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Analysis of exhaled nitric oxide by the helium bolus method.

STUDY OBJECTIVES: The precise anatomic sites contributing to exhaled nitric oxide (eNO) are still unknown. The present study was designed to analyze profiles of eNO by referring to the He exhalation curve and examining the effects of breath-holding and expiratory flow rates on eNO. PARTICIPANTS: Healthy volunteers and patients with stable asthma. MEASUREMENTS AND RESULTS We used the He bolus method of the closing volume, and simultaneously analyzed the concentrations of exhaled He and nitric oxide (NO). By referring to the He exhalation curve, the expired gas was divided into three parts: airway dead space (phase 1), a mixture of airway and alveolar gas (phase 2), and alveolar gas (phase 3 and phase 4). The eNO profiles showed a peak in phase 2 (peak eNO) and decreased gradually to a plateau in the latter half of phase 3 (plateau eNO). The levels of peak eNO were higher than those of plateau eNO in both normal subjects and asthmatic patients. Breath-holding increased levels of peak eNO 2.5-fold in both normal subjects and asthmatic patients, but it did not affect the levels of plateau eNO. The levels of peak eNO increased as the expiratory flow rate decreased, and the levels of plateau eNO showed a similar flow dependency. CONCLUSION: A peak value of eNO concentration profiles may directly express the production of NO in the airway.

Adult↗

Effect of a nonrebreathing exhalation valve on long-term nasal ventilation using a bilevel device.

STUDY OBJECTIVE: To determine whether an exhalation valve designed to minimize rebreathing improves daytime or nocturnal gas exchange or improves symptoms compared with a traditional valve during nocturnal nasal ventilation delivered using a bilevel pressure ventilation device. DESIGN: Prospective direct comparison trial with each patient sequentially using both valves, during a 2-week run-in period with a traditional valve, a 2-week trial with the nonrebreathing valve, and a 2-week washout period with the traditional valve. SETTING: Outpatient pulmonary function laboratory and home nocturnal monitoring. PATIENTS: Seven patients who received long-term (> 1 year) nocturnal nasal bilevel pressure ventilation with an expiratory pressure of <or= 4 cm H(2)O. INTERVENTION: Symptoms, pulmonary function, and arterial blood gas levels were assessed at each of three daytime sessions after the sequential 2-week periods using the different valves. Nocturnal studies used a multichannel recorder that measured heart rate, chest wall impedance, nasal airflow, and oximetry. End-tidal PCO(2) (PetCO(2)) from the mask and transcutaneous PCO(2) (PtcCO(2)) were also monitored nocturnally. RESULTS: Seven patients with a variety of neuromuscular, chest wall, and obstructive defects were enrolled. No mean differences in daytime arterial blood gas levels, pulmonary functions, nocturnal vital signs or oximetry, or PtcCO(2) were apparent regardless of the exhalation valve used. The multichannel recording was indicative of an air leak at least one third of the time, and the PetCO(2) tracing detected a blunted signal or no signal from the mask during the majority of the recording time. CONCLUSION: The use of an exhalation valve designed to minimize rebreathing did not improve daytime or nocturnal gas exchange or symptoms in patients receiving long-term nasal bilevel pressure ventilation in comparison with a traditional exhalation valve, most likely because of air leakage and escape of CO(2) via other routes.

Aged↗

Exhaled metallic mercury in acatalasemic, hypocatalasemic and normal mice injected with mercury (II) chloride.

To clarify the relationship between the catalase activity in mouse organs and the amounts of metallic mercury exhaled, normal, homozygous hypocatalasemic and acatalasemic mice were injected with mercuric chloride. The cumulative amount of metallic mercury exhaled by mice was evidently expressed in the descending order of acatalasemic, hypocatalasemic, and normal mice. Statistically significant differences in the cumulative exhaled metallic mercury levels were observed between acatalasemic and hypocatalasemic mice, between normal and hypocatalasemic mice, and between acatalasemic and normal mice using the method of one way analysis of variance (ANOVA). A linear relationship was obtained through logarithm of catalase activity in the lungs or the blood, and logarithm of the cumulative amount of the exhaled mercury.

Animals↗

Exhaled nitric oxide during exercise.

Endogenously produced nitric oxide (NO) is detectable in the exhaled air of resting humans, and the amount of exhaled NO increases during exercise. It is believed that NO is likely to have an important role in the normal physiological response to exercise. Despite accumulating evidence of exhaled NO during exercise, the effects and relevance of NO to exercise are not yet completely understood. Scientific debate surrounds the site of NO production and the stimuli for production. Resolution of these controversial issues will explain the significance of exhaled NO during exercise.

Animals↗

Comparison of exhaled nitric oxide and cardiorespiratory indices between nasal and oral breathing during submaximal exercise in humans.

In order to examine the origin and role of nitric oxide (NO) in exhaled air during exercise, exhaled NO outputs of 8 healthy human subjects were compared using different breathing methods, through the mouth or nose, at two intensities of bicycle exercise. The concentration of NO in the exhaled air and ventilatory gas exchange variables were measured by a chemiluminescence analyzer and a mixing chamber method, respectively. The concentration and total output of NO in the expired air was significantly higher under nasal breathing than under oral breathing for both exercise intensities, whereas no significant difference was observed in cardiorespiratory variables between them. NO output increased significantly when exercise intensity was increased from unloaded (0 W) to 60 W under nasal breathing, but not under oral breathing. A negative correlation among subjects was found between NO output and minute ventilation in both breathing methods only for unloaded exercise. Data indicate that nasal airways have a large contribution, at least 50% of total NO output in the exhaled air during nasal breathing, but this nasal NO may have no further modulation on respiratory function during submaximal exercise by healthy humans.

Adolescent↗

Evaluation of passive smoking by measuring urinary trans, trans-muconic acid and exhaled carbon monoxide levels.

No method has yet been established to evaluate the exposure to tobacco smoke in passive smoking (PS). We therefore conducted a study on the possibility that the levels of urinary trans, trans-muconic acid (MA) and the exhaled carbon monoxide (CO) could be indices of the passive exposure to tobacco smoke. The moderate correlation was observed between urinary MA levels and the number of consumed cigarettes per day in smokers. The mean urinary MA level of the PS (+) group was significantly higher than that with the PS (-) group. Among the PS (+) group, the mean MA level in the urine obtained in the afternoon was higher than that obtained in the morning. A high correlation was observed between the exhaled CO levels and the number of consumed cigarettes per day in smokers. Like the urinary MA level, the mean exhaled CO level in the PS (+) group, too, gave a significantly higher level than in the PS (-) group. Because the biological half life of MA (7.5 +/- 0.85 h) was longer than that of CO (3.0 +/- 0.36 h), the measurement of urinary MA level is recommended for evaluating the exposure of passive smoking. The measurement of exhaled CO levels is useful only for chain smokers and nonsmokers with PS just before measurement.

Adult↗

A field method for sampling toluene in end-exhaled air, as a biomarker of occupational exposure: correlation with other exposure indices.

A sensitive and rapid method for the determination of toluene in exhaled air is described. We have developed a device for direct breath sampling consisting of a sampler inserted into an empty 58 mL glass vial closed by a Teflon rubber septum. The sorbent cartridge functions as a diffusive sampler and employs a Tenax resin (300 mg, 35/50 mesh) to trap volatile organic compounds from the exhaled air. End-exhaled air is collected "in field" by removing the septum from the vial, by forcibly exhaling into the device through a suitable Teflon tube, and then by sealing the bottle quickly. Environmental toluene levels ranged from 13 to 191 mg/m3, while the concentrations of the solvent in alveolar air, in blood and urine ranged from 159 to 3354 ng/L, from 3.6 to 53.5 microg/L, and from 8.7 to 142.4 microg/L respectively. The correlation coefficients (r) of biological measurements towards environmental toluene levels were 0.822, 0.850 and 0.846 for alveolar air, blood and urine samples, respectively. The breath sampler allowed the rapid and non-invasive collection of data on elimination of toluene.

Adult↗

A highly sensitive gas chromatographic method does not detect exhalation of volatile hydrocarbons from isolated ventilated lungs under massive peroxidative stress.

Lung lipid peroxidation is thought to be a basic pathophysiological phenomenon responsible for pulmonary damage in different types of oxidant attack. Measurement of volatile hydrocarbons, especially ethane and pentane, produced during peroxidative degradation of polyunsaturated fatty acids and exhaled into an animal housing chamber, has attracted increasing interest for the monitoring of in vivo lipid peroxidation. However, this approach cannot distinguish between pulmonary exhalation of hydrocarbons generated in different organs or even the intestinum and pulmonary generation of these lipid peroxidation markers. In the present study we developed a respiration and hydrocarbon trapping system for isolated, ventilated, and perfused lungs that avoided rebreathing and allowed complete sampling and gas chromatographic separation and quantification of exhaled alkanes and alkenes (C1-C5) in the absence of background levels. Using an "artificial lung," the recoveries of exogenously administered hydrocarbons ranged between 80 and 95% with good reproducibility (SD between 1.7 and 9.6%). The detection limit of the system was approximately 3 fmol of each alkane or alkene/g wet lung weight.min. However, neither under basal conditions nor during massive peroxidative stress by the application of high doses of H2O2, FeCl3/ascorbate, paraquat, or ozone was any material with a retention time similar to that of hydrocarbons exhaled from isolated rabbit lungs. We conclude that under the experimental conditions employed, there is only insignificant generation of hydrocarbons in intact lungs.

Animals↗

Increased nitric oxide in the exhaled air of patients with decompensated liver cirrhosis.

OBJECTIVE: To determine if nitric oxide output in exhaled air is increased in patients with liver cirrhosis. DESIGN: Cross-sectional study. SETTING: A university hospital. PATIENTS: 50 patients with liver cirrhosis, 6 patients with chronic hepatitis, and 15 healthy controls. MEASUREMENTS: Nitric oxide in exhaled air was measured using a chemiluminescence analyzer. Cardiac index was determined using echocardiography. RESULTS: Patients with decompensated liver cirrhosis had higher levels of exhaled nitric oxide output (Child C patients, 190 +/- 11 nL/min per m2 body surface area) than controls (97 +/- 8 nL/min per m2 body surface area; P < 0.001), whereas patients with compensated liver cirrhosis or chronic hepatitis had levels of nitric oxide output similar to those found in controls. Cardiac index was greater in patients with liver cirrhosis (Child C patients, 4.3 +/- 0.3 L/min per m2 body surface area) than in controls (2.9 +/- 0.2 L/min per m2 body surface area; P < 0.001). Cardiac index correlated with nitric oxide levels (r = 0.621; P < 0.001). CONCLUSIONS: Increased nitric oxide output in exhaled air is associated with systemic circulatory disturbances in patients with liver cirrhosis.

Aged↗

Characteristics of flow dependency of nitric oxide in exhaled air in children with cystic fibrosis and asthma.

Nitric oxide (NO) is a free radical produced by the lungs which can easily be measured in exhaled air. NO may serve as a non-invasive marker for airway inflammation in chronic inflammatory diseases like asthma. However in patients with cystic fibrosis (CF) and severe airway involvemen normal or low levels of NO have been reported. To investigate this further we measured NO levels in exhaled air at 5 different flow rates in 14 asthmatics, 15 CF-patients and 13 healthy children. A dependency of exhaled NO on expiratory flow was demonstrated in all three groups. At slow flows lower NO levels in CF-patients and significantly higher levels in asthmatics compared to healthy individuals were found. When the data were fitted to a one compartment model of the lung described by NO(MOUTH) = NO(LUNG) - NO(LUNG) x e(-T/Vex) (T = transfer factor; Vex = expiratory flow), NO(LUNG) was increased in asthmatics (191.9 +/- 53.8 ppb) and low in CF (26.7 +/- 5.7 ppb) compared to healthy individuals (76.9 +/- 50.9 ppb; p(anova) = 0.0213). NO produced in the central compartment of the lung behaved similarly and was distinguished from a peripheral compartment with the two compartment model NO(MOUTH) = NO(central) - (NO(central) - NO(peripher) ) x e(-T/Vex). We conclude that NO in exhaled air is flow dependent and at slow expiratory flows elevated in asthmatics and reduced in CF-patients compared to healthy children. Concentrations extrapolated for the whole lung and for the central airways changed proportionally.

Adolescent↗

Validation of a new technique to assess exhaled hydrogen peroxide: results from normals and COPD patients.

Chronic airways inflammation in chronic obstructive pulmonary disease (COPD) induces the activation of several cell types with delivery of proteases and reactive oxygen species (ROS). Assessing oxidant content in the exhaled air of COPD patients has proven useful in monitoring airway inflammation. The present study was designed to confirm the usefulness of exhaled hydrogen peroxide concentration determination in COPD patients using a new technique which allows longer storage of the expired air condensate before the H2O2 assay. The technique was applied in 13 healthy nonsmoking subjects (six male, age range 22-40 yrs) and in seven patients (five male, age range 58-81 yrs) with mild or moderate COPD. Subjects breathed into a one-valve mouthpiece, and the exhaled air was directed into a vial kept at 0 degree C. After approximately 15 min of quiet breathing, 1 mL of expired air condensate was collected. An aliquot, 450 microL, of this sample was immediately added to an equal volume of a reaction mixture containing 2 mM 3,5,3',5'-tetramethylbenzidine and 40 microL of enzyme stock solution (0.5 mg.mL-1). After 15 min, 45 microL sulphuric acid was added (1 N final concentration), resulting in a reaction mixture pH of 1.0. After a further 10-min incubation, H2O2 concentration determination was performed spectrophotometrically at 450 nm. This solution, as well as the H2O2 assay, was stable for > or = 24 h if the sample was kept in the dark and at 4 degrees C. There was high stability on repeated measures, with a coefficient of variation equal to zero. The mean +/- SD H2O2 level in exhaled air from normal subjects was 0.12 +/- 0.09 microM, whereas it was significantly increased in COPD patients (0.50 +/- 0.11 microM; p = 0.0001 compared to healthy subjects). In three healthy control subjects, a normal H2O2 level in expired air increased to 0.70-0.80 microM during an acute upper respiratory tract infection. This new technique of hydrogen peroxide assay in expired air condensate greatly minimizes the inaccuracy deriving from the instability of hydrogen peroxide. The preliminary results obtained using this technique provide direct evidence for increased reactive oxygen species production in the airways of stable chronic obstructive pulmonary disease patients. However, the specificity of the procedure could be reduced by the interference of upper respiratory tract infections.

Adult↗

[Xenon exhalation measurements in the diagnosis of bladder diseases].

Using an exhalameter radioactive marked Xenon, absorbed following bladder instillation, was determined in the expired air of 111 patients. In 65 of these patients the usual criteria in the diagnosis of bladder diseases were simultaneously ascertained. The functional disturbances of the epithelium of the bladder obtained through 133Xenon exhalation measurements did not correlate with the morphological changes. Especially in the so-called "Reizblase" (irritable bladder) functional disturbances were found without a morphological equivalent. Compared with the low Xenon exhalation found in patients with healthy urinary bladders there is a marked Xenon exhalation increase (10-15 times) in inflammation of the urinary bladder. In our opinion Xenon exhalation measurements is at the present time the most sensitive method for determining inflammatory diseases of the urinary bladder.

Air↗

[Exhaled nitric oxide in healthy and asthmatic children].

OBJECTIVES: One of the main findings in asthma is chronic inflammation of the airway. Exhaled nitric oxide may be a useful marker of airway inflammation in asthmatic children. To evaluate the concentration of nitric oxide (NO) in exhaled air in healthy and asthmatic children and to relate this variable with different treatments. MATERIAL AND METHODS: A cross-sectional study was performed in a tertiary hospital. The concentration of exhaled NO (in parts per billion) was analyzed by chemoluminescence using the T technique of exhaling against expiratory resistance with positive mouthpiece pressure in two different study groups: group A (control group) consisted of 105 healthy children aged 6-14 years old without a history of respiratory disease; group B (asthmatic group) consisted of 79 children aged 6-14 years old diagnosed with asthma and undergoing anti-asthmatic treatment for at least the previous two months, depending on the severity of their disease. Quantitative variables were analyzed using Student's t-test and the relationship between qualitative variables was analyzed using the chi-squared test. RESULTS: Expired NO concentrations were significantly higher in the asthma group (15.02 ppb) than in the control group (5.40 ppb) (p < 0.01). No significant differences were found among the asthmatic children in asthma severity. Expired NO was higher in asthmatic children treated with nedocromil (16.62 ppb) than in those treated with inhaled corticosteroids (11.8 ppb) but this difference was not significant (p 0.08). Children who presented signs of acute asthma (22.87 ppb) and those with a positive bronchial dilatation test (20.65) showed higher expired NO values (p < 0.05) than those without asthmatic crises and/or a negative bronchial dilatation test. Likewise, children with atopic dermatitis showed higher expired NO concentrations (23.07 ppb) than those without atopic dermatitis (11.68 ppb) (p < 0.001). CONCLUSIONS: Children with asthma of various degrees of severity have higher levels of expired NO than do healthy children. Measurement of expired NO concentrations can be used to monitor bronchial inflammation and to evaluate the efficacy of anti-inflammatory treatments.

Adolescent↗

The importance of exhaled air condensate in assessing the oxidant-antioxidant system in patients with chronic obstructive pulmonary disease.

The aim of this study was to investigate the relationship between selected lipid peroxidation products as markers of oxidative stress and antioxidant defense capacity in exhaled air condensate in comparison to blood and COPD severity. We detected that the increase of lipids peroxidation products in exhaled air condensate (less in blood) was accompanied by the reduction of total antioxidant capacity (antiradical activity and ceruloplasmin) according to the severity of COPD. Thus, the level of malondialdehyde significantly increased both in blood and exhaled air condensate in COPD1,2,3 (by 24%, 86%, 100% and 58%, 92%, 2,3 times respectively). Antiradical activity level was significantly decreased both in blood and exhaled air condensate in patients with COPD2,3 by 24%, 51% and 23.31% respectively. The results of this study clearly demonstrated the imbalance in oxidant-antioxidant system in advanced COPD.

Adult↗

Analysis of toluene in exhaled air of glue sniffers and workers using thinner at work place.

Toluene concentrations in exhaled air of workers using thinner at work place and glue sniffers were measured by gas chromatography (GC). Toluene concentrations in exhaled air of workers were significantly lower than those of glue sniffers. This suggests that a worker does not inhale as much thinner as a sniffer and that the analysis of thinner in exhaled air can be an indicator for its inhalation. It is also considered that the analysis of toluene concentration in the exhaled air gives an important clue whether the person inhaled thinner during working or self-abuse.

Adolescent↗

Ethene (ethylene) and ethane exhalation in Ni[II]-treated rats, using an improved rebreathing apparatus.

To assess the effects of NiCl2 on lipid peroxidation, exhalation rates of ethene (ethylene) and ethane were measured in Fischer-344 rats, using modifications of a recently published rebreathing apparatus and gas chromatographic assay. Technical improvements included more efficient removal of H2O vapor, NH3, and CO2, use of economical, readily available components, convenient standardization procedure, and no necessity for a charcoal concentrator accessory for the gas chromatograph. The detection limit was one pmol ethene or ethane per five mL air sample; the within-run precision (CV) of analysis was 2.1 percent at an ethane concentration of 16 pmol per five mL sample. A minimum of eight hours post-injection was necessary for exhalation rates of ethene or ethane to become significantly increased in NiCl2-treated rats. Ethene exhalation rate was increased 2.0- to 3.5-fold at 13 to 16 and 20 to 23 hours after NiCl2 injection (0.50 or 0.75 mmol per kg, body wt, sc). Ethane exhalation rate was increased 1.5- to 1.6-fold at the lower dosage, but was not significantly increased at the higher dosage of NiCl2. This study corroborates previous reports that lipid peroxidation is enhanced in target tissues (liver, kidney, lung) of NiCl2-treated rats.

Animals↗

[Duration of inhalation and exhalation in increasing hypercapnia and the effect of additional resistive inspiratory resistance].

In healthy subjects, patterns of inhalation and exhalation durations during growing hypercapnia were studied in free breathing and under the effect of resistive inspiratory resistance 20 and 35 cm H2O/1/sec. Pattern of the inhalation duration was divided into two ranges: the inhalation elongated in the first range and shortened in the second one. The border between these ranges corresponded in free breathing to CO2 tension of exhalation terminal portion (PETCO2)--47.2 +/- 1.0 mm Hg (M +/- m). The 1st range was found in 2/3 of cases in the exhalation duration pattern. Under the effect of additional inspiratory resistance, the border between the two ranges of inhalation pattern shifted towards greater PETCO2 values and was 51.0 +/- 1.0 mm Hg for the greater resistance. The 1st range was found in 1/3 of cases in the exhalation duration dynamics. The shift of the border between the ranges of the inhalation duration pattern occurring in breathing with a resistive load in the course of growing hypercapnia seems to result from an augmentation of cortical effects upon breathing and/or weakening of afferent influences from the lung stretch receptors under these conditions.

Adolescent↗

Ethane exhalation and vitamin E/ubiquinol status as markers of lipid peroxidation in ferrocene iron-loaded rats.

Organ damage caused by iron overload has been mostly attributed to iron-induced peroxidation of membrane lipids. Using the ferrocene iron-loaded rat model, we studied ethane exhalation as a direct marker of in vivo lipid peroxidation, as well as concentrations of alpha-tocopherol and ubiquinol 9/10 in liver and plasma as indirect markers of this process. The feeding of a diet enriched with 0.5% TMH-ferrocene up to 31 weeks resulted in a large increase in liver iron concentration to about 25 mg/g wet weight (w wt). At lower, predominantly hepatocellular liver siderosis, the breath ethane exhalation was dependent on dietary vitamin E (VitE) supplements (onset of ethane exhalation at liver-Fe > 2 mg/g w wt on vitE-restricted diet; > 5 mg Fe per gram on VitE-replete diet). At severe liver siderosis, breath ethane exhalation reached a maximum of approximately 8 nmol/kg/hr independent of VitE supplementation. Plasma as well as hepatic alpha-tocopherol decreased with progressive iron loading. In addition, a significant depletion in hepatic ubiquinol 9 and 10 was noted.

Animals↗