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PubMed2004

Dornase alpha and exhaled NO in cystic fibrosis.

Nitric oxide (NO) that is produced within the airways can be measured in the exhaled air. Concentrations of exhaled NO (FENO) are decreased in cystic fibrosis (CF) and, in cross sectional studies, have been shown to be even lower in patients with more advanced pulmonary disease. This may result from retention and metabolisation of NO within viscous airway secretions. Treatment with recombinant human DNase I (dornase alpha) modifies the rheological properties of airway secretions and thereby improves pulmonary function even in young and apparently healthy patients with CF. We studied FENO and pulmonary function in children with CF with little clinical evidence of lung morbidity in a two-year randomized double-blind placebo-controlled study with nebulized dornase alpha. Mean age at enrollment was 8 years (range 6 to 11 years), mean forced vital capacity (FVC) was 112% (range 86 to 133%), and mean forced expiratory volume in one second (FEV1)was 109% (range 88 to 128%) of predicted values. In five of six (83%) of the dornase alpha treated patients, FENO changed in parallel to changes in pulmonary function tests while no such correlation was observed in any of the eight patients receiving placebo. This difference between treatment groups was statistically significant for both FVC (P = 0.026, Wilcoxon-test) and FEV1 (P = 0.042). These data suggest that FENO may serve as a surrogate measure for evaluating the effectiveness of interventions that affect airway clearance in CF.

Administration, Inhalation↗
PubMed2006

Clinical and technical factors affecting pH and other biomarkers in exhaled breath condensate.

Exhaled breath condensate (EBC) pH appears to be a robust measure of asthma. However, the association between EBC pH and clinical factors and airway inflammatory markers remains unclear. The objectives of this study were to investigate the factors determining EBC pH in asthmatic children, and the reproducibility and effects of collection devices on EBC pH in nine healthy, nonsmoking adults. EBC was collected once from asthmatic children using EcoScreen, and from adults over 3 consecutive days using both RTubes and EcoScreen. EBC pH was measured immediately in non-deaerated samples by microelectrode pH meter. Concentrations of 8-isoprostane, cysteinyl leukotrienes (cys-LT), and leukotriene B4 (LTB4) were measured using enzyme immunoassay. Exhaled nitric oxide concentration (FeNO) was measured by chemiluminescence. Fifty-eight asthmatics (16 intermittent, 12 mild persistent, and 30 moderate-to-severe persistent) were recruited. EBC pH was lower among patients with moderate-to-severe persistent than intermittent asthma (P = 0.046). This marker correlated inversely with disease severity score (rho = -0.276, P = 0.036), but not FeNO or other EBC biomarkers. Bland-Altman analyses found pH but not other EBC biomarkers to be reproducible, which were confirmed by its low coefficient of variation (2.7%; range, 0.4-5.2%). There was poor correlation between pH in EBC collected by RTube and EcoScreen (rho = 0.059, P = 0.784). Factor analysis selected four factors that explained 67.5% of the total variance, and EBC pH clustered with both cys-LT and LTB4. In conclusion, our results suggest that pH in non-deaerated EBC is influenced by asthma severity in children. EBC pH measurement is reproducible, but is dependent on the collection devices used.

Adolescent↗
PubMed2006

Markers of airway inflammation in primary ciliary dyskinesia studied using exhaled breath condensate.

Macroscopically, the airways in primary ciliary dyskinesia (PCD) are inflamed and infected, and the eventual result is bronchiectasis. The measurement of noninvasive markers of inflammation in PCD may allow determination of mechanisms of tissue damage, and even allow monitoring of therapy. The aim of this study was to measure in exhaled breath condensate (EBC) of children with PCD the concentrations of the neutrophil chemoattractants leukotriene (LT) B4 and interleukin (IL)-8 and the marker of oxidative stress 8-isoprostane (8-IP), and to try determining whether these markers can be used to assess mechanisms of airway inflammation in these patients. Concentrations of LTB4, IL-8, and 8-IP in the EBC of 23 PCD and 11 age-matched healthy children were measured using an enzyme immunoassay (EIA). The children also performed spirometry and underwent sputum induction, the latter for differential cell count. The concentrations of 8-IP in EBC of children with stable PCD were significantly increased compared to normal controls (median, 7.8 pg/ml vs. 3.1 pg/ml; P = 0.004). There was no difference in the median concentrations of EBC LTB4 between PCD subjects and healthy controls (28 pg/ml vs. 28 pg/ml; P = 0.5). IL-8 levels were below the detection limit of the assay, and were not analyzed further. There was no correlation between concentrations of either 8-IP or LTB(4) in EBC and forced expired volume in 1 sec in PCD children. Sputum induction was successful in 83% of the subjects; the median induced sputum neutrophil count was 69% (interquartile range, 59.3-73.6). No significant correlation was found between sputum neutrophils and either EBC 8-IP or LTB4 concentrations in PCD children. This study showed that oxidative stress, as reflected by increased exhaled 8-IP concentration, is increased in PCD children. The mechanism of airway neutrophilia is unclear, but is unlikely to be related to increased production of LTB4, at least in stable PCD patients.

Adolescent↗
PubMed2006

Measuring exhaled breath condensates in infants.

There is growing interest in investigating compounds of exhaled breath condensates (EBC) as potential noninvasive markers of airways disease processes. Some of these markers have the potential to provide information on the early stages of disease. In this paper, we present a method for collecting EBC during both oral and nasal breathing in infants. Fifty-four infants (mean age, 13.3 months; range, 1-30 months) undergoing infant lung-function testing were recruited for this study. Breath condensates were collected during sedated sleep, using a custom-made collection device. Collections were made for 10 min during normal tidal breathing. Nasal measurements were attempted in all children by placing a face-mask over the nose and mouth and keeping the mouth closed. In 14 infants, oral measurements were made by placing a face-mask over the mouth only and occluding the nose. Condensates were collected successfully in all but one child. The collected volume ranged from 50-550 microl (mean +/- SD, 281.8 +/- 145.8 microl). The volume of EBC collected was correlated to age, length, weight, and minute ventilation. Significantly more EBC was collected during oral compared to nasal breathing (354.3 vs. 277.5 microl, P=0.03). There were no significant changes in heart rate, respiratory rate, or oxygen saturation during collection. The collection of EBC in young children and infants is feasible and safe, and the method used here allows the successful collection of reasonable amounts of exhaled condensate.

Breath Tests↗
PubMed1999

Detection of nitric oxide in exhaled air of different animal species using a clinical chemiluminescence analyser.

The aim of the present study was to evaluate the nitric oxide (NO) concentrations present in end-expired gas (FENO) of different animal species under basal and stimulated conditions using a clinical chemiluminescence analyser, which has been developed for measurement of single exhalations in humans. Anaesthetised, tracheotomised and artificially ventilated guinea pigs, rats and rabbits were prepared for recording systemic blood pressure and FENO. Stable levels of FENO were detected in expired air over a 1-h observation period in the three animal species tested. Rabbits exhibited the highest concentrations and output (FENO 12.9+/-1.0 ppb, VNO 9.0+/-0.7 nl min-1), followed by guinea pigs (FENO 6.2+/-0.70 ppb, VNO 1.7+/-0.19 nl min-1) and rats (FENO 0.9+/-0.01 ppb, VNO 0.25+/-0.00 nl min-1). L-arginine (1 g kg-1 i.v.) evoked significant increments in VNO in guinea pigs and rabbits but was ineffective in rats. However, L-arginine showed a direct effect on blood pressure in all the animal species tested, causing a rapid fall in the mean arterial blood pressure (MABP; 38, 48 and 50% decrease in rabbits, guinea pigs and rats, respectively; P<0.05). An inhibitor of endogenous NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg kg-1 i.v.), decreased both basal and L-arginine-induced VNO in guinea pigs and rabbits, but was ineffective in rats. L-NAME increased MABP in all the animal species tested (58% in guinea pigs, 43% in rats and 18% in rabbits; P<0.05). The results indicate that it is possible to detect NO in the exhaled air of different animal species using a clinical chemiluminescence analyser and that different species exhibit striking differences in the levels of basal and stimulated NO output.

Animals↗
PubMed2001

Effect of inhaled ciclesonide on airway responsiveness to inhaled AMP, the composition of induced sputum and exhaled nitric oxide in patients with mild asthma.

To assess the efficacy of ciclesonide, a novel corticosteroid pro-drug, we compared its effect on lung function, airway responsiveness to inhaled AMP, the composition of induced sputum, and the level of exhaled nitric oxide (NO) with the effect of budesonide in patients with asthma. Fifteen non-smoking steroid-naive patients (mean FEV(1), 94%pred) inhaled either 400 microg ciclesonide or 400 microg budesonide as a single morning dose for two weeks each separated by a > or =3 week wash-out period. The study was performed in a double-observer, randomized, cross-over design. FEV(1)increased significantly during treatment with budesonide (3.38 vs. 3.64 l P=0,003), but not after ciclesonide (3.60 vs. 3.69 l). PC(20)FEV(1)of AMP increased (P<0,001, each) after both budesonide (4.59 vs. 32.48 mg/ml, 2.8 doubling doses) and ciclesonide (3.92 vs. 20.00 mg/ml, 2.4 doubling doses). The percentage of sputum eosinophils was significantly reduced after ciclesonide (7.9 vs. 3.4% P=0.01), but not budesonide (6.0 vs. 4.3%). After both budesonide and ciclesonide, a significant (P<0.001) reduction in the level of exhaled NO occurred. In none of the parameters studied, the changes differed significantly between treatment with budesonide or ciclesonide. These data suggest that ciclesonide is equi-effective to budesonide with regard to its potency to reduce the airway responsiveness to inhaled AMP as well as airway inflammation in patients with mild asthma.

Adenosine Monophosphate↗
PubMed1983

Detecting indoor CO exposure by measuring CO in exhaled breath.

CO levels in exhaled breath were measured in 29 residents of flats, equipped with a flueless geiser (an instantaneous gas-fired water heater). The flats were selected because they had a geiser with a CO concentration of more than 250 parts per million in its flue gases. Small, but in some cases statistically significant increases in CO levels in exhaled breath were found in both smokers and non smokers, and after periods of cooking and dishwashing when the geisers had been used. Calculated COHb levels remained well below 2.5% for non smokers, but were generally higher for smokers.

Adolescent↗
PubMed1975

Fixation, retention and exhalation of carrier-free 11C-labeled carbon monoxide by man.

Carrier-free 11C-labeled carbon monoxide was produced by proton irradiation of a nitrogen gas flow target via the 14N(p, alpha)11C process followed by on-line reduction of the predominantly formed 11C-carbon dioxide with a yield of 0.4 mCi/muAmin. After appropriate quality control about 2 mCi of carrier-free 11C-carbon monoxide in 500 ml on nitrogen gas were inhaled by test subjects in one breath. The 11C-activity distribution was then followed in vivo by scanning above thorax, head, liver, thigh and os sacrum; simultaneously the 11c-activity of the blood was also followed by batch measurement. The data indicate that part of the 11C-activity migrates from the blood into the intercellular space, while another part is exhaled. The 11C-activity leaves the individual organs with a biological half-life ranging from about 120 to 200 min, a time which is short as compared to the one observed for 51Cr-labeled erythrocytes. A radio gas chromatographic analysis of the exhaled air showed that the 11C-activity leaves the body exculsively in the form of 11C-labeled carbon monoxide. Consequently, metabolism of the 11CO into 11CO2 or other compounds can be excluded.

Carbon Monoxide↗
PubMed1982

Effect of vitamin E on pentane exhaled by rats treated with methyl ethyl ketone peroxide.

One useful method to monitor in vivo lipid peroxidation is the measurement of volatile hydrocarbons, mainly pentane and ethane, that derive from unsaturated fatty acid hydroperoxides. Vitamin E, the biological antioxidant, inhibits lipid peroxidation and the production of pentane and ethane. The rates of pentane production by male Sprague-Dawley rats fed a diet that contained 10% vitamin E-stripped corn oil and 0, 1, 3, 5 or 10 IU dl-alpha-tocopherol acetate/kg were monitored over a 12-wk period. During the eleventh and twelfth weeks, the rats were injected intraperitoneally with 3.3 and 13 mg of methyl ethyl ketone peroxide (MEKP)/kg body wt, respectively. Pentane production was then measured at intervals over a 50-min period, and the total amount of pentane produced over this time interval was estimated. An asymptotic function was found to describe the relationship between exhaled pentane and the low levels of dietary vitamin E that were fed to the rats. As measured by pentane production, rats had a higher minimal vitamin E requirement after they were treated with the potent peroxidation initiator MEKP than they did prior to treatment. The level of pentane exhaled by rats injected with 13 mg MEKP/kg body wt was significantly correlated with kidney and spleen tocopherol levels.

Animals↗
PubMed2002

Silica zeolite scavenging of exhaled isoflurane: a preliminary report.

PURPOSE: We evaluate the effectiveness of a silica zeolite (Deltazite) hydrophobic molecular sieve adsorbent, in removing exhaled isoflurane. METHODS: In three experiments, a simulated anesthesia mannequin was ventilated using 1% isoflurane in nitrous oxide and oxygen (1:1 ratio) at a gas flow of 3 L x min-1. Airway pressures, end-tidal carbon dioxide [ETCO2], inspired and end-tidal isoflurane were measured. The scavenging line was connected to a canister containing 750 g of the silica zeolite. Concentrations of isoflurane entering and exiting the canister were measured, as well as the pressure gradient across the canister and gas flow through the canister. In phase 1 (n = 3), the mannequin was ventilated for 6.5 hr, followed by phase 2 where a test lung replaced the simulator. The time (phase 1 plus phase 2) until isoflurane 'breakthrough' (> 0.02%) was noted. RESULTS: The average canister weight increase was 68 g, however 92 g of isoflurane were used. The isoflurane concentration exiting the canister remained undetectable throughout phase 1 in each experiment. The pressure gradient across the canister averaged 0.13 cm H2O and did not increase throughout phase 1. The time to 'breakthrough' (phase 1 plus phase 2) was 8.0 hr, 8.8 hr and 9.0 hr. CONCLUSIONS: Silica zeolite was effective at completely removing 1% isoflurane from exhaled gases for periods of eight hours. The technology shows promise in removing isoflurane emitted from anesthesia machine scavenging systems.

Adsorption↗
PubMed2005

Comparative measurement of thromboxane A2 metabolites in exhaled breath condensate by different immunoassays.

OBJECTIVE: Differences between detection techniques may be partly responsible for variable mediator concentrations reported in exhaled breath condensate (EBC). We compared two types of immunoassays to estimate thromboxane A(2) (TxA(2)) concentration. MATERIALS AND METHODS: Thromboxane B(2) (TxB(2)) levels were measured by enzyme immunoassay (EIA) and TxB(2)/2,3-dinor TxB(2) by radioimmunoassay (RIA) in 10 healthy subjects and 13 asthmatic patients. 2,3-Dinor TxB(2) was also determined by a separate EIA. RESULTS: Thromboxane was detected in all samples by RIA, but only in about 75% of samples by EIA. 2,3-Dinor TxB(2) was detected in most samples. There was no agreement between the results of the different immunoassays. As compared to healthy subjects, exhaled breath condensates of asthmatic patients contained significantly more immunoreactivity by RIA and TxB(2) EIA (but not by 2,3-dinor TxB(2) EIA). CONCLUSION: RIA and EIA resulted in vastly different absolute values. The difference found between healthy volunteers and asthmatic patients however, suggests an increased level of TxA(2) in the airways of asthmatics.

Adult↗
PubMed1986

Influence of the oropharyngeal microflora on the measurement of exhaled breath hydrogen.

We investigated the possible contribution made by oropharyngeal microfloral fermentation of ingested carbohydrate to the generation of the early, transient exhaled breath hydrogen rise seen after carbohydrate ingestion. Ten subjects ate or were sham fed carbohydrate-containing meals with and without prior chlorhexidine mouthwash during serial collection of exhaled breath and mouth hydrogen samples. Meal ingestion and sham feeding both induced significant (p less than 0.01) elevations of breath and mouth hydrogen that were virtually abolished by prior chlorhexidine mouthwash. In 7 subjects, delivery of the meal directly into the stomach via an orogastric tube did not cause a breath or mouth hydrogen rise. Oral contents incubated anaerobically in vitro with carbohydrate generated hydrogen that was again inhibited by chlorhexidine. These studies indicate that fermentation of ingested carbohydrate by oropharyngeal bacteria can contribute significantly to measured breath hydrogen values soon after meal ingestion, and may introduce avoidable error into the interpretation of serial breath hydrogen data.

Adult↗
PubMed1980

Single-exhalation method for study of lobar and segmental lung function by mass spectrometry in man.

A single-exhalation method, based on a modification of the conventional single-breath technique, was applied to study lung function in normal subjects during fiberoptic bronchoscopy. After a single inspiration of a test gas mixture (1% He, 1% C2H2, 0.07% C18O in air), the test gas concentrations were continuously monitored during subsequent slow exhalation, using a respiratory mass spectrometer that sampled either at the lips (Whole-lung test) or, through the bronchoscope, at various sites within the bronchial tree (Regional test). Changes in concentrations of the test gases with time allowed estimation of alveolar ventilation (Va), blood flow (Q), and diffusing capacity (DLCO), per unit accessible lung volume (Va). In the Whole-lung test, both DLCO and Q agreed closely with values obtained in the same subject by a rebreathing method. No differences were observed between the upright and the lateral decubitus positions. In teh Regional test, VA/VA, DLCO/VA and Q/VA were larger in the dependent than in the upper lung, when sampling was from the main bronchi in the lateral decubitus positions. Sampling from lobar bronchi in the upright position revealed an increase from top to bottom in VA/VA, DLCO/CA and Q/VA, this being most marked for Q. These results are compatible with the regional variations that have been shown by radioactive techniques and have been attributed to gravitational forces. The method appears to be suitable for the study of lobar and segmental lung function in patients with lung disease.

Bronchoscopy↗
PubMed1989

Determining kinetic constants of chlorinated ethane metabolism in the rat from rates of exhalation.

The kinetic constants of chemical metabolism are used to develop physiologically based pharmacokinetic (PB-PK) models which predict the time course distribution of volatile chemicals in mammalian systems. Gas uptake techniques have proved useful in determining kinetic constants for a variety of volatile compounds including the following chloroethanes: ethyl chloride, 1,1-dichloroethane, 1,2-dichloroethane, and 1,1,1-trichloroethane. Unfortunately, low vapor pressure materials and those exhibiting increasing blood and tissue solubilities could not be examined by gas uptake methods. An alternative gas phase method was developed in which rats were first exposed by constant concentration inhalation for 6 hr and then placed in 2.5-liter exhaled breath chambers with fresh air flow and chamber effluent was serially analyzed for test chemical. The resulting elimination behavior was extremely sensitive to metabolism, and kinetic constants for chemical metabolism were estimated by simulation with a PB-PK model containing equations that accurately described the experimental conditions. Optimized maximum metabolic rates (Vmax) were determined for 1,1,2-trichloroethane, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane, pentachloroethane, and hexachloroethane with resulting values of 7.69, 6.39, 12.9, 9.71, and 1.97 mg/kg/hr, respectively. With several of these test chemicals the PB-PK modeling identified fur adsorption of chemical as significantly contributing to the exhalation chamber concentration time course after whole body exposure.

Animals↗
PubMed1985

Radioactivity and radon exhalation rates of building materials in The Netherlands.

About 140 samples of building materials have been analysed by gamma spectrometry for their Ra-226, Th-232 and K-40 concentrations. The radon exhalation rate was measured from concrete slabs of different composition including fly-ash components. The activity concentrations of materials containing soil products, like clay bricks and concrete, proved to be somewhat lower than those reported in some other European countries. This is probably due to the mainly sedimentary structure of the Dutch soil. The normalized radon exhalation rates were found to be substantially lower for concrete containing fly-ash products than for ordinary concrete.

Carbon↗
PubMed1984

Carbon tetrachloride metabolism in vivo and exhalation of volatile alkanes: dependence upon oxygen partial pressure.

Metabolism of carbon tetrachloride in rats at atmospheric and reduced oxygen pressure has been determined indirectly by its disappearance from the inhaled air; it is inversely related to oxygen concentration and increases with decreasing partial pressure, as expected for reductive dehalogenation; oxygen partial pressure has been reduced to about a third of normobaric conditions. Concurrently exhalation of ethane and pentane as indication of lipid peroxidation has been monitored, showing a drastic increase when the oxygen partial pressure is reduced in the presence of carbon tetrachloride. Time course and duration of these processes indicate that the total metabolism of carbon tetrachloride is limited by the concomitant destruction of cytochrome P-450; also, oxidative destruction of polyunsaturated fatty acids apparently does not proceed beyond the end of metabolic activation of carbon tetrachloride. The molar ratios of the amount of metabolized carbon tetrachloride to the amounts of exhaled hydrocarbons lead to the same conclusion, namely that "lipid peroxidation" in this case does not proceed as an autocatalytic, self-propagating chain reaction.

Animals↗
PubMed1982

Influence of a low-selenium diet on erythrocyte glutathione peroxidase and alkane production in exhaled air of rats as a measure of lipid peroxidation in vivo during growth.

Erythrocyte glutathione peroxidase activity and alkane production in exhaled air of growing rats were studied as a measure of lipid peroxidation in vivo. When 4-weeks-old, rats were fed a low-selenium (0.05 mg/kg) refined soy concentrate-based diet but adequate in vitamin E and other nutrients. Rats of control groups were fed the same diet supplemented with varying amounts of selenium as sodium selenite. After 10 weeks, erythrocyte glutathione peroxidase activity in the group fed the low selenium diet had decreased to about 40% of the original level. Feeding this diet for a longer period resulted in a slow increase of the glutathione peroxidase level. After about 37 weeks, this level was equal to the initial level. During the same period of rapid growth, ethane and pentane production in the exhaled air of a group of similar animals on the diet containing 0.05 mg Se per kg was slightly although significantly higher compared with the levels of animals on a supplemented (0.4 mg Se per kg) diet. Differences were highest when glutathione peroxidase activity levels in the erythrocytes were lowest and negligible at the start of the experiment and after the period of rapid growth. These results support the view that the seleno-enzyme glutathione peroxidase is active in the defense mechanism of the cell against lipid peroxidation.

Aging↗
PubMed1985

Methylmercury stimulates the exhalation of volatile selenium and potentiates the toxicity of selenite.

The aim of the present experiments was to investigate whether a single dose of 24 mumol/kg methylmercuric chloride (MeHgCl) in rats can influence the effect of an equimolar dose of sodium selenite (Na2SeO3) on body weight or the exhalation of dimethylselenide, a volatile metabolic product of selenium. Due to the difference in their single-dose toxicities, only selenite depressed body weight gain, when given alone. The experiments indicated that methylmercury, irrespective of whether it was given 1-2 h before, or at the same time as sodium selenite, potentiated the effect of the latter on body weight. Methylmercury also increased the exhalation of volatile selenium, but this effect decreased when the administration of selenite was delayed.

Animals↗