Q43240855
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An instrument integrating thermal desorption (TD) to selected ion flow tube mass spectrometry (SIFT-MS) is presented, and its application to analyze volatile organic compounds (VOCs) in human breath is demonstrated for the first time. The rationale behind this development is the need to analyze breath samples in large-scale multicenter clinical projects involving thousands of patients recruited in different hospitals. Following adapted guidelines for validating analytical techniques, we developed and validated a targeted analytical method for 21 compounds of diverse chemical class, chosen for their clinical and biological relevance. Validation has been carried out by two independent laboratories, using calibration standards and real breath samples from healthy volunteers. The merging of SIFT-MS and TD integrates the rapid analytical capabilities of SIFT-MS with the capacity to collect breath samples across multiple hospitals. Thanks to these features, the novel instrument has the potential to be easily employed in clinical practice.
Úvod: Všechny dostupné metody používané v současnosti v diagnostice a monitoraci aktivity idiopatických střevních zánětů (IBD) mají omezenou senzitivitu a specificitu (RTG metody, biomarkery) nebo jsou přímo spojené s dyskomfortem či přímo se zdravotním rizikem pro pacienta (opakované endoskopie a CT vyšetření). Proto je legitimní snahou hledat nové neinvazivní diagnostické metody. Analýza koncentrace těkavých stopových metabolitů v dechu je potenciálním markerem v diagnostice IBD a monitoraci aktivity onemocnění. Hmotnostní spektrometrie v proudové trubici s vybranými ionty (SIFT-MS) je nová metoda pro kvantitativní analýzu stopových plynů zejména v lidském dechu. Metody a soubor pacientů: V naší pilotní studii bylo SIFT-MS užito pro analýzu přítomnosti těkavých biomarkerů IBD v dechu pacientů, rozdíly v jejich koncentracích byly zkoumány ve vztahu k přítomnosti IBD a aktivitě choroby. Soubor tvořilo celkem 48 IBD pacientů, 28 s ulcerózní kolitidou (UC) a 20 s Crohnovou chorobou (CD) (25 žen a 23 mužů), průměrný věk pacientů byl 30 let a délka trvání choroby 10 let. Výsledky: Významné rozdíly mezi podskupinami pacientů byly zjištěny v koncentracích pentanu, sirouhlíku, acetonu a propanolu: koncentrace pentanu byla signifikantně zvýšena u pacientů s CD (aktivní i v remisi) oproti kontrolní skupině zdravých jedinců (115 vs 61 nmol/mol; p < 0,01) stejně jako u nemocných s aktivní UC (91 vs 61 nmol/mol; p < 0,01). Koncentrace sirouhlíku byla signifikantně zvýšena u pacientů s aktivní CD (111 vs 50 nmol/mol; p < 0,01) a konečně koncentrace acetonu (1 495 vs 509 nmol/mol; p < 0,01) a propanolu byly signifikantně zvýšeny u pacientů, kteří v den měření absolvovali kolonoskopii (pravděpodobný podíl lačnění). Závěr: Na základě výsledků našeho pilotního projektu považujeme užití dechové analýzy pomocí SIFT-MS za přínosné v neinvazivní diagnostice a monitoraci aktivity IBD. Další cílené studie této problematiky jsou nutné.
Introduction: All tests currently used in clinical diagnostics and the activity monitoring of inflammatory bowel disease (IBD) have limited sensitivity and specificity or are directly linked to discomfort or risk to the patient (endoscopy or repeated CT tests), therefore necessitating new, non-invasive methods. The quantification of volatile metabolites in breath is a potential biomarker of IBD presence and activity. Selected ion flow tube mass spectrometry (SIFT-MS) is a relatively new analytical technique for quantitative analysis of the trace gases, chiefly in human breath. Methods and subjects: In our pilot project, SIFT-MS was used for the analysis of volatile IBD biomarkers in breath. Differences in their concentrations were studied in relation to the presence of IBD and activity of the disease. The study sample was composed of 48 IBD patients, 28 with ulcerative colitis (UC) and 20 with Crohn’s disease (CD). Of the 48 patients, 25 were female and 23 male. The mean age was 30 years and the mean disease duration was 10 years. Results: Significant differences between subgroups of patients were found in the concentrations of pentane, carbon disulphide, acetone and propanol. Patients with CD (both with active and quiescent disease) had significantly higher concentrations of pentane compared to the group of healthy individuals (115 vs. 61 nmol/mol; p < 0.01), as was the case for patients with active UC (91 vs. 61 nmol/mol; p < 0.01). The concentration of carbon disulphide (H2S) was significantly higher in patients with active CD (111 vs. 50 nmol/mol; p < 0.01) and concentrations of acetone (1,495 vs. 509 nmol/mol; p < 0.01) and propanol were significantly higher in the breath of patients who had undergone colonoscopy prior to breath analysis (this was likely due to a lack of nutrition). Conclusions: Based on the results of this study, we consider the use of breath testing using SIFT-MS to be a beneficial non- invasive diagnostic and monitoring method for IBD activity. Further targeted studies are necessary to address this issue.
- Klíčová slova
- nespecifické střevní záněty, biomarkery, dechová analýza, hmotnostní spektrometrie v proudové trubici s vybranými ionty, SIFT-MS,
- MeSH
- aceton izolace a purifikace MeSH
- amoniak izolace a purifikace MeSH
- biologické markery MeSH
- Crohnova nemoc diagnóza prevence a kontrola MeSH
- dechové testy metody přístrojové vybavení MeSH
- diagnostické techniky gastrointestinální trendy využití MeSH
- financování organizované MeSH
- hmotnostní spektrometrie metody přístrojové vybavení využití MeSH
- idiopatické střevní záněty diagnóza prevence a kontrola MeSH
- lidé MeSH
- methan izolace a purifikace MeSH
- pentany izolace a purifikace MeSH
- pilotní projekty MeSH
- plyny izolace a purifikace MeSH
- statistika jako téma MeSH
- těkavé organické sloučeniny MeSH
- ulcerózní kolitida diagnóza prevence a kontrola MeSH
- voda MeSH
- Check Tag
- lidé MeSH
PURPOSE OF REVIEW: To summarize the recent progress made in noninvasive monitoring of volatile compounds in exhaled breath and above biological liquids, as they are becoming increasingly important in assessing the nutritional and clinical status and beginning to provide support to conventional clinical diagnostics and therapy. To indicate the potential of these developments in medicine and the specific areas which are currently under investigation. RECENT FINDINGS: The significance of the following breath gases and their concentrations are reported: acetone and the influence of diet; ammonia confirmed as an indicator of dialysis efficacy; hydrogen and the (13)CO(2)/(12)CO(2) ratio (following the ingestion of (13)C-labeled compounds) as related to gastric emptying and bowel transit times; hydrogen cyanide released by Pseudomonas and its detection in breath of children with cystic fibrosis; and multiple trace compounds in breath of patients with specific pathophysiological conditions and 'metabolic profiling'. SUMMARY: Advanced analytical methods, especially exploiting mass spectrometry, are moving breath analysis towards the clinical setting; some trace gas metabolites are already being exploited in diagnosis and therapy. Much effort is being given to the search for biomarkers of tumours in the body. HCN as an indicator of the presence of Pseudomonas in the airways has real potential in therapeutically alleviating the symptoms of cystic fibrosis.
- MeSH
- aceton metabolismus MeSH
- amoniak metabolismus MeSH
- dechové testy metody MeSH
- dýchací soustava metabolismus MeSH
- hmotnostní spektrometrie MeSH
- kyanovodík metabolismus MeSH
- lidé MeSH
- nutriční stav MeSH
- oxid uhličitý metabolismus MeSH
- stopové prvky metabolismus MeSH
- těkavé organické sloučeniny metabolismus MeSH
- vodík metabolismus MeSH
- zdravotní stav MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The development of selected ion flow tube mass spectrometry, SIFT-MS, is described from its inception as the modified very large SIFT instruments used to demonstrate the feasibility of SIFT-MS as an analytical technique, towards the smaller but bulky transportable instruments and finally to the current smallest Profile 3 instruments that have been located in various places, including hospitals and schools to obtain on-line breath analyses. The essential physics and engineering principles are discussed, which must be appreciated to design and construct a SIFT-MS instrument. The versatility and sensitivity of the Profile 3 instrument is illustrated by typical mass spectra obtained using the three precursor ions H(3)O(+), NO(+) and O(2)(+)·, and the need to account for differential ionic diffusion and mass discrimination in the analytical algorithms is emphasized to obtain accurate trace gas analyses. The performance of the Profile 3 instrument is illustrated by the results of several pilot studies, including (i) on-line real time quantification of several breath metabolites for cohorts of healthy adults and children, which have provided representative concentration/population distributions, and the comparative analyses of breath exhaled via the mouth and nose that identify systemic and orally-generated compounds, (ii) the enhancement of breath metabolites by drug ingestion, (iii) the identification of HCN as a marker of Pseudomonas colonization of the airways and (iv) emission of volatile compounds from urine, especially ketone bodies, and from skin. Some very recent developments are discussed, including the quantification of carbon dioxide in breath and the combination of SIFT-MS with GC and ATD, and their significance. Finally, prospects for future SIFT-MS developments are alluded to.
- MeSH
- dechové testy přístrojové vybavení metody MeSH
- design vybavení MeSH
- hmotnostní spektrometrie přístrojové vybavení metody trendy MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Collection of exhaled breath condensate (EBC) is a relatively simple noninvasive method of breath analysis; however, no data have been reported that would relate concentration of volatile compounds in EBC to their gaseous concentrations in exhaled air. The aim of the study was to investigate which volatile compounds are present in EBC and how their concentrations relate to results of direct breath analysis. Thus, samples of EBC were collected in a standard way from several subjects and absolute levels of several common volatile breath metabolites (ammonia, acetone, ethanol, methanol, propanol, isoprene, hydrogen cyanide, formaldehyde and acetaldehyde) were then determined in their headspace using selected ion flow tube mass spectrometry (SIFT-MS). Results are compared with those from on-line breath analyses carried out immediately before collecting the EBC samples. It has been demonstrated that SIFT-MS can be used to quantify the concentrations of volatiles in EBC samples and that, for methanol, ammonia, ethanol and acetone, the EBC concentrations correlate with the direct breath levels. However, the EBC concentrations of isoprene, formaldehyde, acetaldehyde, hydrogen cyanide and propanol do not correlate with direct breath measurements. Copyright (c) 2008 John Wiley & Sons, Ltd.
- MeSH
- analýza selhání vybavení MeSH
- aromatické uhlovodíky analýza MeSH
- dechové testy metody přístrojové vybavení MeSH
- design vybavení MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody přístrojové vybavení MeSH
- lidé MeSH
- odběr biologického vzorku metody přístrojové vybavení MeSH
- průtoková injekční analýza metody přístrojové vybavení MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- volatilizace MeSH
- Check Tag
- lidé MeSH
Samples (210 in total) of broncholaveolar lavages (BALs), obtained from patients hospitalized with pneumonia in various departments of two hospitals, were analysed using the method of solid phase microextraction-gas chromatography (SPME-GC) with FID detection. Up to 20% (9% unequivocally, 11% probably) of these samples was found to contain volatile fatty acids (VFAs) in the series from acetic acid to heptanoic acid. Importantly, the presence of these acids indicates the presence of fermenting anaerobic bacteria, which were not detected by the conventional microbiological examination. Other compounds, namely the heptanol and cyclohexanone, were also detected by this method in some samples. Cyclohexanone occurred almost exclusively in samples from patients receiving intensive care with mechanical ventilation, and is suspected to originate from plastic parts of ventilators. Selected representative samples were also analysed using further methods, namely gas chromatography-mass spectrometry (GC-MS) of native and silylated samples, and selected ion flow tube mass spectrometry (SIFT-MS). These methods confirmed the identities of above mentioned compounds, and detected numerous other compounds tentatively identified as various alcohols, aldehydes, ketones, esters and hydrogen cyanide, HCN. Most of these compounds occurred in small amounts and their origin and diagnostic significance remains uncertain, except, that is, for the HCN, which indicates the presence of Pseudomonas aeruginosa.
- MeSH
- anaerobní bakterie izolace a purifikace metabolismus MeSH
- bakteriální pneumonie metabolismus mikrobiologie MeSH
- bronchoalveolární lavážní tekutina chemie mikrobiologie MeSH
- financování organizované MeSH
- kyseliny mastné těkavé metabolismus MeSH
- lidé MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- Check Tag
- lidé MeSH
The increase in ammonia and ethanol in the exhaled breath stream following mouthwashes by aqueous solutions of urea and sugar (sucrose), respectively, has been investigated by analysing exhaled breath in real time using selected ion flow tube mass spectrometry, SIFT-MS. It is shown that the measured levels of these compounds in the stream of exhaled breath can be much greater than the endogenous levels originating at the alveolar boundary. Thus, it is concluded that without careful preparation, mouth production of these compounds, and other compounds as yet unidentified, can seriously compromise the quantification of truly endogenous trace compounds present in blood and in the alveolar breath, as required for clinical diagnosis, and can probably introduce additional compounds into the breath stream that could seriously mislead breath analysis. The concentrations of both the urea and sucrose solutions used to enhance the ammonia and ethanol levels were larger than normally present in food and drinks and so in most situations such severe enhancements will not occur.
A coordinated study of the dispersal of water between the various body compartments (stomach and gut, blood stream and tissue) and the similar dispersal kinetics of ethanol and its metabolism has been carried out involving two healthy volunteers using flowing afterglow mass spectrometry, FA-MS, and selected ion flow tube mass spectrometry, SIFT-MS. Thus, using these techniques, the variations of HDO and ethanol in breath, measured in successive single exhalations, were followed in real time after the ingestion of measured quantities of D2O and ethanol in proportion to the body weights of the subjects at the dose rates D2O approximately 0.283 g kg-1, ethanol approximately 0.067 g kg-1. During the FA-MS experimental periods (about 2 h), the dispersion of HDO into the body water and finally its equilibration in the total body water is observed from which total body water for each subject was determined. In the SIFT-MS measurements, the dispersion of ethanol into the body water and its loss via metabolism was observed until the physiological (pre-dose) breath level of ethanol for each individual was restored. A simple linear transformation is used to derive the time variations of the blood levels of HDO and ethanol. This has allowed a comparison of the fractions of the ingested ethanol that are metabolized during first-pass metabolism for the two subjects. Thus, in one subject 30% and in the other subject 40% of the ingested alcohol is metabolized in the first 20 min following ingestion. The good time resolution allowed by non-invasive breath analysis ensures that the rates of processes such as ethanol metabolism can be accurately measured. Simultaneous measurements of breath acetaldehyde (largely formed via the ethanol metabolism) and acetone were also performed during the SIFT-MS single breath exhalations.
- MeSH
- aplikace orální MeSH
- dechové testy metody MeSH
- ethanol aplikace a dávkování metabolismus MeSH
- financování vládou MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- kinetika MeSH
- lidé MeSH
- metabolická clearance MeSH
- oxid deuteria analýza diagnostické užití metabolismus MeSH
- spirometrie MeSH
- tělesná voda metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- hodnotící studie MeSH
