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Biomedical subjects

Antonio Mutti

Publications and source records attributed to Antonio Mutti.

At least 19 recordsLinked to original sources

Uteroglobin-related protein 1 and clara cell protein in induced sputum of patients with asthma and rhinitis.

RATIONALE: Uteroglobin-related protein 1 (UGRP1) and Clara cell protein (CC16), members of the secretoglobin family, increasingly appear to play a role in airway inflammatory response. OBJECTIVE: To explore levels of UGRP1 and CC16 in induced sputum of patients with asthma and rhinitis. METHODS: Induced-sputum samples of patients with asthma or rhinitis (n = 32 each; atopic asthma, n = 24; atopic rhinitis, n = 20) and from 19 nonsmoking nonatopic control subjects were analyzed for cytology and levels of UGRP1, CC16, and albumin. MEASUREMENTS AND MAIN RESULTS: Sputum UGRP1 increased in both asthma and rhinitis, most strikingly so in asthma, in which changes were most significant in atopic individuals. By contrast, sputum CC16 did not change significantly in either condition, although it was positively correlated with UGRP1 in patients and control subjects. Changes in sputum UGRP1 in atopic asthma were not linked to permeability changes reflected by increased albumin levels but correlated positively with sputum macrophages and negatively with eosinophils. The observed differences in UGRP1 and CC16 may be linked to different cell populations being responsible for their secretion; UGRP1 is mainly secreted in larger conducting airways, whereas CC16 is mainly secreted by the nasal and peripheral airways epithelium. CONCLUSIONS: The increase in UGRP1 but not of CC16 in asthma and rhinitis suggests that UGRP1 may play a role in these inflammatory diseases.

Adult↗

Exposure assessment at the workplace: implications of biological variability.

Biological monitoring (BM) and biomarkers are widely applied in occupational toxicology. BM is mainly aimed at (i) defining the existence of an occupational exposure; (ii) quantifying the level of internal dose; (iii) verifying that exposure limits (BEI((R)), BAT, BLV) are respected. As compared to ambient monitoring, BM is more expensive and complex. Several biomarkers are available for the same chemical and the meaning of the marker may depend on the sampling time. Therefore, practical issues, including cost and selection of an adequate sampling strategy, should be dealt with when planning a BM program for specific purposes. In addition, several biological and analytical sources of variability may influence biomarker levels, thus making the interpretation of BM data a difficult task. However, we should recognize that the main aim of BM is not to reduce, but to explain biological variance. The decreasing trend in occupational exposure levels highlighted the specificity problems of traditional biomarkers of exposure and prompted the research to the development of new biomarkers, e.g. unchanged volatile compounds in urine, minor metabolites, DNA and protein adducts. Depending on the scope and context (research or routine) different requirements of biomarkers can be envisaged in terms of validation and acceptable variability.

Air Pollutants, Occupational↗

Cell death mechanisms in AtT20 pituitary cells exposed to polychlorinated biphenyls (PCB 126 and PCB 153) and methylmercury.

Polychlorinated biphenyls (PCBs) are persistent food contaminants that can have adverse effects on the endocrine and nervous systems, including the pituitary. In the present study, we have investigated cell death in the AtT20 pituitary cell line after exposure to coplanar PCB 126 and non-coplanar PCB 153. In addition, co-exposure to the PCBs and another neurotoxic food contaminant, methylmercury (MeHg), was studied to test possible interactive effects. Our results show that mainly necrosis is induced after exposure to the selected toxicants. Simultaneous exposure to moderately toxic doses of PCBs and MeHg resulted in additive or slightly synergistic effects on the induction of cell death. Furthermore, our data suggest that both PCB congeners trigger cell death in AtT20 cells via activation of calcium regulated calpains and lysosomal cathepsins, possibly through disruption of mitochondrial function and intracellular calcium signaling. However, caspase-activity appears not to be critical for PCB induced cell death in these cells. Presence of reactive oxygen species (ROS) and protective effects of pre-treatment with antioxidants were only found after MeHg exposure, suggesting that oxidative stress plays a major role in MeHg but not PCB toxicity in this experimental model.

Animals↗

Environmental and biological monitoring of benzene exposure in a cohort of Italian taxi drivers.

An integrated approach based on ambient and biological monitoring, the latter including both biomarkers of exposure and susceptibility, was applied to characterize benzene exposure in a group of 37 taxi drivers of the city of Parma (Italy). Airborne benzene concentrations were assessed by 24 h personal sampling and work-shift sampling inside the taxicab using passive samplers (Radiello). Benzene metabolites, trans,trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA), and urinary cotinine as biomarker of smoking habits were measured by isotopic dilution liquid chromatography tandem mass spectrometry in both pre-shift (PS) and end-of-shift (EOS) samples. Urinary benzene (U-B) levels were determined by solid-phase microextraction gas chromatography-mass spectrometry in EOS samples. Relevant polymorphisms of microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, glutathione S-transferases M1-1 (GSTM1), T1-1, and A1 were characterized by PCR-based methods. Mean airborne benzene concentration was 5.85 +/- 1.65 microg/m3, as assessed by 24 h personal sampling integrating for work-shift, indoor or general environment activities. Significantly, higher benzene concentrations were detected in the taxicab during the work-shift (7.71 +/- 1.95 microg/m3, p < 0.005). Smokers eliminated significantly higher concentrations of U-B and S-PMA than non-smokers in EOS samples [geometric mean (geometric S.D.): 2.58 (4.23) versus 0.44 (1.79) microg/l for U-B; 3.79 (1.50) versus 2.14 (1.87) microg/gcreat. for S-PMA, p < 0.002]. Within smokers, S-PMA concentrations significantly increased at the end of the work-shift compared to pre-shift values (p < 0.05). t,t-MA showed a similar behaviour, although differences were not significant. In the narrow range examined, no correlation was observed between air benzene concentration and urinary biomarkers. All benzene biomarkers but EOS t,t-MA were correlated with U-cotinine (p < 0.05). GSTM1 polymorphism significantly modulated S-PMA excretion, as subjects bearing the GSTM1pos genotype [3.61 (1.15) microg/gcreat.] excreted significantly higher S-PMA concentrations than GSTM1null subjects [2.19 (1.18) microg/gcreat., p < 0.05].

Acetylcysteine↗

Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress.

Exposure of C2C12 muscle cells to hypertonic stress induced an increase in cell content of creatine transporter mRNA and of creatine transport activity, which peaked after about 24 h incubation at 0.45 osmol (kg H(2)O)(-1). This induction of transport activity was prevented by addition of either cycloheximide, to inhibit protein synthesis, or of actinomycin D, to inhibit RNA synthesis. Creatine uptake by these cells is largely Na(+) dependent and kinetic analysis revealed that its increase under hypertonic conditions resulted from an increase in V(max) of the Na(+)-dependent component, with no significant change in the K(m) value of about 75 mumol l(-1). Quantitative real-time PCR revealed a more than threefold increase in the expression of creatine transporter mRNA in cells exposed to hypertonicity. Creatine supplementation significantly enhanced survival of C2C12 cells incubated under hypertonic conditions and its effect was similar to that obtained with the well known compatible osmolytes, betaine, taurine and myo-inositol. This effect seemed not to be linked to the energy status of the C2C12 cells because hypertonic incubation caused a decrease in their ATP content, with or without the addition of creatine at 20 mmol l(-1) to the medium. This induction of creatine transport activity by hypertonicity is not confined to muscle cells: a similar induction was shown in porcine endothelial cells.

Adenosine Triphosphate↗

Reference values for exhaled nitric oxide (reveno) study.

BACKGROUND: Despite the widespread use of fractional exhaled nitric oxide (FENO) as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults. OBJECTIVE: The aim of this study was to establish adult FENO reference values according to the international guidelines. METHODS: FENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently. RESULTS: The main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women. CONCLUSION: We propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.

Adult↗

Longitudinal monitoring of lung injury in children after acute chlorine exposure in a swimming pool.

RATIONALE: Acute exposure to chlorine gas results in respiratory impairment, but few data are available on the pathobiology of the underlying lung damage. OBJECTIVES: To assess lung function and potential lung damage pathways in the acute phase and longitudinally over a 15-mo follow-up after acute chlorine exposure. METHODS: Ten previously healthy children were accidentally exposed to chlorine gas at a swimming pool because of an erroneous servicing procedure. The fraction of nitric oxide in exhaled air (Fe(NO)), exhaled breath condensate compounds, and serum Clara cell-specific protein CC16 were repeatedly measured. MAIN RESULTS: In the acute phase, all patients had respiratory distress (one child required mechanical ventilation) and reduced lung function (median and interquartile range: FVC, 51 [43-60]% predicted; FEV(1), 51 [46-60]% predicted). This was accompanied by low Fe(NO) (4.7 [3.9-7.9] ppb), high exhaled breath condensate leukotriene B(4) (LTB(4)) levels (24.4 [22.5-24.9] pg/ml), and increased serum CC16 levels (mean +/- SEM, 23.4 +/- 2.5 microg/L). Lung function returned to normal in 15 d (FVC, 97% predicted [82-108], and FEV(1), 92% predicted [77-102]). Fe(NO) reached normal values after 2 mo (12.6 [11.4-15] ppb), whereas LTB(4) levels were still increased (12 [9.3-17.1] pg/ml). CONCLUSION: Children acutely exposed to chlorine in a swimming pool presented a substantial lung function impairment associated with biochemical exhaled breath alterations, represented mainly by an increase in LTB(4) and a reduction in Fe(NO). Although lung function and Fe(NO) improved within a few weeks, the increased levels of exhaled LTB(4) persisted for several months.

Accidents↗

Clusterin decreases oxidative stress in lung fibroblasts exposed to cigarette smoke.

RATIONALE: Cigarette smoke causes injury to lung fibroblasts, partly by means of oxidative stress, and oxidative stress can lead to various lung diseases, such as chronic obstructive pulmonary disease. Clusterin is a widely distributed protein with many functions, including cellular protection in response to oxidative stress. OBJECTIVES: To determine whether clusterin is involved in the defense of the lung against cigarette smoke, we investigated the effects of cigarette smoke extract on clusterin expression and its protective effect, if any, against oxidative stress. METHODS: Fibroblasts were coincubated with conditioned medium and cigarette smoke extract, and bronchial biopsy specimens obtained from nonsmokers, smokers, and ex-smokers were analyzed by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: At concentrations of 2.5 and 5.0%, cigarette smoke extract induced oxidative stress. It also markedly increased the expression of two clusterin isoforms (60 and 76-80 kD) and the 76-80-kD isoform was secreted in the incubation medium. Coincubation of fibroblasts with conditioned medium significantly decreased the cellular oxidation caused by the cigarette smoke extract. Immunohistochemical analysis of clusterin on bronchial biopsy specimens obtained from smokers and ex-smokers showed localization of clusterin mainly in the submucosa. CONCLUSIONS: We conclude that clusterin may have a protective effect against cigarette smoke-induced oxidative stress in lung fibroblasts.

Clusterin↗

Determination of hexavalent chromium in exhaled breath condensate and environmental air among chrome plating workers.

Chromium speciation has attracted attention because of the different toxicity of Cr(III), which is considered relatively non-toxic, and Cr(VI), which can cross cell membranes mainly as a chromate anion and has been classified as a class I human carcinogen. The aims of the present study were to measure soluble Cr(VI) levels in environmental samples, to develop a simple method of quantifying Cr(VI) in exhaled breath condensate (EBC), and to follow the kinetics of EBC Cr(VI) in chrome plating workers.Personal air samples were collected from 10 chrome platers; EBC was collected from the same workers immediately after the work shift on Tuesday and before the work shift on the following Wednesday. Environmental and EBC Cr(VI) levels were determined by means of colorimetry and electrothermal absorption atomic spectrometry, respectively.The method of detecting Cr(VI) in environmental air was based on the extraction of the Cr(VI)-diphenylcarbazide (Cr(VI)-DPC) complex in 1-butanol, whereas EBC Cr(VI) was determined using a solvent extraction of Cr(VI) as an ion pair with tetrabutylammonium ion, and subsequent direct determination of the complex (Cr(VI)-DPC) in EBC.Kinetic data showed that airborne Cr(VI) was reduced by 50% in airway lining fluid sampled at the end of exposure and that there was a further 50% reduction after about 15 h. The persistence of Cr(VI) in EBC supports the use of EBC in assessing target tissue levels of Cr(VI).

Journal Article↗

Organic contamination in dialysis water: trichloroethylene as a model compound.

BACKGROUND: Routine water monitoring in a haemodialysis centre revealed high trichloroethylene (TCE) concentrations. The aim of this study is to describe the measures adopted after organic contamination of dialysis water in order to avoid the possibility of patient exposure. We also carried out in vitro experiments to evaluate the accumulation of TCE in various devices normally used in a dialysis water treatment system (DWTS). METHODS: In vivo and in vitro blood and water TCE levels were determined by means of solid phase microextraction-gas chromatography/mass spectrometer. RESULTS: High TCE concentrations were found throughout the DWTS; acceptably low levels were obtained only by replacing the activated charcoal, ionic-exchange resins, microfilters and PVC pipes. The adsorption and realising capacities of these devices were tested in vitro, and the elimination curves made it possible to calculate the total percentage of the previously absorbed TCE mass released into the water. Evidence of exposure was confirmed by the relatively high TCE levels in the patient blood samples taken 30 days after the last exposure even if the subjects were asymptomatic. In vivo experiments showed that the blood gain of TCE through the low flux membrane during the course of dialysis was about 77+/-10.4% of the amount carried by dialysis fluid as calculated on the basis of its partition coefficient value (K(b/w) 3.75). CONCLUSIONS: This study shows that, when present in dialysis water, the lipophilic TCE contaminant can accumulate in various devices, thus transforming them into possible sources of exposure. This highlights the importance of periodically monitoring dialysis water for organic substances that have a great affinity to the blood compartment, in order to prevent occasional or chronic patient exposure.

Aged↗

Cytogenetic biomarkers, urinary metabolites and metabolic gene polymorphisms in workers exposed to styrene.

The present study comprised a biomonitoring study in 95 workers occupationally exposed to styrene and 98 unexposed controls, employing an integrated approach involving biomarkers of exposure, effect, and susceptibility. Airborne styrene was evaluated at workplace, and urinary styrene metabolites, mandelic acid (MA), phenylglyoxylic acid (PGA), vinylphenols (VPTs) and phenylhydroxyethylmercapturic acids (PHEMAs), were measured as biomarkers of internal dose. Cytogenetic alterations were evaluated by analysing the frequency of chromosomal aberrations (CAs) and micronucleated binucleated cells (MNBN) in peripheral blood lymphocytes. The micronucleus assay was coupled with centromeric fluorescence in situ hybridization to distinguish micronuclei (MN) arising from chromosomal breakage (C- MN) from those harboring whole chromosomes (C+ MN). The possible influence of genetic polymorphisms of xenobiotic-metabolizing enzymes involved in styrene biotransformation (EPHX1, GSTT1, GSTM1, GSTP1) and NAT2 on the cytogenetic endpoints was investigated. The exposed workers showed a significantly higher frequency of MNBN (13.8+/-0.5% versus 9.2+/-0.4%; P<0.001) compared to control subjects. The effect appeared to concern both C- and C+ MN. A positive correlation was seen between the frequency of C+ MN and urinary level of MA+PGA (P<0.05) and VPTs (P<0.001). Chromosome-type CAs positively correlated with airborne styrene level and VPTs (P<0.05), whereas chromatid-type CAs correlated with PHEMAs (P<0.05). Workers bearing GSTM1 null genotype showed lowered levels of PHEMAs (P<0.001). The GSTT1 null genotype was associated with increased MNBN frequencies in the exposed workers (P<0.05) and the fast activity EPHX genotype with a moderate decrease in both MNBN and CAs in the controls. Our results suggest that occupational exposure to styrene has genotoxic effects that are potentiated by the GSTT1 gene deletion. These observations may have relevance considering the risk of lymphatic and haematopoietic malignancies tentatively associated with styrene exposure.

Chromosome Aberrations↗

Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure levels.

Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children's health is little known. We studied their effects on two main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and beta2-microglobulin were negatively correlated with blood lead levels (PbB), suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> 55 microg/L; mean, 78.4 microg/L). The urinary excretion of retinol-binding protein, Clara cell protein, and N-acetyl-beta-d-glucosaminidase was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children's renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals. Key words: arsenic, biomarkers, cadmium, dopaminergic, heavy metals, interactions, lead, mercury, renal.

Arsenic↗

The effect of inhaled chromium on different exhaled breath condensate biomarkers among chrome-plating workers.

Chromium is corrosive, cytotoxic, and carcinogenic for humans and can induce acute and chronic lung tissue toxicity. The aim of this study was to investigate Cr levels in exhaled breath condensate (EBC) of workers exposed to Cr(VI) and to assess their relationship with biochemical changes in the airways by analyzing EBC biomarkers of oxidative stress, namely, hydrogen peroxide (H2O2) and malondialdehyde (MDA). EBC samples were collected from 24 chrome-plating workers employed in a chrome-plating plant both before and after the Friday work shift and before the work shift on the following Monday. Cr-EBC levels increased from the beginning (5.3 microg/L) to the end of Friday (6.4 microg/L) but were considerably lower on Monday morning (2.8 microg/L). A similar trend was observed for H2O2-EBC levels (which increased from 0.36 microM to 0.59 microM on Friday and were 0.19 microM on Monday morning) and MDA-EBC levels (which increased from 8.2 nM to 9.7 nM on Friday and were 6.6 nM on Monday). Cr-EBC levels correlated with those of H2O2-EBC (r = 0.54, p < 0.01) and MDA-EBC (r = 0.59, p < 0.01), as well as with urinary Cr levels (r = 0.25, p < 0.05). The results of this study demonstrate that EBC is a suitable matrix that can be used to investigate both Cr levels and biomarkers of free radical production sampling the epithelial-lining fluid of workers exposed to Cr(VI).

Adult↗

Exhaled metallic elements and serum pneumoproteins in asymptomatic smokers and patients with COPD or asthma.

STUDY OBJECTIVES: The aim of this study was to characterize the elemental composition of exhaled breath condensate (EBC) in order to identify new biomarkers of exposure and susceptibility in COPD patients. Serum pneumoproteins were used as lung-specific biomarkers of effect. DESIGN: EBC was obtained from 50 healthy subjects, 30 healthy smokers, 30 asthmatics, and 50 patients with stable COPD, and was collected by cooling exhaled air. Trace elements and toxic metals in the samples were measured by means of inductively coupled plasma-mass spectrometry and electrothermal atomic absorption spectroscopy. The serum pneumoproteins were immunoassayed. RESULTS: The EBC of COPD subjects had higher levels of such toxic elements as lead, cadmium, and aluminum, and lower levels of iron and copper, than that of the nonsmoking control subjects. There were no between-group differences in surfactant protein (SP)-A and SP-B levels. Clara-cell protein and SP-D levels were negatively and positively influenced, respectively, by tobacco smoke. CONCLUSIONS: Our results show that toxic metals and transition elements are detectable in the EBC of studied subjects. We propose new biomarkers of exposure as a means of assessing the target tissue dose of carcinogenic and pneumotoxic substances from tobacco smoke or polluted workplaces, and the use of the transition elements involved in redox systems of oxidative stress as disease biomarkers associated with effect or susceptibility. Together with biomarkers of effect, such as serum pneumoproteins, the elemental composition of EBC may be clinically useful in distinguishing similar diseases.

Adult↗

Application of liquid chromatography-mass spectrometry to biomonitoring of exposure to industrial chemicals.

Recent advances on biomarker research are discussed, primarily relying on experience gained with technologies based on liquid chromatography-tandem mass spectrometry (LC-MS-MS). Determination of urinary metabolites of industrial chemicals (n-hexane, benzene, toluene, and styrene) in samples from occupationally exposed workers and controls was performed by LC-MS-MS with either electrospray (ESI) or atmospheric pressure chemical ionization (APCI), as appropriate. Both phase I and II metabolites (glucuronides, sulfates, and mercapturic acids) can be detected with little or no sample manipulation, thus allowing the identification of a number of artifacts and "new" metabolites. However, experimental evidence indicates the need for properly addressing the matrix effect, which is always associated with the analysis of biological samples. Both efficient sample preparation and the use of isotopically labeled internal standards seem to be necessary to develop validated quantitative methods.

Animals↗

Mercapturic acids of styrene in man: comparability of the results obtained by LC/MS/MS and by HPLC-fluorimeter, and stability of samples under different storage conditions.

Two analytical methods (HPLC-fluorimeter [HPLC-FLD] and tandem mass spectrometry LC/MS/MS) are available to assay phenyl-hydroxyethylmercapturic acids (PHEMAs), the mercapturic acids of styrene in humans. In the past, each method was used to check different populations of subjects, but until now no attempt has been made to compare the two methods. This study was designed to verify whether the two methods actually give comparable results. The influence of different conditions of sample storage in altering the concentration of PHEMAs was also investigated. Urine samples were collected at the beginning and at the end of the workshift from 10 workers exposed to different levels of styrene. Each sample was analysed both by LC/MS/MS after storage under different conditions (respectively, at -20 and +4 degrees C, and after repeated freezing-thawing cycles), and by HPLC-FLD (in the same conditions of storage). Strong correlations were found between the two methods both for total PHEMAs and for each of the isomers measured, including the minor (S,R)-M1. Also an alternative approach, the Bland-Altman test, confirmed the agreement between the two methods. The different storage conditions tested did not decrease the concentration of PHEMAs but, surprisingly, a clear trend to increase was shown, particularly for (R,R)-M1, (S,R)-M2 and (R,R)-M2 in samples stored at +4 degrees C for 1 week. In conclusion, the study demonstrates that the methods give comparable results. Indirectly, this confirms also the main characteristics of PHEMAs, showed in the previous experiments: low biotransformation rates of styrene into PHEMAs; large inter-individual variability; and the presence of a clear preference in the excretion of the isomers deriving from (S)-styrene oxide. PHEMAs appear stable under different storage conditions, but further studies are needed to explain the increase of levels that occurs when samples are not kept frozen. To avoid pre-analytical errors, samples collected for biomonitoring or research purposes should be frozen as soon as possible, and thawed only one time just before the analysis.

Acetylcysteine↗

Influence of condensation temperature on selected exhaled breath parameters.

BACKGROUND: The effects of changes in cooling temperature on biomarker levels in exhaled breath condensate have been little investigated. The aim of the study was to test the effect of condensation temperature on the parameters of exhaled breath condensate and the levels of selected biomarkers. METHODS: Exhaled breath condensate was collected from 24 healthy subjects at temperatures of -10, -5, 0 and +5 C degrees. Selected parameters (condensed volume and conductivity) and biomarkers (hydrogen peroxide, malondialdehyde) were measured. RESULTS: There was a progressive increase in hydrogen peroxide and malondialdehyde concentrations, and condensate conductivity as the cooling temperature increased; total condensate volume increased as the cooling temperature decreased. CONCLUSION: The cooling temperature of exhaled breath condensate collection influenced selected biomarkers and potential normalizing factors (particularly conductivity) in different ways ex vivo. The temperature of exhaled breath condensate collection should be controlled and reported.

Adult↗

Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study.

BACKGROUND: Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs) in exhaled air of patients with non-small cells lung cancer (NSCLC), by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery. METHODS: The subjects' breath was collected in a Teflon bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry. RESULTS: The levels of the selected VOCs ranged from 10(-12) M for styrene to 10(-9) M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80% of cases. Only isoprene and decane levels significantly decreased after surgery. CONCLUSION: As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study.

Aged↗