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Increased carbon monoxide in exhaled air of critically ill patients.

Heme oxygenase produces carbon monoxide (CO) during breakdown of heme molecules primarily in liver and spleen. Recent data suggest that CO is also produced in the lungs. CO is excreted by exhalation via the lungs. A number of inflammatory agents induce the expression of heme oxygenase, possibly leading to increased CO production. To investigate whether critical illness results in increased CO production we measured the CO concentration in exhaled air in 30 critically ill patients and in healthy controls (n = 6). Critically ill patients showed a significantly higher CO concentration in exhaled air (median 2.4 ppm, 95% CI 1.0-7.0 ppm vs median 1.55 ppm, 95% CI 1.2-1.7 ppm, P = 0.01) as well as total CO production (median 20 ml/min, 95% CI 8 to 90 ml/min vs median 13.5 ml/min, 95% CI 11 to 19 ml/min, P = 0.026) compared to healthy controls. No correlation was found between CO concentration in exhaled air and carboxyhemoglobin concentration in arterial and central venous blood (P > 0.05). The increase of CO concentration in exhaled air in critical illness suggests an induction of inducible heme oxygenase (HO-1) and might reflect the severity of illness.

Adult↗

Increased acetone exhalation induced by metabolites of halogenated C1 and C2 compounds.

Rats were exposed, in a closed desiccator jar chamber, to concentrations of various halogenated C1 and C2 compounds at which the metabolizing capacities were saturated (Vmax conditions). Within the exposure period of 50 h concentrations of the xenobiotic and of exhaled acetone were monitored in the gas phase of the system. The quantitative extent of acetone exhalation was dependent on the individual compound examined. Acetone exhalation was stimulated in presence of vinyl chloride, vinyl bromide, vinyl fluoride, vinylidene fluoride, cis- and trans-1,2-dichloroethylene, trichloroethylene, perchloroethylene, methylene chloride, chloroform, carbon tetrachloride and 1,1,2-trichloroethane. No stimulation of acetone exhalation occurred with 1,1,1-trichloroethane and with the reference hydrocarbon n-hexane. Also, acetone exhalation was evoked by infusions of either fluoroacetate or chloroacetate, two anticipated or proven metabolites of some haloethylenes; the infusion rates of which were based on calculations of the metabolic rates of vinylidene fluoride and of vinyl chloride, respectively.

Acetone↗

Tetrachloroethene in exhaled air of persons living near pollution sources.

Exhaled air was analyzed for tetrachloroethene (PER) in teachers and 4-5-year-old pupils of a kindergarten situated near a factory, and in residents of an old folks ' home situated near a former chemical waste dump. The PER concentrations were higher in the exhaled air of children living near the factory (mean 24 micrograms/m3, n = 6) than in control children (mean 2.8 micrograms/m3, n = 11). In the old folks ' home, the PER concentrations in the exhaled air of people living on the first floor were higher (mean 7.8 micrograms/m3, n = 10) than in the exhaled air of the people living on the second floor and higher (mean 1.8 micrograms/m3, n = 19). From the results of this study, it is clear that in environmental exposure to tetrachloroethene, biological monitoring of exhaled air is a simple, efficient, effective and convenient method of assessing total ambient exposure of both young and aged subjects.

Aged↗

Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model.

Oxygen radicals play a key role in inflammation and inflammatory tissue damage. Quantitative determination of pentane, a hydrocarbon generated by membrane lipid peroxidation initiated by oxygen radicals, in expired air has been used as a noninvasive determinant or index of inflammation in various conditions. Herein we report the first examination of the relationship between exhaled pentane and colonic inflammation in a rodent model of colitis. Colitis was induced in rats (n = 33) using the trinitrobenzene-sulfonic acid (TNB) model of colitis. Exhaled air was collected in a closed chamber on randomly selected animals on days 1, 2, 4, 7, 11, 13, 15, 20, and 25 post-TNB treatment, and pentane was assayed by means of gas chromatography. Gross and microscopic evidence of inflammation was compared with exhaled pentane levels. Pentane levels varied from 0.0 to 14.6 nmol/l of air and were significantly increased in TNB-treated rats compared with control rats only on days 7 to 15 after treatment (P < 0.05). Gross inspection showed severe colonic inflammation through the first week (mean score = 4.7 out of a possible 5), persistent inflammation on days 7 to 15 (3.2), and healing and fibrosis from the end of week two until day 25 (1.9 to 0). Histologic evaluation confirmed a progression of inflammation from acute ulceration to chronic inflammation to fibrosis and scarring. We have demonstrated that pentane exhalation is increased after the induction of colonic inflammation, with a seven-day lag time, and returns rapidly to normal as acute inflammation resolves. This suggests that pentane exhalation can be used as a noninvasive measure of colonic inflammation in rodent models of colitis and perhaps clinically in humans.

Air↗

Flow-volume curves as measurement of respiratory mechanics during ventilatory support: the effect of the exhalation valve.

OBJECTIVE: To assess the feasibility of expiratory flow-volume curves as a measurement of respiratory mechanics during ventilatory support: to what extent is the shape of the curve affected by the exhalation valve of the ventilator? DESIGN: Prospective, comparative study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 28 consecutive patients with various conditions, mechanically ventilated with both the Siemens Servo 900C and 300 ventilators, were studied under sedation and paralysis. INTERVENTIONS: The ventilator circuit was intermittently disconnected from the ventilator at end-inspiration in order to obtain flow-volume curves with and without the exhalation valve in place. MEASUREMENTS AND RESULTS: Peak flow (PEF) and the slope of the flow-volume curve during the last 50 % of expired volume (SF50) were obtained both with and without the exhalation valve in place. The exhalation valve caused a significant reduction in peak flow of 0.3 l/s (from 1.27 to 0.97 l/s) with the Siemens Servo 900 C ventilator and of 0.42 l/s (from 1.36 to 0.94 l/s) with the Siemens Servo 300 ventilator (p < 0.001). The SF50 was not affected. CONCLUSION: In mechanically ventilated patients, the exhalation valve causes a significant reduction in peak flow, but does not affect the SF50. This study further suggests that the second part of the expiratory flow-volume curve can be used to estimate patients' respiratory mechanics during ventilatory support.

APACHE↗

The stimulation and inhibition of the exhalation of volatile selenium.

Administration of methylmercury (1.5-24 mumol kg-1; s.c.) to female rats simultaneously with Na2 75SO3 (0.25 or 24 mumol kg-1; s.c.) causes a dose-dependent increase in the exhalation of dimethylselenide. At the low selenite dose level, exhalation of 75Se over a 24 hr period is about fourfold greater after treatment with 24 mumol kg-1 methylmercury than that (approximately 0.75% of the dose) in the controls, but excretion by other routes (urine, faeces) and the liver and kidney contents of 75Se are not affected significantly. At the higher selenite dose level (24 mumol kg-1) exhalation of 75Se is correlated with the log dose of methylmercury. The faecal and urinary excretion remains essentially unaffected, and in rats treated with 24 mumol kg-1 methylmercury the 75Se contents of the liver, kidneys and blood are reduced by 78%, 86% and 18% respectively. The effects of the alkylmercurial are not specific since, at this selenite dose level, ethylmercury increases the exhalation and decreases the liver and kidney contents of 75Se approximately to the same extent as an equimolar dose of methylmercury. In methylmercury-treated and control animals dosed with 24 mumol kg-1 Na 75SeO3 the exhalation of 75Se is inhibited to the same extent by periodate-oxidized adenosine (PAD; 15 mumol kg-1, i.p.) in the first 6 hr. Later inhibition is less pronounced in methylmercury-treated rats. Under these conditions PAD has little effect on the renal content, but increases the hepatic content of 75Se. It seems, therefore, that the methylation of selenite occurs mainly in the liver and in both control and methylmercury-treated animals, S-adenosylmethionine is the major methyl donor. It is possible that methylmercury does not affect directly the methylation enzyme system but, by competition for protein sulphydryl groups, increases the availability of the intermediary selenide anion.

Animals↗

The effects of treatment with selenite before and after the administration of [75Se]selenite on the exhalation of [75Se]dimethylselenide.

The exhalation of dimethylselenium, as indicated by the respiratory loss of 75Se from injected Na75SeO3, depends not only on the dose, but also on previous exposure. Three days pretreatment with 1.2 mumol/100 g unlabelled selenite increased exhalation of 75Se from 0.1 or 1.2 mumol/100 g Na2 75SeO3 and decreased the retention of 75Se in blood and liver from the higher dose. Similarly the injection of 1.2 mumol/100 g unlabelled selenite 24 h after the last of 3 daily doses of 1.2 mumol/100 g labelled selenite increased the exhalation of 75Se in the following 24 h period. Thus, pre-exposure to selenium increased the exhalation of 75Se by making a higher proportion of the newly injected dose accessible for methylation. The exhaled dimethylselenide, however, is not derived solely from the injected dose, since in pretreated animals, it is possible to demonstrate exchange between injected and deposited selenium.

Animals↗

The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma.

The Aerocrine exhaled nitric oxide (NO) monitoring system NIOX was cleared by the US Food and Drug Administration for clinical application in patients with asthma in May 2003. The fractional concentration of exhaled NO has been extensively researched as a marker of airway inflammation in asthma and other diseases and is now poised to enter clinical application. The American Thoracic and European Respiratory Societies' current guidelines recommend measurement at constant expiratory flow, which is difficult for some adults and children. The NIOX NO monitoring system was designed to facilitate standardized measurement according to guidelines. A clinical study was performed together with in vitro testing to obtain clearance. Exhaled NO levels were measured in unstable steroid-naive adult and pediatric asthmatic subjects and again after a 2-week treatment with inhaled corticosteroids. Exhaled NO levels decreased highly significantly, with 95% confidence limits for the decrease of -40% to -60% accompanied by clinical improvement. This trial, together with extensive in vitro testing, led to the clearance of NIOX by the US Food and Drug Administration. This article in the journal's "New products" feature section will describe background material regarding exhaled NO, special features of the NIOX NO monitoring system, and how this tool can be incorporated into clinical asthma management.

Adolescent↗

Exhaled CO, a predictor of lung function?

BACKGROUND: Smoking is associated with an accelerated loss of lung function and inhalation accelerates the decline further. Exhaled CO reflects the exposure of smoke to the lungs. AIM: To investigate whether self-reported inhalation and type of cigarette influenced the level of exhaled CO and whether CO could provide additional information to usual measures of smoking regarding prediction of present lung function and decline in lung function over an extended period of time. METHOD: Cigarette smokers from the Copenhagen City Heart Study with valid measures of lung function and exhaled CO; in total 3738 subjects, 2096 women and 1642 men. RESULTS: Subjects not inhaling had slightly lower exhaled CO values than those inhaling, but substantially higher values than non-smokers (P<0.001). Smokers of plain cigarettes had slightly lower CO values than smokers of filter cigarettes (P<0.001). Increasing CO levels were correlated to a lower FEV(1)%pred and to an accelerated decline in lung function. However, in multiple linear regression analyses these correlations were not significant. CONCLUSION: Inhalation and type of cigarette affects exhaled CO levels. CO measures have no predictive value regarding neither present lung function nor decline in lung function with time in a population survey setting.

Adult↗

Decreased exhaled nitric oxide may be a marker of cardiopulmonary bypass-induced injury.

BACKGROUND: Nitric oxide is an endothelium-derived vasodilator. Cardiopulmonary bypass may induce transient pulmonary endothelial dysfunction with decreased nitric oxide release that contributes to postoperative pulmonary hypertension and lung injury. Exhaled nitric oxide levels may reflect, in part, endogenous production from the pulmonary vascular endothelium. METHODS: We measured exhaled nitric oxide levels before and 30 minutes after cardiopulmonary bypass in 30 children with acyanotic congenital heart disease and left-to-right intracardiac shunts undergoing repair. RESULTS: Exhaled nitric oxide levels decreased by 27.6%+/-5.6% from 7+/-0.8 to 4.4+/-0.5 ppb (p < 0.05) 30 minutes after cardiopulmonary bypass despite a reduction in hemoglobin concentration. CONCLUSIONS: The decrease in exhaled nitric oxide levels suggests reduced nitric oxide synthesis as a result of pulmonary vascular endothelial or lung epithelial injury. This may explain the efficacy of inhaled nitric oxide in the treatment of postoperative pulmonary hypertension. Furthermore, strategies aimed at minimizing endothelial dysfunction and augmenting nitric oxide production during cardiopulmonary bypass may decrease the incidence of postoperative pulmonary hypertension. Exhaled nitric oxide levels may be useful to monitor both cardiopulmonary bypass-induced endothelial injury and the effect of strategies aimed at minimizing such injury.

Biomarkers↗

Application of solid-phase microextraction and gas chromatography-mass spectrometry to the determination of volatile organic compounds in end-exhaled breath samples.

Analysis of exhaled air is of particular interest as an indicator of health as well as a tool for the diagnosis of diseases. It is also a very attractive procedure for the biological control of the exposition to hazardous solvents. This kind of analysis presents numerous advantages over other methods, the most important being that it is not an invasive procedure and, therefore, it is well accepted and can be applied to a wide range of compounds. Furthermore, the analysis is simplified since the matrix is less complex that in the case of blood or urine. In spite of these obvious advantages and the good results obtained, analysis of exhaled air is not in daily use, probably due to the fact that there are no normalized systems of sampling, thus making the interpretation of the results difficult. In this paper, a method for the determination of tetrachloroethylene in exhaled air using solid-phase microextraction is presented. This method, which can be applied to other volatile organic compounds, was developed with special emphasis of end-exhaled breath sampling. The sample is collected in a glass tube whose ends are closed once the exhalation is finished. The tube has an orifice sealed with a septum through which the fiber is inserted. Then, the fiber is desorbed in the injector of a gas chromatograph and the analysis is accomplished using mass spectrometry for the identification and quantification of the components. The proposed system avoids the need of complex sampling equipment and allows analysis of the alveolar fraction. Additionally, the system is economical and easy to handle, thus facilitating the development of normalized methods and its routine use in field studies.

Breath Tests↗

Increased nitric oxide in exhaled air of asthmatic patients.

Nitric oxide (NO) gas is produced by various cells within the lower respiratory tract, including inflammatory and epithelial cells, and is detectable in the exhaled air of normal human subjects. We have measured exhaled NO in patients with asthma, since several cell types that are activated in asthma can produce NO after induction. NO was measured reproducibly by a slow vital capacity manoeuvre and an adapted chemiluminescence analyser. NO was detectable in exhaled air of 67 control subjects (mean peak concentration 80.2 [SE 4.1] ppb) and was significantly reduced by inhalation of the specific NO synthase inhibitor NG-monomethyl-L-arginine. 61 non-steroid-treated asthmatic subjects had significantly higher peak expired NO concentrations than controls (283 [16] ppb, p < 0.001) but 52 asthmatic patients receiving inhaled corticosteroids had levels similar to controls (101 [7] ppb). High exhaled NO concentrations in asthmatic patients may reflect induction of NO synthase, which is known to be inhibited by steroids. Measurement of exhaled NO concentrations may be clinically useful in detection and management of cytokine-mediated inflammatory lung disorders.

Adrenal Cortex Hormones↗

Radon exhalation rate and uranium estimation in rock samples from Bihar uranium and copper mines using the SSNTD technique.

Widespread uranium mineralization is associated with copper, nickel and other sulphides in the Singhbhum shear zone developed at the northern margin of the Singhbhum craton in the state of Bihar of India. The south-eastern part of the shear zone between Surda-Mosabani-Badia is rich in copper mineralization while the central part between Jaduguda-Bhatin-Nimdih and Narwapahar-Garadih-Turamdih is enriched in uranium. In the present study, trace uranium concentration in geological samples from the Mosabani copper mine and the Narwapahar and Jaduguda uranium mine areas have been determined using fission track registration technique. For the measurement of the radon exhalation rate, the 'can technique' using alpha sensitive LR-115 type II plastic track detectors were used. Uranium concentrations were found to vary from 1.5 to 2097.9 ppm whereas the radon exhalation rate varied from 0.2 to 19.2 Bq m-2 h-1. The values of radon exhalation rate from crushed rock and soil samples are found to correspond with the measured values of uranium in the corresponding samples. A positive correlation has been found between radon exhalation rate and uranium concentration in the samples. The linear coefficients are found to be 0.40, 0.98 and 0.95 in the Mosabani, Narwapahar and Jaduguda mine areas respectively. High values of radon exhalation in subsurface mines like Jaduguda (depth approximately 800 m) and Mosabani (depth > 1000 m) seem to emphasize the need for adequate ventilation for the removal of radon and its progenies from the mines.

Copper↗

Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection.

BACKGROUND: Obliterative bronchiolitis (OB) remains one of the leading causes of death in lung transplant recipients after 2 years, and acute rejection (AR) of lung allograft is a major risk factor for OB. Treatment of AR may reduce the incidence of OB, although diagnosis of AR often requires bronchoscopic lung biopsy. In this study, we evaluated the utility of exhaled-breath biomarkers for the non-invasive diagnosis of AR. METHODS: We obtained breath samples from 44 consecutive lung transplant recipients who attended ambulatory follow-up visits for the Johns Hopkins Lung Transplant Program. Bronchoscopy within 7 days of their breath samples showed histopathology in 21 of these patients, and we included them in our analysis. We measured hydrocarbon markers of pro-oxidant events (ethane and 1-pentane), isoprene, acetone, and sulfur-containing compounds (hydrogen sulfide and carbonyl sulfide) in exhaled breath and compared their levels to the lung histopathology, graded as stable (non-rejection) or AR. None of the study subjects were diagnosed with OB or infection at the time of the clinical bronchoscopy. RESULTS: We found no significant difference in exhaled levels of hydrocarbons, acetone, or hydrogen sulfide between the stable and AR groups. However, we did find significant increase in exhaled carbonyl sulfide (COS) levels in AR subjects compared with stable subjects. We also observed a trend in 7 of 8 patients who had serial sets of breath and histopathology data that supported a role for COS as a breath biomarker of AR. CONCLUSIONS: This study demonstrated elevations in exhaled COS levels in subjects with AR compared with stable subjects, suggesting a diagnostic role for this non-invasive biomarker. Further exploration of breath analysis in lung transplant recipients is warranted to complement fiberoptic bronchoscopy and obviate the need for this procedure in some patients.

Acetone↗

Level of exhaled nitric oxide during human anaphylaxis.

BACKGROUND: Nitric oxide (NO) seems to play an important pathophysiologic role in modulating the systemic changes associated with anaphylaxis. Even if some effects of NO may be protective, animal models of anaphylaxis have shown that the summation effects of NO are deleterious, resulting in hypotension and loss of intravascular volume. There are no studies of NO production during anaphylaxis in humans. OBJECTIVE: To measure the level of exhaled NO during anaphylaxis induced by bee venom cluster immunotherapy in a 34-year-old beekeeper. METHODS: Exhaled NO was measured using a chemiluminescence analyzer at different flow rates, and alveolar NO concentration and airway NO production were calculated. RESULTS: We measured a high level of exhaled NO (78 ppb at 50 mL/s, with increased alveolar concentration and airway production) during anaphylaxis induced by bee venom immunotherapy in this patient. Normal values of exhaled NO were measured in the same patient 1 week later before and after a modified regimen of desensitization. CONCLUSIONS: Nitric oxide production was increased in the respiratory tract during anaphylaxis. Having excluded all the common causes of increased exhaled NO levels, these resultssupport the hypothesis that NO plays an important role in anaphylaxis.

Adult↗

Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma.

Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations. Twenty-two atopic children (aged 11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2-adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per billion (ppb) and 4.0+/-0.5 ppb, respectively; p<0.01). Interestingly, 14 out of 22 asthmatic children had NO levels >8.8 ppb (i.e. >2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p<0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p>0.1, each correlation). These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established.

Adolescent↗

Increased exhaled nitric oxide on days with high outdoor air pollution is of endogenous origin.

The aim of this study was to assess the effect of outdoor air pollution on exhaled levels of endogenously released nitric oxide. To exclude bias from exogenous NO in the recovered exhaled air (residual NO or NO in dead volume) an experimental design was used that sampled NO of endogenous origin only. The validity of the presented experimental design was established in experiments where subjects were exposed to high levels of exogenous NO (cigarette smoke or 480 microg x m(-3) synthetic NO). Subsequent 1 min breathing and a final inhalation of NO-free air proved to be sufficient to attain pre-exposure values. Using the presented method detecting only endogenous NO in exhaled air, 18 subjects were sampled on 4 separate days with different levels of outdoor air pollution (read as an ambient NO level of 4, 30, 138 and 246 microg x m(-3)). On the 2 days with highest outdoor air pollution, exhaled NO was significantly (p<0.001) increased (67-78%) above the mean baseline value assessed on 4 days with virtually no outdoor air pollution. In conclusion, the level of endogenous nitric oxide in exhaled air is increased on days with high outdoor air pollution. The physiological implications of this findings need to be investigated further.

Adult↗

Influence of atopy on exhaled nitric oxide in patients with stable asthma and rhinitis.

The level of exhaled NO is increased in patients with allergic asthma and seasonal rhinitis. The aim of this study was to investigate the significance of atopy on NO production in the lower airways. Measurements of exhaled NO were performed in 131 stable asthmatic patients with chronic mild asthma (95 atopics and 36 nonatopics), 72 patients with perennial rhinitis (57 atopics and 15 nonatopics) and 100 healthy controls (20 atopics and 80 non-atopics). Patients with either asthma or rhinitis had higher exhaled NO values (13.3+/-1.2 parts per billion (ppb) and 11.7+/-1.1 ppb) than control subjects (4.8+/-0.3 ppb, p<0.01). Exhaled NO levels were significantly higher in atopic asthmatics (19+/-3.6 ppb) compared with nonatopic patients (5.6+/-0.8 ppb, p<0.001). Similar findings were observed in patients with rhinitis (13.3+/-1.3 ppb in atopics and 5.8+/-1.2 ppb in nonatopics, p<0.001). No difference was found in NO levels between atopic and nonatopic control subjects (4.8+/-0.8 ppb, and 4.5+/-0.3 ppb). In summary, this study has shown that increased exhaled NO levels are detected only in atopic patients with asthma and/or rhinitis and not in nonatopic patients. These findings may suggest that it is rather the allergic nature of airways inflammation, which is mainly responsible for the higher NO production in the lower airways.

Adult↗