Breath analysis

Another investigation examined the presence of acetone in breath using a membrane extraction module, a sorbent trap, and a GC with dual detectors a flame ionization detector and a mobility spectrometer. The last quarter liter portion of the stream of exhaled breath, which better reflects the content of volatile compounds in the lung tissue, was analyzed. The membrane removed much of the respired moisture, blocking interference with the analyses.  

In a way, objective scientifically based analytical techniques for analysis of organic compounds in breath or respired air are consistent with, and supported by, centuries of experience in traditional medicine. Examples of diagnostic vapors include 

A major challenge is to provide sensitive and reliable analytical techniques to detect VOCs in the breath at an early stage of the disease, since this is usually when it is most treatable. Another potential application of PTR-MS and breath analysis is to quickly assess a drug overdose. Successful utilization of this technique could help to determine the drug taken and its concentration in the blood, details of which are needed rapidly if treatment is to be effective and hence life-saving. 

From the above discussion, it is clear that breath contains useful trace gas markers, in the form of VOCs, which could be used as fingerprints to monitor different processes in the human body. To help unlock the messages that volatiles on exhaled breath can provide requires the application of highly reliable, sensitive and selective trace gas detection techniques. A specific breath marker related to a specific disease is the ideal. However, this is unlikely to be the case for the majority of diseases or conditions, where it is more probable that a range of VOCs with varying intensities will have to be used. It still needs to be ascertained whether there are unique patterns of VOCs, made up of specific and/or non-specific biomarkers, for a particular disease that can be discerned from the complex chemical environment of breath. 

Given all of the problems associated with analytical methods for breath sampling and analysis, it is not surprising that to date the majority of research associated with breath analysis and PTR-MS has been limited to proof-of-principle trials which may not have been using ideal breath sampling procedures. Often these studies have also involved an insufficient number of patients and provided little detailed analysis. In-depth clinical trials to substantiate the effectiveness of VOCs as selective biological indicators of disease are required, but these are expensive and time-consuming. 

There are various soft chemical ionization mass spectrometric analytical techniques being used for breath analysis, and after PTR-MS the most popular is SIFT-MS (and most notably the work by Smith and Spanel [74] and their co-workers). In this book, we will only concentrate on those studies that have been undertaken with PTR-MS. However, for the interested reader who wishes to know more about the results from a wide range of analytical instruments, we comment that the International Association for Breath Research (lABR), which was founded in 2005, is establishing a database of volatile substances found in breath (both for humans and animals), as well as from skin, urine, faeces and flatulence. Once available, this database will be accessible through the website http //iabr.voc-research.at. Furthermore, disease markers in breath and their potential diagnostic properties are also comprehensively discussed in a book edited by Marczin and Yacoup [75]. 

In 1998, Lindinger et al. published a review on PTR-MS which included a summary of their medical applications up to that point in time and which also demonstrated advances in improved VOC detection sensitivity (by then to a few pptv) compared to that reached with their prototype instrument [77]. In that review, the online monitoring of the fast enzymatic conversion of isopropanol into acetone was demonstrated. 

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Stewart RD, Hake CL, Peterson JE. 1974b. Use of breath analysis to monitor trichloroethylene exposures. Arch Environ Health 29 6-13. 

Short-term non-invasive biomarkers for processes producing long-term lung damage-evaluation of the feasibility of candidate measurement systems. Toxicokinetic models have been developed to determine whether breath analysis of pentane and ethane can be used to estimate chronic lung damage from toxicants. 

Benoit FM, Davidson WR, Lovett AM, Ngo A. Breath analysis by APl/MS—human exposure to volatile organic solvents. Int. Arch. Occup. Envir. Health 1985 55 113-20. 

Breath analysis for TCE has provided a more accurate index of exposure than the measurement of metabolites (trichloroethanol and trichloroacetic acid) in the urine. ... 

Sensors for Breath Analysis An Advanced Approach to Express Diagnostics and Monitoring of Human Diseases... 

Due to a combination of the modified technique for sensor analysis of composite gas mixture with unique properties of the gas-sensitive point-contact matrix, a complex dynamic of interaction between sensitive matter and volatile compounds of exhaled air has been observed. This interaction is characterized by longer adsorption times. This behavior was not observed in our previous work on breath analysis where fihn samples were used [11]. 

Dweik RA, Amann A (2008) Exhaled breath analysis the new frontier in medical testing. J Breath Res 2(3) 030301, 3 pp... 

Amann A, Smith D (eds) (2005) Breath analysis for medical diagnosis and therapeutic monitoring. World Scientific Publ, New Jersey-London-Singapore, p 536... 

Smith D, Spanel P (2007) The challenge of breath analysis for chnical diagnosis and therapeutic monitoring. Analyst 132(5) 390-396... 

Gelperin A, Johnson ATC (2008) Nanotube-based sensor arrays for clinical breath analysis. J Breath Res 2 037015, 6 pp... 

Thrall KD, Poet TS. 2000. Determination of biokinetic interactions in chemical mixtures using real-time breath analysis and physiologically based pharmacokinetic modeling. J... 

Money CD, Gray CN. 1989. Exhaled breath analysis as a measure of workplace exposure to benzene ppm. Ann Occup Hyg 33 257-262. 

Cao, W., Duan, Y. Current status of methods and techniques for breath analysis. Crit. Rev. Anal. Chem. 37, 3-13 (2007)... 

Blake, R.S., Whyte, C., Monks, P.S., Ellis, A.M. Proton transfer reaction time-of-flight mass spectrometry a good prospect for diagnostic breath analysis. In Amann, A., Smith, D. (eds.) Breath analysis for clinical diagnosis and therapeutic monitoring, p. 45. World Scientific, Toh Tuck Link, Singapore (2005)... 

Miekisch, W., Schubert, J.K. From highly sophisticated analytical techniques to life-saving diagnostics technical developments in breath analysis. Trends Anal. Chem. 25, 665-673 (2006)... 

Breath-by-breath analysis of gases and volatiles is well known in medicine (1). The experimental techniques used, however, were not very well suited to our needs. For our purpose we needed a simple, reliable inlet system without extensive filtering and pressure reduction, but with a high sensitivity and short response times. 

Therefore a (semi-) continuous measuring methodology, like MS was considered. Trace analysis by MS via a membrane separator was known (2), but the decay times of the signal precluded breath-by-breath analysis. 

Where blood or breath analysis is not immediately available after an accident it may be measured hours later and back calculated to what it would have been at the time of the accident. It is usual to assume that the blood concentration falls at about 15 mg/100 ml/h. Naturally, the validity of such calculations leads to acrimonious disputes in the courts of law. 

Blood alcohol concentration can be measured by breath analysis, as shown here. 

Statutory laws for driving under the influence of alcohol were originally based on the concentration of ethanol in venous whole blood. Because the collection of blood is invasive and requires intervention by medical personnel, the determination of alcohol in expired air has long been the mainstay of evidential alcohol measurements.There is also growing clinical interest m the determination of breath alcohol at the point-of-care. The fundamental principle for use of breath analysis is that alcohol in capillary alveolar blood rapidly equilibrates with alveolar air in a ratio... 

Harding P. Methods for breath analysis. In Garriott JC, ed. Medicolegal aspects of alcohol. Tucson, AZ Lawyers Judges Publishing Co., 1996 181-217. 

Hepner G, Vesell E. Assessment of aminopyrine metabolism in man by breath analysis after oral administration of " C-aminopyrine. Effects of phe-nobarbital, disulfiram and portal cirrhosis. N Engl J Med 1974 291 1384-8. 

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