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PubMed1981

The composition of alkanes in exhaled air of rats as a result of lipid peroxidation in vivo. Effects of dietary fatty acids, vitamin E and selenium.

Alkane production in exhaled air of rats has been studied as an index of lipid peroxidation in vivo in these animals. The effect of feeding essential fatty acid-deficient rats varying levels of n-4, n-6 and n-7 polyunsaturated fatty acids for various periods of time has been studied with regard to the composition of the alkanes produced as well as the fatty acid composition of liver phospholipids and liver and adipose tissue triacylglycerols. It was found that the fatty acid composition of liver lipids depended markedly on the nature and the quantity of polyunsaturated fatty acid in the diet. The composition of the alkanes produced on stimulation of lipid peroxidation in vivo by inhalation of small, non-lethal doses of carbon tetrachloride corresponded closely to the fatty acid composition of the liver phospholipids. The results strongly suggest that the alkanes produced as a result of lipid peroxidation in vivo originate from the methyl end of the fatty acid administered. So ethane is produced from n-3 acid, propane from n-4 acid, pentane from n-6 acid and hexane from n-7 acid. The amounts of a specific alkane produced increase as its corresponding fatty acid, as present in the liver phospholipids, increases. There are indications that relatively more ethane than pentane is produced on stimulation of the in vivo lipid peroxidation although there are considerably more n-6 fatty acids than n-3 fatty acids present in the liver phospholipids.

Adipose Tissue↗
PubMed1991

Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans.

The presence of nitric oxide (NO) in the exhaled air of humans and of anaesthetized rabbits and guinea pigs was demonstrated by chemiluminescence, diazotization and mass spectrometry. This NO is endogenously produced in the lung by an NO synthase, since its generation in guinea pigs and rabbits was inhibited by N omega-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, inhibitors of this enzyme. The effect of the inhibitors was reversed by the precursor of NO synthesis, L-arginine. Since NO is produced by normal vascular endothelium for the physiological regulation of blood flow and pressure and also by activated macrophages to contribute to non-specific immunity, our experiments suggest that NO may play both vascular regulatory and host defence roles in pulmonary physiology and pathophysiology.

Amino Acid Oxidoreductases↗
PubMed1984

Metabolism of [14C]carbon tetrachloride to exhaled, excreted and bound metabolites. Dose-response, time-course and pharmacokinetics.

Fasted male rats were given six doses of 14CCl4 ranging from non-hepatotoxic (0.1 mmole/kg) to severely hepatotoxic (26 mmoles/kg). Time-course and pharmacokinetics of CCl4, 14CO2 and CHCl3 elimination by exhalation were monitored by measuring amounts recovered in breath during discrete 15-min intervals for 8-12 hr. Amounts of 14C-labeled metabolite recovered bound to liver macromolecules at 24 hr and excreted in urine or feces for 24 hr were also determined. Comparison pharmacokinetic studies were done with 14CHCl3 and Na(2)14CO3. After all doses of 14CCl4, the major metabolite was CO2, twenty to thirty times less metabolite was recovered bound to liver macromolecules, and intermediate amounts of metabolite were excreted in urine and feces. CHCl3 was the least abundant metabolite at low CCl4 doses, but the second most abundant at high doses. Stronger associations were found between the magnitude of liver injury at 24 hr (quantitated as serum glutamate-pyruvate transaminase activity) and the extent or rate of CCl4 metabolism by pathways leading to CO2 and CHCl3 than by pathways leading to 14C-metabolites bound in liver or excreted in urine. Time-course and pharmacokinetic data indicated that a major pathway of CCl4 metabolism leading to CO2 became impaired within 2 hr after administration of hepatotoxic doses of CCl4.

Animals↗
PubMed1986

Inhibition of ethanol induced ethane exhalation by carcinogenic pretreatment of rats 12 months earlier.

The exhalation of ethane was used as a measure of in vivo lipid peroxidation in rats treated with the hepatocarcinogen diethylnitrosamine followed by 2-acetylaminofluorene (AAF), and carbon tetrachloride, and subsequently fed a liquid diet containing 7% ethanol for 12 months. The other groups consisted of animals treated with methylbenzylnitrosamine (MBN), an esophageal carcinogen, or non-carcinogen pretreated animals with or without 7% ethanol feeding. Ethane production was increased in rats consuming ethanol irrespective of their pretreatment with MBN. In sharp contrast, the ethanol-induced increase of ethane production was absent in rats given the hepatocarcinogenic regime. Our results strengthen recent observations indicating decreased susceptibility of tumor cells to lipid peroxidation. In addition, they confirm the debated concept that there is increased lipid peroxidation following ethanol consumption.

2-Acetylaminofluorene↗
PubMed1985

Reducing radon exhalation from covered tailings: optimization or cost effectiveness?

Reduction of radon exhalation from uranium tailings as a function of the number of radon diffusion lengths in cover materials is discussed, based on dimensionless mathematical functions. Cost effectiveness is examined to determine the least expensive cover with a preselected number of radon diffusion lengths (i.e., a preselected level of radiation protection), and to find the maximum attainable reduction in radon flux with a predetermined cost (i.e., a fixed amount of money). Cost effectiveness rather than optimization through cost benefit analysis can be used advantageously in these cases.

Cost-Benefit Analysis↗
PubMed1985

Radon in soil gas--exhalation tests and in situ measurements.

Radon in soil can move into buildings resulting in high radon daughter concentrations. The foundation of a dwelling should be adapted to the radon "risk" which is determined by the radon concentration and the air permeability of the soil. Different measuring procedures are discussed in this paper, both in situ measurements of radon content and laboratory tests on radon exhalation from different types of soils at different water contents.

Environmental Exposure↗
PubMed1981

Carbon tetrachloride-induced lipid peroxidation: simultaneous in vivo measurements of pentane and chloroform exhaled by the rat.

Simultaneous measurements of pentane, an index of lipid peroxidation, and chloroform (CHCl3), an index of carbon tetrachloride (CCl4) metabolism, were made on samples of breath from rats injected with 30 microliter CCL4/100 g body wt. In the first 3 h after administration of CCl4, rats fasted overnight metabolized less CCl4 and exhaled less pentane than did fed rats. Multiple injections of CCl4 decreased both the metabolism of CCl4 to CHCl3 and the level of in vivo lipid peroxidation following administration of a subsequent dose of CCl4. Dietary vitamin E provided limited protection from CCl4-induced lipid peroxidation and had no effect on the rate of CCl4 metabolism to CHCl3.

Animals↗
PubMed1994

Absence of in vivo lipid peroxidation in CdCl2-treated rats as measured by exhaled pentane.

We have used a new sensitive and non-invasive method, measuring exhaled pentane production, to evaluate in vivo lipid peroxidation (LP) in rats treated i.p. with CdCl2. Pentane, a by-product of LP, was measured 2, 6, 12, 24, 72 h and 8, 15, 22 days after treatment. No increase in pentane production was detected at these time periods for cadmium (Cd) doses reported to increase malondialdehyde (MDA) in major organs such as liver and lungs. This suggests that Cd cannot induce LP in vivo, but a prooxidant state which fragilized the tissues. Cd could also cause changes either in the production or in the metabolism of LP by-products (e.g. pentane).

Animals↗
PubMed1995

Measurement of volatile organic compounds in exhaled breath as collected in evacuated electropolished canisters.

A set of three complementary analytical methods were developed specifically for exhaled breath as collected in evacuated stainless steel canisters using gas chromatographic-mass spectrometric detection. The first is a screening method to quantify the carbon dioxide component (generally at 4-5% concentration), the second method measures the very volatile high-level endogenous compounds [e.g. acetone and isoprene at 500-1000 parts per billion by volume (ppbv), methanol, ethanol, dimethylsulfide at 2-10 ppbv], and the third method is designed to measure trace-level environmental contaminants and other endogenous volatile organic compounds (VOCs) (sub-ppbv) in breath. The canister-based sample format allows all three methods to be applied to each individual sample for complete constituent characterization. Application of these methods is shown to be useful in the following ways: analysis of CO2 levels indicates the approximate quantity of alveolar breath collected (as opposed to whole breath) in a sample; levels of major endogenous compounds are shown to be influenced by physical activities and subsequent recovery periods; and environmental exposures to xenobiotic VOCs can be characterized by assessment of post-exposure breath elimination curves. The instrumentation and methodology are described and example chromatograms and quantitative data plots demonstrating the utility of the methods are presented.

Acetone↗
PubMed2006

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↗
PubMed2005

Exhaled breath condensate analysis in patients with COPD.

Exhaled breath condensate (EBC) is a non-invasive method for studying the composition of airway lining fluid. EBC is mainly formed by water vapor but also contains aerosol particles in which several biomolecules including hydrogen peroxide, leukotrienes, prostaglandins, isoprostanes, nitric oxide-derived products, and hydrogen ions have been measured in healthy subjects. Some inflammatory mediators are elevated in patients with chronic obstructive pulmonary disease (COPD). Analysis of EBC has several advantages over other methods for assessing lung inflammation: it is completely non-invasive; this technique is particularly suitable for longitudinal studies; this method is potentially useful for assessing the efficacy of pharmacological therapy. Identification of selective profiles of inflammatory markers in EBC might also be of diagnostic value in patients with COPD. EBC analysis is currently more reliable for relative measures than for determining absolute levels of inflammatory mediators. The lack of standardization of the EBC analysis is currently the primary limitation of this technique making it difficult comparisons of data obtained in different laboratories. Reference analytical techniques are required to provide definitive evidence for the presence of several biomolecules in EBC and an accurate assessment of their concentrations in this biological fluid. Moreover, several methodological issues need to be addressed before this technique can be considered in the clinical management of patients with COPD. Despite important current limitations, further research in this area is warranted due to the lack of non-invasive methods for assessing lung inflammation which has a central role in the pathophysiology of COPD.

Breath Tests↗
PubMed2005

Clinical applications of exhaled nitric oxide for the diagnosis and management of asthma: a consensus report.

BACKGROUND: Patients with asthma routinely exhibit elevated levels of fractionated exhaled nitric oxide (FE(NO)), and this observation has led to studies investigating FE(NO) as a potential marker of airway inflammation. FE(NO) has been shown to enhance the diagnosis of asthma, detect deterioration in control of patients with asthma, and monitor response to anti-inflammatory therapy. OBJECTIVES: The aim of this work was to determine if FE(NO) measurement provides a noninvasive, well-tolerated, and standardized technique to monitor airway inflammation, and if it has the potential to complement standard asthma monitoring tools (eg, symptom diaries, control questionnaires, and pulmonary function testing) and to improve asthma control and patient outcomes. METHODS: Thirteen experts in the diagnosis and treatment of asthma met to discuss the use of FE(NO) in the diagnosis and management of patients with asthma. Participants were selected by Aerocrine, a medical, technical company with headquarters in Stockholm, Sweden, in consultation with their medical education partner Cadent Medical Communications located in Irving, Texas, to represent a diversity of specialists, including both clinicians and investigators, in the fields of allergy, immunology, and pulmonology. All participants were nominally compensated for their time to attend this closed scientific roundtable discussion. The meeting was supported by an educational grant from Aerocrine. This report represents the overall consensus reached by the participants on the clinical applicability of this technique. RESULTS: Our understanding of asthma has expanded so that investigators are now focusing on inflammation in addition to airway obstruction and hyper-reactivity. Whereas patient history, symptoms, and pulmonary function testing can assist in diagnosing asthma, they are not direct measures of the extent of airway inflammation. Elevated FE(NO) levels have been shown to reflect airway inflammation and to occur together with other conventional markers used to detect inflammation. Studies have confirmed increased levels of FE(NO) in both adults and children with asthma. In most studies, FE(NO) was found to be elevated 2- to 3-fold compared with normal controls. There are many determinants of FE(NO) levels, however, and factors other than inflammation must be considered when FE(NO) measurement is used to diagnose and monitor asthma. FE(NO) measurement alone is not sufficient for diagnosing or monitoring asthma, but it can be a valuable addition to current clinical tools. CONCLUSIONS: FE(NO) measurement is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with asthma. The test has demonstrated utility in diagnosing and managing asthma and in predicting response to therapy and, therefore, may be an important tool to incorporate into clinical care.

Adult↗
PubMed2006

AI-700 pharmacokinetics, tissue distribution and exhaled elimination kinetics in rats.

The purpose of these studies was to determine the pharmacokinetics, tissue distribution, and exhaled elimination kinetics in rats for intravenously administered AI-700, which consists of porous microspheres containing decafluorobutane (DFB), for use as an ultrasound contrast agent. [Pd]-AI-700 was administered intravenously to rats (10 mg microspheres/kg). Blood and tissue samples collected at specified times were analyzed for palladium by inductively coupled plasma-mass spectrometry (ICP-MS). AI-700 was also administered intravenously to rats (40 mg microspheres/kg) and expired air was collected over time. Expired air samples were analyzed for DFB by validated adsorbent trapping-thermal desorption-gas chromatography-mass spectrometry methodology. Pd from [Pd]-AI-700 was cleared from blood with a ca. 50-85% decline from peak concentration within 5 min. At 1440 min post-dose, 52-72% of the Pd dose was recovered from organs of the reticuloendothelial system. Approximately 77% of the intravenously injected DFB was found in expired air within 3h after dosing, with most of the DFB dose (61+/-6%) expired within the first 10 min after dosing. As expected, the microspheres were cleared through the reticuloendothelial system, and the DFB was eliminated in expired air, with more than half of the DFB eliminated within the first 10 min after dosing.

Air↗
PubMed2003

Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children.

BACKGROUND: Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation. Insufficient information is available concerning correlations between eNO and biologic, physiologic, and clinical characteristics of asthma in children currently not taking controller medications. OBJECTIVE: The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications. METHODS: Children aged 6 to 17 years with mild to moderate persistent asthma, taking only albuterol as needed, were characterized during 2 visits 1 week apart before being randomly assigned into a clinical trial. At the screening visit, online measurements of eNO, spirometry before and after bronchodilator, and biomarkers of peripheral blood eosinophils, serum eosinophil cationic protein, total serum IgE, and urinary leukotriene E4 were obtained. During a week characterization period before randomization, symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device. At the randomization visit, eNO was repeated followed by a methacholine challenge and aeroallergen skin testing. Correlations and rank regression analyses between eNO and clinical characteristics, pulmonary function, and biomarkers were evaluated. RESULTS: eNO was significantly correlated with peripheral blood eosinophils (r =.51, P <.0001), IgE (r =.48, P <.0001), and serum eosinophil cationic protein (r =.31, P =.0003) but not with urinary leukotriene E4 (r =.16, P =.08). A moderate correlation was found between eNO and the number of positive aeroallergen skin tests (r =.45, P <.0001). eNO did not correlate with FEV1% predicted but was weakly correlated with FEV1/forced vital capacity (r = -.19, P =.032), bronchodilator response (r =.20, P =.023), and FEV1 PC20 methacholine (r = -.31, P =.0005). No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements. The rank regression analysis demonstrated that 5 variables accounted for an R square of.52 (eosinophils [P <.0001], IgE [P =.0023], age [P <.0001], months of inhaled corticosteroid use in the year before study entry [P =.01], and FEV1 PC20 [P =.0061]). CONCLUSIONS: These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.

Adolescent↗
PubMed2004

Leukotrienes and 8-isoprostane in exhaled breath condensate of children with stable and unstable asthma.

BACKGROUND: Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity. METHODS: EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children. RESULTS: In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01). CONCLUSIONS: Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.

Adolescent↗
PubMed2005

Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma.

BACKGROUND: The fractional concentration of exhaled nitric oxide (FENO) is increased in asthma, correlates with eosinophilic inflammation, and decreases after steroid therapy. OBJECTIVE: We sought to examine whether persistent eosinophilia would be accompanied by an increased FENO level despite steroid therapy in patients with severe refractory asthma (SRA) as manifestations of steroid resistance. METHODS: Subjects with SRA, subjects with mild-moderate asthma, and healthy control subjects had FENO measured, followed by endobronchial biopsy and bronchoalveolar lavage. Tissue and bronchoalveolar lavage inflammatory cells were assessed for all subjects, and eosinophil status (EOS+/EOS-) was determined for subjects with SRA. RESULTS: Twenty-four subjects with SRA, 15 subjects with moderate-mild asthma, and 17 healthy control subjects were studied. Subjects with EOS+ SRA had significantly higher median FENO levels compared with levels in subjects with EOS- SRA (P = .0084) and all other groups. In subjects with SRA, FENO levels correlated with tissue eosinophils (r(s) = 0.54, P = .007), lymphocytes (r(s) = 0.40, P = .003), and mast cells (r(s) = 0.44, P = .05). FENO levels of greater than 72.9 ppb were associated with a sensitivity of 0.56 and a specificity of 1.0 for EOS+ status in subjects with SRA. CONCLUSION: FENO measurement identified the subgroup of subjects with SRA with persistent eosinophilia despite steroid therapy. Further studies are needed on the use of FENO to monitor response to therapy over time in subjects with SRA.

Adult↗
PubMed2006

Airway cytokine expression measured by means of protein array in exhaled breath condensate: correlation with physiologic properties in asthmatic patients.

BACKGROUND: Simultaneous monitoring of airway inflammation and physiology might be useful for asthma management. OBJECTIVE: We examined the upregulated molecules in asthmatic airways. Furthermore, we investigated the relationship between these molecules and the airway physiologic properties of asthma. METHODS: Ten nonsmoking healthy subjects and 16 steroid-naive asthmatic patients were enrolled. Exhaled breath condensate (EBC) sampling, spirometry, and methacholine inhalation challenge were performed on one occasion in this cross-sectional study. Peak expiratory flow was also measured for 4 weeks. Airway cytokine-chemokine-growth factor production was analyzed with a protein array. RESULTS: The expressions of IL-4, IL-8, IL-17, TNF-alpha, RANTES, IFN-gamma-inducible protein 10, TGF-beta, and macrophage inflammatory protein 1alpha and 1beta were significantly upregulated in asthmatic airways compared with those of nonsmoking healthy subjects. Among the upregulated molecules, RANTES expression was significantly correlated with the parameters that represent airway caliber, FEV(1) and respiratory resistance values. In addition, the levels of both TNF-alpha and TGF-beta were significantly correlated with the methacholine threshold and peak expiratory flow variability for the week. CONCLUSION: Inflammatory molecule analysis with EBC appeared to be useful for monitoring the asthmatic airway condition. CLINICAL IMPLICATIONS: Measurements of cytokine levels in EBC might be a promising approach to assess the efficacy of pharmacologic interventions and to investigate the pathophysiology of asthma.

Adult↗
PubMed2006

Buffering airway acid decreases exhaled nitric oxide in asthma.

BACKGROUND: The human airway is believed to be acidified in asthma. In an acidic environment nitrite is converted to nitric oxide (NO). OBJECTIVE: We hypothesized that buffering airway lining fluid acid would decrease the fraction of exhaled NO (F(ENO)). METHODS: We treated 28 adult nonsmoking subjects (9 healthy control subjects, 11 subjects with mild intermittent asthma, and 8 subjects with persistent asthma) with 3 mL of 10 mmol/L phosphate buffered saline (PBS) through a nebulizer and then serially measured F(ENO) levels. Six subjects also received PBS mouthwash alone. RESULTS: F(ENO) levels decreased after buffer inhalation. The maximal decrease occurred between 15 and 30 minutes after treatment; F(ENO) levels returned to pretreatment levels by 60 minutes. The decrease was greatest in subjects with persistent asthma (-7.1 +/- 1.0 ppb); this was more than in those with either mild asthma (-2.9 +/- 0.3 ppb) or healthy control subjects (-1.7 +/- 0.3 ppb, P < .001). Levels did not decrease in subjects who used PBS mouthwash. CONCLUSION: Neutralizing airway acid decreases F(ENO) levels. The magnitude of this change is greatest in persistent asthma. These data suggest that airway pH is a determinant of F(ENO) levels downstream from NO synthase activation. CLINICAL IMPLICATIONS: Airway biochemistry modulates F(ENO) levels. For example, nitrite is converted to NO in the airway, particularly the inflamed airway, by means of acid-based chemistry. Thus airway pH should be considered in interpreting clinical F(ENO) values. In fact, PBS challenge testing integrates airway pH and F(ENO) analysis, potentially improving the utility of F(ENO) as a noninvasive test for the type and severity of asthmatic airway inflammation.

Acids↗