Modelling of Breath and Various Blood Volatilomic Profiles-Implications for Breath Volatile Analysis.

Researchers looking for biomarkers from different sources, such as breath, urine, or blood, frequently search for specific patterns of volatile organic compounds (VOCs), often using pattern recognition or machine learning techniques. However, they are not generally aware that these patterns change depending on the source they use. Therefore, we have created a simple model to demonstrate that the distribution patterns of VOCs in fat, mixed venous blood, alveolar air, and end-tidal breath are different. Our approach follows well-established models for the description of dynamic real-time breath concentration profiles. We start with a uniform distribution of end-tidal concentrations of selected VOCs and calculate the corresponding target concentrations. For this, we only need partition coefficients, mass balance, and the assumption of an equilibrium state, which avoids the need to know the volatiles' metabolic rates and production rates within the different compartments.

Quantification of selected volatile organic compounds in human urine by gas chromatography selective reagent ionization time of flight mass spectrometry (GC-SRI-TOF-MS) coupled with head-space solid-phase microextraction (HS-SPME).

Selective reagent ionization time of flight mass spectrometry with NO(+) as the reagent ion (SRI-TOF-MS(NO(+))) in conjunction with gas chromatography (GC) and head-space solid-phase microextraction (HS-SPME) was used to determine selected volatile organic compounds in human urine. A total of 16 volatiles exhibiting high incidence rates were quantified in the urine of 19 healthy volunteers. Amongst them there were ten ketones (acetone, 2-butanone, 3-methyl-2-butanone, 2-pentanone, 3-methyl-2-pentanone, 4-methyl-2-pentanone, 2-hexanone, 3-hexanone, 2-heptanone, and 4-heptanone), three volatile sulphur compounds (dimethyl sulfide, allyl methyl sulfide, and methyl propyl sulfide), and three heterocyclic compounds (furan, 2-methylfuran, 3-methylfuran). The concentrations of the species under study varied between 0.55 nmol L(-1) (0.05 nmol mmol(-1)creatinine) for allyl methyl sulfide and 11.6 µmol L(-1) (1.54 µmol mmol(-1)creatinine) for acetone considering medians. Limits of detection (LODs) ranged from 0.08 nmol L(-1) for allyl methyl sulfide to 1.0 nmol L(-1) for acetone and furan (with RSDs ranging from 5 to 9%). The presented experimental setup assists both real-time and GC analyses of volatile organic compounds, which can be performed consecutively using the same analytical system. Such an approach supports the novel concept of hybrid volatolomics, an approach which combines VOC profiles obtained from two or more body fluids to improve and complement the chemical information on the physiological status of an individual.

Monitoring of selected skin-borne volatile markers of entrapped humans by selective reagent ionization time of flight mass spectrometry in NO+ mode.

Selective reagent ionization time-of-flight mass spectrometry with NO(+) as the reagent ion (SRI-TOF-MS (NO(+))) was applied for near real-time monitoring of selected skin-borne constituents which are potential markers of human presence. The experimental protocol involved a group of 10 healthy volunteers enclosed in a body plethysmography chamber mimicking the entrapment environment. A total of 12 preselected omnipresent in human scent volatiles were quantitatively monitored. Among them there were six aldehydes (n-propanal, n-hexanal, n-heptanal, n-octanal, n-nonanal, and 2 methyl 2-propenal), four ketones (acetone, 2-butanone, 3-buten-2-one, and 6-methyl-5-hepten-2-one), one hydrocarbon (2-methyl 2-pentene), and one terpene (DL-limonene). The observed median emission rates ranged from 0.28 to 44.8 nmol × person(-1) × min(-1) (16-1530 fmol × cm(-2) × min(-1)). Within the compounds under study, ketones in general and acetone in particular exhibited the highest abundances. The findings of this study provide invaluable information about formation and evolution of a human-specific chemical fingerprint, which could be used for the early location of entrapped victims during urban search and rescue operations (USaR).

Product ion distributions for the reactions of NO(+) with some physiologically significant volatile organosulfur and organoselenium compounds obtained using a selective reagent ionization time-of-flight mass spectrometer.

RATIONALE: The reactions of NO(+) with volatile organic compounds (VOCs) in Selective Reagent Ionization Time-of-Flight Mass Spectrometry (SRI-TOF-MS) reactors are relatively poorly known, inhibiting their use for trace gas analysis. The rationale for this product ion distribution study was to identify the major product ions of the reactions of NO(+) ions with 13 organosulfur compounds and 2 organoselenium compounds in an SRI-TOF-MS instrument and thus to prepare the way for their analysis in exhaled breath, in skin emanations and in the headspace of urine, blood and cell and bacterial cultures. METHODS: Product ion distributions have been investigated by a SRI-TOF-MS instrument at an E/N in the drift tube reactor of 130 Td for both dry air and humid air (4.9% absolute humidity) used as the matrix gas. The investigated species were five monosulfides (dimethyl sulfide, ethyl methyl sulfide, methyl propyl sulfide, allyl methyl sulfide and methyl 5-methyl-2-furyl sulfide), dimethyl disulfide, dimethyl trisulfide, thiophene, 2-methylthiophene, 3-methylthiophene, methanethiol, allyl isothiocyanate, dimethyl sulfoxide, and two selenium compounds - dimethyl selenide and dimethyl diselenide. RESULTS: Charge transfer was seen to be the dominant reaction mechanism in all reactions under study forming the M(+) cations. For methanethiol and allyl isothiocyanate significant fractions were also observed of the stable adduct ions NO(+) M, formed by ion-molecule association, and [M-H](+) ions, formed by hydride ion transfer. Several other minor product channels are seen for most reactions indicating that the nascent excited intermediate (NOM)(+) * adduct ions partially fragment along other channels, most commonly by the elimination of neutral CH3 , CH4 and/or C2 H4 species that are probably bound to an NO molecule. Humidity had little effect on the product ion distributions. CONCLUSIONS: The findings of this study are of particular importance for data interpretation in studies of volatile organosulfur and volatile organoselenium compounds employing SRI-TOF-MS in the NO(+) mode.

Product ion distributions for the reactions of NO+ with some physiologically significant aldehydes obtained using a SRI-TOF-MS instrument.

Product ion distributions for the reactions of NO+ with 22 aldehydes involved in human physiology have been determined under the prevailing conditions of a selective reagent ionization time of flight mass spectrometry (SRI-TOF-MS) at an E/N in the flow/drift tube reactor of 130 Td. The chosen aldehydes were fourteen alkanals (the C2-C11 n-alkanals, 2-methyl propanal, 2-methyl butanal, 3-methyl butanal, and 2-ethyl hexanal), six alkenals (2-propenal, 2-methyl 2-propenal, 2-butenal, 3-methyl 2-butenal, 2-methyl 2-butenal, and 2-undecenal), benzaldehyde, and furfural. The product ion fragmentations patterns were determined for both dry air and humid air (3.5% absolute humidity) used as the matrix buffer/carrier gas in the drift tube of the SRI-TOF-MS instrument. Hydride ion transfer was seen to be a common ionization mechanism in all these aldehydes, thus generating (M-H)+ ions. Small fractions of the adduct ion, NO+M, were also seen for some of the unsaturated alkenals, in particular 2-undecenal, and heterocyclic furfural for which the major reactive channel was non-dissociative charge transfer generating the M+ parent ion. Almost all of the reactions resulted in partial fragmentation of the aldehyde molecules generating hydrocarbon ions; specifically, the alkanal reactions resulted in multiple product ions, whereas, the alkenals reactions produced only two or three product ions, dissociation of the nascent excited product ion occurring preferentially at the 2-position. The findings of this study are of particular importance for data interpretation in studies of aldehydes reactions employing SRI-TOF-MS in the NO+ mode.

Blood and breath profiles of volatile organic compounds in patients with end-stage renal disease.

BACKGROUND: Monitoring of volatile organic compounds (VOCs) in exhaled breath shows great potential as a non-invasive method for assessing hemodialysis efficiency. In this work we aim at identifying and quantifying of a wide range of VOCs characterizing uremic breath and blood, with a particular focus on species responding to the dialysis treatment. METHODS: Gas chromatography with mass spectrometric detection coupled with solid-phase microextraction as pre-concentration method. RESULTS: A total of 60 VOCs were reliably identified and quantified in blood and breath of CKD patients. Excluding contaminants, six compounds (isoprene, dimethyl sulfide, methyl propyl sulfide, allyl methyl sulfide, thiophene and benzene) changed their blood and breath levels during the hemodialysis treatment. CONCLUSIONS: Uremic breath and blood patterns were found to be notably affected by the contaminants from the extracorporeal circuits and hospital room air. Consequently, patient exposure to a wide spectrum of volatile species (hydrocarbons, aldehydes, ketones, aromatics, heterocyclic compounds) is expected during hemodialysis. Whereas highly volatile pollutants were relatively quickly removed from blood by exhalation, more soluble ones were retained and contributed to the uremic syndrome. At least two of the species observed (cyclohexanone and 2-propenal) are uremic toxins. Perhaps other volatile substances reported within this study may be toxic and have negative impact on human body functions. Further studies are required to investigate if VOCs responding to HD treatment could be used as markers for monitoring hemodialysis efficiency.

Release and uptake of volatile organic compounds by human hepatocellular carcinoma cells (HepG2) in vitro.

BACKGROUND: Volatile organic compounds (VOCs) emitted by human body offer a unique insight into biochemical processes ongoing in healthy and diseased human organisms. Unfortunately, in many cases their origin and metabolic fate have not been yet elucidated in sufficient depth, thus limiting their clinical application. The primary goal of this work was to identify and quantify volatile organic compounds being released or metabolized by HepG2 hepatocellular carcinoma cells. METHODS: The hepatocellular carcinoma cells were incubated in specially designed head-space 1-L glass bottles sealed for 24 hours prior to measurements. Identification and quantification of volatiles released and consumed by cells under study were performed by gas chromatography with mass spectrometric detection (GC-MS) coupled with head-space needle trap device extraction (HS-NTD) as the pre-concentration technique. Most of the compounds were identified both by spectral library match as well as retention time comparison based on standards. RESULTS: A total of nine compounds were found to be metabolised and further twelve released by the cells under study (Wilcoxon signed-rank test, p<0.05). The former group comprised 6 aldehydes (2-methyl 2-propenal, 2-methyl propanal, 2-ethylacrolein, 3-methyl butanal, n-hexanal and benzaldehyde), n-propyl propionate, n-butyl acetate, and isoprene. Amongst the released species there were five ketones (2-pentanone, 3-heptanone, 2-heptanone, 3-octanone, 2-nonanone), five volatile sulphur compounds (dimethyl sulfide, ethyl methyl sulfide, 3-methyl thiophene, 2-methyl-1-(methylthio)- propane and 2-methyl-5-(methylthio) furan), n-propyl acetate, and 2-heptene. CONCLUSIONS: The emission and uptake of the aforementioned VOCs may reflect the activity of abundant liver enzymes and support the potential of VOC analysis for the assessment of enzymes function.

Stability of selected volatile breath constituents in Tedlar, Kynar and Flexfilm sampling bags.

The stability of 41 selected breath constituents in three types of polymer sampling bags, Tedlar, Kynar, and Flexfilm, was investigated using solid phase microextraction and gas chromatography mass spectrometry. The tested molecular species belong to different chemical classes (hydrocarbons, ketones, aldehydes, aromatics, sulphurs, esters, terpenes, etc.) and exhibit close-to-breath low ppb levels (3-12 ppb) with the exception of isoprene, acetone and acetonitrile (106 ppb, 760 ppb, 42 ppb respectively). Stability tests comprised the background emission of contaminants, recovery from dry samples, recovery from humid samples (RH 80% at 37 °C), influence of the bag's filling degree, and reusability. Findings yield evidence of the superiority of Tedlar bags over remaining polymers in terms of background emission, species stability (up to 7 days for dry samples), and reusability. Recoveries of species under study suffered from the presence of high amounts of water (losses up to 10%). However, only heavier volatiles, with molecular masses higher than 90, exhibited more pronounced losses (20-40%). The sample size (the degree of bag filling) was found to be one of the most important factors affecting the sample integrity. To sum up, it is recommended to store breath samples in pre-conditioned Tedlar bags up to 6 hours at the maximum possible filling volume. Among the remaining films, Kynar can be considered as an alternative to Tedlar; however, higher losses of compounds should be expected even within the first hours of storage. Due to the high background emission Flexfilm is not suitable for sampling and storage of samples for analyses aiming at volatiles at a low ppb level.

Blood and breath levels of selected volatile organic compounds in healthy volunteers.

Gas chromatography with mass spectrometric detection (GC-MS) was used to identify and quantify volatile organic compounds in the blood and breath of healthy individuals. Blood and breath volatiles were pre-concentrated using headspace solid phase micro-extraction (HS-SPME) and needle trap devices (NTDs), respectively. The study involved a group of 28 healthy test subjects and resulted in the quantification of a total of 74 compounds in both types of samples. The concentrations of the species under study varied between 0.01 and 6700 nmol L(-1) in blood and between 0.02 and 2500 ppb in exhaled air. Limits of detection (LOD) ranged from 0.01 to 270 nmol L(-1) for blood compounds and from 0.01 to 0.7 ppb for breath species. Relative standard deviations for both measurement regimes varied from 1.5 to 14%. The predominant chemical classes among the compounds quantified were hydrocarbons (24), ketones (10), terpenes (8), heterocyclic compounds (7) and aromatic compounds (7). Twelve analytes were found to be highly present in both blood and exhaled air (with incidence rates higher than 80%) and for 32 species significant differences (Wilcoxon signed-rank test) between room air and exhaled breath were observed. By comparing blood, room air and breath levels in parallel, a tentative classification of volatiles into endogenous and exogenous compounds can be achieved.

Human blood and plasma partition coefficients for C4-C8 n-alkanes, isoalkanes, and 1-alkenes.

Human blood:air and plasma:air partition coefficients for C(4)-C(8) n-alkanes, isoalkanes, and 1-alkenes were determined using multiple headspace extraction coupled with solid phase microextraction and gas chromatography. Mean blood:air partition coefficients expressed in the form of dimensionless blood-to-air concentration ratio (g/mL(b)/g/mL(a)) were 0.183, 0.416, 1.08, 2.71, and 5.77 for C(4)-C(8) n-alkanes; 0.079, 0.184, 0.473, 1.3, and 3.18 for C(4)-C(8) isoalkanes; and 0.304, 0.589, 1.32, 3.5, and 7.01 for C(4)-C(8) 1-alkenes, respectively (n = 8). The reported partition coefficient values increased exponentially with boiling points, molecular weights, and the carbon atoms in the particle. The solubility of 1-alkenes in blood was higher than in plasma, whereas the blood:air and plasma:air partition coefficients of n-alkanes and isoalkanes did not differ significantly. Consequently, additional interactions of 1-alkenes with whole blood seem to occur. The presented findings are expected to be particularly useful for assessing the uptake, distribution, and elimination of hydrocarbons in human organism.

A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone.

Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide (NO) have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which may reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways, (ii) the concentrations in the tracheo-bronchial lining fluid, (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, the model illuminates the discrepancies between observed and theoretically predicted blood-breath ratios of acetone during resting conditions, i.e., in steady state. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases and thus is expected to have general relevance for a wider range of blood-borne inert gases. The chief intention of the present modeling study is to provide mechanistic relationships for further investigating the exhalation kinetics of acetone and other water-soluble species. This quantitative approach is a first step towards new guidelines for breath gas analyses of volatile organic compounds, similar to those for nitric oxide.

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.

Effect of inhaled acetone concentrations on exhaled breath acetone concentrations at rest and during exercise.

Real-time measurements of the differences in inhaled and exhaled, unlabeled and fully deuterated acetone concentration levels, at rest and during exercise, have been conducted using proton transfer reaction mass spectrometry. A novel approach to continuously differentiate between the inhaled and exhaled breath acetone concentration signals is used. This leads to unprecedented fine grained data of inhaled and exhaled concentrations. The experimental results obtained are compared with those predicted using a simple three compartment model that theoretically describes the influence of inhaled concentrations on exhaled breath concentrations for volatile organic compounds with high blood:air partition coefficients, and hence is appropriate for acetone. An agreement between the predicted and observed concentrations is obtained. Our results highlight that the influence of the upper airways cannot be neglected for volatiles with high blood:air partition coefficients, i.e. highly water soluble volatiles.

Studies pertaining to the monitoring of volatile halogenated anaesthetics in breath by proton transfer reaction mass spectrometry.

Post-operative isoflurane has been observed to be present in the end-tidal breath of patients who have undergone major surgery, for several weeks after the surgical procedures. A major new non-controlled, non-randomized, and open-label approved study will recruit patients undergoing various surgeries under different inhalation anaesthetics, with two key objectives, namely (1) to record the washout characteristics following surgery, and (2) to investigate the influence of a patient's health and the duration and type of surgery on elimination. In preparation for this breath study using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), it is important to identify first the analytical product ions that need to be monitored and under what operating conditions. In this first paper of this new research programme, we present extensive PTR-TOF-MS studies of three major anaesthetics used worldwide, desflurane (CF3CHFOCHF2), sevoflurane ((CF3)2CHOCH2F), and isoflurane (CF3CHClOCHF2) and a fourth one, which is used less extensively, enflurane (CHF2OCF2CHFCl), but is of interest because it is an isomer of isoflurane. Product ions are identified as a function of reduced electric field (E/N) over the range of approximately 80 Td to 210 Td, and the effects of operating the drift tube under 'normal' or 'humid' conditions on the intensities of the product ions are presented. To aid in the analyses, density functional theory (DFT) calculations of the proton affinities and the gas-phase basicities of the anaesthetics have been determined. Calculated energies for the ion-molecule reaction pathways leading to key product ions, identified as ideal for monitoring the inhalation anaesthetics in breath with a high sensitivity and selectivity, are also presented.

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 > 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 > 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 > 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.

In vitro profiling of volatile organic compounds released by Simpson-Golabi-Behmel syndrome adipocytes.

Breath analysis offers a non-invasive and rapid diagnostic method for detecting various volatile organic compounds that could be indicators for different diseases, particularly metabolic disorders including type 2 diabetes mellitus. The development of type 2 diabetes mellitus is closely linked to metabolic dysfunction of adipose tissue and adipocytes. However, the VOC profile of human adipocytes has not yet been investigated. Gas chromatography with mass spectrometric detection and head-space needle trap extraction (two-bed Carbopack X/Carboxen 1000 needle traps) were applied to profile VOCs produced and metabolised by human Simpson Golabi Behmel Syndrome adipocytes. In total, sixteen compounds were identified to be related to the metabolism of the cells. Four sulphur compounds (carbon disulphide, dimethyl sulphide, ethyl methyl sulphide and dimethyl disulphide), three heterocyclic compounds (2-ethylfuran, 2-methyl-5-(methyl-thio)-furan, and 2-pentylfuran), two ketones (acetone and 2-pentanone), two hydrocarbons (isoprene and n-heptane) and one ester (ethyl acetate) were produced, and four aldehydes (2-methyl-propanal, butanal, pentanal and hexanal) were found to be consumed by the cells of interest. This study presents the first profile of VOCs formed by human adipocytes, which may reflect the activity of the adipose tissue enzymes and provide evidence of their active role in metabolic regulation. Our data also suggest that a previously reported increase of isoprene and sulphur compounds in diabetic patients may be explained by their production by adipocytes. Moreover, the unique features of this profile, including a high emission of dimethyl sulphide and the production of furan-containing VOCs, increase our knowledge about metabolism in adipose tissue and provide diagnostic potential for future applications.

Non-contact breath sampling for sensor-based breath analysis.

Breath analysis holds great promise for real-time and non-invasive medical diagnosis. Thus, there is a considerable need for simple-in-use and portable analyzers for rapid detection of breath indicators for different diseases in their early stages. Sensor technology meets all of these demands. However, miniaturized breath analyzers require adequate breath sampling methods. In this context, we propose non-contact sampling; namely the collection of breath samples by exhalation from a distance into a miniaturized collector without bringing the mouth into direct contact with the analyzing device. To evaluate this approach different breathing maneuvers have been tested in a real-time regime on a cohort of 23 volunteers using proton transfer reaction mass spectrometry. The breathing maneuvers embraced distinct depths of respiration, exhalation manners, size of the mouth opening and different sampling distances. Two inhalation modes (normal, relaxed breathing and deep breathing) and two exhalation manners (via smaller and wider lips opening) forming four sampling scenarios were selected. A sampling distance of approximately 2 cm was found to be a reasonable trade-off between sample dilution and requirement of no physical contact of the subject with the analyzer. All four scenarios exhibited comparable measurement reproducibility spread of around 10%. For normal, relaxed inspiration both dead-space and end-tidal phases of exhalation lasted approximately 1.5 s for both expiration protocols. Deep inhalation prolongs the end-tidal phase to about 3 s in the case of blowing via a small lips opening, and by 50% when the air is exhaled via a wide one. In conclusion, non-contact breath sampling can be considered as a promising alternative to the existing breath sampling methods, being relatively close to natural spontaneous breathing.

Removal of CPR artifacts from the ventricular fibrillation ECG by adaptive regression on lagged reference signals.

BACKGROUND AND OBJECTIVE: Removing cardiopulmonary resuscitation (CPR)-related artifacts from human ventricular fibrillation (VF) electrocardiogram (ECG) signals provides the possibility to continuously detect rhythm changes and estimate the probability of defibrillation success. This could reduce "hands-off" analysis times which diminish the cardiac perfusion and deteriorate the chance for successful defibrillations. METHODS AND RESULTS: Our approach consists in estimating the CPR part of a corrupted signal by adaptive regression on lagged copies of a reference signal which correlate with the CPR artifact signal. The algorithm is based on a state-space model and the corresponding Kalman recursions. It allows for stochastically changing regression coefficients. The residuals of the Kalman estimation can be identified with the CPR-filtered ECG signal. In comparison with ordinary least-squares regression, the proposed algorithm shows, for low signal-to-noise ratio (SNR) corrupted signals, better SNR improvements and yields better estimates of the mean frequency and mean amplitude of the true VF ECG signal. CONCLUSIONS: The preliminary results from a small pool of human VF and animal asystole CPR data are slightly better than the results of comparable previous studies which, however, not only used different algorithms but also different data pools. The algorithm carries the possibility of further optimization.

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

In a recent paper (Unterkofler et al 2015 J. Breath Res. 9 036002) 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.

Detecting ventricular fibrillation by time-delay methods.

A pivotal component in automated external defibrillators (AEDs) is the detection of ventricular fibrillation (VF) by means of appropriate detection algorithms. In scientific literature there exists a wide variety of methods and ideas for handling this task. These algorithms should have a high detection quality, be easily implementable, and work in realtime in an AED. Testing of these algorithms should be done by using a large amount of annotated data under equal conditions. For our investigation we simulated a continuous analysis by selecting the data in steps of 1 s without any preselection. We used the complete BIH-MIT arrhythmia database, the CU database, and files 7001-8210 of the AHA database. For a new VF detection algorithm we calculated the sensitivity, specificity, and the area under its receiver operating characteristic curve and compared these values with the results from an earlier investigation of several VF detection algorithms. This new algorithm is based on time-delay methods and outperforms all other investigated algorithms.