Elevated concentrations of hydrogen cyanide (HCN) have been detected in the headspace of Pseudomonas aeruginosa (PA) cultures and in the breath of children with cystic fibrosis (CF) and PA infection. The use of mouth-exhaled breath HCN as a marker of PA infection in adults is more difficult to assess as some without PA infection generate HCN in their mouths. The analysis of breath exhaled via the nose, thereby avoiding volatile compounds produced in the mouth, will demonstrate elevated concentrations of HCN in adult CF patients chronically infected with PA. Using selected ion flow mass spectrometry (SIFT-MS), the mouth and the nose-exhaled breaths of 20 adult CF patients; 10 with chronic PA infection and 10 free from PA infection, were analysed for HCN. Acetone and ethanol were also measured as controls. SIFT-MS allows direct sampling and analysis of single breath exhalations, obviating the need to collect samples into bags or onto traps, which can compromise samples. HCN was detected in the mouth-exhaled breath of patients in both groups and in the nose-exhaled breath of patients with chronic PA infection. The difference in median (IQR) nose-exhaled HCN between the groups is statistically significant (11 (0.8-18) ppbv versus 0 (0-3.2) ppbv, p = 0.03). The concentrations of acetone and ethanol in nose-exhaled and mouth-exhaled breath are in keeping with previous studies. HCN in nose-exhaled breath is a biomarker of chronic airway infection with PA in adults with CF. Its application as a non-invasive diagnostic test for early PA infection warrants further investigation.

Asthma control, evaluated by symptoms, exacerbations rate and lung function may be greatly influenced by comorbidities, particularly chronic rhinosinusitis (CRS). Measurement of nasal nitric oxide (nNO) is a simple way to assess the severity of CRS. We aimed to analyze the relationship between asthma control and nasal NO. All patients with moderate-to-severe asthma on regular follow-up at our Outpatients' Clinic between November 2009 and April 2010 were included into the study. All patients were evaluated for asthma control by asthma control questionnaire (ACQ) and comorbidities (rhinitis, chronic rhinosinusitis with (CRSwNP) or without nasal polyps, obesity). Exhaled nitric oxide and nNO were obtained in all patients. Eighty-two patients were enrolled (mean age: 48 years, range: 21-80; 42 females). According to ACQ, 53 patients (64.6%) reported controlled asthma. Patients with uncontrolled asthma had lower nNO and higher prevalence of CRSwNP, with a significant correlation between nNO and ACQ. nNO is a biomarker negatively related to asthma control. As low nNO values were associated to CRSwNP, our results indicate that asthma control is highly influenced by this comorbidity.

Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FENO) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FENO levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FENO was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aixao) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FENO and Aixao were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FENO with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FENO and Aixao (r = -0.17; 95%CI:-0.32,-0.02). FENO showed a significant negative genetic correlation with Aixao (rg = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FENO are explained both by genetic and non-shared environmental effects. Covariance between FENO and Aixao is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.

This paper introduces the advanced breath analysis (ABA) platform, an innovative scientific research platform for the entire breath research domain. Within the ABA project, we are investigating novel data management concepts and semantic web technologies to document breath analysis studies for the long run as well as to enable their full automatic reproducibility. We propose several concept taxonomies (a hierarchical order of terms from a glossary of terms), which can be seen as a first step toward the definition of conceptualized terms commonly used by the international community of breath researchers. They build the basis for the development of an ontology (a concept from computer science used for communication between machines and/or humans and representation and reuse of knowledge) dedicated to breath research.

Exhaled breath has recently been identified as a matrix for the detection of drugs of abuse. This work aims to further document this application using a new and simple collection device in patients following recovery from acute intoxication. Breath, plasma and urine samples were collected from 47 patients (38 males, age range 25-74) together with interview data. Analysis of breath and plasma samples was done by liquid chromatography-mass spectrometry methods. Urine was screened using immunochemical reagents and positive findings confirmed with liquid chromatography-mass spectrometry methods. The 12 analytes investigated were: methadone, amphetamine, methamphetamine, 6-acetylmorphine, morphine, benzoylecgonine, cocaine, diazepam, oxazepam, alprazolam, buprenorphine and tetrahydrocannabinol. In all 47 cases, recent intake of an abused substance prior to admission was reported, but in one case the substance (ketobemidone) was not investigated. In 40 of the remaining cases (87%) breath analysis gave a positive finding of any of the substances that were part of the analytical investigation. Identifications were based on correct chromatographic retention time and product ion ratios obtained in selected reaction monitoring mode. In general, data from breath, plasma, urine and self-reporting were in good agreement, but in 23% of the cases substances were detected that had not been self-reported. All substances covered were detected in a number of breath samples. Considering that breath sampling was often done about 24 h after intake, the detection rate was considered to be high for most substances. Analytes with low detection rates were benzodiazepines, and a further increase in analytical sensitivity is needed to overcome this. This study further supports use of exhaled breath as a new matrix in clinical toxicology.

Volatile organic compounds (VOCs) in exhaled human breath can serve as potential disease-specific and exposure biomarkers and therefore can reveal information about a subject's health and environment. Pyridine, a VOC marker for exposure to tobacco smoke, and isoprene, a liver disease biomarker, were studied using atmospheric pressure chemical ionization mass spectrometry (APCI-MS). While both molecules could be detected in low-ppb levels, interactions of the ionized analytes with their neutral forms and ambient air led to unusual ion/molecule chemistry. The result was a highly dynamic system and a nonlinear response to changes in analyte concentration. Increased presence of ambient water was found to greatly enhance the detection limit of pyridine and only slightly decrease that of isoprene. APCI-MS is shown to be a promising analytical tool in breath analysis with good detection limits, but its application requires a better understanding of the ion/molecule chemistry that may affect VOC quantification from a chemically complex system such as human breath.

Previous research has shown the oral malodor reducing abilities of an herbal formulation delivered using a palatal mucoadhesive tablet. The aim of the present study was to test the day-long effect of this preventive treatment on oral malodor reduction as compared with placebo and commercial mouthwash. Forty young healthy subjects (mean age, 25.8 ± 1.8 yrs, 19 females) presenting with oral malodor were randomly assigned to use one of the three tested products: herbal mucoadhesive tablets, placebo mucoadhesive tablets and a commercial mouthwash. Following baseline measurements, subjects were instructed to use the products in the evening of the same day and the following morning. Baseline and follow-up measurements were conducted in the afternoon and included odor judge scores (two judges), volatile sulfide compounds (VSC) levels using a sulfide monitor (Halimeter™) and saliva sample for β-galactosidase activity assay. The herbal mucoadhesive tablet caused a significant reduction in malodor scores (p = 0.004), VSC levels (p = 0.002) and β-galactosidase assay (p = 0.02) as compared to the placebo, and reduced malodor level to below the clinical threshold (mean odor judge score of 1.7). These results demonstrate the efficacy of the herbal formulation delivered using a mucoadhesive tablet for day-long prevention of oral malodor.

Sugar malabsorption in the bowel can lead to bloating, cramps, diarrhea and other symptoms of irritable bowel syndrome as well as affecting absorption of other nutrients. The hydrogen breath test is now a well established noninvasive test for assessing malabsorption of sugars in the small intestine. However, there are patients who can suffer from the same spectrum of malabsorption issues but who produce little or no hydrogen, instead producing relatively large amounts of methane. These patients will avoid detection with the traditional breath test for malabsorption based on hydrogen detection. Likewise the hydrogen breath test is an established method for small intestinal bacterial overgrowth (SIBO) diagnoses. Therefore, a number of false negatives would be expected for patients who solely produce methane. Usually patients produce either hydrogen or methane, and only rarely there are significant co-producers, as typically the methane is produced at the expense of hydrogen by microbial conversion of carbon dioxide. Various studies show that methanogens occur in about a third of all adult humans; therefore, there is significant potential for malabsorbers to remain undiagnosed if a simple hydrogen breath test is used. As an example, the hydrogen-based lactose malabsorption test is considered to result in about 5-15% false negatives mainly due to methane production. Until recently methane measurements were more in the domain of research laboratories, unlike hydrogen analyses which can now be undertaken at a relatively low cost mainly due to the invention of reliable electrochemical hydrogen sensors. More recently, simpler lower cost instrumentation has become commercially available which can directly measure both hydrogen and methane simultaneously on human breath. This makes more widespread clinical testing a realistic possibility. The production of small amounts of hydrogen and/or methane does not normally produce symptoms, whereas the production of higher levels can lead to a wide range of symptoms ranging from functional disorders of the bowel to low level depression. It is possible that excess methane levels may have more health consequences than excess hydrogen levels. This review describes the health consequences of methane production in humans and animals including a summary of the state of the art in detection methods. In conclusion, the combined measurement of hydrogen and methane should offer considerable improvement in the diagnosis of malabsorption syndromes and SIBO when compared with a single hydrogen breath test.

The objectives were to determine if tumor necrosis factor (TNF)-α, leukotriene (LT)B4 and 8-isoprostane (IP) were present in the exhaled breath condensate (EBC) and total lung lavage (TLL) of mechanically ventilated rats, 4 and 24 h after administration of Staphylococcal entertoxin (SEB) and to find out if these mediators in the EBC correlate with the concentration in the TLL. Rats were assigned to control (n = 8); 4 h (n = 8) or 24 h (n = 8) groups after SEB. The rats were mechanically ventilated and EBC and TLL were collected for TNF-α, LTB4 and 8-IP. TNF-α was higher in the EBC of rats at 24 h after SEB when compared to control [34.5 (16-62 versus 2 (14-30) pg ml(-1), p < 0.05] and also in the TLL [113.5 (70-460) versus 59 (35-79) pg ml(-1), p < 0.04]. LTB4 was higher in the EBC of 24 h SEB rats, when compared to control [42 (28-50) versus 36 (29-37) pg ml(-1), p < 0.01] and also in the TLL [179 (116-232) versus 114 (80-187) pg ml(-1), p < 0.05). 8-IP was similar among the groups. No correlation was observed between TNF-α, LTB4 or 8-IP in the EBC compared to the TLL. TNF-α and LTB4 may be indicators of inflammation and oxidative lung injury but the EBC does not correlate with TLL concentrations.