Analyses have been performed, using on-line selected ion flow tube mass spectrometry (SIFT-MS), of the breath of three healthy volunteers, as exhaled via the mouth and the nose and also of the air in the oral cavity during breath hold, each morning over a period of one month. Nine trace compounds have been quantified and concentration distributions have been constructed. Of these compounds, the levels of acetone, methanol and isoprene are the same in the mouth-exhaled and the nose-exhaled breath; hence, we deduce that these compounds are totally systemic. The levels of ammonia, ethanol and hydrogen cyanide are much lower in the nose-exhaled breath than in the mouth-exhaled breath and highest in the oral cavity, indicating that these compounds are largely generated in the mouth with little being released at the alveolar interface. Using the same ideas, both the low levels of propanol and acetaldehyde in mouth-exhaled breath appear to have both oral and systemic components. Formaldehyde is at levels in mouth- and nose-exhaled breath and the oral cavity that are lower than that of the ambient air and so its origin is difficult to ascertain, but it appears to be partially systemic. These results indicate that serious contamination of alveolar breath exhaled via the mouth can occur and if breath analysis is to be used to diagnose metabolic disease then analyses should be carried out of both mouth- and nose-exhaled breath to identify the major sources of particular trace compounds.

No abstract

Aims To characterize the volatile metabolites produced by genotypically diverse strains of Pseudomonas aeruginosa in order to evaluate their potential for use as biomarkers of lung infection in noninvasive breath analysis. Methods and Results Volatile organic compounds (VOCs) emitted from 36 clinical strains of Ps. aeruginosa (belonging to different multilocus sequence types) cultured in liquid and on solid media were analysed by gas chromatography mass spectrometry (GC‐MS) and selected ion flow tube mass spectrometry (SIFT‐MS). Several previously identified VOCs were detected, including ethanol, acetone, 2‐butanone, 2‐pentanone, isoprene, aminoacetophenone, dimethyl sulphide, dimethyl disulphide, dimethyl trisulphide and methyl thiocyanate. Additionally, significant production of 3‐methyl‐butanone, acetophenone, methylthioacetate and methyl thiobutanoate was observed for the first time in this study. SIFT‐MS quantifications of VOCs showed high variability between genotypically distinct strains. Conclusions The data obtained indicate that the production rates of the volatile biomarkers of Ps. aeruginosa vary by two orders of magnitude between different strains cultured under the same conditions. Similar variability was observed for both liquid and solid media. Significance and Impact of the Study Inter‐strain genotypic variability strongly influences the concentrations of the volatile biomarkers from Ps. aeruginosa. A group of several biomarkers quantified in real time in exhaled breath may thus provide a more valuable indicator of the course of pulmonary infections compared to a single biomarker.

Infection by Pseudomonas aeruginosa (PA) is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Breath analysis could potentially be a useful diagnostic of such infection, and analyses of volatile organic compounds (VOCs) emitted from PA cultures are an important part of the search for volatile breath markers of PA lung infection. Our pilot experiments using solid-phase microextraction, SPME and gas chromatography/mass spectrometric (GC/MS) analyses of volatile compounds produced by PA strains indicated a clear presence of methyl thiocyanate. This provided a motivation to develop a method for real-time online quantification of this compound by selected ion flow tube mass spectrometry, SIFT-MS. The kinetics of reactions of H(3)O(+), NO(+) and O(2)(+•) with methyl thiocyanate at 300 K were characterized and the characteristic product ions determined (proton transfer for H(3)O(+), rate constant 4.6 × 10(-9) cm(3) s(-1); association for NO(+), 1.7 × 10(-9) cm(3) s(-1) and nondissociative charge transfer for O(2)(+•) 4.3 × 10(-9) cm(3) s(-1)). The kinetics library was extended by a new entry for methyl thiocyanate accounting for overlaps with isotopologues of hydrated hydronium ions. Solubility of methyl thiocyanate in water (Henry's law constant) was determined using standard reference solutions and the linearity and limits of detection of both SIFT-MS and SPME-GC/MS methods were characterized. Thirty-six strains of PA with distinct genotype were cultivated under identical conditions and 28 of them (all also producing HCN) were found to release methyl thiocyanate in headspace concentrations greater than 6 parts per billion by volume (ppbv). SIFT-MS was also used to analyze the breath of 28 children with CF and the concentrations of methyl thiocyanate were found to be in the range 2-21 ppbv (median 7 ppbv).

Original on-line measurements of acetone, ammonia and hydrogen cyanide in the exhaled breath of several volunteers within the age ranges 4-6 years and 60-83 years are reported and compared with previous data on volunteer cohorts covering ages 17-18 years and 20-60 years. The compiled data show that a significant statistical increase in breath ammonia occurs with increasing age, but that acetone and hydrogen cyanide do not vary greatly with age.