Breath biomarkers of liver cirrhosis.

The diagnosis of asymptomatic cirrhosis in patients with liver disease is of importance to start screening for complications in due time. Liver biopsy is neither sensitive nor practical enough to be used as a frequent follow-up test in patients with chronic liver disease. The volatile organic compounds present in exhaled breath offer the possibility of exploring internal physiologic and pathologic process in a non invasive way. This study examined whether a specific pattern of biomarkers can be found in breath samples of patients with cirrhosis. To this aim samples of alveolar breath from patients with cirrhosis and healthy volunteers were analyzed using gas chromatography-mass spectrometry. When linear discriminant analysis was used to search for a model(s)/pattern of compounds characteristic for liver cirrhosis, 24 models of 8 independent compounds could distinguish between the groups. The sensitivity and specificity (between 82% and 88%, and 96% and 100%, respectively) of the models suggest that a specific pattern of breath biomarkers can be found in patients with cirrhosis, which may allow detecting this complication of chronic liver disease in an early stage.

A novel and visual test for oral malodour: first observations.

Until now, the application of biogenic amines as bio-markers of oral malodour has been limited because of the complexity of their detection. This study explores the usability of a simple colorimetric reaction detecting amines in saliva as an adjunct test for the diagnosis of oral malodour. The colour reaction caused by a newly discovered enzyme capable of detecting amines in saliva was characterized in vitro. Two colour scales were developed by transforming the colours of selected dilutions of a mixture of cadaverine and putrescine into a 5- and a 10-point pink-colour scale. Afterwards, this new enzymatic test was used to assess the amount of amines in saliva samples of 50 volunteers with different degrees of oral malodour. The enzymatic reaction was shown to be linear towards the concentration of amines and stable over a time of ≥4 h. Colour scores correlated well with organoleptic scores and the volatile sulfur compounds. More importantly differences between patients with and without oral malodour were significant. Based on these results, we conclude that this new enzymatic test, interpreted by means of a simple colour scale, has the potential to be used as an adjunct chair-side test for oral malodour diagnosis.

Clinical reliability of non-organoleptic oral malodour measurements.

AIM: Measurement of volatile sulphur compounds (VSC) by portable sulphur monitors (Halimeter, OralChroma) is a common practice for diagnosis of oral malodour. In this study, the clinical value of these devices was examined. MATERIALS AND METHODS: Two hundred and eighty patients with bad breath complaints attending a halitosis consultation were enrolled. Organoleptic scores were given by a trained and calibrated judge, before measurement of the VSC levels (Halimeter, OralChroma), to avoid any bias. RESULTS: Significant correlations were found between the organoleptic assessment, the Halimeter, and the OralChroma (R=0.74 for organoleptic versus Halimeter; 0.66 for organoleptic versus OralChroma; 0.63 for Halimeterversus OralChroma). The sensitivity and specificity (with regard to the organoleptic score) to detect patients with/without oral malodour for the Halimeter were 63% and 98%, respectively, and for the OralChroma 69% and 100% when using the cutoffs suggested by the manufacturer. By lowering these values, sensitivity could be improved without a significant decrease in specificity (both devices). CONCLUSIONS: We concluded that the measurement of the VSC levels can be used as an adjunct to the organoleptic assessment. Thresholds should be revisited in order to improve their clinical utility. These devices can prove the absence of malodour in case of pseudo-halitosis.

Characteristics of 2000 patients who visited a halitosis clinic.

AIMS: The aim of this paper was to analyse the aetiology and characteristics of 2000 patients who visited a multidisciplinary bad breath clinic in Leuven, Belgium and to correlate organoleptic ratings with portable device measurements. MATERIALS AND METHODS: The characteristics and aetiology of breath malodour of two thousand consecutive patients who visited a halitosis consultation were explored by means of a standard questionnaire and a clinical examination, including organoleptic scores provided by a trained and calibrated judge, and a portable bad breath detector (Halimeter). RESULTS: Most patients came without referral and had complaints for several years (mean: 7 years, SD: 8 years). For 76% of the patients, an oral cause was found [tongue coating (43%), gingivitis/periodontitis (11%) or a combination of the two (18%)]. Pseudo-halitosis/halitophobia was diagnosed in 16% of the cases; and ear, nose and throat/extra-oral causes were found in 4% of the patients. Most patients had an organoleptic score <3 and a Halimeter value <240 p.p.b. CONCLUSIONS: Even though it was observed that halitosis has a predominantly oral origin, a multidisciplinary approach remains necessary to identify ear, nose and throat or extra-oral pathologies and/or pseudo-halitosis/halitophobia.

GC-MS analysis of breath odor compounds in liver patients.

BACKGROUND: Liver diseases can cause a sweet, musty aroma of the breath, called fetor hepaticus. Even in a stage of cirrhosis, the disease can be asymptomatic for many years. Breath analysis might be helpful to detect occult liver pathology. STUDY OBJECTIVE: This study examined whether specific breath odor compounds can be found in liver patients, suffering from cirrhosis, which might be useful for diagnosis. MATERIALS AND METHODS: Fifty-two liver patients and 50 healthy volunteers were enrolled. Alveolar air was analyzed by gas chromatography-mass spectrometry. Using discriminant analysis a model for liver disease was built. RESULTS: Dimethyl sulfide, acetone, 2-butanone and 2-pentanone were increased in breath of liver patients, while indole and dimethyl selenide were decreased. Sensitivity and specificity of the model were respectively 100% and 70%. CONCLUSIONS: Fetor hepaticus is caused by dimethyl sulfide and to a lower extent by ketones in alveolar air. Breath analysis by GC-MS makes it possible to discriminate patients with breath malodor related to hepatic pathologies.

Halitosis associated volatiles in breath of healthy subjects.

BACKGROUND: Halitosis can have an intra- or extra-oral origin. In all cases, bad breath is caused by the presence of volatile organic compounds originating from the mouth or the expired air. They can be specific for certain diseases or infections. STUDY OBJECTIVE: This study explored the presence and concentration of these volatile compounds normally associated with halitosis in the breath of healthy symptomless volunteers. METHODS: Alveolar and mouth air of 40 healthy volunteers as well as environmental air were analyzed by gas chromatography-mass spectrometry (GC-MS) and by a commercially available GC device (OralChroma). RESULTS: 14 compounds, associated with halitosis could be detected. All of them except carbon disulfide, appeared to be (partly) produced endogenously and/or in the mouth. Acetone, 2-butanone, 2-pentanone and 1-propanol were common to all volunteers in both alveolar and mouth air and indole and dimethyl selenide in alveolar air. CONCLUSIONS: GC-MS seems a promising tool for differential diagnosis of halitosis, with the possibility to detect extra-oral causes, which often remain undetected unless characterized by a specific smell.

Differences between alveolar air and mouth air.

Our breath contains an intraoral and an alveolar part, the latter being the last to be exhaled. As such, major differences in composition can be expected, with for alveolar air the inclusion of more metabolic compounds released during the blood-air exchange. This study explored the differences between breath air from the oropharynx and from the lungs in healthy volunteers. Mouth and alveolar air of 40 volunteers was analyzed using gas chromatography-mass spectrometry, together with a sample of room air. A chromatogram of a single person contains on average 145 different compounds. Altogether, 618 compounds were detected. A total of 35 compounds were common to all volunteers. The number of compounds was significantly higher in mouth air than in alveolar air. For 47 compounds, very significant differences in detection/concentration were recorded. Gas chromatography-mass spectrometry offers a detailed overview of the compounds in a person's breath. One should be aware of the distinction between alveolar air and oropharyngeal air.

Species identification of corynebacteria by cellular fatty acid analysis.

We evaluated the usefulness of cellular fatty acid analysis for the identification of corynebacteria. Therefore, 219 well-characterized strains belonging to 21 Corynebacterium species were analyzed with the Sherlock System of MIDI (Newark, DE). Most Corynebacterium species have a qualitative different fatty acid profile. Corynebacterium coyleae (subgroup 1), Corynebacterium riegelii, Corynebacterium simulans, and Corynebacterium imitans differ only quantitatively. Corynebacterium afermentans afermentans and C. coyleae (subgroup 2) have both a similar qualitative and quantitative profile. The commercially available database (CLIN 40, MIDI) identified only one third of the 219 strains correctly at the species level. We created a new database with these 219 strains. This new database was tested with 34 clinical isolates and could identify 29 strains correctly. Strains that remained unidentified were 2 Corynebacterium aurimucosum (not included in our database), 1 C. afermentans afermentans, and 2 Corynebacterium pseudodiphtheriticum. Cellular fatty acid analysis with a self-created database can be used for the identification and differentiation of corynebacteria.