Effects of ventilation on the collection of exhaled breath in humans.

A computerized system has been developed to monitor tidal volume, respiration rate, mouth pressure, and carbon dioxide during breath collection. This system was used to investigate variability in the production of breath biomarkers over an 8-h period. Hyperventilation occurred when breath was collected from spontaneously breathing study subjects (n = 8). Therefore, breath samples were collected from study subjects whose breathing were paced at a respiration rate of 10 breaths/min and whose tidal volumes were gauged according to body mass. In this "paced breathing" group (n = 16), end-tidal concentrations of isoprene and ethane correlated with end-tidal carbon dioxide levels [Spearman's rank correlation test (r(s)) = 0.64, P = 0.008 and r(s) = 0.50, P = 0.05, respectively]. Ethane also correlated with heart rate (r(s) = 0.52, P < 0.05). There was an inverse correlation between transcutaneous pulse oximetry and exhaled carbon monoxide (r(s) = -0.64, P = 0.008). Significant differences were identified between men (n = 8) and women (n = 8) in the concentrations of carbon monoxide (4 parts per million in men vs. 3 parts per million in women; P = 0.01) and volatile sulfur-containing compounds (134 parts per billion in men vs. 95 parts per billion in women; P = 0.016). There was a peak in ethanol concentration directly after food consumption and a significant decrease in ethanol concentration 2 h later (P = 0.01; n = 16). Sulfur-containing molecules increased linearly throughout the study period (beta = 7.4, P < 0.003). Ventilation patterns strongly influence quantification of volatile analytes in exhaled breath and thus, accordingly, the breathing pattern should be controlled to ensure representative analyses.     

Improvement in symptoms and pulmonary function of asthmatic patients due to their treatment according to the Global Strategy for Asthma Management (GINA)

Background

Endothelin-1 (ET-1) and Nitric Oxide (NO) are crucial mediators for establishing pulmonary artery hypertension (PAH). We tested the hypothesis that their imbalance might also occur in COPD patients with PAH.

Methods

The aims of the study were to measure exhaled breath condensate (EBC) and circulating levels of ET-1, as well as exhaled NO (FENO) levels by, respectively, a specific enzyme immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD with PAH (12), COPD only (36), and healthy individuals (15). In order to evaluate pulmonary-artery systolic pressure (PaPs), all COPD patients underwent Echo-Doppler assessment.

Results

Significantly increased exhaled and circulating levels of ET-1 were found in COPD with PAH compared to both COPD (p < 0.0001) only, and healthy controls (p < 0.0001). In COPD with PAH, linear regression analysis showed good correlation between ET-1 in EBC and PaPs (r = 0.621; p = 0.031), and between arterial levels of ET-1 and PaPs (r = 0.648; p = 0.022), while arterial levels of ET-1 inversely correlated with FEV₁%, (r = -0.59, p = 0.043), and PaPs negatively correlated to PaO₂ (r = -0.618; p = 0.032). Significantly reduced levels of FENO were found in COPD associated with PAH, compared to COPD only (22.92 ± 11.38 vs.35.07 ± 17.53 ppb; p = 0.03). Thus, we observed an imbalanced output in the breath between ET-1 and NO, as expression of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to COPD only. Whether this imbalance is an early cause or result of PAH due to COPD is still unknown and deserves further investigations.     

Nitric oxide in the breath of bottlenose dolphins: Effects of breath hold duration,feeding, and lung disease

Breath analysis, including measurement of nitric oxide (NO), is a noninvasive diagnostic tool that may help evaluate cetacean health. This is the first report on the effects of breath hold duration, feeding, and lung disease on NO in dolphin exhaled breath. Three healthy dolphins were trained to hold their breath for 30, 60, 90, and 120 s and then exhale into an underwater funnel. Exhaled NO values from 157 breath samples were compared among three healthy dolphins by breath hold time and after fasting and feeding. Exhaled NO values were also measured in two dolphins with pulmonary disease. NO in dolphin breath was higher compared to ambient air; healthy dolphins had higher NO concentrations in their breath after feeding compared to after overnight fasting; and there were no significant differences in exhaled NO levels by breath hold duration. A dolphin with Mycoplasma‐associated pneumonia and chronic gastrointestinal disease had higher postprandial exhaled NO levels compared to healthy controls. This study demonstrates, contrary to previous publications, that dolphins exhale NO. Given the high standard deviations present in exhaled breath NO values, future studies are needed to further standardize collection methods or identify more reliable samples (e.g., blood).     

Mixed exhaled nitric oxide and plasma nitrites and nitrates in newborn infants.

Plasma nitrite (NO2-) and nitrate (NO3-) are the stable end-products of endogenous nitric oxide (NO) metabolism. NO is present in the exhaled air of humans, but it is not clear if exhaled NO may be an indicator of the systemic endogenous NO production. The aims of the study were to determine the levels of exhaled NO and plasma NO2-/NO3- in healthy term and preterm newborns, and to assess if exhaled NO correlates with plasma NO2-/NO3- at birth. After the stabilization of the newborn, we measured by chemiluminescence the concentration of NO in the mixed expired breath of 133 healthy newborns. Measurement of exhaled NO was repeated after 24 and 48 hours. Plasma NO2-/NO3- levels at birth were measured by the Griess reaction. NO concentrations were 8.9 (CI 8.1-9.8) parts per billion (ppb), 7.7 (CI 7.2-8.3) ppb and 9.0 (CI 8.4-9.6) ppb at birth, 24 and 48 hours, respectively. At birth, exhaled NO was inversely correlated with gestational age (p=0.008) and birth weight (p<0.001). Plasma NO2-/NO3- level was 27.30 (CI 24.26-30.34) micromol/L. There was no correlation between exhaled NO and plasma NO2-/NO3- levels at birth (p=0.88). We speculate that the inverse correlation between exhaled NO and gestational age and birth weight may reflect a role of NO in the postnatal adaptation of pulmonary circulation. At birth, exhaled NO does not correlate with plasma NO2-/NO3- and does not seem to be an index of the systemic endogenous NO production.     

Exhaled breath condensate as matrix for toluene detection: A preliminary study

The study was designed to investigate whether exhaled breath condensate, obtained by cooling exhaled air in spontaneous breathing, could be a suitable matrix for toluene quantitative analyses. Nine healthy subjects were exposed for a short period (20 min) to a known concentration of toluene. Exhaled breath condensate samples were collected before and at the end of the exposure, while the environmental concentration of toluene was continuously monitored. Toluene was analysed by head-space gas-chromatography mass spectrometry, and assay repeatability was also estimated in vitro. Baseline and post-exposure measurement of hippuric acid, the urinary toluene metabolite, was performed to assess current toluene exposure. Before the exposure toluene concentrations in the exhaled breath condensate were lower than the detectable limit in all subjects, while after the exposure toluene was detectable with a median value 0.35 µg l^-1 (range 0.15-0.55 µg l^-1) in all the exhaled breath condensate samples. As compared with the standard calibration in distilled water, the curves obtained by exhaled breath condensate were linear and comparable with the range examined in vivo for toluene. A significant correlation was found between the environmental toluene levels and toluene in the exhaled breath condensate at the end of exposure. Furthermore, a significant relationship between increased exhaled breath condensate toluene levels and urinary hippuric acid after the exposure was found. In conclusion, exhaled breath condensate is a promising matrix for toluene assessment, although its application in humans requires further investigations.     

Exhaled breath condensate as matrix for toluene detection: A preliminary study

Abstract

The study was designed to investigate whether exhaled breath condensate, obtained by cooling exhaled air in spontaneous breathing, could be a suitable matrix for toluene quantitative analyses. Nine healthy subjects were exposed for a short period (20 min) to a known concentration of toluene. Exhaled breath condensate samples were collected before and at the end of the exposure, while the environmental concentration of toluene was continuously monitored. Toluene was analysed by head-space gas-chromatography mass spectrometry, and assay repeatability was also estimated in vitro. Baseline and post-exposure measurement of hippuric acid, the urinary toluene metabolite, was performed to assess current toluene exposure. Before the exposure toluene concentrations in the exhaled breath condensate were lower than the detectable limit in all subjects, while after the exposure toluene was detectable with a median value 0.35 µg l^?1 (range 0.15–0.55 µg l^?1) in all the exhaled breath condensate samples. As compared with the standard calibration in distilled water, the curves obtained by exhaled breath condensate were linear and comparable with the range examined in vivo for toluene. A significant correlation was found between the environmental toluene levels and toluene in the exhaled breath condensate at the end of exposure. Furthermore, a significant relationship between increased exhaled breath condensate toluene levels and urinary hippuric acid after the exposure was found. In conclusion, exhaled breath condensate is a promising matrix for toluene assessment, although its application in humans requires further investigations.     

Nitric oxide metabolites level in human serum in acute normobaric hypoxia

The influence of acute normobaric hypoxia on NO metabolites level of the blood serum in volunteers at respiration of hypoxic gas mixture containing 8 % of O2 during 25 min was investigated. Health status of participants and the hypoxia intensity were monitored with a complex of indexes: EEC, ECG, blood pressure, oxygen saturation of haemoglobin, cardiac output, gas composition of exhaled air. Cluster analysis (k-means clustering) conducted among volunteers that have successfully passed the test has shown presence of two groups differing in NO metabolites level during experiment. Statistically significant differences on NO metabolites level between groups were observed before hypoxia exposure, on 10th minute of acute hypoxia (maximum difference) and on 5th minute of recovery. Differences on NO metabolites level between groups have been caused by changes in nitrates concentration whereas nitrites level did not differ. The least NO and nitrates levels have been revealed in volunteers that have been in volunteers that had interrupted performance of the test after 10 minutes of respiration of hypoxic gas mixture. Thus the moderate increase of NO metabolites level due to accumulation of nitrates at acute hypoxia testifies to good adaptive reserves of system of nitric oxide generation in organism.     

Ginseng reduces the micronuclei yield in lymphocytes after irradiation

To assess the effect of Chinese ginseng in modifying the radiation-induced micronuclei (MN) yield in human G(o) peripheral blood lymphocytes (PBL), we conducted the cytokinesis-blocked (CB) MN assay in blood samples obtained from healthy volunteers (n=4). Before (137)Cs ex vivo irradiation, mononuclear cell cultures from each sample were incubated 24 h with different concentrations (0-2000 microg ml(-1)) of crude water extract of ginseng dry root. We found that (1) at 0 Gy and without the presence of ginseng, MN yield (mean+/-S.E.M.) was 11.7+/-2.7 per 1000 binucleated (BN) cells. Different concentrations of ginseng crude water extract did not affect the MN yields and the proliferative activity of PBL; (2) after 1 and 2 Gy exposure, radiation alone sharply increased the MN yields, respectively, to 119.6+/-17.4 and 340.5+/-20.9 per 1000 BN cells. However, treatment with ginseng for 24 h before radiation exposure, resulted in a significant linear decline of MN yields as ginseng concentration increases. Compared to radiation alone, the extent to which ginseng water extract reduced the MN yields induced by 1 Gy exposure was 46.0% at 1500 microg ml(-1) and 61.5% at 2000 microg ml(-1), and with 2 Gy exposure, it was 38.6% at 1500 microg ml(-1) and 46.5% at 2000 microg ml(-1); (3) MN data suggested a tendency for overdispersion relative to the Poisson model; and (4) over the different levels of ginseng concentrations, the trend in micronucleated BN index was as similar as that of the MN yields. These results indicated that (1) ginseng crude water extract exerts no apparent cytogentic effect on human PBL at concentrations up to 2000 microg ml(-1) as evaluated by the CBMN assay; and (2) the protection of ginseng water extract against (137)Cs-induced MN in human PBL is concentration-dependence. Therefore, our findings indicated that ginseng may have therapeutic value as a possible radioprotector for normal tissue during radiotherapy of cancer patients.     

Biomarkers of some pulmonary diseases in exhaled breath

Analysis of various biomarkers in exhaled breath allows completely non-invasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis and interstitial lung diseases. The technique is simple to perform, may be repeated frequently, and can be applied to children, including neonates, and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, ammonia), and many non-volatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate. Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the monitoring of therapy. Most progress has been made with exhaled nitric oxide (NO), which is increased in atopic asthma, is correlated with other inflammatory indices and is reduced by treatment with corticosteroids and antileukotrienes, but not (β₂-agonists. In contrast, exhaled NO is normal in COPD, reduced in CF and diagnostically low in primary ciliary dyskinesia. Exhaled carbon monoxide (CO) is increased in asthma, COPD and CF. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite and 3-nitrotyrosine are found in exhaled breath condensate in inflammatory lung diseases. Furthermore, increased levels of lipid mediators are found in these diseases, with a differential pattern depending on the nature of the disease process. In the future it is likely that smaller and more sensitive analysers will extend the discriminatory value of exhaled breath analysis and that these techniques may be available to diagnose and monitor respiratory diseases in the general practice and home setting.     

人的粪便、血浆、唾液、呼出气体中短链脂肪酸的分析

目的建立一种顶空气相色谱-串联质谱法(HS-GC/MS)快速检测人的粪便、血浆、唾液、呼出气体中短链脂肪酸(SCFAs)的方法,初步探索人的粪便、血浆、唾液、呼出气体中短链脂肪酸的相关性。方法样品无需处理直接封存于顶空进样瓶中,顶空进样;采用DB-FFAP毛细管柱(30 m×0.25 mm×0.25μm)分离;全扫描模式检测。结果人的粪便、血浆、唾液、呼出气体中均含有短链脂肪酸。在人的粪便、唾液样本中均检测到8个短链脂肪酸(乙酸、丙酸、异丁酸、丁酸、异戊酸、戊酸、异己酸、己酸);血浆、呼出气体样本中均检测到7个短链脂肪酸(未检测到异己酸)。结论初步推测人的粪便、血浆、唾液、呼出气体中的短链脂肪酸具有一定的相关性。本方法简单、快速、灵敏,可用于人的生物样品中短链脂肪酸的快速检测。     

Collecting Protein Biomarkers in Breath Using Electret Filters: A Preliminary Method on New Technical Model and Human Study

Biomarkers in exhaled breath are useful for respiratory disease diagnosis in human volunteers. Conventional methods that collect non-volatile biomarkers, however, necessitate an extensive dilution and sanitation processes that lowers collection efficiencies and convenience of use. Electret filter emerged in recent decade to collect virus biomarkers in exhaled breath given its simplicity and effectiveness. To investigate the capability of electret filters to collect protein biomarkers, a model that consists of an atomizer that produces protein aerosol and an electret filter that collects albumin and carcinoembryonic antigen-a typical biomarker in lung cancer development- from the atomizer is developed. A device using electret filter as the collecting medium is designed to collect human albumin from exhaled breath of 6 volunteers. Comparison of the collecting ability between the electret filter method and other 2 reported methods is finally performed based on the amounts of albumin collected from human exhaled breath. In conclusion, a decreasing collection efficiency ranging from 17.6% to 2.3% for atomized albumin aerosol and 42% to 12.5% for atomized carcinoembryonic antigen particles is found; moreover, an optimum volume of sampling human exhaled breath ranging from 100 L to 200 L is also observed; finally, the self-designed collecting device shows a significantly better performance in collecting albumin from human exhaled breath than the exhaled breath condensate method (p<0.05) but is not significantly more effective than reported 3-stage impactor method (p>0.05). In summary, electret filters are potential in collecting non-volatile biomarkers in human exhaled breath not only because it was simpler, cheaper and easier to use than traditional methods but also for its better collecting performance.     

Low levels of nitric oxide and carbon monoxide in alpha 1-antitrypsin deficiency.

Quantitations of exhaled nitric oxide (NO) and carbon monoxide (CO) have been proposed as noninvasive markers of airway inflammation. We hypothesized that exhaled CO is increased in individuals with alpha(1)-antitrypsin (AT) deficiency, who have lung inflammation and injury related to oxidative and proteolytic processes. Nineteen individuals with alpha(1)-AT deficiency, 22 healthy controls, and 12 patients with non-alpha(1)-AT-deficient chronic obstructive pulmonary disease (COPD) had NO, CO, CO(2), and O(2) measured in exhaled breath. Individuals with alpha(1)-AT deficiency had lower levels of NO and CO than control or COPD individuals. Alpha(1)-AT-deficient and COPD patients had lower exhaled CO(2) than controls, although only alpha(1)-AT-deficient patients had higher exhaled O(2) than healthy controls. NO was correlated inversely with exhaled O(2) and directly with exhaled CO(2), supporting a role for NO in regulation of gas exchange. Exhaled gases were not significantly related to corticosteroid use or lung function. Demonstration of lower than normal CO and NO levels may be useful as an additional noninvasive method to evaluate alpha(1)-AT deficiency in individuals with a severe, early onset of obstructive lung disease.     

Impact of axial diffusion on nitric oxide exchange in the lungs.

Nitric oxide (NO) appears in the exhaled breath and is a potentially important clinical marker. The accepted model of NO gas exchange includes two compartments, representing the airway and alveolar region of the lungs, but neglects axial diffusion. We incorporated axial diffusion into a one-dimensional trumpet model of the lungs to assess the impact on NO exchange dynamics, particularly the impact on the estimation of flow-independent NO exchange parameters such as the airway diffusing capacity and the maximum flux of NO in the airways. Axial diffusion reduces exhaled NO concentrations because of diffusion of NO from the airways to the alveolar region of the lungs. The magnitude is inversely related to exhalation flow rate. To simulate experimental data from two different breathing maneuvers, NO airway diffusing capacity and maximum flux of NO in the airways needed to be increased approximately fourfold. These results depend strongly on the assumption of a significant production of NO in the small airways. We conclude that axial diffusion may decrease exhaled NO levels; however, more advanced knowledge of the longitudinal distribution of NO production and diffusion is needed to develop a complete understanding of the impact of axial diffusion.     

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders.

When O2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 +/- 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 +/- 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O2 delivery without the consequences of higher pulmonary arterial pressure.     

Exercise changes volatiles in exhaled breath assessed by an electronic nose

Exercise-caused metabolic changes can be followed by monitoring exhaled volatiles; however it has not been previously reported if a spectrum of exhaled gases is modified after physical challenge. We have hypothesized that changes in volatile molecules assessed by an electronic nose may be the reason for the alkalization of the exhaled breath condensate (EBC) fluid following physical exercise.Ten healthy young subjects performed a 6-minute running test. Exhaled breath samples pre-exercise and post-exercise (0 min, 15 min, 30 min and 60 min) were collected for volatile pattern ("smellprint") determination and pH measurements (at 5.33 kPa CO2), respectively. Exhaled breath smellprints were analyzed using principal component analysis and were related to EBC pH.Smellprints (p=0.04) and EBC pH (p=0.01) were altered during exercise challenge. Compared to pre-exercise values, smellprints and pH differed at 15 min, 30 min and 60 min following exercise (p<0.05), while no difference was found at 0 min post-exercise. In addition, a significant correlation was found between volatile pattern of exhaled breath and EBC pH (p=0.01, r=-0.34).Physical exercise changes the pattern of exhaled volatiles together with an increase in pH of breath. Changes in volatiles may be responsible for increase in EBC pH.     

Immediate Effect of Specific Nostril Manipulating Yoga Breathing Practices on Autonomic and Respiratory Variables

The effect of right, left, and alternate nostril yoga breathing (i.e., RNYB, LNYB, and ANYB, respectively) were compared with breath awareness (BAW) and normal breathing (CTL). Autonomic and respiratory variables were studied in 21 male volunteers with ages between 18 and 45 years and experience in the yoga breathing practices between 3 and 48 months. Subjects were assessed in five experimental sessions on five separate days. The sessions were in fixed possible sequences and subjects were assigned to a sequence randomly. Each session was for 40 min; 30 min for the breathing practice, preceded and followed by 5 min of quiet sitting. Assessments included heart rate variability, skin conductance, finger plethysmogram amplitude, breath rate, and blood pressure. Following RNYB there was a significant increase in systolic, diastolic and mean pressure. In contrast, the systolic and diastolic pressure decreased after ANYB and the systolic and mean pressure were lower after LNYB. Hence, unilateral nostril yoga breathing practices appear to influence the blood pressure in different ways. These effects suggest possible therapeutic applications.     

Effect of heterogeneous ventilation and nitric oxide production on exhaled nitric oxide profiles.

Elevated exhaled nitric oxide (NO) in the breath of asthmatic subjects is thought to be a noninvasive marker of lung inflammation. Asthma is also characterized by heterogeneous bronchoconstriction and inflammation, which impact the spatial distribution of ventilation in the lungs. Since exhaled NO arises from both airway and alveolar regions, and its level in exhaled breath depends strongly on flow, spatial heterogeneity in flow patterns and NO production may significantly affect the exhaled NO signal. To investigate the effect of these factors on exhaled NO profiles, we developed a multicompartment mathematical model of NO exchange using a trumpet-shaped central airway segment that bifurcates into two similarly shaped peripheral airway segments, each of which empties into an alveolar compartment. Heterogeneity in flow alone has only a minimal impact on the exhaled NO profile. In contrast, placing 70% of the total airway NO production in the central compartment or the distal poorly ventilated compartment can significantly increase (35%) or decrease (-10%) the plateau concentration, respectively. Reduced ventilation of the peripheral and acinar regions of the lungs with concomitant elevated NO production delays the rise of NO during exhalation, resulting in a positive phase III slope and reduced plateau concentration (-11%). These features compare favorably with experimentally observed profiles in exercise-induced asthma and cannot be simulated with single-path models. We conclude that variability in ventilation and NO production in asthmatic subjects impacts the shape of the exhaled NO profile and thus impacts the physiological interpretation.     

Metabolic monitoring and assessment of anaerobic threshold by means of breath biomarkers

Volatile breath constituents such as acetone and ammonia have been linked to dextrose, fat, and protein metabolism. Non-invasive breath analysis, therefore, may be used for metabolic monitoring, identification of fuel sources actually used for energy production and determination of the anaerobic threshold (AT). This study was intended to assess correlations between exhaled volatile organic compound (VOC) concentrations, metabolism, and physiological parameters. In addition, we tried to find out whether AT could be determined by means of non-invasive analysis of VOCs in breath. Exhaled concentrations of acetone, ammonia, and isoprene were determined in 21 healthy volunteers under controlled ergometric exercise by means of continuous real time Proton Transfer Reaction Mass Spectrometry (PTR-MS). In parallel, spiro-ergometric parameters ( $ {\dot{\text{V}}} $ O₂, $ {\dot{\text{V}}} $ CO₂, respiratory rate and minute ventilation) and hemodynamic data such as heart rate were recorded. AT was determined from serum lactate, by means of respiratory exchange rate and by means of exhaled acetone concentrations. Exhaled acetone concentrations mirrored exercise induced changes of dextrose metabolism and lipolysis. Bland?CAltman statistics showed good agreement between lactate threshold, respiratory compensation point (RCP), and determination of AT by means of exhaled acetone. Exhaled ammonia concentration seemed to be linked to protein metabolism and changes of pH under exercise. Isoprene concentrations showed a close correlation to cardiac output and minute ventilation. Breath biomarkers represent a promising alternative for metabolic monitoring under exercise as they can be determined non-invasively and continuously. In addition, these markers may add complementary information on biochemistry, energy production and fuel consumption.     

Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation

BackgroundKorean red ginseng (KRG) is a traditional herbal medicine made by steaming and drying the fresh ginseng, leading to chemical transformation of some components by heat. It ameliorates various inflammatory diseases and strengthens the endocrine, immune, and central nervous systems. The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumorigenesis.PurposeIn this study we examined the effects and the mechanism underlying Korean red ginseng water extract (KRG-WE) inhibition of hypoxia-induced COX-2 in human distal lung epithelial A549 cells.Study designThe effect of the KRG on suppression of hypoxia-induced COX-2 in A549 cells were determined by Western blot and/or qRT-PCR. The anti-invasive effect of KRG-WE was evaluated on A549 cells using matrigel invasion assay. The activation of glucocorticoid receptor (GR) and sirtuin1 (Sirt1) was examined by using specific inhibitors.ResultsWe first observed that hypoxia induced COX-2 protein and mRNA levels and promoter activity were suppressed by KRG-WE. Second, we observed that hypoxia-induced cell migration is dramatically reduced by KRG-WE. Third, we found that the effect of KRG-WE was not antagonized by the GR antagonist RU486 implying that the effect is mediated other than GR pathway. Finally, we demonstrated that inhibition of Sirt1 abolished the effect of KRG-WE on hypoxia-induced COX-2 suppression and cell-invasion indicating that the suppression is mediated by Sirt1.ConclusionTaken together, KRG-WE inhibits the hypoxic induction of COX-2 expression and cell invasion through Sirt1 activation. Our results imply that KRG-WE could be effective for suppression of inflammation under hypoxia.     

Measuring airway exchange of endogenous acetone using a single-exhalation breathing maneuver.

Exhaled acetone is measured to estimate exposure or monitor diabetes and congestive heart failure. Interpreting this measurement depends critically on where acetone exchanges in the lung. Health professionals assume exhaled acetone originates from alveolar gas exchange, but experimental data and theoretical predictions suggest that acetone comes predominantly from airway gas exchange. We measured endogenous acetone in the exhaled breath to evaluate acetone exchange in the lung. The acetone concentration in the exhalate of healthy human subjects was measured dynamically with a quadrupole mass spectrometer and was plotted against exhaled volume. Each subject performed a series of breathing maneuvers in which the steady exhaled flow rate was the only variable. Acetone phase III had a positive slope (0.054+/-0.016 liter-1) that was statistically independent of flow rate. Exhaled acetone concentration was normalized by acetone concentration in the alveolar air, as estimated by isothermal rebreathing. Acetone concentration in the rebreathed breath ranged from 0.8 to 2.0 parts per million. Normalized end-exhaled acetone concentration was dependent on flow and was 0.79+/-0.04 and 0.85+/-0.04 for the slow and fast exhalation rates, respectively. A mathematical model of airway and alveolar gas exchange was used to evaluate acetone transport in the lung. By doubling the connective tissue (epithelium+mucosal tissue) thickness, this model predicted accurately (R2=0.94+/-0.05) the experimentally measured expirograms and demonstrated that most acetone exchange occurred in the airways of the lung. Therefore, assays using exhaled acetone measurements need to be reevaluated because they may underestimate blood levels.