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['Inflammometry' with nitric oxide in exhaled air: a new test for lung diseases].

The gas nitric oxide (NO) is produced in increased amounts in certain types of inflammatory responses and its presence in exhaled air can be demonstrated. The nitric oxide fraction in exhaled air (FeNO) is elevated in patients with asthma and lowered in the case of several other lung diseases such as cystic fibrosis and primary ciliary dyskinesia. The FeNO can be quickly measured in a non-invasive and reproducible manner: on-line if the patient (adult or child), having taken a deep breath in, breathes out with a low flow rate into the NO measuring device or off-line if the expired air is collected in an NO inert reservoir. Confounding factors are contamination of inhaled air with ambient NO and contamination of exhaled air with NO that has been produced in the paranasal sinuses and the nose. The possible applications of FeNO measurement as a new lung function test include diagnostic tests for chronic respiratory symptoms and the possible guidance of anti-inflammatory therapy for asthma and, perhaps, other respiratory disorders.

Breath Tests↗

[Assessment of exhaled NO concentration in monitoring radiation pneumonitis in patient who underwent thoracic radiotherapy for lung cancer].

To monitor radiation pneumonitis, we assessed the exhaled nitrogen oxide (NO) level in patient with lung cancer. A 73-year-old man with idiopathic interstitial pneumonitis underwent thoracic radiotherapy without chemotherapy for squamous cell lung cancer (T2N1M0). He showed elevation of exhaled NO level at 30 Gy-50 Gy, after a decrease at 10-20 Gy. He also showed an abnormal shadow on CT examination at 50 Gy. Although exhaled NO may have had the benefit of predicting radiation pneumonitis before severe clinical symptom appeared, he died three months after radiotherapy because of worsening of the radiation pneumonitis.

Aged↗

How can we best read exhaled nitric oxide flow curves in asthmatic children?

Orally exhaled nitric oxide (NO) levels are increased in children with asthma and thought to reflect the local inflammatory events in the airways. NO production in the lower respiratory airway is reflected in the plateau values of the NO curve, recorded while the patient is performing a slow vital capacity manoeuvre. In young patients, however, plateau values may be difficult to obtain, because the slow vital capacity manoeuvre is often terminated prematurely. In the present study, 60 steroid-naive atopic asthmatic children and 17 normal age-matched controls were asked to perform a slow vital capacity manoeuvre, during which fractional exhaled NO (FEno) levels were measured and evaluated as: a) FEno plateau levels of last part of exhalation (NO plateau); b) FEno peak values, c) area under the FEno curve (AUC). Thirteen out of the 60 steroidnaive patients were reevaluated after a short course of inhaled corticosteroid treatment. Independently of the type of data analysis, FEno values of asthmatics were significantly higher than those observed in normal controls (P < 0.001, each comparison). In addition, possibly because of upper airway NO contamination, FEno peak values were significantly higher than FEno plateau levels in asthmatic patients and in control subjects (P < 0.001, each comparison). Both in asthmatics and controls, highly positive correlations were observed between: a) FEno plateau and peak values (r > 0.7, P < 0.01, each correlation), b) FEno plateau and AUC values (r > 0.7, P < 0.01, each correlation) and c) FEno peak and AUC values (r > 0.9, P < 0.001, each correlation). In asthmatic patients, the three types of data analysis were equally sensitive in detecting the decrease in FEno levels induced by inhaled steroid therapy (P < 0.05, each comparison), with a good correlation between the three data analyses (r > 0.5, P < 0.05, each correlation). Thus, although quantitatively different, comparable data reflecting airway inflammation can be obtained evaluating FEno plateau, FEno peak, and area under the curve, on account of possible upper airway contamination in FEno peak, FEno plateau should be preferred to measure lower airway NO production.

Adolescent↗

Exhaled hydrogen peroxide, nitrite and nitric oxide in healthy children: decrease of hydrogen peroxide by atmospheric nitric oxide.

Hydrogen peroxide (H2O2) and nitrite (NO2-) in exhaled breath condensate have recently been suggested as non-invasive markers of airway inflammation. The goal of this study was to clarify the role of factors that may potentially influence the measurement of H2O2 and nitrite and to look for possible correlations among these inflammatory markers. H2O2 and nitrite values were assessed fluorometrically in breath condensate of 102 healthy children (age 4-18 years) and a detailed status of atopy (including history, lung function and skin prick test) was taken in all children. To find out the role of atmospheric nitric oxide, eNO and envNO were measured via chemiluminescence in association with the sampling of the breath condensate. Median (interquartile range) H2O2 was 0.51 (0.26 - 0.74) microM and nitrite was 3.3 (2.7 4.1) microM. A significant negative correlation between H2O2 and envNO was observed (r = -0.50; p < 0.0001). ENO was independent of envNO at our envNO range up to 56 ppb. No further correlation was found. The inflammatory markers in exhaled breath condensate H2O2, nitrite and eNO are not interrelated to each other in healthy children. Whereas eNO was not dependent on envNO values, high envNO values must be taken into account when measuring H2O2 in exhaled breath condensate.

Adolescent↗

[Numerical simulation of dynamic characteristic of exhalation valve plate in pressure oxygen mask].

Objective. To find out the reason of "dithering" of exhalation valve plate in pressure oxygen mask under high overpressure condition. Method. Dynamic model of the exhalation valve plate in pressure oxygen mask was established. Aerodynamic force on the plate was determined by flowfield computing. The dynamic characteristic of the exhalation valve plate was analyzed by experimental measurement [correction of measurment] integrated with numerical simulation. Result. The movement of valve plate could be simulated with the method proposed, and the course of the"dithering" was found out. Conclusion. The "dithering" of the valve plate can be averted by cutting down the area of the film or increasing the diameter of the valve pedestal moderately.

Atmospheric Pressure↗

[Concentration of nitric oxide in exhaled air in patients with sarcoidosis--pilot study].

Exhaled nitric oxide (eNO) concentration measurement may allow for noninvasive estimation of severity of airways inflammation in asthma and other airways diseases. The purpose of this study was to evaluate usefulness of eNO concentration measurements in patients with pulmonary sarcoidosis. Study group consisted of 22 patients with sarcoidosis (8 women, 14 men aged 26-46). They included 11 patients with radiographically stage I and II and 11 patients with stage III of disease. Sixteen patients had active pulmonary sarcoidosis and 6 had nonactive disease. Ten patients had indications for treatment, 12 patients had not any. Exhaled NO was measured by means of SIEVERS 280 Nitric Oxide Analyser (USA). There was no significant difference in mean eNO concentration in study group (6.91 +/- 0.60 ppb) and in normal control (5.2 +/- 0.73 ppb, p = 0.10). Exhaled NO concentration was similar in patients with sarcoidosis stage I and II (7.5 +/- 1.08 ppb) and in patients with stage III disease (6.2 +/- 0.51 ppb, p = 0.27). We failed to found significant difference in eNO concentration between patients with active (6.7 +/- 0.71 ppb) and nonactive sarcoidosis (7.5 +/- 1.1 ppb; p = 0.57). Neither did eNO concentration differ between patients with and without indications for therapy (5.77 +/- 0.50 ppb vs. 7.8 +/- 0.95 ppb; p = 0.08). In conclusion our pilot study results indicate that measurement of eNO concentrations may be of little value in patients with sarcoidosis.

Adult↗

Caffeine, quercetin and alizarin stimulate the exhalation of metabolic products of [14C]-N-nitrosodiethylamine in mice.

Naturally occurring plant products belonging to different chemical classes namely alizarin, an anthraquinone, caffeine, a methylxanthine derivative and quercetin, a flavonol were studied for their effect on elimination of metabolites of [14C]-N-nitrosodiethylamine (14C-NDEA) through respiration in mice. Treatment with caffeine, quercetin and alizarin at doses of 200, 9 and 9 microg/ml respectively, in drinking water enhanced the exhalation of 14CO2, one of the major end products of NDEA metabolism. Radioactive CO2 exhaled in 60 min increased by 2, 1.61 and 1.4-folds in animals treated with caffeine, quercetin and alizarin for 8 weeks respectively. This increase in exhalation in caffeine-treated animals was achieved even in 2 weeks. These compounds had no adverse effects on the absorption of radioactive NDEA from the gut of the animals as shape and time of 14CO2 peak was similar in i.p. and orally administered [14C-NDEA]. Increased detoxification/elimination of the carcinogen could be one of the mechanisms for the anticarcinogenic properties of these phytochemicals in lung tumorigenesis induced by orally administered NDEA.

Administration, Oral↗

Leukotriene-B4 concentrations in exhaled breath condensate and lung function after thirty minutes of breathing technically dried compressed air.

In previous studies it had been shown that leukotriene-B4 [LTB4] concentrations in the exhaled breath mirror the inflammatory activity of the airways if the respiratory tract has been exposed to occupational hazards. In diving the respiratory tract is exposed to cold and dry air and the nasopharynx, as the site of breathing-gas warming and humidification, is bypassed. The aim of the present study was to obtain LTB4-concentrations in the exhaled breath and spirometric data of 17 healthy subjects before and after thirty minutes of technically dried air breathing at normobar ambient pressure. The exhaled breath was collected non-invasively, via a permanently cooled expiration tube. The condensate was measured by a standard enzyme immunoassay for LTB4. Lung function values (FVC, FEV1, MEF 25, MEF 50) were simultaneously obtained by spirometry. The measured pre- and post-exposure LTB4- concentrations as well as the lung function values were in the normal range. The present data gave no evidence for any inflammatory activity in the subjects' airways after thirty minutes breathing technically dried air.

Air↗

Exhaled nitric oxide as a marker of adverse respiratory health effect in environmental disease.

The presence of, and the possibility to assay, nitric oxide (NO) in exhaled breath of humans caused a great deal of interest in relation to understanding the physiological and pathophysiological role of this molecule. Most studies have measured exhaled NO by chemiluminescence and detection depends on the photochemical reaction between NO and ozone generated in the analyzer. Here we discuss the role of exhaled NO as a physiological method to evaluate the effect of environmental changes on lower and upper airways in healthy subjects; particularly, its potential application as non invasive marker of the effect of outdoor and indoor air pollution on the respiratory tract.

Air Pollutants↗

Effects of dose, strain, and dosing vehicle on methacrylonitrile disposition in rats and identification of a novel-exhaled metabolite.

Methacrylonitrile (MAN), an aliphatic nitrile used in the production of plastics and elastomers, is structurally related to the known animal carcinogen, acrylonitrile. Although MAN has potential to cause significant toxicity, minimal information is available on its toxicity or fate. Current studies were designed to investigate the biological fate of [2-14C]MAN in male F344 rats. Following gavage administration of 115, 11.5, or 1.15 mg MAN/kg in water, male F344 rats were placed in glass metabolism cages and urine, expired air, and feces were collected. Rats were sacrificed at various times, and the concentration of MAN-derived radioactivity in tissues was determined. MAN was rapidly absorbed from the gastrointestinal tract and distributed to all major tissues. After gavage administration of 1.15-115 mg/kg, [2-14C]MAN is primarily eliminated in the expired air. Sixty to 70% of the low and medium doses were exhaled as 14CO2 in 72 hr compared with 25% of the highest dose. Whereas 40% of the high dose was expired as organic volatiles in 72 hr, only 9-12% of the low and medium doses were exhaled as such. It is therefore apparent that saturation of MAN metabolism occurs at the high dose. HPLC analysis of expired organic volatiles from MAN-treated rats showed that it contained two components that were identified as unchanged MAN and acetone. The MAN:acetone ratio was directly proportional to dose and decreased as a function of time. Urinary excretion accounted for 20-30% of all MAN doses within 72 hr after dosing. Investigating the effect of dosing vehicle on MAN disposition in rats revealed that administration of 115 mg MAN/kg in oil resulted in the death of rats within 24 hr after treatment. Furthermore, monitoring the fate of MAN in these rats before death showed that a significantly higher percentage of the dose was eliminated in urine and expired air. Analysis of this expired air also revealed that significantly more acetone and less unchanged MAN were exhaled by these animals. It is apparent that administration of MAN to F344 rats in oil resulted in slower absorption, decreased elimination of unchanged MAN, and increased metabolism to acetone and/or decreased degradation of acetone to CO2. The combination of these effects of an oil vehicle may have contributed to the death of rats by MAN. Comparison of the metabolism and disposition of MAN in F344 and Sprague-Dawley rats showed minor differences between the two strains.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Exhaled carbon monoxide is not flow dependent in children with cystic fibrosis and asthma.

STUDY OBJECTIVES: Exhaled nitric oxide (eNO) and carbon monoxide (eCO) concentrations are elevated in inflammatory airway diseases like asthma and have been investigated as potential diagnostic markers. For eNO concentrations knowledge about the inverse flow dependency is essential for reproducibility and comparability of measurements. The aim of this investigation was to evaluate a possible expiratory flow dependency of eCO in children with different inflammatory airway diseases. DESIGN: ENO and eCO concentrations were measured electrochemically and via chemiluminescence in the exhaled air of 20 healthy children, 17 stable cystic fibrosis (CF)-patients and 15 steroid-naive asthmatics in a combined analyzer at five different expiratory flows (10, 20, 45, 86, 184 ml/sec). RESULTS: ECO was not flow dependent in any of the three groups. At 45 ml/sec the mean eCO-concentration of healthy children was 3.72 +/- 0.23 ppm, of CF-patients 3.67 +/- 0.37 ppm and of asthmatics 4.99 +/- 0.45 ppm. Elevated eCO (p<0.0122) was found in asthmatics but not in CF-children. There was no age dependency and no correlation between eNO and eCO. CONCLUSIONS: In contrast to CF-patients in the exhaled air of steroid-naive asthmatics elevated eCO concentrations are found that may serve as non-invasive inflammatory marker. In contrast to eNO, eCO did not show any expiratory flow dependency.

Adolescent↗

[Exhaled nitric oxide: a new biomarker for respiratory pathologies].

There has been a growing interest for exhaled biomarkers. We review studies examining NO as a potential marker of airway inflammation, enabling noninvasive repeated monitoring of airway inflammation. The measurement technique has been standardized. We have determined the local normal levels for the Liège region. The exhaled NO level is elevated in asthma, and can predict asthma exacerbation. Exhaled NO has a value for the diagnosis of cystic fibrosis and primary ciliary dyskinesia.

Asthma↗

Exhalation of N-nitrosoethylvinylamine after application of N-nitrosodiethylamine to Sprague-Dawley rats.

Our method of endotracheal intubation makes it possible to collect exhaled air directly from the respiratory tract, thus eliminating the possibility of artefact formation and decomposition of metabolites. N-Nitrosodiethylamine (NDEA) has been postulated as a precursor of N-nitrosoethylvinylamine (NEVA), however, NEVA has not been detected as a metabolite of NDEA. Following endotracheal intubation and intravenous application of 550 micrograms NDEA to Sprague-Dawley rats, appreciable amounts of NEVA and unaltered NDEA were found in exhaled air. Further confirmation that NEVA is a metabolite of NDEA was obtained when, after eliminating oxidative decomposition of the nitrosamine with disulfiram in an enzyme inhibition assay, pretreated rats exhaled only traces of NEVA. Such findings could be informative with respect to the organotropism of nitrosamine carcinogenesis.

Animals↗

Aminopyrine demethylation kinetics. Use of metabolite exhalation rates as an index of enhanced mixed-function oxidase activity in vivo.

The usefulness of determining aminopyrine demethylation kinetics via monitoring of metabolite exhalation rats had been assessed. In rats receiving [N-dimethyl-14C]aminopyrine, a biexponential decline in the 14CO2 exhalation rate is apparent when monitoring is continued over a 5 to 6-hr period. Both the fast phase (representing the first demethylation) and the slower phase (representing the second demethylation) are markedly influenced by phenobarbital and promethazine pretreatment. These changes are consistent with enhanced mixed-function oxidase activity. Examination of the urinary excretion products of aminopyrine obtained in these studies support this claim. The sensitivity of the above index of mixed-function oxidase activity is increased considerably by the use of crossover experimental designs. Considerable interanimal variation is observed in the metabolite production in both exhaled air and urine from rats administered aminopyrine.

Aminopyrine↗

Lung transfer factor for carbon monoxide measured during a slow single breath without breath-holding and during slow exhalation.

We considered whether a slow single breath with neither breath-holding nor carefully controlled flows could provide estimates of lung transfer factor for CO (TLCO) similar to those obtained with the usual standardized single breath technique. This technique requires actual flow rates and volume variations to be taken into account [10], as well as the use of a fast CO analyser and computerized calculations. TLCO values found with this method (TLCOsb) for 5 normal subjects and 29 patients with various respiratory diseases did not differ from those obtained with the standardized test (p less than 0.001). TLCO was also measured during exhalation only, by the use of a single compartment, constant TLCO equation and a computational procedure which provided a mean TLCO value for a given expired volume range (TLCOex). A unique TLCOex was sufficient to account for the whole exhalation in normal subjects and certain patients. In most patients two TLCOex were necessary, one for large lung volume after dead space washout and the other one accounting for the second half of expiration until closing volume. Most TLCOex were larger than TLCOsb calculated during the same slow breath. This over-estimation was found to be correlated (p less than 0.001) with the phase III argon slope. In patients where two TLCOex values were required to describe the exhaled CO course, we found that TLCOex decreased with lung volume. This decrease was also correlated with the argon slope (p less than 0.001). The observed difference between TLCOsb and TLCOex values and the decrease of TLCOex with lung volume probably reflect inhomogeneous ventilation distribution.

Adult↗

Diagnosis of lactose intolerance through the quantification of hydrogen in exhaled air.

Considerations are made on diarrhea secondary to intestinal malabsorption of carbohydrates and on the diagnostic means available in our environment, among which are the reactive strip, the clinitest tablet, tolerance curves and research of intestinal enzymes. The quantification of exhaled hydrogen is mentioned as a diagnostic method, used by several other authors, and a review of the literature on the subject is made. Considerations are made on a hydrogen quantification in the breath of patients with a transitory lactose intolerance. 16 patients were studied, 15 of whom showed an increase in the exhaled H2. 32 children with diarrhea, free from lactose intolerance, were studied. The method used did not show a significant increase in the exhaled hydrogen. 27 patients showed no H2 in their breath. In 4 there was elimination of H2 (false positives). 17 diarrhea-free children were studied. A significant difference was found when comparing the children with diarrhea and lactose intolerance to the other two groups who were free from lactose-intolerance. It is considered that this method can be useful in the diagnosis of intolerance to lactose and other sugars.

Chromatography, Gas↗

[Gas chromatographic analysis of ethanol and acetone in the air exhaled by patients].

A new method for analysis of volatile endogenous compounds in exhaled air using portable gas chromatographer with photoionization detector has been developed. Detection threshold for ethanol and acetone is 0.1 mg/ml, this permitting one to omit the step of concentrating the exhaled air samples. The accuracy of detection is 5.9 to 7.7%. The concentration of endogenous ethanol in health was 0.12 to 0.3 mg/m3, that of acetone 0.6 to 2.8 mg/m3, that in cardiopulmonary patients 0.8 to 6.4 mg/m3 for ethanol and 2.9 to 47.2 mg/m3 for acetone. Fasting for 24 h led to 15-fold increase of acetone concentration in exhaled air.

Acetone↗

[Measurement of exhaled nitric oxide. A new lung function test?].

Nitric oxide (NO) is a gas molecule produced endogenously in the lungs. It can be detected in the exhaled air of animals and humans. Nitric oxide can be generated in the air passages by a synthase which is induced in several cell types by exposure to proinflammatory cytokines. Its induction is blocked by glucocorticoids. An increased concentration of nitric oxide can be found in the exhaled air of patients with asthma and other inflammatory lung disorders. Gas analysers for measuring nitric oxide in exhaled air have recently been made commercially available. The test is non-invasive, simple to perform, and can also be used in patients with reduced lung function. The method seems to provide a unique non-invasive means of diagnosing and monitoring inflammation of the air passages, and in the future the test may become a useful tool in a clinical setting. Preliminary recommendations for measurements and technical standardization have recently been proposed by the European Respiratory Society.

Humans↗