Laser spectroscopy for breath analysis : towards clinical implementation

Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.Peer reviewe

Teoretické studium difúze iontů dúležitých pro analýzu dechu metodou SIFT-MS

Accuracy of quantitative Selected Ion Flow Tube Mass Spectrometry SIFT-MS is ultimately determined by the proper accounting in the data analysis for the effect of differential diffusion. Diffusion loss of the product ions can be typically lower by a factor of up to 3 in comparison with the precursor ions. Hard sphere model of diffusion of polyatomic ions in helium has been used to calculate diffusion coefficients of the precursor and product ions involved in SIFT-MS quantification of common breath metabolites ammonia, acetone, isoprene, acetaldehyde and ethanol. Calculation involves semiempirical PM3 method for determination of the geometries of the ions, numerical averaging of the geometrical cross section for collisions with helium atoms and construction of a model interaction (12, 4) model potential followed by the analytical calculation of ionic mobility using momentum-transfer collision integral. Finally the values of diffusion enhancement factors have been calculated

Increase of methanol in exhaled breath quantified by SIFT-MS following aspartame ingestion

Aspartame, methyl-L-α-aspartyl-L-phenylalaninate, is used worldwide as a sweetener in foods and drinks and is considered to be safe at an acceptable daily intake (ADI) of 40 mg per kg of body weight. This compound is completely hydrolyzed in the gastrointestinal tract to aspartic acid, phenylalanine and methanol, each being toxic at high levels. The objective of the present study was to quantify the volatile methanol component in the exhaled breath of ten healthy volunteers following the ingestion of a single ADI dose of aspartame. Direct on-line measurements of methanol concentration were made in the mouth and nose breath exhalations using selected ion flow tube mass spectrometry, SIFT-MS, several times before aspartame ingestion in order to establish individual pre-dose (baseline) levels and then during two hours post-ingestion to track their initial increase and subsequent decrease. The results show that breath methanol concentrations increased in all volunteers by 1082   ±   205 parts-per-billion by volume (ppbv) from their pre-ingestion values, which ranged from 193 to 436 ppbv to peak values ranging from 981-1622 ppbv, from which they slowly decreased. These observations agree quantitatively with a predicted increase of 1030 ppbv estimated using a one-compartment model of uniform dilution of the methanol generated from a known amount of aspartame throughout the total body water (including blood). In summary, an ADI dose of aspartame leads to a 3-6 fold increase of blood methanol concentration above the individual baseline values

Quantitative analysis of volatile metabolites released in vitro by bacteria of the genus Stenotrophomonas for identification of breath biomarkers of respiratory infection in cystic fibrosis

The aim of the present study was to characterize the volatile metabolites produced by genotypically diverse strains of the Stenotrophomonas genus in order to evaluate their potential as biomarkers of lung infection by non-invasive breath analysis. Volatile organic compounds (VOCs) emitted from 15 clinical and five environmental strains belonging to different genogroups of Stenotrophomonas maltophilia (n = 18) and Stenotrophomonas rhizophila (n = 2) cultured in Mueller-Hinton Broth (MHB) liquid media were analysed by gas chromatography mass spectrometry (GC-MS) and selected ion flow tube mass spectrometry (SIFT-MS). Several VOCs were detected in high concentration, including ammonia, propanol, dimethyl disulphide propanol and dimethyl disulphide. The GC-MS measurements showed that all 15 clinical strains produced similar headspace VOCs compositions, and SIFT-MS quantification showed that the rates of production of the VOCs by the genotypically distinct strains were very similar. All in vitro cultures of both the Stenotrophomonas species were characterised by efficient production of two isomers of methyl butanol, which can be described by known biochemical pathways and which is absent in other pathogens, including Pseudomonas aeruginosa. These in-vitro data indicate that methyl butanol isomers may be exhaled breath biomarkers of S. maltophilia lung infection in patients with cystic fibrosis

Breath concentration of acetic acid vapour is elevated in patients with cystic fibrosis

A study has been carried out of the volatile organic compounds present in the exhaled breath of 58 cystic fibrosis (CF) patients. An important observation is that the acetic acid vapour concentration measured by selected ion flow tube mass spectrometry (SIFT-MS) is significantly elevated in the exhaled breath of CF patients, independent of the Pseudomonas aeruginosa (PA) infection status (PA-infected median 170 ppbv; PA-negative median 182 ppbv), compared to that of healthy controls (median 48 ppbv). The cause for this may be decreased pH of the mucus lining the CF airways. Thus, we speculate that non-invasive measurement of breath acetic acid concentration could serve as an indicator of the acidity of the CF airways mucosa