Article
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Hepatocellular carcinoma (HCC) biomarkers are lacking in clinical practice. We therefore explored the pattern and composition of urinary volatile organic compounds (VOCs) in HCC patients. This was done in order to assess the feasibility of a potential non-invasive test for HCC, and to enhance our understanding of the disease. This pilot study recruited 58 participants, of whom 20 were HCC cases and 38 were non-HCC cases. The non-HCC cases included healthy individuals and patients with various stages of non-alcoholic fatty liver disease (NAFLD), including those with and without fibrosis. Urine was analysed using gas chromatography–ion mobility spectrometry (GC–IMS) and gas chromatography–time-of-flight mass spectrometry (GC–TOF-MS). GC–IMS was able to separate HCC from fibrotic cases with an area under the curve (AUC) of 0.97 (0.91–1.00), and from non-fibrotic cases with an AUC of 0.62 (0.48–0.76). For GC-TOF-MS, a subset of samples was analysed in which seven chemicals were identified and tentatively linked with HCC. These include 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene (2TMS derivative), 2-butanone, 2-hexanone, benzene, 1-ethyl-2-methyl-, 3-butene-1,2-diol, 1-(2-furanyl)-, bicyclo(4.1.0)heptane, 3,7,7-trimethyl-, [1S-(1a,3β,6a)]-, and sulpiride. Urinary VOC analysis using both GC–IMS and GC-TOF-MS proved to be a feasible method of identifying HCC cases, and was also able to enhance our understanding of HCC pathogenesis.
... In addition to limonene, several studies have reported increased ketones on breath as markers of cirrhosis [94,99,100], of which two reported significant elevations of 2-pentanone. The origins of this compound are less clear but may be linked to chronic inflammation. ...
Article
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Human breath offers several benefits for diagnostic applications, including simple, noninvasive collection. Breath is a rich source of clinically-relevant biological information; this includes a volatile fraction, where greater than 1,000 volatile organic compounds (VOCs) have been described so far, and breath aerosols that carry nucleic acids, proteins, signaling molecules, and pathogens. Many of these factors, especially VOCs, are delivered to the lung by the systemic circulation, and diffusion of candidate biomarkers from blood into breath allows systematic profiling of organismal health. Biomarkers on breath offer the capability to advance early detection and precision medicine in areas of global clinical need. Breath tests are noninvasive and can be performed at home or in a primary care setting, which makes them well-suited for the kind of public screening program that could dramatically improve the early detection of conditions such as lung cancer. Since measurements of VOCs on breath largely report on metabolic changes, this too aids in the early detection of a broader range of illnesses and can be used to detect metabolic shifts that could be targeted through precision medicine. Furthermore, the ability to perform frequent sampling has envisioned applications in monitoring treatment responses. Breath has been investigated in respiratory, liver, gut, and neurological diseases and in contexts as diverse as infectious diseases and cancer. Preclinical research studies using breath have been ongoing for some time, yet only a few breath-based diagnostics tests are currently available and in widespread clinical use. Most recently, tests assessing the gut microbiome using hydrogen and methane on breath, in addition to tests using urea to detect Helicobacter pylori infections have been released, yet there are many more applications of breath tests still to be realized. Here, we discuss the strengths of breath as a clinical sampling matrix and the technical challenges to be addressed in developing it for clinical use. Historically, a lack of standardized methodologies has delayed the discovery and validation of biomarker candidates, resulting in a proliferation of early-stage pilot studies. We will explore how advancements in breath collection and analysis are in the process of driving renewed progress in the field, particularly in the context of gastrointestinal and chronic liver disease. Finally, we will provide a forward-looking outlook for developing the next generation of clinically relevant breath tests and how they may emerge into clinical practice.
... Two studies have directly compared HF patients to HC and were included in the diagnostic and prognostic accuracy analysis [25,26]. Seven studies have compared ExA concentration in HC to other patients (diabetes [27,28], cancer patients [29,30], respiratory [31,32], or liver disease [33]). Nine studies were not comparative [6,11,[34][35][36][37][38][39]. ...
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... Volatilomics is focused on the analysis of the VOCs emitted by a living organism and is integrated with breathomics and salivaomics research [127,128]. VOCs can be detected in the headspace area of saliva [129] and directly in exhaled breath [130]. It is mostly GC-MS detection that is used for studying the VOCs present in saliva. ...
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... Van den Velde et al. (2008) [84] analyzed the breath of 52 patients with liver cirrhosis of different etiology and that of 50 healthy controls using GC-MS. A total of 12 discriminatory compounds were identified, of which the levels of dimethyl sulfide, acetone, 2-butanone, and 2-pentanone were increased, while indole and dimethyl selenide were decreased. ...
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... The anodic peak of the limonene was observed at + 1.3 V whereas the acetoin anodic peak is observed at + 1.4. Acetoin is also reported to be present in the breath of cirrhotic patients [106] however they synthesized and optimized monolayer hexane thiol AuNPs which shows specific response producing characteristic peaks to each VOC it encounters. This is encouraging in developing the process to an e-nose application where it can specifically detect a VOC compound. ...
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... We found the mean DMS concentration in patients higher than the healthy group (Fig. 6) and this type of result is also observed by www.nature.com/scientificreports/ other authors 25 . There is a possibility that a liver with a progressing stage of dysfunction may cause a change in the concentration of exhaled sulfur compounds 22,48 . ...
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... VSC formation by bacteria in the oral cavity or oropharynx can be objectively measured by portable gas chromatography, and currently, VSCs are considered an important causative factor for halitosis. These sulfur compounds could also be manifestations of systemic disease, such as hepatic failure, or isolated persistent hypermethioninemia [7,[28][29][30][31]. ...
Chapter
Although relatively rare, especially among the ambulatory population, breath odors may be a sign of a systemic condition or a metabolic disorder (Table 7.1). Usually, this symptom will appear in a later stage of the disease when the patient is already diagnosed. However, sometimes the breath odor may be an early sign or even the only sign for the underlying disorder or disease.
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Diabetes mellitus (DM), an ailment caused by unregulated blood sugar levels, can lead to the failure of more than one organ in patients. Currently, blood tests are being conducted in scientific trials to analyse and track blood sugar and ketone levels. In this method, a drop of blood from a pricked finger is placed on a sensitive strip area, which is then pre-inserted into an electronic device to be analysed. However, this method is painful, invasive, and costly, which can be unsafe if not handled properly. Human breath analysis is a rapid and non-invasive approach for detecting different volatile organic compounds (VOCs), which could be indicators of various illnesses. In patients with DM, the body produces excessive amounts of ketones together with acetoacetate, β-hydroxybutyrate (BOHB), and acetone. Acetone is exhaled in the breath. It is produced when the body metabolizes fat, instead of glucose, for energy. Conventional exhalation analysis techniques are based entirely on spectrometric strategies; however, they are becoming increasingly appealing from a clinical point of view with the advancement of gas sensors. This study describes modern-day improvements to semiconductor metal oxide (SMO) gas sensors for the detection of exhaled acetone. Since 2011, all the sensor materials have been used to detect low concentrations of acetone gas (0.1 ppm–20 ppm). Several parameters that affect the performance of the sensor device are mentioned in detail, including the composite materials, morphology, doping, temperature, humidity, acetone concentration, and stability of the sensor. Finally, the applicability of the sensor is discussed.
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Currently, no device is available for the rapid screening of ventilator-associated pneumonia (VAP) at an early stage. Accordingly, we propose the design of an offline gas detection system to monitor and detect metabolites of pneumonia at an early stage. An electronic nose (e-nose) with 28 metal oxide semiconductor gas sensors was developed for predicting the presence of infection after patients have been intubated in the intensive care unit. The effectiveness of VAP identification was verified using clinical data. A total of 40 patients were included in this study, of whom 20 were infected with Pseudomonas aeruginosa and the remaining were uninfected. The results revealed that good accuracy rates of 0.9208% ± 0.0302% and 0.8547% ± 0.0214% were achieved by support vector machine and artificial neural network models, respectively. This study provides a simple, low-cost solution for the rapid screening of VAP at an early stage.
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In this work, the analytical approach to fast diagnostics of gynecological conditions based on the screening of volatile compounds in cervical mucus using a portable electronic nose system was developed for the first time. The highly sensitive electronic nose system based on seven mass-sensitive piezo-sensors with nanostructured modifiers of electrodes was utilized for the detection of highly volatile biomolecules (amines, ketones, alcohols, aldehydes, carbonic acids) in cervical mucus samples directly in a consulting room. We were solving the task to develop a model for rapid identification of patients with gynecologic inflammation diseases according to results from gaseous sensors or a single sensor scanning of a mixture composition of volatile molecules released by mucus. Whereupon we propose the following group ranking as «conditionally healthy», «remission», and «inflammation/infection». Preliminary, by individual substances we estimated selectivity and kinetic features of sorption-desorption processes on the selected array of stabilized gaseous sensors. According to the groups of compounds the detection limit by an array of sensors is 20 ррm for ketones by acetone, 10 ppm for alcohols by ethanol, for arenas 2 ppm by toluene, 20 ppb by ammonia and for amines 5 ppb by diethylamine. For the correct interpretation of the "electronic nose" results, we used the doctor’s diagnosis, their description of the condition and the severity of the lesion, which was defined by the results of microbiological research in the laboratory. At the first stage, it was established that to ensure the reliability of solution-making during sample ranking into groups, time from the moment of biomaterial sampling to the measurement should not exceed 3-5 min. At the appointment in the doctor’s office and as part of a preventative medical check-up, there were analyzed 83 bioassays according to the developed method. To elaborate a model of gynecological status assessment, there were chosen 30 conditionally healthy patients (scheduled patient care) and the ones with deviations from the conditional norm, suggesting antibacterial treatment with various inflammation histories (active form, remission, and exacerbation). To make a decision, we utilized the full amount of data, which is achieved while measuring volatile molecules above mucus during sorption (80 sec) and spontaneous desorption (120 sec). The methods and results of experimental processing of patients’ data obtained directly in a consulting room are described below. The most informative sensors were identified applying an unsupervised model for processing the output curves in bio-sample vapours. The reduction of the number of sensors in the array to one was justified. There was proved high accuracy of mucus sample ranking by presence/ absence of gynecologic disease within mere 60seconds. Sensors’ data processing was carried out using machine-learning methods without a coach but with the pseudo markup. We proposed a self-learning model for bioassay separation into three classes based on the signals from the most sensitive sensor with a classification error of no more than 10%. We conducted distribution into diagnostic groups and verification of the correct classification of new samples according to the results of microbiological analysis for microflora and key cells, according to the culture test method for infectious agents of sexually transmitted diseases (Gardnerella, Candida. alb, ureaplasmosis Ureap. Parvum, Trichomonas vaginalis). For accurate confirmation of pathogens’ presence, the polymerase chain reaction method was used. The model allows us to predict processes of remission and the presence of previous illnesses in remission, not necessarily infectious (e.g., adhesion formation). Active inflammation processes of any nature are also predicted well. Characteristics of the model for prediction of the presence of sexually transmitted infections by the signals of one sensor are sensitivity – 64 %, and specificity – 86 %. The capacity of an analysis based on the developed method and the model constitutes 30-35 samples per shift. The minimal lifetime of the studied sensors with bio-hydroxyapatite phase is more than 12 months. In such a case, there was neither sensor calibration nor their training on test substances required. A comparative study was conducted to validate the accuracy of using the electronic nose system versus classic cultural and polymerase chain reaction methods.
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A serpentine-shaped semi-packed micro gas chromatography (GC) column with mesoporous inner surface and ionic liquid (IL) coating was developed for the separation of various typical volatile organic compounds (VOCs) in exhaled air. The mesoporous surface was prepared by coating silica nanoparticles on the inner surface of the micro GC column through static method and used as stationary phase support to improve the separation performance by its high surface area. The micro GC columns provide efficient separations for analytes including nonpolar (alkanes), weak polar (benzene series) and polar compounds (alcohols), as well as various typical markers of non-alcoholic fatty liver disease (NAFLD). The test results show that the resolution of most analytes is higher than 1.5, the elution peaks are symmetrical. Moreover, due to the chemical stability of IL, the micro GC had good repeatability, thermal stability and oxygen robustness. The maximum relative standard deviation of retention time was 0.44% in four weeks. During the programmed heating, a stable baseline was achieved and the baseline drift value was less than 4.8 mV when the operating temperature increased from 50℃ to 140℃. The oxygen robustness was verified by a decrease of 7.2% in the peak capacity after exposure to dry air at 140 ℃ for 48 h. These characteristics showed the micro GC column is suitable for a portable breath analyzer.
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The effect of hydration on the formation mechanism of clusters consisting of methanesulfonic acid (MSA) and methylamine (MA) is investigated by quantum chemistry (Density Functional Theory, DFT) and kinetics simulation (Atmospheric Chemical Dynamic Code, ACDC) methods. The results showed that the process of hydration is favorable from the thermodynamic point of view, and the presence of water molecules can promote proton transfer significantly. Although MA has a significant influence on the formation rate of MSA-based clusters at the parts per trillion (ppt) levels, the effective nucleation of MSA-MA anhydrous clusters hardly seems to occur under common typical atmospheric conditions. The high concentrations of precursors ([MSA] > 6 × 107 molecules·cm-3 and [MA] > 1 ppt or [MSA] > 1 × 106 molecules·cm-3 and [MA] > 100 ppt) is necessary for the effective nucleation of the MSA-MA system. The formation rate of the MSA-MA system is enhanced significantly by hydration. The formation rate increases with the relative humidity (RH) and reached up to a factor of 2700 at RH = 40%. The formation mechanism of the hydrous system is different from the anhydrous system. The formation of (MSA)2 and (MSA)(MA) dimers is the rate-determining step of the anhydrous and hydrous systems, respectively. In addition, the growth pathway of clusters was complicated by low temperature and simplified by high humidity, respectively. In general, although humidity is a very favorable factor for the formation of the MSA-MA system, the involvement of other species (such as sulfuric acid) may be more effective to promote the nucleation of the MSA-MA system under typical atmospheric environment.
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Metabolic profiling of breath analysis involves processing, alignment, scaling and clustering of thousands of features ex-tracted from Gas Chromatography Mass spectrometry (GC-MS) data from hundreds of participants. The multi-step data processing is complicated, operator error-prone and time-consuming. Automated algorithmic clustering methods that are able to cluster features in a fast and reliable way are necessary. These accelerate metabolic profiling and discovery plat-forms for next generation medical diagnostic tools. Our unsupervised clustering technique, VOCCluster, prototyped in Py-thon, handles features of deconvolved GC-MS breath data. VOCCluster was created from a heuristic ontology based on the observation of experts undertaking data processing with a suite of software packages. VOCCluster identifies and clusters groups of volatile organic compounds (VOCs) from deconvolved GC-MS breath with similar mass spectra and retention index profiles. VOCCluster was used to cluster more than 15,000 features extracted from 74 GC-MS clinical breath samples obtained from participants with cancer before and after a radiation therapy. Results were evaluated against a panel of ground truth compounds and compared to other clustering methods (DBSCAN and OPTICS) that were used in previous metabolomics studies. VOCCluster was able to cluster those features into 1081 groups (including endogenous, exogenous compounds and instrumental artefacts) with an accuracy rate of 96% (± 0.04 at 95% confidence interval).
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Breath-based non-invasive diagnostics have the potential to provide valuable information about a person's health status. However, they are not yet widely used in clinical practice due to multiple factors causing variability and the lack of standardized procedures. This study focuses on the comparison of oral and nasal breathing, and on the variability of volatile metabolites over the short and long term. Selected ion flow tube mass spectrometry (SIFT-MS) was used for online analysis of selected volatile metabolites in oral and nasal breath of 10 healthy individuals five times in one day (short-term) and six times spread over three weeks (long-term), resulting in nearly 100 breath samplings. Intra-class correlation coefficients (ICCs) were used to assess short- and long-term biological variability. Additionally, the composition of ambient air was analyzed at different samplings. The selected volatiles common in exhaled breath were propanol, 2,3-butanedione, acetaldehyde, acetone, ammonia, dimethyl sulfide, isoprene, pentane, and propanal. Additionally, environmental compounds benzene and styrene were analyzed as well. Volatile metabolite concentrations in ambient air were not correlated with those in exhaled breath and were significantly lower than in breath samples. All volatiles showed significant correlation between oral and nasal breath. Five were significantly higher in oral breath compared to nasal breath, while for acetone, propanal, dimethyl sulfide, and ammonia, concentrations were similar in both matrices. Variability depended on the volatile metabolite. Most physiologically relevant volatiles (acetone, isoprene, propanol, acetaldehyde) showed good to very good biological reproducibility (ICC > 0.61) mainly in oral breath and over a short-term period of one day. Both breathing routes showed relatively similar patterns; however, bigger differences were expected. Therefore, since sampling from the mouth is practically more easy, the latter might be preferred.
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Progression of liver failure to coma is a dynamic process. Its prognosis depends primarily on early diagnosis, real-time monitoring of the disease, and appropriate therapy. Current detection methods and repeated blood sampling do not effortlessly meet the clinical requirements. This pilot study aimed to assess the potential of exhaled breath analysis by extractive electrospray ionization mass spectrometry (EESI-MS) as a noninvasive clinical tool to diagnose and provide real-time monitoring of liver failure. A total of 24 healthy controls, 20 chronic hepatitis B patients, and 20 liver failure patients were enrolled in this study. Patients were diagnosed prior to exhaled breath collection; serological biochemical indicators and clinical characteristics were recorded. Exhaled breath samples were detected by EESI-MS; principal component analysis and partial least square discriminant analysis was used to process the final data. Twenty-two mass-to-charge ratio (m/z) values differed significantly between liver failure patients and healthy controls (variable importance plot (VIP)>3.5, P<0.001), and eight metabolites were identified to be 1-butylene, acetone, glycolaldehyde, isoprene, butanone, 2-ethylacrylic acid, ethylmethylacetic acid, and 2,3-octanedione. Four m/z values differed significantly between liver failure and chronic hepatitis B patients (VIP > 3.5, P<0.001) and 2 metabolites were identified to be isoprene and glycolaldehyde. Exhaled breath analysis may be valuable as a noninvasive clinical tool to diagnose and provide real-time monitoring of liver failure.
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Breath volatile biomarkers are capable of distinguishing patients with various cancers. However, high throughput analytical technology is a prerequisite to a large‐cohort study intended to discover reliable breath biomarkers for cancer diagnosis. Single photon ionization (SPI) is a universal ionization technology and SPI mass spectrometry (SPI‐MS) shows a remarkable advantage in the comprehensive detection of volatile organic compounds (VOCs), in particular, non‐polar compounds. In this study, we have introduced SPI‐MS coupled with on‐line thermal desorption (TD‐SPI‐MS) to demonstrate non‐target analysis of breath VOCs for gastric cancer patients. The breath fingerprints of the gastric cancer patients were significantly distinct from that of the control group. Acetone, isoprene, 1,3‐dioxolan‐2‐one, phenol, meta‐xylene, 1,2,3‐trimethylbenzene and phenyl acetate showed higher relative peak intensities in the breath profiles of gastric cancer patients. A diagnostic prediction model was further developed by using a training set (121 samples) and validated with a test set (53 samples). The predication accuracy of the developed model was 96.2% and the area under the curve (AUC) of the receiver operator characteristic curve (ROC) was 0.997, indicating a satisfactory prediction ability of the developed model. Thus, by taking gastric cancer as an example, we have shown that TD‐SPI‐MS will be a promising tool for high throughput analysis of breath samples to discover characteristic VOCs in patients with various cancers.
Article
Human breath analysis provides a non-invasive and fast method for identifying numerous volatile organic compounds that are disease markers. Breath analysis on a small device that is connected to the Internet of Things and uses chemi-resistive semiconductor with extremely low energy usage will build new roads for detection of diseases and monitoring patients. Nano-structures of various forms, synthesized by diverse nano-meter-scale synthesis methods, can be utilized to achieve this aim. Metal oxide nano-structures allow a well-built gas-sensing layer interaction and, as a result, show a higher sensitivity than traditional materials due to features such as high surface-to-volume ratios and, consequently a large number of surface sites exposed to gas. This paper provides an overview of advances in chemi-resistive nano-structures as gas sensing materials for exhaled breath detection, with the goal of assisting patients with various conditions in their disease screening. The many types of chemi-resistive materials utilized in breath sensors have been discussed, as well as their limits and future prospects also presented.
Article
Organic semiconductor (OSC) gas sensors have grown into a widely discussed technology because of the presence of nanoscale fabrication processes. Thanks to the rapid development of nanotechnology, the performance of the OSC gas sensor has been pushed to the peak of its own and now can be used on numerous biomedical and environmental monitoring purposes that require high-precision sensing capability. However, the sophisticated and non-standard fabrication process of most of those sensors has become the major impediment on the way of commercialization. Here, we demonstrate a micrometer-scale structure with a coupling layer using the current spreading effect to further enhance the sensing performance. The high conductivity material Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS PH1000) was used as the coupling layer to increase the device operational current. The sensor exhibits a remarkably enhanced operational current of the microampere level without sacrificing the ammonia sensing capability. The issues of the structural profile are discussed carefully, and the sensor was tested with human breath samples to demonstrate a promising result. With the most common micrometer-scale fabrication technology, a ppb-regime sensing capability has been achieved, and the result of this work gives us a whole new cut-in point regarding the high sensitivity OSC gas sensors.
Article
Inflammation may alter volatile organic compounds (VOCs) in exhaled breath. We therefore used ion mobility spectrometry (IMS) to evaluate exhaled breath components in two non-infectious inflammatory models. Fifty male Sprague Dawley rats were anesthetized and ventilated for 24 h. Five treatments were randomly assigned: (1) lipopolysaccharide low dose [5 mg/kg]; (2) lipopolysaccharide high dose [10 mg/kg]; (3) alpha toxin low dose [40 µ g/kg]; (4) alpha toxin high dose [80 µ g/kg]; and, (5) NaCl 0.9% as control group. Gas was sampled from the expiratory line of the ventilator every 20 min and analyzed with IMS combined with a multi-capillary column. VOCs were identified by comparison with an established database. Survival analysis was performed by log-rank test, other analyses by one-way or paired ANOVA-tests and post-hoc analysis according to Holm – Sidak. Rats given NaCl and low-dose alpha toxin survived 24 h. The median survival time in alpha toxin high-dose group was 23 (95%-confidence interval (CI): 21, 24) h. In contrast, the median survival time in rats given high-dose lipopolysaccharide was 12 (95% CI: 9, 14) and only 13 (95% CI: 10, 16) h in those given high-dose lipopolysaccharide. 73 different VOCs were detected, of which 35 were observed only in the rats, 38 could be found both in the blank measurements of ventilator air and in the exhaled air of the rats. Forty-nine of the VOCs were identifiable from a registry of compounds. Exhaled volatile compounds were comparable in each group before injection of lipopolysaccharide and alpha toxin. In the LPS groups, 1-pentanol increased and 2-propanol decreased. After alpha toxin treatment, 1-butanol and 1-pentanol increased whereas butanal and isopropylamine decreased. Induction of a non-infectious systemic inflammation (niSI) by lipopolysaccharide and alpha toxin changes VOCs in exhaled breath. Exhalome analysis may help identify niSI.
Article
By means of glass bottle sampling followed by solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS) technique, the change characteristics of volatile organic compounds (VOCs) in breaths, between before gargling and after gargling, were investigated, respectively, in 41 healthy subjects and 50 esophageal cancer patients. Using an untargeted strategy, 143 VOC chromatographic peaks were enrolled in the statistical analysis. Based on the orthogonal partial least squares discriminant analysis (OPLS-DA), the VOC variations after gargling for each breath test group were obtained according to the combined criteria of variable importance in projection (VIP > 1.5), Wilcoxon signed-rank test (P < 0.05), and fold change (FC > 2.0). When gargled, the levels of indole, phenol, 1-propanol, and p-cresol in the breath of healthy people decreased; meanwhile, for esophageal cancer patients, the declined VOCs in breath were indole, phenol, dimethyl disulfide, and p-cresol. Particularly, these substances were previously reported as breath biomarkers in some diseases such as esophageal, gastric, thyroid, breast, oral, and lung cancers, as well as certain non-cancer disorders. The present work indicates that expiratory VOCs involve the prominent oral cavity source, and in the breath biomarkers study, the potential impact that originates from oral volatiles should be considered. In view of the present results, it is also proposed that gargle pretreatment could eliminate possible interference from the oral cavity VOCs that might benefit breath biomarker investigation.Graphical abstract Gargle pretreatment helps to distinguish oral-source VOCs and control their potential impact on breath biomarkers
Article
Aim The aim of this study was to use a metabonomics approach to identify potential biomarkers of exhaled breath condensate (EBC) for predicting the prognosis of acute‐on‐chronic liver failure (ACLF). Methods Using liquid chromatography mass spectrometry, EBC metabolites of ACLF patients surviving without liver transplantation (n=57) and those with worse outcomes (n=45), and controls (n=16) were profiled from a specialized liver disease center in Beijing. The metabolites were used to identify candidate biomarkers, and the predicted performance of potential biomarkers was tested. Results 41 metabolites, involving glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism and amino acid metabolism, as candidate biomarkers for discriminating the different outcomes of ACLF were selected. A prognostic model was constructed by a panel of four metabolites including phosphatidylinositol [20:4(5Z,8Z,11Z,14Z)/13:0], phosphatidyl ethanolamine (12:0/22:0), l‐metanephrine and ethylbenzene, which could predict the worse prognosis in ACLF patients with sensitivity (84.4%) and specificity (89.5%) (area under the receiver operating characteristic curve [AUC] = 0.859, 95% confidence interval [CI] = 0.787−0.931). Compared with MELD score (AUC = 0.639, 95% CI = 0.526‐0.753) and MELD‐Na score (AUC = 0.692, 95% CI = 0.582‐0.803), EBC‐associated metabolite signature model could better predict worse outcomes in patients with ACLF (p<0.05). Using the MELD‐Na score and EBC metabolite signatures, a decision tree model was built for predicting the prognosis of ACLF identified on logistic regression analyses (AUC = 0.906, 95% CI = 0.846‐0.965). Conclusion EBC metabolic signatures show promise as potential biomarkers for predicting worse prognosis of ACLF.
Article
Volatile organic compounds (VOCs) in breath and skin gas are promising samples for non-invasive and simple disease screening and metabolism assessment. In addition, simultaneous measurement of multiple VOCs helps to improve the examination quality and allows for more reliable disease screening and investigation of detailed metabolic pathways. In this study, we have developed a dual-target gas-phase biosensor (bio-sniffer) that allows for measurement of isopropanol (IPA) and acetone vapours, relevant VOCs for lipid metabolisms, by simply exchanging coenzyme solutions. The measurement exploited a reversible redox reaction that was catalysed by secondary alcohol dehydrogenase (S-ADH). IPA/acetone was oxidised/reduced together with reduction/oxidation of a coenzyme, oxidised (NAD⁺)/reduced (NADH) form of β-nicotinamide adenine dinucleotide, depending on surrounding pH (8.5/7.5). This reaction resulted in producing/consuming NADH which exhibited autofluorescence (λex = 340 nm, λfl = 490 nm), by which IPA/acetone was measured. The characterization of the dual-target bio-sniffer showed the dynamic ranges for IPA and acetone vapour were 3.3–1000 ppb and 13.0–3000 ppb, respectively, which encompasses those in the breath of healthy people (IPA, 10–30 ppb; acetone, 200–900 ppb). Finally, the dual-target bio-sniffer was applied for measurement of IPA and acetone in the breath of healthy people. As with the standard IPA and acetone vapour, intermittent and repeated measurement of both VOCs in the breath was demonstrated. These results indicated that the dual-target bio-sniffer would be a useful tool to assess the lipid metabolism in detail by measuring temporal changes of IPA and acetone concentrations in the breath.
Article
Biofluorometric bio-sniffers (biochemical gas sensor) for acetone and isopropanol (IPA) were constructed by connecting a UV-LED and a photomultiplier tube to an optical fiber with a flow-cell equipped an S-ADH (secondary alcohol dehydrogenase) membrane. Gaseous acetone and IPA were measured by detecting auto-fluorescence of nicotinamide adenine dinucleotide (NADH) (ex. 340 nm, fl. 491 nm) as a coenzyme of S-ADH redox reactions. Both breath volatiles from healthy and diabetic subjects were analyzed by the bio-sniffers, thus diabetic acetone showing significant higher than that of heathy subjects. Similarly, a volatile-imaging system (sniff-cam) employing alcohol dehydrogenase (ADH) that detects acetaldehyde (AcH) vapor was also developed using a ADH mesh, a UV-LED array sheet and high sensitive camera, and applied for imaging AcH in breath and skin gas after drinking. The ADH sniff-cam allowed to visualize the concentration distribution of AcH in breath and skin gas. The biofluorometric sniff-devices would be useful for non-invasive disease screening and assessment.
Article
The concentration of acetone in exhaled breath is an efficient indicator for the diagnosis of diabetes. However, it is difficult to detect acetone in exhaled breath due to the extremely low acetone concentration, rather complex composition and very high humidity. Herein, we report Pt-decorated foam-like Ga-In bimetal oxide nanofibers (Pt-GIO) for trace concentration acetone detection. We found that the Pt-GIO based sensor exhibits enhanced sensing response towards acetone compared with that of Ga-In bimetal oxide (GIO), due to the formation of Schottky contact between Pt and n-type GIO, leading to the increased chemisorbed oxygen. As a result, the Pt-GIO based sensors gives a high response (3.2), short response time (13 s) to 1.8 ppm acetone and very low detection limit (300 ppb). The Pt-GIO sensor also gives good stability and is nearly insensitive to moisture in the range of 40% RH to 95%. These advantages including high response, low detection limit, short response time and high moisture resistance endow Pt-GIO a promising sensing material for acetone detection in exhaled breath.
Article
Water-soluble organic acids (WSOAs) are important chemical components of fine particulate matter (PM2.5). WSOAs can aggravate PM2.5 pollution and contribute to the acidity of aerosol and rain. PM2.5 pollution in the North China Plain (NCP) has been extensively researched. However, with the decrease in PM2.5 and enhancement of atmospheric oxidation in the NCP, it is unclear how the amount and source of WSOAs in ambient PM2.5 change. In this study, we investigated WSOAs in PM2.5 from 2018 to 2019 at urban and rural sites in the NCP. Our results showed that WSOAs accounted for 0.8% of the PM2.5 mass with a dominance of oxalic acid (OA), followed by formic acid (FA) and methanesulfonic acid (MSA). High MSA concentrations at inland sites, such as Yucheng, indicated that MSA in PM2.5 primarily originated from anthropogenic activities rather than marine sources, as previously inferred. WSOAs in ambient PM2.5 were comparable at rural and urban sites with 0.73 ± 0.46 μg/m³ and 0.66 ± 0.40 μg/m³, respectively. The secondary transformation of pollutants from coal combustion and vehicle exhaust emissions was the major WSOAs source, with an average contribution of 70% at all sites. Photochemical oxidation played a stronger role in WSOAs transformations than aqueous oxidation processes. The potential source contribution function analysis revealed that southern Hebei and central Shandong provinces are potential source areas for WSOAs in the NCP. In the future, the integrated regional control of precursor and oxidant emissions will be important in the NCP.
Article
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Volatile organic compounds (VOCs) released through skin (transcutaneous gas) has been increasing in importance for the continuous and real-time assessment of diseases or metabolisms. For stable monitoring of transcutaneous gas, finding a body part with little interference on the measurement is essential. In this study, we have investigated the possibility of external ears for stable and real-time measurement of ethanol vapour by developing a monitoring system that consisted with an over-ear gas collection cell and a biochemical gas sensor (bio-sniffer). The high sensitivity with the broad dynamic range (26 ppb–554 ppm), the high selectivity to ethanol, and the capability of the continuous measurement of the monitoring system uncovered three important characteristics of external ear-derived ethanol with alcohol intake for the first time: there is little interference from sweat glands to a sensor signal at the external ear; similar temporal change in ethanol concentration to that of breath with delayed peak time (avg. 13 min); relatively high concentration of ethanol relative to other parts of a body (external ear-derived ethanol:breath ethanol = 1:590). These features indicated the suitability of external ears for non-invasive monitoring of blood VOCs.
Chapter
Exhaled air analyses are an attractive and emerging technology. It is a noninvasive and easy-to-handle method and may especially be suitable for health monitoring under conditions with limited access to standard diagnostic equipment i.e. for extended space missions. Based on the current knowledge together with ongoing and future clinical and space-related—earthbound and on the ISS—research, air analyses might become a suitable tool to monitor the adaption of various physiological systems (immune, organs, metabolism) to the stressful condition in space, thereby helping to assess overall health status as well to establish the diagnosis of diseases. As the concentration of volatile organic and inorganic components in exhaled breath is usually found in the low parts per billion of volume range highly sensitive diagnostic platforms are a prerequisite. These requirements are now met by recent technical improvements leading to an increase in the sensitivity of direct mass spectrometric and gas chromatographic methods. Particular interest is focused to direct mass spectrometric methods as they allow breath-by-breath analyses without evaluation delays. Recent developments in metal oxide sensor technology have awoke the interest in this technology above all due to low energy consumption and maintenance requirements. Furthermore, the recent discoveries of close relationships between specific compounds present in exhaled breath and physiological changes feeds the hope of developing possible noninvasive diagnostic and monitoring tools to diagnose immune dysfunctional states, infections, and cancer. With these recent progresses the technical cornerstone for exhaled breath gas analyses during space missions has been realized. Current research projects focus on the evaluation of exhaled breath gas compound standard values and the impact of stressors in space akin weightlessness, confinement, nutritional changes, hypoxia, and radiation exposure.
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Background: The authors review the clinical features, epidemiology, pathophysiology, medical management, dental findings and dental treatment of patients with alcoholism. Literature reviewed: The authors conducted a MEDLINE search for 1995 through 2001 using the key terms of alcoholism, epidemiology, pathophysiology, treatment and dentistry. Reports selected for further review included those published in English in peer-reviewed journals. The authors gave preference to articles reporting randomized, controlled trials. Conclusions: Alcoholism is a chronic and progressive psychiatric illness that afflicts more than 14 million Americans. It is characterized by a loss of control over the use of alcohol, resulting in impaired social functioning, and the consequent development of medical illnesses. The disease arises in genetically vulnerable people when they are overwhelmed by their cravings for the alcohol-associated euphoria that results from the actions of several neurotransmitter systems in the brain's pleasure center. New medications to counteract alcohol-induced neurotransmission imbalance may assist patients in reducing their craving. Clinical implications: The prevalence of dental disease usually is extensive because of a disinterest in performing appropriate oral hygiene techniques and diminished salivary flow. Concurrent abuse of tobacco products worsens dental disease and heightens the risk of developing oral cancer. Identification of the alcohol-abusing patient, a cancer-screening examination, preventive dental education, and use of saliva substitutes and anticaries agents are indicated. Special precautions must be taken when performing surgery and when prescribing or administering analgesics, antibiotics or sedative agents that are likely to have an adverse interaction with alcohol or psychiatric medications.
Article
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The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses – the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferroni-type procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
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Forty-one subjects with bad breath were assessed for oral malodor and periodontal status on three occasions, at intervals of approximately one week. Oral malodor was assessed by measurement of peak and steady-state volatile sulphide levels with a portable sulphide monitor and by organoleptic measurement of whole-mouth, tongue dorsum, and interproximal dental odors by two independent judges. Reproducibility of measurements, assessed by paired t tests and Kappa testing, demonstrated no significant differences between any of the test results from the first and second appointments. Steady-state sulphide levels were the most reproducible of all tests. The ability of the tests to detect an expected reduction of malodor following a 0.2% chlorhexidine mouthrinse regimen was investigated by comparison of test values between the second and third appointments. Following the mouthrinsing treatment, 43% reductions of peak, 47% reductions of steady-state volatile sulphide levels, and 15-58% reductions in all other measurement categories were observed. The majority of the participants (22/41) had no pockets greater than 5 mm and exhibited both moderate gingival inflammation (Mean Gingival Index = 1.17) and moderate plaque accumulation (Mean Plaque Index = 1.84). Plaque Index and presence of pockets greater than 7 mm were weakly related to sulphide measurements. Whereas assessment of steady-state sulphide levels by the sulphide monitor does not constitute a direct measure of oral malodor, its relation to organoleptic measurement, superior reproducibility, objectivity, and sensitivity support the use of the sulphide monitor in clinical studies.
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The capacity to form volatile sulfur compounds was tested in bacteria isolated from subgingival microbiotas and in a representative number of reference strains. A majority of the 75 tested oral bacterial species and 7 unnamed bacterial taxa formed significant amounts of hydrogen sulfide from L-cysteine. The most active bacteria were found in the genera Peptostreptococcus, Eubacterium, Selenomonas, Centipeda, Bacteroides and Fusobacterium. Methyl mercaptan from L-methionine was formed by some members of the genera Fusobacterium, Bacteroides, Porphyromonas and Eubacterium. When incubated in serum for 7 d, the most potent producers of hydrogen sulfide were Treponema denticola and the black-pigmented species, Bacteroides intermedius, Bacteroides loescheii, Porphyromonas endodontalis and Porphyromonas gingivalis. P. endodontalis and P. gingivalis also produced significant amounts of methyl mercaptan in serum. No other volatile sulfur compound was detected in serum or in the presence of L-cysteine and L-methionine. These findings significantly increase the list of oral bacteria known to produce volatile sulfur compounds.
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Parotid flow was determined in rabbits during feeding. The animals produced more saliva when chewing hard laboratory pellets than with carrots, confirming the findings of Gjörstrup (1980a). We showed that one gland always produced more secretion than the other, and that the dominant gland alternated from side to side with changes in the chewing side. Strain-gauge recordings revealed a remarkable similarity in pattern between mandibular strain and ipsilateral parotid flow. Together, these data suggest that chewing movements and chewing force are involved in the control of parotid secretion. In man, flow rates of parotid saliva collected with a Lashley cup and cannula were recorded. During intermittent clenching on a bite block, we found: (1) a positive correlation between rectified integrated masseter EMG and parotid flow; and (2) that anesthesia of various intra-oral nerves could reduce the flow almost to zero. Crushing a particle of breakfast cereal between two teeth resulted in a reproducible parotid flow which was reduced by infiltration anesthesia around one of these teeth. These data point to the involvement of periodontal mechanoreceptors in the control of parotid secretion in rabbits and man.
Book
With nearly 1700 references, Disease Markers in Exhaled Breath is essential reading for pulmonologists; anesthesiologists; physiologists; chest, pulmonary, thoracic, and cardiovascular physicians and surgeons; asthmologists; and upper-level undergraduate, graduate, and medical school students in these disciplines. It discusses the potential diagnostic value of markers in several disorders including cancer, asthma, transplant rejection, and heart disease.
Article
The concentration of putrescine in human saliva 66.3 ± 34.9 μmol/liter was much higher than that of in plasma, cerebrospinal fluid and urine. But spermidine and spermine were not detectable. Considerable concentrations of arginine, ornithine, citrulline, urea, glutamate, glutamine and proline were present in human saliva.
Conference Paper
Both acute and chronic liver failure result in impaired cerebral function known as hepatic encephalopathy (HE). Evidence suggests that HE is the consequence of the accumulation in brain of neurotoxic and/or neuroactive substance including ammonia, manganese, aromatic amino acids, mercaptans, phenols, short-chain fatty acids, bilirubin and a variety of neuroactive medications prescribed as sedatives to patients with liver failure. Brain ammonia concentrations may attain levels in excess of 2 mM, concentrations which are known to adversely affect both excitatory and inhibitory neurotransmission as well as brain energy metabolism. Manganese exerts toxic effects on dopaminergic neurones. Prevention and treatment of HE continues to rely heavily on the reduction of circulation ammonia either by reduction of gut production using lactulose or antibiotics or by increasing its metabolism using L-ornithine-L-aspartate. No specific therapies have so far been designed to reduce circulation concentrations of other toxins. Liver assist devices offer a potential new approach to the reduction of circulating neurotoxins generated in liver failure. In this regard, the Molecular Absorbents Recirculating System (MARS) appears to offer distinct advantages over hepatocyte-based systems.
Article
Background/aims: To compare venous, arterial and partial pressure of ammonia (pNH(3)) in 27 consecutive cirrhotics with hepatic encephalopathy, 15 cirrhotics without hepatic encephalopathy and nine controls; to reevaluate all parameters after the improvement of encephalopathy. Methods: Patients were studied by clinical examination and psychometric testing. pNH(3) was calculated from arterial ammonia and pH. Results: In patients with encephalopathy, each form of ammonia was higher than in both controls and patients without encephalopathy. The correlation with the severity of hepatic encephalopathy was similar for venous (r=0.72), arterial ammonia (r=0.76) and pNH(3) (r=0.75). The sensitivity and specificity of each variable in correctly classifying the patients as having or not having hepatic encephalopathy was also similar. Each form of ammonia decreased after the resolution or amelioration of symptoms. However, even in the 17 patients with complete resolution of hepatic encephalopathy, all three ammonia determinations resulted unchanged or increased in some patients. Conclusions: Despite the significant correlation between pNH(3) and hepatic encephalopathy, our study suggests that neither pNH(3) nor arterial ammonia are, from a clinical point of view, more useful than venous ammonia: all three determinations being limited both for the diagnosis of hepatic encephalopathy and for the clinical management of the patients.
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A project supported under the EC Measurements and Testing Programme and involving 12 participants has evaluated potentially useful sorbents for the collection and measurement of airborne volatile organic compounds (VOCs) in the workplace. The standard method uses Tenax as sorbing agent, but this is not suitable for very volatile or very polar compounds because of its low capacity for these compounds. Consensus on the best sorbents has been reached on the basis of an evaluation of sorbent performance, using about 20 test compounds with a wide range of volatilities and polarities. The sorbent which satisfied the agreed acceptance criteria for the largest number of compounds was Chromosorb 106. It is therefore recommended for use when sampling the more volatile and polar organic vapours encountered in workplace atmospheres. However, a number of other sorbents also satisfied the acceptance criteria for the majority of compounds and are suitable for a more limited (Higher molecular mass) range of organic vapours. These sorbents included Carbotrap, Tenax GR, Tenax TA and Carbopack B. Carboxen 569 was found suitable for sampling the most volatile compounds (ethylene oxide, methanol and propane).
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Many persons use mouthrinses as a part of their routine oral hygiene. Although rinses impart some benefits to users, improper use of mouthrinses may result in various side effects. This paper reviews the adverse effects of mouthwash use as reported in the English-language literature.
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This text presents essential data on over 2,000 organic chemicals: synonyms, formulas, properties; effects on plants, animals, people, air, water.
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Fully expanded and revised, this handbook lists over 2,000 organic chemicals while incorporating the extensive new information available on the environmental impact of these substances. New coverage is given on mixtures and preparations, individual chemicals, pesticides, detergents, pthalates, polynuclear aromatics, and PCBs. Special attention is given to pollutants of the abiotic and biotic environment, the correlation of bioaccumulation of chemicals to molecular structure, and the use of water solubility data to estimate the fate of chemicals in the environment. Data for each organic chemical includes synonyms, formula, properties, air and water pollution factors, and biological effects.
Article
The sampling of vapor-phase organics in the presence of reactive inorganic gases with the Tenax GC sampling cartridge was statistically evaluated. A factorial experiment and the use of toluene-d//8, styrene-d//8, and cyclohexene-d//1//0 coupled with GC/MS analysis provided insight to those reaction products from the sorbent itself and those from adsorbed analytes. The removal of oxidants prior to capturing organic vapors was investigated by use of mild reducing agents impregnated in filters for particulate. Sodium thiosulfate impregnated glass fiber and Teflon filters quantitatively decomposed ozone.
Article
The most important features of Tenax and Carbotrap, solid sorbents used widely for sampling organic pollutants in air, have been tested under the conditions requested for surveys in indoor spaces and for determinations of VOC emitted from indoor sources by chamber experiments. The performances of samplers, tested with 10 nonpolar and polar (mostly lipophilic) hydrocarbons, present as vapours in 0.5 to 2.0 litre air samples, include: (a) accuracy and reproducibility of the measured concentration, (b) background or “blank” of samplers, (c) stability upon storage (at ambient and below ambient temperatures) of clean samplers and of samplers loaded with VOC, and (d) performance stability after several sampling desorption cycles. The results fulfil the requirements for both adsorbents, though each presents some different drawbacks. In particular (a) Tenax samplers show a “blank” (90 percentile) of 16 ng of benzene and 5 ng of toluene, Carbotrap samplers roughly twice as much; (b) the samplers may be stored for one month either before or after use and (c) they may withstand many cycles without discernible deterioration.
Article
Halitosis is most often caused by oral conditions. Volatile sulfur compounds (VSC), constituting the major components of oral malodor, are produced by anaerobic, gram-negative bacteria retained mainly in periodontal pockets or on the tongue dorsum. Sulfur-containing amino acids serve as substrate for these bacteria. VSC have also been found to have unfavorable effect on the tissue. The aim of this study was to examine whether normal, healthy individuals with no history of halitosis were able to produce VSC from cysteine, when applied as a mouthrinse. A further aim of the study was to investigate and compare the potential of other sulfur-containing amino acids and peptides as substrates for oral VSC production and to localize the odor-production sites. A portable sulfide monitor was used for VSC registration. Results showed that all test subjects produced high oral concentrations of VSC upon rinses with cysteine, which thus seems to be a major substrate for VSC production. The other sulfur-containing substrates had much less effect. It was found that the tongue was the major site for VSC production, and that saliva per se caused low VSC production.
Article
A simple technique has been developed for preconcentration of gaseous trace organic compounds on solid sorbents, followed by gas chromatography. The sorbent is packed in a cartridge from a syringe needle placed in the gas chromatographic injector and the analytes previously adsorbed are thermally desorbed at the injector temperature and then directly swept by the carrier gas into the column. The system has been tested for a charcoal-based adsorbent and silica gel, with pentane, methanol, ethanol and acetone as the model analytes. The procedure is rapid, the detection limits vary from a few nmol l−1 to values below 0.1 nmol l−1 (i.e., a few ppb), the linear dynamic range amounts to at least five concentration decades and a typical relative standard deviation is 10% at the nmol l−1 concentrations. It has been shown that the method is readily applicable to determination of instantaneous concentrations of the analytes in natural and industrial atmosphere and to their monitoring in human breath which is important for medical and hygienic practice. In general, the procedure is applicable to low-molecular volatile organic compounds.
Article
A 29-year-old man presented to the Emergency Department with acute mental status changes. He was unable to give a history. He was found to be in diabetic ketoacidosis, although his family reported no prior history of diabetes. A toxic exposure work-up revealed the presence of isopropyl alcohol in the patient’s blood. His condition improved with treatment of the ketoacidosis, and he subsequently denied any exposure to isopropyl alcohol prior to presentation to the hospital. This case provides further support to a growing body of evidence that the detection of isopropyl alcohol may not represent an acute ingestion but, rather, a byproduct of acetone metabolism in certain disease states.
Article
Dynamic recovery data with a simple test system show that many volatile organic compounds (VOC) found in trace amounts in air can be determined quantitatively by adsorption on Tenax TA or Carbotrap and thermal desorption. Tenax TA seems to be inert towards the compounds tested as opposed to Carbotrap, on which α-pinene and aldehydes show some reactivity. Compounds with higher boiling points up to 270°C could be quantitatively desorbed from Tenax TA, but not from Carbotrap. For very volatile organic compounds and various polar VOC, substantial losses, most probably due to breakthrough, were observed on both adsorbents. Therefore, for an overview of all VOC in air, additional adsorbents or methods must be considered.
Article
The effect of ozone on four adsorbents (Tenax-TA, Tenax GR, Carbotrap, and Chromosorb 106) during the passive sampling of air has been investigated by exposure to ozone at 180 ppb for 1 week. Generally no artifact compounds were found to form on Carbotrap or Chromosorb 106. Several new peaks appeared in the chromatograms of Tenax-TA and Tenax-GR, the most significant being benzaldehyde and acetophenone. The effect of ozone on selected hydrocarbons (isoprene, benzene, toluene, p-xylene, o-xylene, alpha-pinene, and beta-pinene), adsorbed on Tenax-GR during passive sampling, was also investigated by exposure to ozone at different concentrations (60, 120, and 180 ppb) for 1 week. Minor destruction by ozone was only observed for beta-pinene (4 %) at an ozone concentration of 180 ppb.
Article
Organoleptic studies indicate that the oral cavity is usually the principal source of physiologic malodor associated with the early morning halitosis. In all individuals, regardless of the age or health status of the oral tissues, the most intense oral malodor is exhibited after prolonged periods of reduced saliva flow and abstinence from food and liquid. This results from normal metabolic activity in the oral cavity and is accentuated in cases with poriodontal involvement. Physiologic oral malodor is transient in duration as it can be controlled to varying degrees in most individuals by oral hygiene measures, such as tooth brushing, dental prophylaxis, tongue scraping and rinsing with antiseptic mouth washes. Experimental evidence strongly suggests that putrefaction of sulphur containing proteinaceous substrates by predominantly gram negative oral microorganisms is the primary cause of oral malodor. Brushing studies indicate that both plaque and tongue are important sources of malodor with most of the odor emanating from the dorso posterior surface of the tongue. None of the gas chromatographic or mass spectrometric analyses have detected the presence of amines, indole, or skatole in the head space, mouth air, or breath vapor samples.
Three patients are described in whom a putrid breath odor was the only or fist manifestation of anaerobic infection of the lung. Fever, productive cough, and pleuritic pain, common findings in anaerobic pulmonary infection, were not initally present. "Bad breath" may be an early due to the presence of anaerobic pulmonary infection.
Article
A sensitive gas chromatographic method was developed to determine the amounts of volatile sulfur compounds in gingival fluid. Hydrogen sulfide was the predominant volatile sulfur compound and was detected in 61 out of 79 studied periodontal pockets. Methyl mercaptan was found in about 20% of the pockets. No other volatile sulfur compounds were detected. The highest concentration of hydrogen sulfide in gingival fluid was 1.9 mmol/liter, and of methyl mercaptan 0.16 mmol/liter.
Article
The present investigation describes a method for collection and analysis of volatile sulphur compounds (VSC) from gingival crevicular sites in humans. Tenax-GC trapping devices were used to adsorb and concentrate VSC from crevicular air at -55 degrees C, which were then thermally desorbed at 120 degrees C. Gas chromatographic (GC) analyses were performed using a Tracor 550 GC equipped with a flame-photometric detector and a Teflon column packed with 5% polyphenyl ether and 0.05% phosphoric acid on 30-40 mesh Teflon. Sulfides identified from crevicular sites include hydrogen sulfide [H2S], methyl mercaptan [CH3SH], dimethyl sulfide [(CH3)2S], and dimethyl disulfide [(CH3S)2]. Of the seventeen patients studied, crevicular sites that were either deep (P.D. > or = 4 mm) or inflamed (BoP = 1) exhibited significantly larger CH3SH to H2S ratios than corresponding crevicular shallow (P.D. < or = 3 mm) sites (p < .10) or noninflamed (BoP = 0) sites (p < .05). Similarly, total sulphur in deep and inflamed sites was significantly higher than in corresponding shallow (p < .01) and noninflamed (p < .05) sites. This is the first known in vivo study to quantitate VSC directly from individual gingival crevices.
Article
The amounts of volatile sulfur compounds (VSC) and methyl mercaptan/hydrogen sulfide ratio in mouth air from patients with periodontal involvement were 8 times greater than those of control subjects. Our studies demonstrated that, in patients with periodontal disease: 1) the concentration of disulfide, which is converted to VSC, increased in proportion to the total pocket depth; 2) 60% of the VSC was produced from the tongue surface; 3) the amount of tongue coating was 4 times greater than in control subjects; and 4) VSC production and the methyl mercaptan/hydrogen sulfide ratio of the tongue coating were increased. 2-Ketobutyrate, which is a byproduct of the metabolism of methionine to methyl mercaptan, was higher in the saliva of patients with periodontal disease. This implies that metabolism of methionine to methyl mercaptan increases in the oral cavity of patients with periodontal pockets. Since free L-methionine, rather than protein, is the main source for methyl mercaptan, we estimated the methionine supply from the gingival fluid into the oral cavity of patients with periodontal involvement. The results showed that the ratio of methionine to whole free amino acids was significantly higher than that of cysteine. Our studies suggest that not only microorganisms, but also the tongue coating and gingival fluid are factors which enhance VSC production in patients with periodontal disease.
Article
Measurement of oral malodor is complicated by a variety of parameters including complexity of gaseous molecular species, sampling difficulties, temporal variations, choice of suitable subject populations, and lack of agreement on reference standards. Since oral malodor is a perceived olfactory stimulus, direct sampling and assessment by human judges may be the most logical measurement approach. However, as with other psychophysical assessments, human malodor measurement by the human nose may vary widely among and between judges, and consequently cannot be confidently reproduced in other laboratories. Such shortcomings have led several investigators to propose quantitative approaches based on measurement of volatile sulfide compounds which are associated with oral malodor. Highly sensitive and discriminatory measurements of volatile sulfides can be made using gas chromatography although for rapid sampling of larger subject populations, portable sulfide monitors may be more appropriate. Future research in this field should consider: 1) improved and simplified instrumentation for more rapid through-put and reliability; 2) development and definition of reference standards for oral malodor assessment; 3) formulation of clinical studies with appropriately sized, well-defined patient populations; and 4) further development of within mouth, site-specific measurements.
Article
Volatile sulfur compounds (VSC) in mouth air were estimated by gas chromatography. The amount of VSC and the methyl mercaptan/hydrogen sulfide ratio were significantly increased in patients with periodontal disease. These two parameters also increased in proportion to the bleeding index and probing depth. A study was also done on the effect of removal of tongue coating on VSC concentrations in mouth air from patients with periodontal involvement. VSC and the methyl mercaptan/hydrogen sulfide ratio were reduced to 49% and 35%, respectively, by removal of the tongue coating. The average amount of tongue coating removed from patients with periodontal disease was significantly higher than from controls (90.1 mg vs. 14.6 mg, p less than 0.01). Estimated production of VSC from tongue coating was 4 times higher than the control value, and the methyl mercaptan/hydrogen sulfide ratio was also markedly increased. However, a saliva putrefaction study suggested that saliva does not contribute to the elevated ratio of methyl mercaptan in mouth air. These results strongly suggest that, in addition to periodontal pockets, tongue coating has an important role in VSC production, in particular leading to an elevated concentration of methyl mercaptan, which is more pathogenic than hydrogen sulfide.
Article
Enamel spurs projecting from the cemento-enamel junction into the furcation as well as small islands and droplets of enamel deposited on furcational root surfaces are characteristic morphological features of human maxillary and mandibular molars. The furrows and recesses created by these structures form pathways for bacterial invasion and predispose for local periodontitis. Furthermore, the furcations are often covered by thick central cementum ridges, with steplike or tongue-like deepenings around enamel droplets. In the cementum, there is a variable number of small and large openings, representing either cementum-inherent channels or large open connections between pulp chamber and furcation. These structures offer ample opportunities for uncontrollable bacterial retention and colonisation, and the possibility for pulpal infections to spread into the furcation. The literature covering these issues is summarized.
Article
Mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4-methylthio-2-oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy, in patients with chronic kidney failure and in healthy subjects. In patients with hepatic encephalopathy, the mean serum concentrations of all these compounds were elevated. However, the elevations of methanethiol-mixed disulfides were small and partly caused by decreased renal function. In addition, the levels of methanethiol-mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy. The concentrations of methanethiol-mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase, the latter without causing encephalopathy. We concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor, if not insignificant. In the patients with hepatic encephalopathy, a significant correlation was found between the concentrations of methionine and 4-methylthio-2-oxobutyrate and between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting the theory that methanethiol is formed by way of the methionine transamination pathway. Evidence is provided that, besides the methionine transsulfuration pathway, the transamination pathway is also impaired in patients with hepatic encephalopathy.
Article
Hydrogen sulfide is formed by the subgingival microbiotas of periodontal pockets. The capacity of these microbiotas to form various volatile sulfur compounds in human serum was studied. Bacterial samples from nine deep periodontal pockets were incubated for 7 days in human serum and the amounts of volatile sulfur compounds and the degradation of serum proteins were determined. Hydrogen sulfide was the predominant volatile sulfur compound, but also methyl mercaptan was formed in significant amounts. Only traces of dimethyl sulfide and dimethyl disulfide were detected. There was an extensive degradation of the serum proteins. In most of the reaction mixtures hydrogen sulfide reached highly toxic levels.
Article
Most dentists fail to instruct their patients to routinely clean the tongue. Debris on the dorsal surface of the tongue is removed by fibrous foods and by brushing and scraping. A reduction in plaque formation and tooth root caries in the elderly may be achieved. A source of halitosis will be removed and the taste acuity heightened. The tongue should no longer be neglected in oral hygiene regimes.
Article
The metabolism of methanethiol in whole blood has been described. Incubation of carbon 14-labeled or sulfur 35-labeled gaseous methanethiol resulted in complete trapping of methanethiol by whole blood within 30 minutes. After trapping, both labels were found to be equally distributed over plasma and erythrocytes. Eighty to ninety percent of both labels could be extracted from erythrocytes incubated in saline solution. The chemical properties of the 14C and 35S labels in saline solution differed completely. The 14C label was not precipitated by BaCl2, was moderately volatile, and could be extracted by either (pH 1). In contrast, the 35S label was precipitated by BaCl2, was not volatile, and was not extracted by ether. It is concluded that the central carbon-sulfur bond of methanethiol is split by incubation with whole blood. Plasma components are not involved in this process. Most likely, methanethiol becomes largely oxidized by erythrocytes to formic acid and sulfite or sulfate. Only 10% of methanethiol became firmly bound to erythrocytes. One to two percent was transformed to protein--S--S--CH3 and 1% to dimethyl sulfide by the enzyme thiol methyltransferase.
Article
The surface area of the mouth was measured to calculate the average thickness of the salivary film which separates the opposing layers of the oral mucosa and which also overlies the dental plaque. The subjects were 10 adults of each sex, all of whom had essentially a full complement of teeth. Impressions were taken of the upper and lower jaws, the buccal and labial vestibular mucosa, and the ventral surface of the tongue, and stone models were cast. The dorsum of the tongue was assumed to have the same area as the palate plus that of the palatal surfaces of the upper teeth. The six separate areas considered were the teeth, the palate, the buccal and lingual gingival and alveolar mucosa, the buccal and labial vestibular mucosa, the ventral surface of the tongue, including the floor of the mouth, and the dorsum of the tongue. Aluminum foil, of known weight per unit area, was adapted to the models of the different regions of the mouth, and the surface areas were calculated from the weights of the foil. The mean total surface area of the mouth was 214.7 ± 12.9 cm ² , and there was no significant difference due to gender. The teeth, keratinized epithelium, and non-keratinized epithelium occupied about 20%, 50%, and 30% of the total surface area, respectively. Given that the average volumes of saliva present in the mouth before and after swallowing have been estimated to be 0.77 and 1.07 mL, respectively, it can be calculated that the average thickness of the salivary film in the mouth varies between 0.07 and 0.10 mm. Since we have previously assumed that dental plaque is washed by a relatively thick layer of saliva, the results have important implications with regard to diffusion of substances in and out of dental plaque and with regard to the sensation of oral dryness caused by fluid absorption through the oral mucosa or by salivary evaporation.
Article
The concentration of breath acetone has been found to correlate with the β-hydroxybutyrate concentration of venous blood in fasting obese patients. Overnight fasting levels of both breath acetone and blood-sugar were measured in 251 diabetics, after which the patients were grouped for analysis by the type of diabetic management and the fasting blood-sugar found. Amongst the subgroups with near-normal fasting blood-sugar (<120 mg. per 100 ml.) the mean breath acetone was normal only in the group whose diabetes was controlled by a non-reducing diet ( > 100 g. carbohydrate per day); it was raised in similarly well-controlled patients receiving either reducing diets (< 100 g. carbohydrate per day) or hypoglycæmic tablets or insulin. Among those with higher simultaneous blood-sugar levels the mean acetone concentration was abnormal and rose progressively with the blood-sugar. In insulin-dependent diabetics similar measurements made before meals showed a progressive decrease in mean acetone levels during the day (for the same simultaneous blood-sugar), lowest levels being attained in the late afternoon. This mild ketosis, present in 40–50% of diabetics apparently well controlled on hypoglyæmic tablets or insulin, was not relatable to diet, degree of obesity, or the occurrence of hypoglycæmia. In such patients, measurement of the breath acetone can detect inadequacies of control not revealed by measure- ment of the blood-sugar alone.