In the last 30 days

• Open/close A new ¹³C breath test to detect vitamin B12 deficiency: a prevalent and poorly diagnosed health problem

  David A Wagner et al 2011 J. Breath Res. 5 046001 Tag this article

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  Vitamin B12 deficiency is emerging as a growing public health problem. The most commonly used diagnostic tests are limited in accuracy, sensitivity, and are non-specific for B12 deficiency. The aim of this study was to develop a simple B12 breath test (BBT) to more accurately evaluate vitamin B12 status as an alternative to the most common diagnostic test, serum B12 levels. The breath test is based on the metabolism of sodium 1- ¹³C-propionate to ¹³CO ₂ which requires B12 as a cofactor. We initially compared the BBT to current B12 diagnostic methods in 58 subjects. Subjects also received a second BBT 1–3 days after initial testing to evaluate reproducibility of results. Propionate dosage, fasting times, and collection periods were compared, respectively. The dose of sodium 1- ¹³C-propionate (10–50 mg) gave equivalent results while an 8 h fast was essential. Statistical analysis revealed that breath collection times could be reduced to just a baseline and 10 and 20 min following propionate dosing. We also measured the incidence of B12 deficiency with the BBT in 119 patients with chronic pancreatitis, Crohn's disease, small intestinal bacterial overgrowth, and subjects over 65 years of age. The BBT results agreed with previous publications showing a higher incidence of B12 deficiency in these patients. The BBT may provide clinicians with a non-invasive, accurate, reliable, and reproducible diagnostic test to detect vitamin B12 deficiency.

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

  Joachim D Pleil et al 2011 J. Breath Res. 5 037104 Tag this article

  Article References Full text PDF (1.31 MB)

  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.

• Open/close Volatile biomarkers in the breath of women with breast cancer

  Michael Phillips et al 2010 J. Breath Res. 4 026003 Tag this article

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  We sought biomarkers of breast cancer in the breath because the disease is accompanied by increased oxidative stress and induction of cytochrome P450 enzymes, both of which generate volatile organic compounds (VOCs) that are excreted in breath. We analyzed breath VOCs in 54 women with biopsy-proven breast cancer and 204 cancer-free controls, using gas chromatography/mass spectroscopy. Chromatograms were converted into a series of data points by segmenting them into 900 time slices (8 s duration, 4 s overlap) and determining their alveolar gradients (abundance in breath minus abundance in ambient room air). Monte Carlo simulations identified time slices with better than random accuracy as biomarkers of breast cancer by excluding random identifiers. Patients were randomly allocated to training sets or test sets in 2:1 data splits. In the training sets, time slices were ranked according their C-statistic values (area under curve of receiver operating characteristic), and the top ten time slices were combined in multivariate algorithms that were cross-validated in the test sets. Monte Carlo simulations identified an excess of correct over random time slices, consistent with non-random biomarkers of breast cancer in the breath. The outcomes of ten random data splits (mean (standard deviation)) in the training sets were sensitivity = 78.5% (6.14), specificity = 88.3% (5.47), C-statistic = 0.89 (0.03) and in the test sets, sensitivity = 75.3% (7.22), specificity = 84.8 (9.97), C-statistic = 0.83 (0.06). A breath test identified women with breast cancer, employing a combination of volatile biomarkers in a multivariate algorithm.

• Open/close Special section on Breath Gas Analysis

  Jürgen Röpcke and Mario Hannemann 2011 J. Breath Res. 5 020201 Tag this article

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  In Spring 2009 an idea was born to bring together the leading specialists from Germany and Austria working in the emerging field of breath gas research and its application for clinical diagnosis and therapeutic monitoring within an internationally open workshop. To bring this idea to fruition the first German–Austrian Workshop on Breath Gas Analysis was held in Greifswald, Germany, 7–9 June 2010. The conference was organized by the Leibniz Institute for Plasma Research and Technology (INP), Greifswald, in cooperation with the Institute of Community Medicine (ICM) of the University of Greifswald. The scientific program of the workshop covered all modern aspects of exhaled breath gas analysis ranging from sampling techniques and analytical approaches to pilot cases studies. The 54 participants came from nine European and non-European countries. The five invited speakers originated from Germany, Austria, Great Britain and the USA.

  The workshop showed that over the few last years analytical methods for the detection of volatile compounds released through exhaled breath, the nasal cavity, oral cavity, urine or sweat and the determination of their concentrations, have been considerably improved or even newly developed. Most of these methods, used today, were the focus of the workshop including:

  • gas-chromatography with mass spectrometric detection (GC-MS), often combined with thermal desorption (TD-GC-MS)
  • proton-transfer-reaction mass spectrometry (PTR-MS)
  • laser absorption spectroscopy (LAS)
  • ion mobility spectrometry (IMS), mostly coupled to multi-capillary columns (MCC/IMS)
  • differential ion mobility spectrometry (DMS)
  • sensors or sensor arrays

  We would like to mention some highlights of the workshop, which are (in part) now published as a special section in this issue.

  One of the first marketable methods of breath analysis based on LAS was introduced with the flow-through fast liver investigation packet (FLIP) to quantitatively measure the amount of exhaled ¹³CO ₂ (see the paper by T Rubin et al [1]).

  Differential ion mobility spectrometry (DMS), a further development of conventional IMS using strong oscillating electric fields perpendicular to the flow of carrier gas and ions, was adopted for VOC analysis in exhaled breath and headspace of feces (see the paper by R Purkhart et al [2]).

  A new sensor to measure the asthma marker NO was presented (see the paper by E Magori et al [3]). The sensor is based on the conversion of NO into NO ₂ followed by a NO ₂ work function gas sensing. Furthermore a nano-medical artificial olfactory system (AOS) for cancer detection that is based on an array of cross-reactive sensors of nanoparticles and/or single-walled carbon nanotubes for detecting volatile biomarkers of cancer was introduced.

  Clinical studies were mostly directed to lung cancer verification using VOC detection in exhaled breath. Also, rapid diagnosis in nephrology was reported. TD-GC-MS, PTR-MS, MCC/IMS or electronic noses (arrays of chemo sensors) were used. Sometimes the methods of pattern recognition were taken into account.

  A number of low-molecular breath gas constituents using LAS have been monitored (see the paper by M Hannemann et al [4]). These investigations were included in the population-based epidemiological Study of Health in Pomerania (SHIP-TREND) performed at the University of Greifswald. SHIP-TREND covers about 5000 adult subjects, aged 20–79 years, within three years.

  Finally, we would like to give our special thanks to the Scientific Advisory Board and to the Local Organizing Committee for their important contributions to the success of the workshop. We are also particularly grateful to the Editorial Board of the Journal of Breath Research for peer-reviewing the submitted articles and for the publication of this special issue.

  References
  [1] Rubin T, von Haimberger T, Helmke A and Heyne K 2011 Quantitative determination of metabolization dynamics by a real time ¹³CO ₂ breath test J. Breath Res. 5 027102
  [2] Purkhart R, Köhler H, Liebler-Tenorio E, Meyer M, Becher G, Kikowatz A and Reinhold P 2011 Chronic intestinal Mycobacteria infection: Discrimination via VOC analysis in exhaled breath and headspace of feces using differential ion mobility spectrometry J. Breath Res. 5 027103
  [3] Magori E, Hiltawsky K, Fleischer M, Simon E, Pohle R, von Sicard O and Tawil A 2011 Fractional exhaled nitric oxide (FeNO) measurement with a handheld device J. Breath Res. 5 027104
  [4] Hannemann M, Antufjew A, Borgmann K, Hempel F, Ittermann T, Welzel S, Weltmann K D, Völzke H and Röpcke R 2011 Influence of age and sex in exhaled breath samples investigated by means of infrared laser absorption spectroscopy J. Breath Res. 5 027101

  Jürgen Röpcke and Mario Hannemann
  INP Greifswald, Germany
  Guest Editors

• Open/close LC-ESI-MS/MS method for oxidative stress multimarker screening in the exhaled breath condensate of asbestosis/silicosis patients

  K Syslová et al 2010 J. Breath Res. 4 017104 Tag this article

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  The sensitive assay method was developed for a parallel, rapid and precise determination of the most prominent oxidative stress biomarkers: 8- iso-prostaglandin F _2α a lipid oxidation biomarker, o-tyrosine an amino acid oxidation biomarker and 8-hydroxy-2'-deoxy-guanosine a nucleic acid oxidation biomarker. The method consisted of a pre-treatment part, freeze drying (lyophilization), serving the purpose of biomarkers concentration from the exhaled breath condensate and detection method LC-ESI-MS/MS, where the selected reaction-monitoring mode was used for its extremely high degree of selectivity and the stable-isotope-dilution assay for its high precision of quantification. The developed method is characterized by the following parameters: the precision was higher than 84.3% and the mean accuracy (relative error) was determined lower than 11.6%. The method was tested on samples obtained from patients diagnosed with asbestosis and silicosis, occupational diseases induced by oxidative stress, and then compared with samples from healthy subjects. The difference in biomarkers' concentration levels found between the two groups was statistically significant.

• Open/close Exhaled breath condensates in asthma: diagnostic and therapeutic implications

  Shamsah Kazani and Elliot Israel 2010 J. Breath Res. 4 047001 Tag this article

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  Exhaled breath condensate (EBC) collection and analysis offers a unique non-invasive method to sample the airway lining fluid. It enables classification and quantification of airway inflammation associated with various pulmonary diseases such as asthma. Over the last decade, innumerable efforts have been made to identify biomarkers in EBC for diagnosis and management of asthma. The aim of this review is to consolidate information available to date, summarize findings from studies and identify potential biomarkers which need further refinement through translational research prior to application in clinical practice.

• Open/close Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus?

  David Smith et al 2011 J. Breath Res. 5 022001 Tag this article

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  Although it has been known for centuries that there are compounds in exhaled breath that are altered in disease, it is only in the last few decades that it has been possible to measure them with sufficient accuracy and precision to make them clinically useful. The clinical utility of breath analysis has also been limited by the practical difficulties of collecting representative breath samples, free from contaminants. More recent methods of breath analysis have allowed real-time analysis of breath, eliminating the need for sample collection, and therefore potentially allowing the rapid feedback of results to patient and clinician. One possible future application of breath analysis may be the monitoring of metabolic control in patients with diabetes mellitus. This perspective article provides an overview of the studies of breath analysis in diabetes, focusing on the breath metabolites; acetone, isoprene and also methyl nitrate that have previously been reported to be altered in diabetes, highlighting the factors that may potentially confound their interpretation. Specific attention is given to selected ion flow tube mass spectrometry (SIFT-MS) and proton transfer reaction mass spectrometry (PTR-MS), because they are techniques that have been developed specifically for the absolute quantification of breath metabolites in real time, although reference is made to some of the alternative techniques, including sensors and optical devices. Whilst breath analysis, using SIFT-MS, PTR-MS and other sensitive techniques, can potentially be used for the non-invasive monitoring of metabolic conditions that may include diabetes mellitus, further work is required in terms of the clinical and analytical validation. Furthermore, it is unclear at present what breath metabolites should be monitored and what factors may confound their interpretation. Although a non-invasive method of monitoring glycaemic control is clearly desirable, it will be important to demonstrate its analytical comparability with the well-established and validated methods for blood glucose measurement.

• Open/close Inhaled today, not gone tomorrow: pharmacokinetics and environmental exposure of volatiles in exhaled breath

  J Beauchamp 2011 J. Breath Res. 5 037103 Tag this article

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  The chemical analysis of exhaled breath gas to assess state of health or identify disease biomarkers has gained growing interest in recent years, with advances in new technologies providing scientists and physicians with a powerful analytical arsenal with which to tackle pertinent issues. The application of these methods for pharmacokinetic studies, however, has received less attention despite its enormous potential in this field. For instance, breath gas analysis may be employed to characterize uptake and distribution within the body of exogenous volatile compounds, either from a pharmaceutical point of view, or in relation to environmental inhalation exposure. Both of these topics can benefit greatly from utilizing breath gas complementarily or as a surrogate to blood as an analytical medium, since breath sampling is non-invasive, inexhaustible, and is achievable with a frequency far exceeding that which is feasible for blood. However, because of the efficiency with which certain exogenous compounds are reflected in breath, this can also often be a significant source of confounding variables that require consideration in routine breath gas analyses. This paper provides an overview of the possibilities of breath gas analysis for pharmacokinetics and environmental exposure investigations and discusses the presence of exogenous compounds in standard breath analyses and their repercussions in terms of erroneous data interpretation.

• Open/close Ion mobility spectrometry coupled with multi-capillary columns for metabolic profiling of human breath

  Jörg Ingo Baumbach 2009 J. Breath Res. 3 034001 Tag this article

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  Recently, ion mobility spectrometry (IMS) started to be used for direct breath analysis with respect to metabolic profiling, biomarker finding and gas trace analysis. The present review describes the basic operation of an ion mobility spectrometer including the ionization process, humidity effects and sampling procedures. To enhance the resolution, pre-separation by multi-capillary columns (MCCs) is discussed and examples for IMS chromatograms are presented. The focus is to review the analytical method IMS with respect to potential use for direct investigations of humid air in direct breath analysis but not on detailed discussion of results of specific medical application of MCC/IMS or on specific analytes found in exhaled air.

• Open/close Breath analysis system based on phase-shifting interferometric microscopy readout of microcantilever arrays

  S Kelling et al 2011 J. Breath Res. 5 037106 Tag this article

  Article References Full text PDF (1.05 MB)

  Microcantilever (MC) sensors can provide ultrasensitive bio-chemical detection. Monitoring the bending response of large arrays of MC sensors coated with a library of receptors will produce a characteristic 'breath-print' corresponding to the breath composition; this promises to be suitable for non-invasive medical diagnostics. While MC arrays with hundreds of individual sensors can be produced readily, conventional MC readout methods are not suitable for the parallel readout of tens or hundreds of individual sensors. We have developed a MC sensor-array readout method based on phase-shifting interferometric microscopy (PSIM) which allows for the simultaneous monitoring of the response of all MCs within the field of view of the readout microscope optics. Based on this sensor technology, we have built an exhaled breath-analysis research instrument for the Point of Care Diagnostics Development Unit at the University of Leicester, UK. In this paper, we describe the PSIM readout system and the breath-analysis instrument that will be used to test sensor surface coatings and develop sensor sets with response patterns suitable for clear correlation to patients' health condition.