Breath analysis science at PittCon 2012, Orlando, Florida

• Published in: Journal of breath research Vol. 6; no. 3; p. 039001
• Main Authors: Pleil, Joachim D, Stiegel, Matthew A, Kormos, Tzipporah M, Sobus, Jon R
• Format: Journal Article Conference Proceeding
• Language: English
• Published: England IOP Publishing 01.09.2012
• Subjects: Biomarkers; Biomarkers - analysis; Breath Tests - methods; Humans; Laboratories; Metabolites; Sensors; Canada; Italy; Austria; Florida; United States > US; Germany
• ISSN: 1752-7155; 1752-7163
• DOI: 10.1088/1752-7155/6/3/039001

BackgroundBreath analysis science was featured in three organized sessions at this year's PittsburghConference and Exposition, or 'PittCon 2012' (http://www.pittcon.org/). As described inprevious meeting reports, PittCon is one of the largest international conferences foranalytical chemistry and instrumentation, typically attracting about 20 000 attendees and1000 commercial exhibitors (Pleil 2010, 2011). This year the conference was held inOrlando, Florida, USA at the Orange County Conference Center.In the past few years, breath analysis science has taken on an ever-increasing role atPittCon through the success of the International Association of Breath Research (IABR) andthe Journal of Breath Research (JBR). We have also had a presence at a recent conference ofthe Submarine Air Monitoring and Air Purification (SAMAP) organization in Taranto, Italy,wherein breath analysis and other biomarker measurements are taking on an increasinglyimportant role in assessing exposures and health in artificial atmospheres includingsubmarines, aircraft and spacecraft (Pleil and Hansel 2012).In 2012, members of IABR organized or participated in three distinct PittCon events: acontributed technical session, a conferee networking session, and an invited symposiumseries. The common thread among these three different conferencing settings was theconcept of 'non-invasive' environmental, medical, and diagnostic biomarker assessment. Ofparticular interest was how breath is being considered more and more mainstream as abiological medium, and is often discussed favorably as complementary or alternative toblood and urine measurements.Technical session: non-invasive biomedical analysisThis was our JBR/IABR signature session organized and co-chaired by Dr Joachim Pleilfrom the US Environmental Protection Agency and Dr Wolfram Miekisch1 from the RostockUniversity Hospital in Rostock, Germany. Our speakers were carefully selected to cover abroad range on breath diagnostic techniques with some topics including urinary biomarkers,the 'other' non-invasive (or at least minimally invasive) biomarker approach.The first presentation, 'Non-invasive biomedical analysis—dawning of a new area ofdiagnostic information' was given by Professor Jochen K Schubert2 from the University ofRostock, Germany. Professor Schubert discussed the important role that diagnostic tests playin life-saving therapy and in early stage disease detection. He particularly stressed theincreasing need for non-invasive techniques (especially for critical care medicine) and forrapid assessments preferably performed at the bedside. He discussed new technologies forinstrument miniaturization for breath analysis and presented results showing the potential ofreal-time mass spectrometers based on proton transfer reactions (PTR). He also gave anintriguing example for a minimally invasive blood test based on a gas-phase (breath)technology wherein specially coated fibers are inserted directly into the blood stream toabsorb certain compounds of interest for subsequent desorption analysis using standard solidphase micro-extraction (SPME) methods.Dr Jens Herbig3 from Ionimed Analytik in Innsbruck, Austria gave the secondpresentation, entitled 'Applications of PTR-MS in medicine and biotechnology'. Dr Herbigbegan his talk with an introduction to proton-transfer-reaction mass spectrometers(PTR-MS), highlighting benefits of these analytical tools for real-time analysis of volatileorganic compounds (VOCs) in biological media, and articulating differences betweenavailable quadrupole and time-of-flight (ToF) based detections systems. He thendemonstrated how, via real-time monitoring of exhaled breath, PTR-MS instruments can beused to evaluate chemical uptake, distribution and metabolism in the human body. Finally, heshowed applications of the PTR-MS systems for real-time monitoring of in vitro systems. Anexample was given of the analysis of fermentation off-gas produced by micro-organisms.Together these descriptions and examples showed unique advantages of real-time monitoringequipment over classical offline tools, drawing considerable interest from session attendees.Dr Jon Sobus from the US Environmental Protection Agency presented 'Statisticalconsiderations for interpreting urinary biomarker concentrations'. He discussed how urine,like breath, is a preferred sample medium for biomedical analysis since it is available inabundant supply and collected using non-invasive techniques. He highlighted that urinarybiomarker measurements are generally reported in units of concentration, and are thereforesubject to variations from changing urine output, as well as changing exposure or healthstate. Dr Sobus stressed that, given this dependence, careful evaluation of urinary biomarkermeasurements is critical for decision making in medical and public health investigations. Hefurther proposed a mathematical approach to correct for changing urine output; correctionfactors, based in part on urinary creatinine measurements, used empirical observations ofhealthy adults made during a recent EPA study. In closing, Dr Sobus highlighted implicationsof using and not using correction factors for biomedical urine analysis.Dr Sobus was followed by Professor Cristina E Davis4 from the University of California,Davis with a presentation entitled 'Mammalian cell culture headspace volatile organiccompounds hold vital clues as putative biomarkers of cellular changes'. Professor Davisdescribed the analysis of VOCs from cell culture using gas chromatography-massspectrometry (GC-MS) to develop an odor fingerprint. She illustrated how VOC headspaceanalysis can distinguish between human B cells differing by a single human leukocyteantigen (HLA) gene, demonstrating how VOC analysis can illustrate changes occurring on acellular level. Professor Davis then showed that different viral infections result in uniquefluctuations to VOC fingerprints indicating tremendous biomedical potential. She suggestedthe potential for such a VOC analysis as a non-invasive technique for diagnosing infectionsgiven the development of appropriate sensor devices.Next, Dr Tzipporah M Kormos from the US Environmental Protection Agency presented'Metabolomics evaluation: perturbations of organic metabolites in human breath and urine'.Dr Kormos provided an overview of the attempts underway in method development at the USEPA for applying non-targeted top-down approaches to link environmental exposures tohuman health effects. She described the goal of characterizing the human exposome in orderto effectively link exposure to health effects. However, she also denoted how the eclecticchemical composition of the exposome poses an analytical challenge requiring a range ofinstrumentation to effectively characterize its components (including liquidchromatography-mass spectrometry (LC-MS), nuclear magnetic resonance spectroscopy(NMR), immunochemistry, and GC-MS). Dr Kormos stressed the need for non-invasivesampling in such exposure studies as the only way to obtain a sufficient number of biologicalsamples from the general populace in field studies.The sixth presentation of the session, entitled 'Real-time measurements andmathematical modeling of breath biomarkers to address the impact of physiological effects',was presented by Dr Julian King5 of the Austrian Academy of Sciences, Dornbirn, Austria.Here, Dr King presented real-time measurements of VOCs in breath samples, collectedduring periods of rest, exercise and sleep, and determined using PTR-MS and solid phasemicro-extraction (SPME)/GC-MS. Dr King focused on acetone and isoprene as targetmolecules, and showed how measurements of these analytes, combined with mathematicalmodels, can be used to explore mechanistic relationships governing the general behaviors of VOCs in breath. Dr King suggested that these results provide a basis for experimental designand general guidance for interpreting empirical results. Specifically, he recommended breathgas analysis for evaluating metabolic processes of VOCs, namely storage, transport, andbiotransformation, in vivo.Matthew Stiegel from the University of North Carolina at Chapel Hill, NC, gave theseventh talk, entitled 'Correlations of inflammatory cytokines in blood, exhaled breathcondensate, and urine'. This talk focused on multi-media biological measurements ofinterleukins, interferon-γ, and tumor necrosis factor-a made as part of a controlled chamberexperiment using human volunteers. Here, the TH1/TH2 cytokines were evaluated as makersof inflammatory/endogenous response to various controlled exposures, including dieselexhaust, ozone, and diesel exhaust plus ozone. Stiegel showed that cytokine levels andpatterns changed across media and subjects, and suggested that these changes reflectsubject-specific responses to the controlled exposures. He concluded that cytokine levels inblood, exhaled breath condensate (EBC), and urine are probative indicators of exposureand/or endogenous response, and thus, are useful for exposure and health monitoring.Phillip Trefz6 from the University of Rostock, Germany gave the final talk 'Microextraction techniques as a link between clinical application and hyphenated analyticaltechniques'. Mr Trefz explained how a current hindrance to the biomedical application ofbreath analysis is sampling. As analytical instrumentation is not yet a bedside technique,reliable tools are required for breath collection, concentration, and storage in order to enablethe detection of trace VOCs. He explained the benefits of needle trap devices (NTDs) oversolid phase extraction (SPE) and SPME techniques in terms of sensitivity and sampling time.A comparison of different sorbents showed the possibility of storing samples over a weekwhile retaining high levels of recovery and reproducibility. He then described an interestingpilot study using NTDs to sample from ventilators of patients with various health conditions.Networking session: non-invasive biomedical analysis—the fast