Discriminant Profiles of Volatile Compounds in the Alveolar Air of Patients with Squamous Cell Lung Cancer, Lung Adenocarcinoma or Colon Cancer.

The objective of the present work was to analyze volatile compounds in alveolar air in patients with squamous cell lung cancer, lung adenocarcinoma or colon cancer, to prepare algorithms able to discriminate such specific pathological conditions. The concentration of 95 volatile com-pounds was measured in the alveolar air of 45 control subjects, 36 patients with lung adenocarci-noma, 25 patients with squamous cell lung cancer and 52 patients with colon cancer. Volatile compounds were measured with ion molecule reaction mass spectrometry (IMR-MS). An iterat-ed least absolute shrinkage and selection operator multivariate logistic regression model was used to generate specific algorithms and discriminate control subjects from patients with differ-ent kinds of cancer. The final predictive models reached the following performance: by using 11 compounds, patients with lung adenocarcinoma were identified with a sensitivity of 86% and specificity of 84%; nine compounds allowed us to identify patients with lung squamous cell car-cinoma with a sensitivity of 88% and specificity of 84%; patients with colon adenocarcinoma could be identified with a sensitivity of 96% and a specificity of 73% using a model comprising 13 volatile compounds. The different alveolar profiles of volatile compounds, obtained from pa-tients with three different kinds of cancer, suggest dissimilar biological-biochemistry condi-tions; each kind of cancer has probably got a specific alveolar profile.

Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air.

BACKGROUND: In the last decade many studies showed that the exhaled breath of subjects suffering from several pathological conditions has a peculiar volatile organic compound (VOC) profile. The objective of the present work was to analyse the VOCs in alveolar air to build a diagnostic tool able to identify the presence of pancreatic ductal adenocarcinoma in patients with histologically confirmed disease. METHODS: The concentration of 92 compounds was measured in the end-tidal breath of 65 cases and 102 controls. VOCs were measured with an ion-molecule reaction mass spectrometry. To distinguish between subjects with pancreatic adenocarcinomas and controls, an iterated Least Absolute Shrinkage and Selection Operator multivariate Logistic Regression model was elaborated. RESULTS: The final predictive model, based on 10 VOCs, significantly and independently associated with the outcome had a sensitivity and specificity of 100 and 84% respectively, and an area under the ROC curve of 0.99. For further validation, the model was run on 50 other subjects: 24 cases and 26 controls; 23 patients with histological diagnosis of pancreatic adenocarcinomas and 25 controls were correctly identified by the model. CONCLUSIONS: Pancreatic cancer is able to alter the concentration of some molecules in the blood and hence of VOCs in the alveolar air in equilibrium. The detection and statistical rendering of alveolar VOC composition can be useful for the clinical diagnostic approach of pancreatic neoplasms with excellent sensitivity and specificity.

Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry.

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds' (VOCs) pattern when compared to controls. Patients 10-17 years of age, were divided into four groups: Crohn's disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non-invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients.

Biological monitoring of cobalt in hard metal factory workers.

PURPOSE: The main aim of this study was to investigate the cobalt (Co) concentrations in urine along 4 months and their relationship with Co concentrations in blood and haemoglobin (adducts) in 34 workers from a hard metal manufacturing plant where metallic Co and Co oxide were used. Furthermore, the excretion kinetics of Co was investigated and the half-lives of Co in blood, plasma and urine were calculated along 18 days of non-exposure in the same workers. METHODS: Co was analysed, in all biological samples, by ICP/MS. RESULTS: Wide fluctuations in the urinary Co concentration were observed throughout the work shift and during the work week. A highly significant linear correlation was found between Co concentration (geometrical mean) in urine samples provided each Thursday (end shift) during 16 subsequent weeks and levels of Co-haemoglobin adducts or blood Co concentrations at the end of the same period. The Co elimination kinetics in globin calculated along 18 days without Co exposure was slow, being related to the physiological metabolism of haemoglobin, while in blood, plasma and urine Co half-lives were 12.3, 9.1 and 5.3 days, respectively. CONCLUSION: Co concentrations in haemoglobin or blood are highly related to the geometrical mean concentration of urinary Co when samples are collected weekly for several subsequent weeks. The biological monitoring of occupational exposure to Co in hard metal facilities provides reliable results by using the Co concentrations in haemoglobin or in whole blood. The urinary findings, though, do not show the same reliability because of their wide daily and weekly fluctuations.

S-(acetamidomethyl)mercapturic acid (AMMA): a new biomarker for occupational exposure to N,N-dimethylacetamide.

N,N-dimethylacetamide (DMA) is used in the textile and plastics industry as a solvent alternative to more toxic N,N-dimethylformamide. Here we studied toxicokinetics of two major urinary metabolites of DMA, namely, S-(acetamidomethyl)mercapturic acid (AMMA) and N-methylacetamide (NMA). Urine samples were collected from workers exposed to DMA in a factory manufacturing acrylic fibers. AMMA and NMA were determined by HPLC/MS and GC/MS, respectively. The working scheme in the factory consisted of periods of three consecutive working shifts alternated regularly with two days off work. In the first stage of the study, NMA and AMMA were determined in urine samples collected before, in the middle, and at the end of one working shift. In the second stage, urine was collected five times during three consecutive days after a two-day rest: before and at the end of the first and second working shifts and before the third shift. It was found that the end-of-shift NMA levels were several folds higher than the pre-shift levels of the same day and dropped significantly until the next shift. On the other hand, there were no significant differences in AMMA levels before and at the end of the same shift but a continuous rise during the three-day working period was observed. Median values of NMA concentrations at the end of working shifts were between 10.1 and 17.3 mg/g creatinine, median AMMA concentrations in the second or third day of the working period varied between 12.4 and 38.1 mg/g creatinine. The approximate half-lives of NMA and AMMA (means) in the exposed workers were about 9 and 29 h, respectively. Thus, while NMA in the end-of-shift urine samples remains a preferential biomarker of DMA exposure during that shift, AMMA determined at the end of a work-week reflects cumulative exposure over the last few days. Further studies are needed to determine AMMA concentrations corresponding to the threshold limit value of DMA.

Comparison of breath, blood and urine concentrations in the biomonitoring of environmental exposure to 1,3-butadiene, 2,5-dimethylfuran, and benzene.

OBJECTIVES: To investigate and compare alveolar, blood, and urine concentrations of 1,3-butadiene, 2,5 dimethylfuran, and benzene, in non-occupational exposure to these products. METHODS: Benzene, 2,5-dimethylfuran and 1,3-butadiene were measured in the breath, blood, and urine samples of 61 subjects living in small mountain villages. All 61 were regularly employed as forestry workers. Sampling was done during the long winter-season non-working period. Samples were collected after overnight rest and analysed by headspace and GC-mass spectrometry methods. RESULTS: The median 1,3-butadiene level was 1.2 ng/l (range: <0.8-13.2 ng/l) in alveolar air, 2.2 ng/l (range: <0.5-50.2 ng/l) in blood, and 1.1 ng/l (range: <1-8.9 ng/l) in urine. The median benzene level was 5.7 ng/l (range: <1-24.9 ng/l) in alveolar air, 62.3 ng/l (range: 33.5-487.2 ng/l) in blood, and 63.4 ng/l (range: 25.8-1099.1 ng/l) in urine. The median 2,5-dimethylfuran level was 0.5 ng/l (range: <1-12.5 ng/l) in alveolar air, 2.5 ng/l (range: <5-372.9 ng/l) in blood, and 51.8 ng/l (range: <5-524.9 ng/l) in urine. In several cases, 2,5-dimethylfuran levels were below the detection limit in alveolar air and blood, especially in non-smokers. 1,3-Butadiene, 2,5-dimethylfuran and benzene levels were significantly higher in smokers than non-smokers in all biological media. CONCLUSIONS: 1,3-Butadiene and benzene, as ubiquitous pollutants, are detectable and quantifiable in human alveolar air, blood and urine. 2,5-Dimethylfuran, which is not a usual environmental pollutant, is almost always detectable in biological media, but only in smokers.

Mercapturic acids in the biological monitoring of occupational exposure to chemicals.

This paper reviews several procedures for determination of mercapturic acids in urine. Special attention was paid to methods useful in relation to human exposure to industrial pollutants, without any description for less sensitive methods used in animal research. Gas chromatographic and liquid chromatographic procedures were considered together with the little information available about thin layer chromatography and immunochemical techniques. After a description of the main industrial pollutants which lead to synthesis of their specific mercapturic acids, the methods for analysing these products are synthetically reported. The comparison among difficulties in sample preparation, complexity of instrumentation and their cost/benefit ratio are discussed.

Analysis of benzene, toluene, ethylbenzene and m-xylene in biological samples from the general population.

A method for the determination of benzene, toluene, ethylbenzene and xylene in blood and urine of people not occupationally exposed to solvents is described. The headspace technique combined with gas chromatography with a mass spectrometer detector is used. The sensitivity of recent mass spectrometers is good enough to furnish reliable results also in biological samples collected from the general population. No treatment for concentrating solvents present in the blood or urine is necessary. The main features of the method are easy preparation of biological samples, small volumes (7 ml), good repeatability and linearity in the range of interest. The limits of detection in blood were 16, 43, 22 and 52 ng/l for benzene, toluene, ethylbenzene and m-xylene respectively. Slightly greater sensitivity was found for urine samples. The results obtained in biological samples from 25 woodworkers not occupationally exposed to BTEX (15 non-smokers and 10 smokers) are comparable to those obtained by other investigators.