Biomarkers In Exhaled Breath Research Articles

Exhaled volatile organic compounds as lung cancer biomarkers during one-lung ventilation.

In this study, single-lung ventilation was used to detect differences in the volatile organic compound (VOCs) profiles between lung tissues in healthy and affected lungs. In addition, changes that occurred after lung cancer resection in both the VOCs profiles of exhaled breath from ipsilateral and contralateral lungs and the VOCs profiles of exhaled breath and blood sample headspaces were also determined. Eighteen patients with non-small cell carcinoma were enrolled. Alveolar breath samples were taken separately from healthy and diseased lungs before and after the tumor resection. Solid phase microextraction–gas chromatography/mass spectrometry was used to assess the exhaled VOCs of the study participants. The VOCs exhibited significant differences between the contralateral and ipsilateral lungs before surgery, the contralateral and ipsilateral lungs after surgery, the ipsilateral lungs before and after surgery, and the blood samples from before and after surgery; 12, 19, 12 and 5 characteristic metabolites played decisive roles in sample classification, respectively. 2,2-Dimethyldecane, tetradecane, 2,2,4,6,6-pentamethylheptane, 2,3,4-trimethyldecane, nonane, 3,4,5,6-tetramethyloctane, and hexadecane may be generated from lipid peroxidation during surgery. Caprolactam and propanoic acid may be more promising exhaled breath biomarkers for lung cancer.

Canine scent detection of human cancers

ABSTRACTA review of literature published between January and July 2013 was undertaken to explore the findings relating to the viability of the use of dogs to detect the presence of cancer in human subjects. It was found that a significant percentage of the dogs used in the studies could successfully detect the presence of cancer biomarkers in urine or exhaled breath. The review explores and discusses the methodology of training the dogs, the viability of the cancer research, ethics and the types of cancer that dogs are being trained to detect.

Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors

Cancer diagnosis is typically delayed to the late stages of disease due to the asymptomatic nature of cancer in its early stages. Cancer screening offers the promise of early cancer detection, but most conventional diagnostic methods are invasive and remain ineffective at early detection. Breath analysis is, however, non-invasive and has the potential to detect cancer at an earlier stage by analyzing volatile biomarkers in exhaled breath. This paper summarizes breath sampling techniques and recent developments of various array-based sensor technologies for breath analysis. Significant advancements were made by a number of different research groups in the development of nanomaterial-based sensor arrays, and the ability to accurately distinguish cancer patients from healthy controls based on the volatile organic compounds (VOCs) in exhaled breath has been demonstrated. Optical sensors based on colorimetric sensor array technology are also discussed, where preliminary clinical studies suggest that metabolic VOC profiles could be used to accurately diagnose various forms of lung cancer. Recent studies have demonstrated the potential of using metabolic VOCs for cancer detection, but further standardization and validation is needed before breath analysis can be widely adopted as a clinically useful tool.

Cell culture metabolomics in the diagnosis of lung cancer—the influence of cell culture conditions

Lung cancer is the leading cause of cancer deaths. Unfortunately, lung cancer is often diagnosed only when it becomes symptomatic or at an advanced stage when few treatment options are available. Hence, a diagnostic test suitable for screening widespread populations is required to enable earlier diagnosis. Analysis of exhaled breath provides a non-invasive method for early detection of lung cancer. Analysis of volatile organic compounds (VOCs) by various mass spectral techniques has identified potential biomarkers of disease. Nevertheless, the metabolic origins and the disease specificity of VOCs need further elucidation. Cell culture metabolomics can be used as a bottom-up approach to identify biomarkers of pathological conditions and can also be used to study the metabolic pathways that produce such compounds. This paper summarizes the current knowledge of lung cancer biomarkers in exhaled breath and emphasizes the critical role of cell culture conditions in determining the VOCs produced in vitro. Hypoxic culture conditions more closely mimic the conditions of cancer cell growth in vivo. We propose that since hypoxia influences cell metabolism and so potentially the VOCs that the cancer cells produce, the cell culture metabolomics projects should consider culturing cancer cells in hypoxic conditions.

Towards the determination of isoprene in human breath using substrate-integrated hollow waveguide mid-infrared sensors

Selected volatile organic compounds (VOCs) in breath may be considered biomarkers if they are indicative of distinct diseases or disease states. Given the inherent molecular selectivity of vibrational spectroscopy, infrared sensing technologies appear ideally suitable for the determination of endogenous VOCs in breath. The aim of this study was to determine that mid-infrared (MIR; 3–20 µm) gas phase sensing is capable of determining isoprene in exhaled breath as an exemplary medically relevant VOC by hyphenating novel substrate-integrated hollow waveguides (iHWG) with a likewise miniaturized preconcentration system. A compact preconcentrator column for sampling isoprene from exhaled breath was coupled to an iHWG serving simultaneously as highly miniaturized gas cell and light conduit in combination with a compact Fourier transform infrared spectrometer. A gas mixing system enabled extensive system calibration using isoprene standards. After system optimization, a calibration function obtaining a limit of quantification of 106 ppb was achieved. According to the literature, the obtained sensitivity is sufficient for quantifying middle to high isoprene concentrations occurring in exhaled breath. Finally, a volunteer breath sample was analysed proving comparable values of isoprene in a real-world scenario. Despite its fundamental utility, the proposed methodology contains some limitations in terms of sensitivity and temporal resolution in comparison with the readily available measurement techniques that should be addressed during future optimization of the system. Nonetheless, this study presents the first determination of endogenous VOCs in breath via advanced hollow waveguide MIR sensor technology, clearly demonstrating its potential for the analysis of volatile biomarkers in exhaled breath.

A novel optical chemical sensor based AuNR-MTPP and dyes for lung cancer biomarkers in exhaled breath identification

In this work, the gold nanorod (AuNR) was prepared by the seed mediated growth method and characterized by SEM and UV–vis spectrum. MTPP-AuNR nanocomposites were synthetized by solution co-blending method and used to fabricate an optical chemical sensor for identification of lung cancer biomarkers in exhaled breath (VOCs: decane, undecane, hexanal, heptanal, benzene and 1,2,4-trimethylbenzene). Series of color difference maps of six VOCs were obtained, and principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used for further data analysis. The results demonstrated that VOCs could be identified rapidly and accurately by the novel sensor due to the modest sensitivity and selectivity of sensitive materials for VOCs. This noninvasive, low cost and fast method could be used for wide-spread screening for lung cancer in the high-risk groups.

Discovery of potential biomarkers in exhaled breath for diagnosis of type 2 diabetes mellitus based on GC-MS with metabolomics

Eight breath biomarkers of T2DM were discovered by a new SPME-GC-MS based metabolic profiling tool.

Asymmetric Dimethylarginine

Asymmetric Dimethylarginine

From Olympians to Mere Mortals

From Olympians to Mere Mortals

Machine Learning Applied to Chemical Analysis: Sensing Multiple Biomarkers in Simulated Breath Using a Temperature-Pulsed Electronic-Nose

Monitoring of chemical species in breath offers an approach for the detection of disease and other conditions that cause homeostatic imbalance. Here, we demonstrate the use of microsensor-based devices for detecting select biomarkers in simulated exhaled breath as a step toward enabling fast and inexpensive breath-screening technology. Microhotplate elements functionalized with three chemiresistive metal-oxide films (SnO(2), In(2)O(3), and CuO) were used to acquire data in simulated breath containing single targets [(5 to 20) μmol/mol ammonia, methanol, and acetone], as well as mixtures of those species. All devices were operated with programmed thermal cycles featuring rapid temperature excursions, during which film resistances were measured. Material-specific temperature programs were optimized to achieve temperature-dependent metal-oxide sensing film conductance levels and target selectivity. A supervised hierarchical machine-learning algorithm using linear discriminant analysis for dimensional reduction of sensing data and discrimination was developed. This algorithm was employed in the classification and quantification of biomarkers. This approach to microsensor data collection and processing was successful in classifying and quantifying the model biomarkers in validation-set mixtures.

The analysis of volatile organic compounds biomarkers for lung cancer in exhaled breath, tissues and cell lines

Volatile organic compounds (VOCs) biomarkers in breath provide a novel, noninvasive and quick approach to diagnosis lung cancer. The aim of the proposed study was to investigate the VOCs biomarkers in exhaled breath for lung cancer. The VOCs in exhaled breath of 88 lung cancer patients, 70 lung benign disease and 85 healthy people were analyzed by Solid Phase Micro Extraction - Gas Chromatography Mass Spectrometry (SPME-GCMS). Three types of lung cancer cells and 18 lung cancer patients' tissues were cultured in vitro. The VOCs in the headspace of these cultivations were analyzed as an evidence of production mechanism of the VOCs in breath. Three lung cancer diagnosis models were constructed respectively in exhaled breath samples using Linear Discriminant Analysis (LDA). Leave one out cross validation was employed to evaluate these models. 23 VOCs, whose areas under curve (AUC) of receiver operating characteristic (ROC) > 0.60 and p < 0.01, were confirmed as the VOCs biomarkers for lung cancer. Three diagnostic models based on 23 VOCs could easily discriminate lung cancer patients from controls with 96.47% sensitivity and 97.47% specificity. However, the discrimination between early stage and later stage lung cancer was not very obvious.

Cardiovascular Biomarkers in Exhaled Breath

With each breath that we exhale, thousands of molecules are expelled in our breath, giving individuals a “breath-print” that can tell a lot about them and their state of health. Breath analysis is rapidly evolving as the new frontier in medical testing. The end of the 20th century and the beginning of the 21st century have arguably witnessed a revolution in our understanding of the constituents of exhaled breath and the development of the field of breath analysis and testing. Thanks to major breakthroughs in new technologies (infrared, electrochemical, chemiluminescence, and others) and the availability of mass spectrometers, the field of breath analysis has made considerable advances in the 21st century. Several methods are now in clinical use or nearly ready to enter that arena.Breath analysis has the potential to offer relatively inexpensive, rapid, noninvasive methods for detecting and/or monitoring a variety of diseases. Breath analysis also has applications in fields beyond medicine, including environmental monitoring, security, and others. This review will focus on exhaled breath as a potential source of biomarkers for medical applications with specific attention to applications (and potential applications) in cardiovascular disease.

Exhaled breath analysis for early cancer detection: principle and progress in direct mass spectrometry techniques

Volatile biomarker analysis in exhaled breath is becoming one of the desirable strategies for cancer detection because it may offer a relatively inexpensive, rapid, and non-invasive screening method for early diagnosis. Breath analysis has attracted a considerable amount of scientific and clinical interest over the past decade. However, breath is not yet used for routine medical diagnostic purposes. Challenges faced in the development of breath analysis for cancer diagnosis include developing techniques that can measure biomarkers in exhaled breath at ultratrace levels, providing definitive evidence for their presence and for the relationship between the proposed biomarker and the underlying condition. Various analytical methods are used for the detection of breath biomarkers. Gas chromatography-based methods which involve sample collection, analyte preconcentration, desorption, and separation steps are the most popular. However, direct-sampling mass spectrometry techniques have been proven more reliable for air analysis without prior sample pretreatment or chromatographic separation. This review focuses on the most commonly used direct mass spectrometry methods for the direct online analysis of endogenous cancer biomarkers in exhaled breath, with particular attention to principle of detection, method performance, advantages, shortcomings, recent advances, and applications within health-related studies for cancer biomarkers research. The principle behind the science of breath analysis for cancer diagnosis is also discussed.

Combining a DS-DBR laser with QPM-DFG for mid-infrared spectroscopy

Studies into the suitability of a novel, widely tunable telecom L-band (1563–1613 nm) digital supermode distributed Bragg reflector (DS-DBR) laser for spectroscopy in the mid-IR are presented. Light from the DS-DBR laser was mixed with 1064 nm radiation in a periodically poled lithium niobate (PPLN) crystal to generate mid-IR light by quasi phase matching difference frequency generation (QPM-DFG). The resultant continuous wave radiation covered the range 3000–3200 cm−1 with powers of up to 2.6 μW. The use of such laser light for spectroscopic applications was illustrated by performing absorption experiments on both narrow-band and broad-band absorbers, namely methane (CH4) and methanethiol (CH3SH). Wavelength modulation spectroscopy (WMS) on CH4 demonstrated that the modulation characteristics of the DS-DBR laser observed in the near-IR were transposed to the mid-IR and yielded a sensitivity of 3.1×10−6 cm−1 Hz−1/2 over a 47 cm path length. In the CH3SH spectrum, the absorption feature at 3040 cm−1 was identified as a potential useful region for monitoring this biomarker in exhaled breath at reduced pressures.

The application of exhaled breath gas and exhaled breath condensate analysis in the investigation of the lower respiratory tract in veterinary medicine: A review

The analysis of biomarkers in exhaled breath (EB) and exhaled breath condensate (EBC) may allow non-invasive and repeatable assessment of respiratory health and disease in mammals. Compared to human medicine, however, research data from EB and EBC analysis in veterinary medicine are limited and more patient variables influencing concentrations of EB/EBC analytes may be present. In addition, variations in methodologies between studies may influence results. A comparison of the approaches used in veterinary research by different groups may aid in the identification of potentially reliable and repeatable biomarkers suitable for further investigation. To date, changes in acid-base status and increased concentrations of inflammatory mediators have been the main findings in studies of pulmonary disease states in animals. Whilst these biomarkers are unlikely to represent specific and sensitive diagnostic parameters, they do have potential application in monitoring disease progression and treatment response.

Observing the human exposome as reflected in breath biomarkers: heat map data interpretation for environmental and intelligence research

Over the past decade, the research of human system biology and the interactions with the external environment has permeated all phases of environmental, medical and public health research. Similar to the fields of genomics and proteomics research, the advent of new instrumentation for measuring breath biomarkers and their associated meta-data also provide very useful, albeit complex, data structures. The biomarker research community is beginning to invoke tools from system biology to assess the impact of environmental exposures, as well as from internal health states, on the expression of suites of chemicals in exhaled breath. This new approach introduces the concept of the exposome as a complement to the genome in exploring the environment–gene interaction. In addition to answering questions regarding health status for the medical community, breath biomarker patterns are useful for assessing public health risks from environmental exposures. Furthermore, breath biomarker patterns can inform security risks from suspects via covert interrogation of blood borne chemical levels that reflect previous activities. This paper discusses how different classes of exhaled breath biomarker measurements can be used to rapidly assess patterns in complex data. We present exhaled breath data sets to demonstrate the value of the graphical ‘heat map’ approach for hypothesis development and subsequent guidance for stochastic and mixed effect data interpretation. We also show how to graphically interpret exhaled breath measurements of exogenous jet fuel components, as well as exhaled breath condensate measurements of endogenous chemicals.

Lung cancer biomarkers in exhaled breath

Lung cancer is the leading cause of cancer-related mortality worldwide. Methods for early detection of lung cancer, such as computerized tomography scanning technology, often discover a large number of small lung nodules, posing a new problem to radiologists and chest physicians. The vast majority of these nodules will be benign, but there is currently no easy way to determine which nodules represent very early lung cancer. Adjuvant testing with PET imaging and nonsurgical biopsies has a low yield for these small indeterminate nodules, carries potential morbidity and is costly. Indeed, purely morphological criteria seem to be insufficient for distinguishing lung cancer from benign nodules at early stages with sufficient confidence, therefore false positives undergoing surgical resection frequently occur. A molecular approach to the diagnosis of lung cancer through the analysis of exhaled breath could greatly improve the specificity of imaging procedures. A biomarker-driven approach to signs or symptoms possibly due to lung cancer would represent a complementary tool aimed at ruling out (with known error probability) rather than diagnosing lung cancer. Volatile and nonvolatile components of the breath are being studied as biomarkers of lung cancer. Breath testing is noninvasive and potentially inexpensive. There is promise that an accurate lung cancer breath biomarker, capable of being applied clinically, will be developed in the near future. In this article, we summarize some of the rationale for breath biomarker development, review the published literature in this field and provide thoughts regarding future directions.

Real-time, in vivo monitoring and pharmacokinetics of valproic acid via a novel biomarker in exhaled breath

Extractive electrospray ionization mass spectrometry is shown to allow real-time, in vivo drug monitoring and pharmacokinetic measurement in a non-invasive, pain-free manner as demonstrated by the mass spectral measurement of a novel exhaled breath biomarker for valproic acid, a medication used to control epilepsy.

Measurement of CO amount fractions using a pulsed quantum-cascade laser operated in the intrapulse mode

Carbon monoxide (CO) is an important molecule for environmental monitoring, industrial process control, and a biomarker in exhaled human breath. Obtaining reliable and traceable data is indispensable. We employed direct absorption spectroscopy-based absolute amount fraction measurements of CO in a gravimetrically prepared gas mixture. A quantum-cascade laser operated in the intrapulse mode was used to probe the P(1) line of CO at 2139.4 cm−1. The spectrometrically determined CO amount fraction agrees perfectly with the gravimetric reference value. We focused on the method, the uncertainty analysis of the spectrometry-based data retrieval and the respective traceability of input parameters to the SI. An uncertainty budget is presented. Our reproducibility is better than 1%. The relative deviation of the spectrometric CO amount fractions from the gravimetric reference value reads minus 1.8%, which is covered by a 4% relative expanded uncertainty of single measurements (k=2).

Effects of sample processing, time and storage condition on cysteinyl leukotrienes in exhaled breath condensate

Cysteinyl leukotrienes (CysLTs) can be measured in exhaled breath condensate (EBC); however, there is considerable variation in reported EBC CysLT concentrations from asthmatic and healthy subjects between published studies, which may be partially explained by CysLT degradation during processing and storage. We assessed CysLT stability over 6 months in EBC from healthy subjects stored at −80 °C, layered with argon and then stored at −80 °C or stored in 0.2% formic acid in methanol at −80 °C following solid-phase extraction (SPE). We found significant CysLT degradation over time in both spiked and unspiked EBC samples stored at −80 °C or layered with argon. CysLT recovery was significantly greater after storage for 6 months in 0.2% formic acid in methanol following SPE; however, there was substantial variability in endogenous CysLT recovery over time, possibly attributable to inter- and intra-assay variability at the low end of the CysLT assay range. Despite the greater recovery of CysLTs in EBC stored in methanol following SPE, the degree of variability introduced by this method appears unacceptably high. We believe that the development of more sensitive and less variable methods for quantifying CysLTs in EBC are required before CysLTs can reliably be utilized as biomarkers in exhaled breath. Sample processing and storage, as well as inter- and intra-assay variability, should be carefully considered in the design of clinical studies that include assessments of EBC constituents as biomarkers.