Patrik Spanel

Breath Analysis: The Approach Towards Clinical Applications

Exhaled breath analysis for clinical diagnosis and therapeutic monitoring is described with special reference to the techniques used and the underlying chemistry and physics involved. Brief outlines are given of the research carried out to date, and prospects for the future of this potentially valuable non-invasive technique are indicated.

Time variation of ammonia, acetone, isoprene and ethanol in breath: a quantitative SIFT-MS study over 30 days

A study of the concentrations of the common breath metabolites ammonia, acetone, isoprene, ethanol and acetaldehyde in the breath of five subjects over a period of 30 days has been carried out. Breath samples were taken and analysed in the early morning on arrival at the laboratory. The real time analyses of three consecutive breath exhalations were carried out using selected ion flow tube mass spectrometry (SIFT-MS) on line to the instrument. Sufficient data were obtained to allow meaningful concentration distributions to be obtained for ammonia, acetone, isoprene and ethanol. These showed that the ammonia, acetone and isoprene concentrations exhibited sensibly normal distributions, with coefficients of variation of typically 0.3. Obvious and statistically significant (p < 0.01) differences are apparent in the mean concentrations of these metabolites between the five individuals. The acetaldehyde concentrations were relatively low and close to the instrument detection limit, and the differences between the mean concentrations of the five subjects were not statistically significant (p = 0.4), so distributions were not obtained. The mean concentrations, in parts per billion (ppb), of each metabolite range amongst the five subjects are as follows: ammonia, 422-2389: acetone, 293-870; isoprene, 55-121; ethanol, 27-153; acetaldehyde, 2-5. There are no obvious patterns in the distributions of these particular metabolites for these individuals, except that the ammonia levels were greatest in the breath of the two oldest subjects.

SIFT studies of the reactions of H3O+, NO+ and O2+ with a series of alcohols☆

Abstract We report the results of a selected ion flow tube (SIFT) study of the reactions of H3O+, NO+ and O2+ with some 17 alcohols ranging in complexity from methanol to octanol and menthol, and including some structural isomers. This study was carried out in order to extend the database (i.e. rate coefficients and product ions of appropriate ion/molecule reactions) required for the SIFT method of trace gas analysis which utilises the aforementioned ions for chemical ionisation. The H3O+ reactions proceed via exothermic proton transfer, which we assume to proceed at the collisional rate. Thus all of the 51 reactions (except two) occur at or close to the collisional rate. Only in a minority of these proton transfer reactions is the protonated parent molecule the single ion product; rather it is seen that the protonation of most of these alcohols by H3O+ is followed by the ejection of an H2O molecule from the excited product ion thus leaving the appropriate hydrocarbon ion. The NO+ reactions proceed largely via the processes of hydride ion transfer producing the appropriate carboxy ion (and HNO), and hydroxide ion transfer producing the appropriate hydrocarbon ion (and HNO2). The O2+ reactions proceed via charge transfer, the large majority of the reactions resulting in more than one product ion, which are mostly hydrocarbon fragment ions but in a few cases carboxy ions are formed. The product ions for the reactions of the various structural isomers are sometimes different, and this offers a way of distinguishing between the isomeric forms of some alcohols.

The Novel Selected-ion Flow Tube Approach to Trace Gas Analysis of Air and Breath

We present an overview of the development and use of our selected-ion flow tube (SIFT) technique as a sensitive, quantitative method for the rapid, real-time analysis of the trace gas content of atmospheric air and human breath, presenting some pilot data from various research areas in which this method will find valuable application. We show that it is capable of detecting and quantifying trace gases, in complex mixtures such as breath, which are present at partial pressures down to about 10 parts per billion. Following discussions of the principles involved in this SIFT method of analysis, of the experiments which we have carried out to establish its quantitative validity, and of the air and breath sampling techniques involved, we present sample data on the detection and quantification of trace gases on the breath of healthy people and of patients suffering from renal failure and diabetes. We also show how breath ammonia can be accurately quantified from a single breath exhalation and used as an indicator of the presence in the stomach of the bacterium Helicobacter pylori. Health and safety applications are exemplified by analyses of the gases of the gases of cigarette smoke and on the breath of smokers. The value of this analytical method in environmental science is demonstrated by the analyses of petrol vapour, car exhaust emissions and the trace organic vapours detected in town air near a busy road. Final examples of the value of this analytical method are the detection and quantification of the gases emitted from crushed garlic and from breath following the chewing of a mint, which demonstrate its potential in food and flavour research. Throughout the paper we stress the advantages of this SIFT method compared to conventional mass spectrometry for trace gas analysis of complex mixtures, emphasizing its selectivity, sensitivity and real-time analysis capability. Finally, we note that whilst the current SIFT is strictly laboratory based, both transportable and portable instruments are under construction and development. These instruments will surely extend the application of this analytical technique into more areas and allow greater exploitation of their on-line and real-time features.

An exploratory comparative study of volatile compounds in exhaled breath and emitted by skin using selected ion flow tube mass spectrometry

Selected ion flow tube mass spectrometry (SIFT-MS) has been used to carry out a pilot parallel study on five volunteers to determine changes occurring in several trace compounds present in exhaled breath and emitted from skin into a collection bag surrounding part of the arm, before and after ingesting 75 g of glucose in the fasting state. SIFT-MS enabled real-time quantification of ammonia, methanol, ethanol, propanol, formaldehyde, acetaldehyde, isoprene and acetone. Following glucose ingestion, blood glucose and trace compound levels were measured every 30 min for 2 h. All the above compounds, except formaldehyde, were detected at the expected levels in exhaled breath of all volunteers; all the above compounds, except isoprene, were detected in the collection bag. Ammonia, methanol and ethanol were present at lower levels in the bag than in the breath. The aldehydes were present at higher levels in the bag than in breath. The blood glucose increased to a peak about 1 h post-ingestion, but this change was not obviously correlated with temporal changes in any of the compounds in breath or emitted by skin, except for acetone. The decrease in breath acetone was closely mirrored by skin-emitted acetone in three volunteers. Breath and skin acetone also clearly change with blood glucose and further work may ultimately enable inferences to be drawn of the blood glucose concentration from skin or breath measurements in type 1 diabetes.

Plasma Volume, Albumin, and Fluid Status in Peritoneal Dialysis Patients

BACKGROUND AND OBJECTIVES Peritoneal dialysis (PD) patients may be overhydrated especially when inflammation is present. We hypothesized that patients with a plasma albumin below the median value would have measurable overhydration without a proportional increase in plasma volume (PV). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We investigated a cross-sectional sample of 46 prevalent PD patients powered to detect a proportional increase in PV associated with whole body overhydration and hypoalbuminemia. PV was determined from (125)I-labeled albumin dilution, absolute total body water from D dilution (TBW(D)), and relative hydration from multifrequency bioimpedance analysis (BIA; Xitron 4200) expressed as the extracellular water (ECW):TBW(BIA) ratio. RESULTS Whereas patients with plasma albumin below the median (31.4 g/dl) were overhydrated as determined both by BIA alone (ECW:TBW(BIA) 0.49 versus 0.47, P < 0.036) and the difference between estimated TBW(BIA) and measured TBW(D) (3.55 versus 0.94 L, P = 0.012), corrected PV was not different (1463 versus 1482 ml/m(2), NS). Mean PV was not different from predicted, and its variance did not correlate with any other clinical measures. Multivariate analysis showed that the only independent predictor of whole body overhydration was reduced plasma albumin. CONCLUSIONS Hypoalbuminemia is an important determinant of tissue overhydration in PD patients. This overhydration is not associated with an increased plasma volume. Attempts to normalize the ECW:TBW ratio in hypoalbuminemic, inflamed PD patients may lead to hypovolemia and loss of residual renal function.

The concentration distributions of some metabolites in the exhaled breath of young adults

The concentrations of ammonia, acetone, methanol, ethanol, propanol and hydrogen cyanide have been measured in the exhaled breath of 26 young adults of age 17/18 years, using selected ion flow tube mass spectrometry (SIFT-MS). Thus the concentration distributions have been constructed and are seen to be essentially log normal with median values in parts per billion (ppb), being ammonia, 317; acetone, 363; methanol, 238; ethanol, 104; propanol, 13; hydrogen cyanide (HCN), 8. There is a clear separation in the median breath ethanol levels between those volunteers who had ingested sugary food/drinks (109 ppb) and those who had not (48 ppb). These data are compared with the results of a study of the same breath compounds, excepting HCN, for a similar sized cohort of healthy volunteers within the age range of 20 to 60 years, which shows that the median levels of these compounds are lower in the young adult volunteer cohort. These HCN measurements are the first to be made in the breath of healthy individuals. The potential implications of these combined results for clinical diagnosis are alluded to.

Quantification of hydrogen cyanide in humid air by selected ion flow tube mass spectrometry

Following our recent observation that Pseudomonas bacteria in vitro emit hydrogen cyanide, we have found it necessary to investigate the ion chemistry of this compound and to extend the kinetics database for selected ion flow tube mass spectrometry (SIFT-MS) to allow the accurate quantification of HCN in moist air samples, including exhaled breath. Because of the proximity of the proton affinities of HCN and H2O molecules, the presence of water vapour can significantly distort HCN analysis in the presence of water vapour and a more sophisticated analytical procedure has to be developed. Thus, the reactions of H3O+(H2O)0,1,2,3 ions with HCN molecules have been studied in the presence of varying concentrations of water vapour, reactions on which SIFT-MS analysis of HCN relies. The results of these experiments have allowed an analytical procedure to be developed which has extended the kinetics database of SIFT-MS, such that HCN can now be quantified in humid air and in exhaled breath.

Electron attachment to C60 at low energies

Abstract Measurements are described of the rate coefficients, β, for electron attachment to C 60 molecules within the electron temperature range 500–4500 K obtained using our flowing afterglow/Langmuir probe (FALP) apparatus. At a T e of 500 K, the β is small but it increases rapidly with T e reaching a value of 3 × 10 −7 cm 3 s −1 at 4500 K. Thus an activation energy barrier of 0.26 eV is indicated for electron attachment to C 60 . The β at a T e of 4500 K is greater than is expected on the basis of s-wave capture theory which we attribute to the large size of the C 60 molecule.

On-line determination of the deuterium abundance in breath water vapour by flowing afterglow mass spectrometry with applications to measurements of total body water.

We have developed a new method for the on-line quantification of deuterium in water vapour. We call this method flowing afterglow mass spectrometry (FA-MS). A swarm of H3O+ precursor ions is created in flowing helium carrier gas by a microwave discharge. These precursor ions react with the H2O, HDO, H2(17)O and H2(18)O molecules in a water vapour sample that is introduced into the carrier gas/H3O+ ion swarm. The hydrated ions, H3O+.(H2O)3 at m/z 73, and their isotopic variant ions H8DO4(+) and H9(17)OO(3)(+) at m/z 74 and H9(18)OO(3)(+) at m/z 75, are thus formed. By adopting the known fractional abundance of 18O in water vapour, and accounting for the contribution of the isotopic ions H9(17)OO(3)(+) to the ion signal at m/z 74, a measurement of the 74/75 ion signal ratio under equilibrium conditions provides the fractional deuterium abundance in the water vapour sample. Using this technique, the deuterium abundance in the water vapour present in single exhalations of breath can be determined. Thus, from the temporal variations of breath deuterium following the ingestion of a known quantity of D(2)O, we show that total body water can be determined non-invasively and the kinetics of water flow around the body can be tracked.