Potential of volatile organic compounds as markers of entrapped humans for use in urban search-and-rescue operations

Volatile organic compounds emitted by a human body form a chemical signature capable of providing invaluable information on the physiological status of an individual and, thereby, could serve as signs-of-life for detecting victims after natural or man-made disasters. In this review a database of potential biomarkers of human presence was created on the basis of existing literature reports on volatiles in human breath, skin emanation, blood, and urine. Approximate fluxes of these species from the human body were estimated and used to predict their concentrations in the vicinity of victims. The proposed markers were classified into groups of different potential for victim detection. The major classification discriminants were the capability of detection by portable, real-time analytical instruments and background levels in urban environment. The data summarized in this review are intended to assist studies on the detection of humans via chemical analysis and accelerate investigations in this area of knowledge.Comment: 38 page

Modeling-based determination of physiological parameters of systemic VOCs by breath gas analysis, part 2

In a recent paper we presented a simple two compartment model which describes the influence of inhaled concentrations on exhaled breath concentrations for volatile organic compounds (VOCs) with small Henry constants. In this paper we extend this investigation concerning the influence of inhaled concentrations on exhaled breath concentrations for VOCs with higher Henry constants. To this end we extend our model with an additional compartment which takes into account the influence of the upper airways on exhaled breath VOC concentrations

A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds

Isothermal rebreathing has been proposed as an experimental technique for estimating the alveolar levels of hydrophilic volatile organic compounds (VOCs) in exhaled breath. Using the prototypic test compound acetone we demonstrate that the end-tidal breath profiles of such substances during isothermal rebreathing show characteristics that contradict the conventional pulmonary inert gas elimination theory due to Farhi. On the other hand, these profiles can reliably be captured by virtue of a previously developed mathematical model for the general exhalation kinetics of highly soluble, blood-borne VOCs, which explicitly takes into account airway gas exchange as major determinant of the observable breath output. This model allows for a mechanistic analysis of various rebreathing protocols suggested in the literature. In particular, it clarifies the discrepancies between in vitro and in vivo blood-breath ratios of hydrophilic VOCs and yields further quantitative insights into the physiological components of isothermal rebreathing.Comment: 21 page

Modeling-based determination of physiological parameters of systemic VOCs by breath gas analysis: a pilot study

In this paper we develop a simple two compartment model which extends the Farhi equation to the case when the inhaled concentration of a volatile organic compound (VOC) is not zero. The model connects the exhaled breath concentration of systemic VOCs with physiological parameters such as endogenous production rates and metabolic rates. Its validity is tested with data obtained for isoprene and inhaled deuterated isoprene-D5.Comment: 16 page

Physiological modeling of isoprene dynamics in exhaled breath

Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs. Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.Comment: 14 page

Modeling of breath methane concentration profiles during exercise on an ergometer

We develop a simple three compartment model based on mass balance equations which quantitatively describes the dynamics of breath methane concentration profiles during exercise on an ergometer. With the help of this model it is possible to estimate the endogenous production rate of methane in the large intestine by measuring breath gas concentrations of methane.Comment: 17 pages, 4 figure

PTR-MS studies of the reactions of H₃O⁺ with a number of deuterated volatile organic compounds and the subsequent sequential reactions of the primary product ions with water under normal and humid drift tube conditions::implications for use of deuterated compounds for breath analysis

Product ion distributions resulting from the primary reactions of H3O+ with nine D-labeled volatile organic compounds and the subsequent sequential reactions with H2O have been determined using a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF 8000 (IONICON Analytik GmbH)) at various reduced electric field (E/N) values ranging from 80 up to 150 Td and for two different absolute humidity levels of air sample < 0.1% and 5%. The specific D-labeled compounds used in this study are acetone-d6, toluene-d8, benzene-d6, ethanol-d (C2H5OD), ethanol-d2 (CH3CD2OH), ethanol-d6, 2-propanol-d8, 2-propanol-d3 (CD3CH(OH)CH3), and isoprene-d5 (CH2CHC(CD2)CD3). With the exception of the two 2-propanol compounds, non-dissociative proton transfer is the dominant primary reaction pathway. For 2-propanol-d8 and 2-propanol-d3 the major primary reaction channel involved is dissociative proton transfer. However, unlike their undeuterated counterparts, the primary product ions undergo subsequent deuterium/hydrogen isotope exchange reactions with the ever present water in the drift tube, the extent of which of course depends on the humidity within that tube. This exchange leads to the generation of various isotopologue product ions, the product ion branching percentages of which are also dependent on the humidity in the drift tube. This results in complex mass spectra and the distribution of product ions leads to issues of reduced sensitivity and accuracy. However, the effect of D/H exchange considerably varies between the compounds under study. In the case of acetone-d6 it is very weak (<1%), because the exchange process is not facile when the deuterium is in the methyl functional group. In comparison, the H3O+/ benzene-d6 (C6D6) reaction and sequential reactions with water result in the production of the isotopologue ions C6Dn(H7-n)+ (where n = 0–6). Changing the value of E/N and/or the humidity in the drift tube considerably affects the amount of the isotope exchange reactions and hence the resulting sequential product ion distributions. An important conclusion of the findings from this work is that care must be taken in the choice of an exogenous deuterated compound for use in breath pharmacokinetic studies using proton transfer reaction mass spectrometry; otherwise the resulting D/H exchange processes impose interpretative problems. © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Unrecognized High Occurrence of Genetically Confirmed Hereditary Carnitine Palmitoyltransferase II Deficiency in an Austrian Family Points to the Ongoing Underdiagnosis of the Disease

Adult muscle carnitine palmitoyltransferase (CPT) II deficiency is a rare autosomal recessive disorder of long-chain fatty acid metabolism. It is typically associated with recurrent episodes of exercise-induced rhabdomyolysis and myoglobinuria, in most cases caused by a c.338C &gt; T mutation in the CPT2 gene. Here we present the pedigree of one of the largest family studies of CPT II deficiency caused by the c.338C &gt; T mutation, documented so far. The pedigree comprises 24 blood relatives of the index patient, a 32 year old female with genetically proven CPT II deficiency. In total, the mutation was detected in 20 family members, among them five homozygotes and 15 heterozygotes. Among all homozygotes, first symptoms of CPT II deficiency occurred during childhood. Additionally, two already deceased relatives of the index patient were carriers of at least one copy of the genetic variant, revealing a remarkably high prevalence of the c.338C &gt; T mutation within the tested family. Beside the index patient, only one individual had been diagnosed with CPT II deficiency prior to this study and three cases of CPT II deficiency were newly detected by this family study, pointing to a general underdiagnosis of the disease. Therefore, this study emphasizes the need to raise awareness of CPT II deficiency for correct diagnosis and accurate management of the disease