Organic Compounds In Exhaled Air Research Articles

There’s something in the air – the role of volatile organic compounds in exhaled air in the diagnosis and treatment of asthma in children

There’s something in the air – the role of volatile organic compounds in exhaled air in the diagnosis and treatment of asthma in children

Analysis of Volatile Organic Compounds in Exhaled Air in Patients with Sickle Cell Disease during Vaso-Occlusive Episodes

Background: Sickle cell disease (SCD) is an inherited red blood cell disorder characterized by hemolytic anemia, inflammation and vaso-occlusion. Due to the process of vaso-occlusion patients with SCD experience unpredictable and painful vaso-occlusive episodes (VOE), causing stress and disruption of daily life. To date, we lack adequate markers to predict the development of a VOE before it occurs. In other conditions such as asthma, exhaled air analyses have shown to be of diagnostic value and may predict exacerbations. In the human body, metabolic processes generate volatile organic compounds, that are first released into the blood, and then exhaled by the lungs. As a result, exhaled air consists of several volatile, organic compounds that may reflect pathophysiological disease processes. As we presently lack urgently needed biomarkers to predict VOEs, the aim of this study was to identify distinctive volatile organic compounds in exhaled air (eVOC) during VOE in patients with SCD, that may serve as predictors of VOE when detected in low quantities as a VOE is evolving. Methods: In this longitudinal, observational single center cohort study, patients with SCD aged 6 years or older were eligible if they were hospitalized for a VOE at Amsterdam University Medical Centers between October 2021 and March 2023. Following informed consent, an exhaled air sample was taken during hospitalization, and one at least 4 weeks after discharge from the hospital (steady state). Clinical data were collected from medical files including demographics, medical history, medication use and laboratory values during steady state, and during hospitalization for VOE. Patients were instructed not to eat, drink or take medication orally 2 hours prior to the measurements. Exhaled air samples were collected in Nalophan bags, and the eVOCs were transferred to stainless steel thermal desorption tubes filled with Tenax GR for analysis by gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to test for differences in eVOCs between VOE and steady state. Significantly different eVOCs were tentatively identified by linking raw chromatograms to corresponding metabolites based on NIST-library matching. The significance level was set to 0.05. All analyses were performed using R Studio (version 1.3.1093) software. Results: In total, 25 patients with SCD were included in this study, providing 71 exhaled air samples. The mean age at inclusion was 25.7 years (SD ±10.2). The majority of the participants had SCD genotype HbSS (60%). At time of exhaled air measurement during hospitalization, participants had symptoms for the median number of 1 day (IQR 0.5-3), and the median pain score was 6 out of 10 (IQR 3-7). A total of 58 different fragments could be identified between VOE and steady state (Wilcoxon rank p< 0.05), representing 26 unique eVOCs. The majority of these eVOCs were alkanes, alkenes, and esters. A representing compound for each chemical group is shown in Figure 1. In the majority of the patients, cyclohexane,1,2,4-trimethyl and propanoic acid, ethyl ester were upregulated during VOE, while 1-propene, 2-methyl- was downregulated. Conclusion: This pilot study identified 26 compounds in exhaled air that differentiated VOE from steady state in patients with SCD. Thus, analysis of exhaled air could serve as a promising, non-invasive and patient-friendly biomarker to predict VOE in SCD. Further identification of the discriminative compounds in exhaled air could provide valuable insights into the metabolic processes during VOE.

Towards detection of cancer biomarkers in human exhaled air by transfer-learning-powered analysis of odor-evoked calcium activity in rat olfactory bulb

Detection of volatile organic compounds in exhaled air is a promising approach to non-invasive and scalable gastric cancer screening. This work proposes a new approach for the detection of volatile organic compounds by analyzing odor-evoked calcium responses in the rat olfactory bulb. We estimate the feasibility of gastric cancer biomarker detection added to the exhaled air of healthy participants. Our detector consists of a convolutional encoder and a similarity-based classifier over encoder outputs. To minimize overfitting on a small available training set, we involve a pre-training where the encoder is trained on synthetic data representing spatiotemporal patterns similar to real calcium responses in the olfactory bulb. We estimate the classification accuracy of exhaled air samples by matching their encodings with encodings of calibration samples of two classes: 1) exhaled air and 2) a mixture of exhaled air with the cancer biomarker. On our data, the accuracy increased from 0.68 on real data up to 0.74 if pre-training on synthetic data is involved. Our work is focused on proving the feasibility of proposed new approach rather than on comparing its efficiency with existing methods. Such detection is often performed with an electronic nose, but its output becomes unstable over time due to a sensor drift. In contrast to the electronic nose, rats can robustly detect low concentrations of biomarkers over lifetime. The feasibility of gastric cancer biomarker detection in exhaled air by bio-hybrid system is shown. Pre-training of neural models for images analysis increases the accuracy of detection.

A microfabricated semi-packed column coated with porous layer and ionic liquid for the separation of characteristic markers of non-alcoholic fatty liver disease

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 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. 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 °C to 140 °C. The oxygen robustness was verified by a decrease of 7.2% in the peak capacity after exposure to dry air at 140 °C for 48 h. These characteristics showed the micro GC column is suitable for a portable breath analyzer.

Optimization of the Conditions of Analysis of Exhaled Air by Gas Chromatography–Mass Spectrometry for the Noninvasive Diagnostics of Lung Cancer

We optimized procedures for the collection, preparation, and storage of samples of exhaled air and the conditions for determining volatile organic compounds in exhaled air by gas chromatography–mass spectrometry (GC–MS), the presence or change in the concentration of which can be caused by lung cancer. The analysis circuit includes group adsorption preconcentration followed by the thermal desorption and determination of analytes by GC–MS. Polymer bags of a Tedlar® film were used for sample collection. The conditions and periods of the storage of samples in bags and adsorption tubes are determined. A method for cleaning and conditioning bags is proposed. For preconcentrating exhaled air components, we used hydrophobic adsorbents (Porapak™ P, Porapak™ Q, and Tenax® TA) and three-section tubes containing Tenax® GR, Carbopack™ B, and Carbosieve® S-III. Their relative efficiency was evaluated by assessing the residual background of gas emission from the adsorbent, the magnitude of the analytical signal, the efficiency of adsorption/desorption, and the efficiency of storage. The conditions for the preconcentration of volatile organic compounds (volume and rate of aspiration, time, and temperature of thermal desorption) are optimized. The main volatile organic compounds in the exhaled air of conditionally healthy volunteers were identified, and their concentrations are evaluated.

Volatile Organic Compounds in Exhaled Air and Sweat of Patients Treated by Immunotherapy for Lung Cancer: Research on Biomarkers for Early Therapeutic Response

Volatile Organic Compounds in Exhaled Air and Sweat of Patients Treated by Immunotherapy for Lung Cancer: Research on Biomarkers for Early Therapeutic Response

A profile of volatile organic compounds in exhaled air as a potential non-invasive biomarker for liver cirrhosis.

Early diagnosis of liver cirrhosis may prevent progression and development of complications. Liver biopsy is the current standard, but is invasive and associated with morbidity. We aimed to identify exhaled volatiles within a heterogeneous group of chronic liver disease (CLD) patients that discriminates those with compensated cirrhosis (CIR) from those without cirrhosis, and compare this with serological markers. Breath samples were collected from 87 CLD and 34 CIR patients. Volatiles in exhaled air were measured by gas chromatography mass spectrometry. Discriminant Analysis was performed to identify the optimal panel of serological markers and VOCs for classifying our patients using a random training set of 27 CIR and 27 CLD patients. Two randomly selected independent internal validation sets and permutation test were used to validate the model. 5 serological markers were found to distinguish CIR and CLD patients with a sensitivity of 0.71 and specificity of 0.84. A set of 11 volatiles discriminated CIR from CLD patients with sensitivity of 0.83 and specificity of 0.87. Combining both did not further improve accuracy. A specific exhaled volatile profile can predict the presence of compensated cirrhosis among CLD patients with a higher accuracy than serological markers and can aid in reducing liver biopsies.

Volatile Organic Compounds in Exhaled Air as Novel Marker for Disease Activity in Crohn's Disease: A Metabolomic Approach.

Disappearance of macroscopic mucosal inflammation predicts long-term outcome in Crohn's disease (CD). It can be assessed by ileocolonoscopy, which is, however, an invasive and expensive procedure. Disease activity indices do not correlate well with endoscopic activity and noninvasive markers have a low sensitivity in subgroups of patients. Volatile organic compounds (VOCs) in breath are of increasing interest as noninvasive markers. The aim of this study was to investigate whether VOCs can accurately differentiate between active CD and remission. Patients participated in a 1-year follow-up study and Harvey-Bradshaw index, blood, fecal, and breath samples were collected at regular intervals. Patients were stratified into 2 groups: active (fecal calprotectin >250 µg/g) or inactive (Harvey-Bradshaw index <4, C-reactive protein <5 mg/L, and fecal calprotectin <100 µg/g) disease. Breath samples were analyzed by gas chromatography-time-of-flight mass spectrometry. Random forest analyses were used to find the most discriminatory VOCs. Eight hundred thirty-five breath-o-grams were measured, 140 samples were assigned as active, 135 as inactive disease, and 110 samples of healthy controls. A set of 10 discriminatory VOCs correctly predicted active CD in 81.5% and remission in 86.4% (sensitivity 0.81, specificity 0.80, AUC 0.80). These VOCs were combined into a single disease activity score that classified disease activity in more than 60% of the previously undetermined individuals. We showed that VOCs can separate healthy controls and patients with active CD and CD in remission in a real-life cohort. Analysis of exhaled air is an interesting new noninvasive application for monitoring mucosal inflammation in inflammatory bowel disease.

Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air

BackgroundSeveral classifications of adult asthma patients using cluster analyses based on clinical and demographic information has resulted in clinical phenotypic clusters that do not address molecular mechanisms. Volatile organic compounds (VOC) in exhaled air are released during inflammation in response to oxidative stress as a result of activated leukocytes. VOC profiles in exhaled air could distinguish between asthma patients and healthy subjects. In this study, we aimed to classify new asthma endotypes by combining inflammatory mechanisms investigated by VOC profiles in exhaled air and clinical information of asthma patients.MethodsBreath samples were analyzed for VOC profiles by gas chromatography–mass spectrometry from asthma patients (n = 195) and healthy controls (n = 40). A total of 945 determined compounds were subjected to discriminant analysis to find those that could discriminate healthy from asthmatic subjects. 2-step cluster analysis based on clinical information and VOCs in exhaled air were used to form asthma endotypes.ResultsWe identified 16 VOCs, which could distinguish between healthy and asthma subjects with a sensitivity of 100% and a specificity of 91.1%. Cluster analysis based on VOCs in exhaled air and the clinical parameters FEV1, FEV1 change after 3 weeks of hospitalization, allergic sensitization, Junipers symptoms score and asthma medications resulted in the formation of 7 different asthma endotype clusters. We identified asthma clusters with different VOC profiles but similar clinical characteristics and endotypes with similar VOC profiles, but distinct clinical characteristics.ConclusionThis study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0136-8) contains supplementary material, which is available to authorized users.

Non-alcoholic steatohepatitis: A non-invasive diagnosis by analysis of exhaled breath

Histological evaluation of a liver biopsy is the current gold standard to diagnose non-alcoholic steatohepatitis (NASH), but the procedure to obtain biopsies is associated with morbidity and high costs. Hence, only subjects at high risk are biopsied, leading to underestimation of NASH prevalence, and undertreatment. Since analysis of volatile organic compounds in breath has been shown to accurately identify subjects with other chronic inflammatory diseases, we investigated its potential as a non-invasive tool to diagnose NASH. Wedge-shaped liver biopsies from 65 subjects (BMI 24.8-64.3 kg/m(2)) were obtained during surgery and histologically evaluated. The profile of volatile organic compounds in pre-operative breath samples was analyzed by gas chromatography-mass spectrometry and related to liver histology scores and plasma parameters of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Three exhaled compounds were sufficient to distinguish subjects with (n=39) and without NASH (n=26), with an area under the ROC curve of 0.77. The negative and positive predictive values were 82% and 81%. In contrast, elevated ALT levels or increased AST/ALT ratios both showed negative predictive values of 43%, and positive predictive values of 88% and 70%, respectively. The breath test reduced the hypothetical percentage of undiagnosed NASH patients from 67-79% to 10%, and of misdiagnosed subjects from 49-51% to 18%. Analysis of volatile organic compounds in exhaled air is a promising method to indicate NASH presence and absence. In comparison to plasma transaminase levels, the breath test significantly reduced the percentage of missed NASH patients and the number of unnecessarily biopsied subjects.

A nanomaterial-based breath test for short-term follow-up after lung tumor resection

In this case study, we demonstrate the feasibility of nanomaterial-based sensors for identifying the breath-print of early-stage lung cancer (LC) and for short-term follow-up after LC-resection. Breath samples were collected from a small patient cohort prior to and after lung resection. Gas-chromatography/mass-spectrometry showed that five volatile organic compounds were significantly reduced after LC surgery. A nanomaterial-based sensor-array distinguished between pre-surgery and post-surgery LC states, as well as between pre-surgery LC and benign states. In contrast, the same sensor-array could neither distinguish between pre-surgery and post-surgery benign states, nor between LC and benign states after surgery. This indicates that the observed pattern is associated with the presence of malignant lung tumors. The proof-of-concept presented here has initiated a large-scale clinical study for post-surgery follow-up of LC patients. From the Clinical EditorMonitoring for tumor recurrence remains very challenging due to post-surgical and radiation therapy induced changes in target organs, which often renders standard radiological identification of recurrent malignancies inaccurate. In this paper a novel nanotechnology-based sensor array is used for identification of volatile organic compounds in exhaled air that enable identification of benign vs. malignant states.

Classifier Ensemble Methods for Diagnosing COPD from Volatile Organic Compounds in Exhaled Air

The diagnosis of Chronic Obstructive Pulmonary Disease (COPD) is based on symptoms, clinical examination, exposure to risk factors (smoking and certain occupational dusts) and confirming lung airflow obstruction (on spirometry). However, most people with COPD remain undiagnosed and controversies regarding spirometry persist. Developing accurate and reliable automated tests for the early diagnosis of COPD would aid successful management. We evaluated the diagnostic potential of a non-invasive test of chemical analysis (volatile organic compounds - VOCs) from exhaled breath. We applied 26 individual classifier methods and 30 state-of-the-art classifier ensemble methods to a large VOC data set from 109 patients with COPD and 63 healthy controls of similar age; we evaluated the classification error, the F measure and the area under the ROC curve (AUC). The results show that classifying the VOCs leads to substantial gain over chance but of varying accuracy. We found that Rotation Forest ensemble (AUC 0.825) had the highest accuracy for COPD classification from exhaled VOCs.

189 Analysis of Volatile Organic Compounds in Exhaled Air As a Non Invasive Biomarker for Inflammatory Bowel Disease (IBD)

189 Analysis of Volatile Organic Compounds in Exhaled Air As a Non Invasive Biomarker for Inflammatory Bowel Disease (IBD)

Volatile organic compounds in exhaled air from patients with lung cancer.

Using a specially developed breath collection technique and computer-assisted gas chromatography/mass spectrometry (GC/MS), we have identified in the exhaled air of lung cancer patients several volatile organic compounds that appear to be associated with the disease. The GC/MS profiles of 12 samples from lung cancer patients and 17 control samples were analyzed by using general computerized statistical procedures to distinguish lung cancer patients from controls. The selected volatile compounds had sufficient diagnostic power in the GC/MS profiles to allow almost complete differentiation between the two groups in a limited patient population.