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A recognition of David Smith’s unique contributions to the field of breath analysis

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Journal of Breath Research J. Breath Res. 8 (2014) 030201 (4pp)

doi:10.1088/1752-7155/8/3/030201

Editorial

A recognition of David Smith’s unique contributions to the field of breath analysis Jonathan Beauchamp

Department of Sensory Analytics, Fraunhofer Institute for Processing and Packaging IVV, Freising, Germany E-mail: jonathan.beauchamp@ ivv.fraunhofer.de Terence H Risby

Bloomberg School of Public Health, The Johns Hopkins ­University, Baltimore, MD, USA E-mail: [email protected]

1752-7155/14/030201+4$33.00

Breath gas analysis has received steadily increasing interest from the scientific and clinical communities over the years, particularly in the past two decades. The number of researchers actively targeting biomarkers in breath as a means for medical diagnoses or to monitor ­therapeutic interventions has increased from just a handful 20 years ago to numerous research groups from diverse disciplines, spread throughout the globe. David Smith belongs to the scattering of pioneering scientists that were active in the earlier years of breath analysis. Professor David Smith, FRS, of the Institute for Science and Technology in Medicine at Keele University, UK started his career a long distance from breath. He obtained his BA degree from the University of Keele in physics and chemistry, received both a PhD degree in electron physics and a DSc degree in space research from the University of Birmingham, UK. He remained at the University of Birmingham rising through the ranks to become Professor of Chemical Physics. From Birmingham he moved to the University of Innsbruck in Austria where he was appointed Professor at the Institut für Ionenphysik. Subsequently, he returned to his Alma Mater where he was appointed Professor and has remained there. His expertise in physical chemistry and ion–molecule reactions made him a leading figure in the investigation of ion chemistry in the Earth’s upper atmosphere and in interstellar gas clouds. His research was recognized both nationally and internationally by the awards of Fellow of the Royal Society, London, UK, Honorary DSc, University of Keele, UK, SASP Schrödinger Prize, Austria, Medal of Masaryk University, Brno, Czech Republic, and Gold Medal of the Faculty of Mathematics and Physics of Comenius University, Bratislava, Slovakia. His research activities in this field led to his co-development of a technique called selected ion flow tube mass spectrometry (SIFT-MS) in the mid-1970s [1], which was used to characterize the ion chemistry occurring in the aforementioned environments. SIFT-MS is now widely known in the breath gas community as one of the main online tools for the comprehensive analysis of breath gas constituents, but the technology had to wait a further 20 years after its initial development before it first saw an application in breath. In 1996, David and his close colleague Patrik Španěl published the first article outlining the utility of SIFT-MS for the quantitative and sensitive analysis of trace gases in breath [2]. Today the breath gas literature is abundant with articles reporting on breath-related studies employing SIFT-MS. David Smith has co-authored the majority of these papers, which clearly illustrates his impact on the development of breath research over the past two decades. David’s extensive involvement in breath research is also reflected in him being a founding member of the International Association of Breath Research (IABR), as well as a founding editorial board member of this journal. David’s unique contribution to the field of breath analysis was his pioneering studies using SIFT-MS to measure the composition and concentration of molecules in breath in real-time. This approach provides novel information on the presence of reactive substances in breath that could not be observed in offline analysis of collected breath samples. This special issue of Journal of Breath Research is published in recognition of David’s substantial contributions to the field of breath gas analysis. This issue contains 10 articles on diverse aspects of breath research, from technical instrumental developments to specific applications in breath and cell culture analyses. It commences with an article that addresses one of the major challenges currently facing breath analysis, namely the lack of conformity in sampling approaches [3, 4], a concern that David Smith has voiced on numerous occasions. The paper by Herbig and Beauchamp entitled ‘Towards standardization in the analysis of breath gas volatiles’ [5] presents a roadmap for a suggested approach in establishing © 2014 IOP Publishing Ltd  Printed in the UK

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standardized methods in breath gas analysis. Due to the large diversity in breath analysis techniques and the resulting impossibility of having a standardized practice applicable to all, the paper proposes to create standard procedures for the discrete steps of breath analysis, which can then be used as appropriate. It is a first step in the long road to introducing standardized practices in breath gas analysis. Despite the wealth of published information on breath gas studies, some aspects have been largely overlooked. Identifying some of the most fundamental aspects of breath analysis in terms of methods and procedures is essential if it is to be elevated in its status as a routine diagnostic tool. The paper on ‘Immediate effects of breath holding maneuvers onto composition of exhaled breath’ provides breath researchers with indispensable information on how the mode of breathing can affect the outcome of the analysis. Sukul et al used on-line proton transfer reaction time-of-flight mass spectrometry (PTR-TOFMS) to analyse the breath composition of subjects during different breathing manoeuvres [6]. Their findings that VOCs are affected by varying degrees to breathing manoeuvres should be heeded by all researchers working in breath gas analysis to avoid misinterpretation of their datasets. Another issue that currently hampers the development of breath analysis as a diagnostic tool is the lack of knowledge on the general composition of breath and the range of concentrations expected in healthy individuals, as well as how these are affected by physiological status. Some comprehensive and longitudinal studies have been performed to these ends [7–10], including several by David Smith and co-workers [11–16], but these are certainly not exhaustive. The paper entitled ‘Changes in the concentration of breath ammonia in response to exercise: a preliminary investigation’ by Solga and colleagues [17] demonstrates that some compounds, in this case ammonia, can vary dramatically with physiological status. Such changes present a substantial confounding factor in breath analysis, whereby a patient who has been physically active before providing a breath sample (perhaps having cycled to the doctor’s surgery prior to donating a breath sample; cf Storer et al [18], described below) might show reduced or elevated levels of specific compounds compared to someone at rest (e.g. a patient who has arrived by car). Equally the concentrations of common endogenous compounds can be subject to large inter-individual variations amongst the healthy population. Huang et al have focussed their attention on a series of aldehydes that have frequently received strong interest as disease biomarkers in breath. Their paper on ‘Investigation of C3–C10 aldehydes in the exhaled breath of healthy subjects using selected ion flow tube-mass spectrometry (SIFT-MS)’ [19] makes progress in generating typical baseline levels by quantifying selected aldehydes in 26 healthy volunteers and showing that most of the aldehydes under investigation were present in exhaled breath in trace amounts of below 3 ppbv, with some showing high inter-individual variability. The quality and outcome of a breath investigation is highly dependent on the analytical equipment employed. Sub-optimal instrumentation can lead to unreliable results, thus it is of utmost importance that chemical analytical tools are well suited to the challenges presented by breath analysis. In their paper on ‘Analysis of human breath samples using a modified thermal desorption–gas chromatography electrospray ionization interface’, Reynolds et al [20] demonstrate that even minor modifications of analytical tools can yield substantial improvements in the quality of the data generated. By implementing two simple yet crucial changes to their secondary electrospray ionization mass spectrometer (SESI-MS) the authors achieved significant performance enhancements of their system. A special issue dedicated to David would not be complete without some articles that utilize SIFT-MS. In addition to the aforementioned paper by Huang et al, Storer et al contribute a SIFT-MS paper entitled ‘Mobile selected ion flow tube mass spectrometry (SIFT-MS) devices and their use for pollution exposure monitoring in breath and ambient air—a pilot study’ [18]. The paper focuses on the effects of ambient air pollution on breath profiles and clearly highlights the influence of the environment on the composition of exhaled breath, which is another critical issue in breath analysis at present. Indeed some members of the population may experience extensive exposure to specific pollutants, which can disrupt their physiology and initiate adverse outcome pathways (AOP) that result in disease. Occupational exposure is one route for such situations. The investigation on ‘Exploratory breath analyses for assessing toxic dermal exposures of firefighters during suppression of structural burns’ by Pleil et al [21] demonstrates that the protective uniforms worn by firefighters significantly reduce exposure to aromatic and polycyclic aromatic hydrocarbon (PAH) compounds compared with other occupational groups. It also 2

Editorial

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highlights that occupational exposure should not be overlooked as a potential major contributor to the exposome [22]. We return to SIFT-MS for the next research article, this time with its use in disease monitoring, specifically for blood glucose levels in type 1 diabetics. In their paper entitled ‘The use of a portable breath analysis device in monitoring type 1 diabetes patients in a hypoglycaemic clamp: validation with SIFT-MS data’ Walton et al used SIFT-MS to validate a mixed metal oxide sensor used to monitor acetone in the exhaled breath and in comparison to blood glucose levels [23]. The paper is an excellent example of how some of the more sophisticated tools currently used in breath research can be utilized for evaluating newer and simpler technologies that have the potential for widespread implementation due to low cost and ease of use. Biomarker discovery is, of course, the main objective of most current breath research. Dryahina et al investigated potential biomarkers in their paper ‘Exhaled breath concentrations of acetic acid vapour in gastro-esophageal reflux disease (GERD)’ [24]. In their study they utilized an in vitro model to identify specific volatiles that were subsequently searched for in the breath of patients and controls. They thereby gathered evidence that linked acetic acid to this disease, whereby significantly higher concentrations of this compound were measured in the exhaled breath of GERD patients compared to controls. This special issue of Journal of Breath Research concludes with an article that focuses on a growing field in breath analysis, namely the investigation of volatiles in the headspace of cell (or bacterial) cultures for translation to characteristic signals in exhaled breath. In this case the article deals with ‘Volatile emanations from in vitro airway cells infected with human rhinovirus’ [25]. Schivo and colleagues investigated the aforementioned infected cells and could demonstrate that there was a differential expression of aliphatic alcohols and branched alcohols in comparison with control samples that could be potential biomarkers of the human rhinovirus infection. Studies such as these lay the foundation for eventual detection and diagnosis of such viral infections in exhaled breath. This collection of high quality papers on varied aspects of breath analysis is representative of the great diversity, complexity and richness of this field of research. Many of the methods or scientific background described or discussed in these publications, be it instrumental aspects, ion chemistry, sampling methodologies, or exhaled breath compounds, are founded on knowledge acquired by the extensive contributions of David Smith to breath gas research. This special issue is a tribute to these achievements. J D Beauchamp and T H Risby, August 2014

References [1] Adams N G and Smith D 1976 The selected ion flow tube (SIFT); a technique for studying ion-neutral reactions Int. J. Mass Spectrom. Ion Phys. 21 349–59 [2] Smith D and Spanel P 1996 The novel selected-ion flow tube approach to trace gas analysis of air and breath Rapid Commun. Mass Spectrom. 10 1183–98 [3] Risby T H 2008 Critical issues for breath analysis J. Breath Res. 2 030302 [4] Beauchamp J D and Pleil J D 2013 Simply breath-taking? Developing a strategy for consistent breath sampling J. Breath Res. 7 042001 [5] Herbig J and Beauchamp J 2014 Towards standardization in the analysis of breath gas volatiles J. Breath Res. 8 037101 [6] Sukul P, Trefz P, Schubert J and Miekisch W 2014 Immediate effects of breath holding maneuvers onto composition of exhaled breath J. Breath Res. 8 037102 [7] Ligor T, Ligor M, Amann A, Ager C, Bachler M, Dzien A and Buszewski B 2008 The analysis of healthy volunteers’ exhaled breath by the use of solid-phase microextraction and GC-MS J. Breath Res. 2 046006 [8] O’Hara M E, Clutton-Brock T H, Green S and Mayhew C A 2009 Endogenous volatile organic compounds in breath and blood of healthy volunteers: examining breath analysis as a ­surrogate for blood measurements J. Breath Res. 3 027005 [9] Schwarz K et al 2009 Breath acetone—aspects of normal physiology related to age and gender as determined in a PTR-MS study J. Breath Res. 2 027003 [10] de Lacy Costello B, Amann A, Al-Kateb H, Flynn C, Filipiak W, Khalid T, Osborne D and ­Ratcliffe N M 2014 A review of the volatiles from the healthy human body J. Breath Res. 8 014001 3

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[11] Španěl P, Davies S and Smith D 1998 Quantification of ammonia in human breath by the selected ion flow tube analytical method using H3O+ and O2+ precursor ions Rapid Commun. Mass Spectrom. 12 763–6 [12] Turner C, Španěl P and Smith D 2006 A longitudinal study of ethanol and acetaldehyde in the exhaled breath of healthy volunteers using selected-ion flow-tube mass spectrometry Rapid Commun. Mass Spectrom. 20 61–8 [13] Turner C, Španěl P and Smith D 2006 A longitudinal study of methanol in the exhaled breath of 30 healthy volunteers using selected ion flow tube mass spectrometry, SIFT-MS Physiol. Meas. 27 637 [14] Španěl P, Dryahina K and Smith D 2007 Acetone, ammonia and hydrogen cyanide in exhaled breath of several volunteers aged 4–83 years J. Breath Res. 1 011001 [15] Enderby B, Lenney W, Brady M, Emmett C, Španěl P and Smith D 2009 Concentrations of some metabolites in the breath of healthy children aged 7–18 years J. Breath Res. 3 036001 [16] Smith D, Španěl P, Enderby B, Lenney W, Turner C and Davies S J 2010 Isoprene levels in the exhaled breath of 200 healthy pupils within the age range 7–18 years studied using SIFT-MS J. Breath Res. 4 017101 [17] Solga S, Mudalel M, Spacek L, Lewicki R, Tittel F, Loccioni C, Russo A, Ragnoni A and Risby T 2014 Changes in the concentration of breath ammonia in response to exercise: a preliminary investigation J. Breath Res. 8 037103 [18] Storer M, Salmond J, Dirks K, Kingham S and Epton M 2014 Mobile selected ion flow tube mass spectrometry (SIFT-MS) devices and their use for pollution exposure monitoring in breath and ambient air J. Breath Res. 8 037106 [19] Huang J, Kumar S and Hanna G 2014 Investigation of C3–C10 aldehydes in the exhaled breath of healthy subjects using selected ion flow tube-mass spectrometry (SIFT-MS) J. Breath Res. 8 037104 [20] Reynolds J, Jimoh M, Guallar-Hoyas C, Creaser C, Siddiqui S and Thomas P 2014 Analysis of human breath samples using a modified thermal desorption–gas chromatography electrospray ionization interface J. Breath Res. 8 037105 [21] Pleil J D, Stiegel M A and Fent K W 2014 Exploratory breath analyses for assessing toxic dermal exposures of firefighters during suppression of structural burns J. Breath Res. 8 037107 [22] Pliel J D 2008 Role of exhaled breath biomarkers in environmental health science J. Toxicol. Env. Health B II 613–29 [23] Walton C, Patel M, Pitts D, Knight P, Hoashi S, Evans M and Turner C 2014 The use of a portable breath analysis device in monitoring type 1 diabetes patients in a hypoglycaemic clamp: validation with SIFT-MS data J. Breath Res. 8 037108 [24] Dryahina K, Pospíšilova V, Sovová K, Shestivska V, Kubišta J, Spesysyi A, Pehal F, Turzíková J, Votruba J and Spanel P 2014 Exhaled breath concentrations of acetic acid vapour in gastroesophageal reflux disease J. Breath Res. 8 037109 [25] Shivo M, Aksenov A, Linderholm A, McCartney M, Simmons J, Harper R and Davis C 2014 Volatile emanations from in vitro airway cells infected with human rhinovirus J. Breath Res. 8 037110

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A recognition of David Smith's unique contributions to the field of breath analysis.

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