Title: Breath analysis as diagnostic tool in oral malodour and cirrhosis.
Other Titles: Ademtesten als diagnostisch hulpmiddel voor slechte adem en cirrhose.
Authors: Dadamio, Jesica; S0207011
Issue Date: 10-Dec-2014
Abstract: Summary
The main objective of this PhD thesis has been to explore the usefulness of different breath tests as diagnostic tools. The research has been focused on two main pathologies: oral malodour and cirrhosis.
Oral Malodour
First, the usefulness of breath tests for the diagnosis of oral malodour has been examined. Our data have shown that, within their limitations, portable devices such as the Halimeter  and the OralChroma™ are useful adjunct tools. The measurements of volatile sulphur compounds (VSCs) obtained with either of these devices have shown to correlate very well with the results of the organoleptic evaluation (gold standard), and their high specificity (75-100%) makes the identification of patients who do not suffer from bad breath (pseudohalitosis/halitophobia) feasible. Unfortunately, the same cannot be said of the BB Checker™device recently introduced in the market. Neither has its sensitivity shown to be adequate, nor do its measurements of different sample types appear to be independent (Chapter 2).
In the search for an alternativetest, the usefulness of amines as salivary markers of oral malodour hasbeen explored. A simple colorimetric reaction, able to reflect the level of amines in saliva, has been evaluated. In vitro experiments have confirmed that the enzymatic reaction is linear with regards to the concentration of amines, and its results remain stable long enough to make a correct reading. An explorative clinical study using a liquid prototype has shown that this test correlates with the current gold standard of diagnosis, and that the test is both sensitive and specific enough to identify cases with and without oral malodour (Chapter 3). A first paper prototype version of the chairside test seems to reproduce these results. Even though some adjustments are still necessary, the test is at least in line with currently available salivary tests (Chapter 4).
When the metabolizing function of the liver fails, the concentration ofsome metabolites normally processed in the liver increases, and these metabolites re-enter the systemic circulation. Some of them are small volatile organic compounds (VOCs) that can be detected in people's breath. Based on this assumption, the possibility of detecting a specific pattern of biomarkers in the breath of patients suffering from cirrhosis has been explored (Chapter 5). Breath samples from patients diagnosed with r cirrhosis were collected, and their VOC profiles were compared with those obtained from a group of healthy volunteers. Breath samples were collected into a sorbent tube containing sorbent material able to trap the VOCs. These VOCs were later released from the sorbent material by thermal desorption (TD), and injected into a gas chromatograph (GC) for compoundseparation. Identification of the VOCs was made by means of a mass spectrometer (MS). VOCs showing significant differences between healthy volunteers and patients with liver disease were used to search for a characteristic compound model/pattern of cirrhosis by means of linear discriminant analysis. Several models were able to distinguish between the groups, with a sensitivity and specificity varying between 82 and 88%, and between 96 and 100%, respectively.
Since the water content in the breathsamples offered some difficulties during the analyses, several strategies in order to avoid this interference have been investigated (Chapter 6). More specifically, three strategies —warm trap method, cold tube condensation and drying agent— aimed at reducing the amount of water collected together with the VOCs have been evaluated in a small scale study. The most effective approach, and also the easiest to implement, was the use of the drying agent (LiCl). Further evaluation of the impact on the recovery of the VOCs in breath samples has shown no significant losses in VOCs, and also an apparent improvement in the recovery of some compounds.
Finally, using an improved protocol, the possibility of distinguishing between the different stages of cirrhosis has been explored (Chapter7). Results have shown that the VOCs present in breath are significantly different when considering compensated and decompensated cirrhosis according to the definition of the two mostly-used clinical scores up to date —the Child-Pugh classification and the MELD score. Even when our results have been obtained using a rather small number of samples, they can be considered as “proof of concept” regarding the usefulness of breath biomarkers in the diagnosis and follow up of liver pathologies. All the same, these observations need further validation.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Periodontology
Pharmaceutical Analysis

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