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L-arginine increases exhaled nitric oxide in normal human subjects.

1. Endogenous nitric oxide plays an important physiological role and is synthesized by several isoforms of nitric oxide synthase from the semiessential amino acid L-arginine. Nitric oxide is detectable in the exhaled air of normal individuals and may be used to monitor the formation of nitric oxide in the respiratory tract. 2. We have investigated the effect of orally administered L-arginine (0.05, 0.1, 0.2 g/kg) compared with matched placebo on the concentration of nitric oxide in the exhaled air in 23 normal individuals. 3. L-Arginine caused significant increases in the concentration of nitric oxide in exhaled air at doses of 0.1 and 0.2 mg/kg, which was maximal 2 h after administration. This was associated with an increase in the concentration of L-arginine and nitrate in plasma. There were no significant changes in heart rate, blood pressure or forced expiratory volume in 1 s. 4. These results suggest that an increase in the amount of substrate for nitric oxide synthase can increase the formation of endogenous nitric oxide. This may have therapeutic relevance in diseases in which there is defective production of nitric oxide.

Administration, Oral↗

Relationship between decreased oxyhaemoglobin saturation and exhaled nitric oxide during exercise.

Decreases in oxyhaemoglobin saturation (SaO2) are frequently observed in highly trained male endurance athletes during heavy work and has been termed exercise-induced hypoxaemia (EIH). Ventilation perfusion (VA/Q) mismatching and diffusion limitations are thought to be responsible. Nitric oxide (NO), a potent vasodilator, is present in the exhaled air of resting and exercising humans. Endogenously produced NO is thought to play a role in VA/Q matching and maintenance of low pulmonary vascular resistance. The purpose of this study was to determine the relationship between exhaled NO and EIH. It was hypothesized that athletes with EIH would have lower NO levels compared with non-EIH athletes. Eighteen highly trained male cyclists (VO2max=67.7 +/- 5.2 mL kg-1 min-1, mean +/- SD) were divided into normal (NORM, n=12, SaO2= 93.9 +/- 0.8) or low (LOW, n=6, SaO2=90.3 +/- 1.0) group, based on significantly different peak exercise SaO2 values (P < 0.05). All other descriptive and physiological characteristics were similar between the groups. Subjects performed a ramped cycle test to exhaustion breathing NO-free gas. The concentration (CNO) and production rate (VNO) of NO were determined from mixed gas samples at rest and during exercise at 100, 200, 250, 300, 350, 400 and 450 W using a chemiluminescent analyser. CNO remained unchanged from resting values in all subjects. VNO increased significantly during exercise in all subjects but was not different between LOW and NORM groups. The correlation between change in SaO2 and VNO from rest to maximal exercise was not significant (r=-0.12, P > 0.05). Collectively, these data suggest that exhaled NO is not related to decreased SaO2 during heavy exercise in highly trained male cyclists.

Adult↗

Effect of medroxyprogesterone on pulmonary arterial pressure, exhaled nitric oxide, ECG and arterial blood gases.

OBJECTIVES: To evaluate the effect of medroxyprogesterone acetate (MPA) therapy on pulmonary arterial pressure (PAP), exhaled nitric oxide (NO), electrocardiogram (ECG), and on arterial blood gases (ABG). DESIGN: A double-blind randomized placebo-controlled cross-over trial. SETTING: University hospital in Turku, Finland. SUBJECTS: Fourteen postmenopausal women with respiratory impairment. INTERVENTIONS: A 2-week placebo and a 2-week MPA period (60 mg day -1) followed by 6-week placebo or MPA washout periods. MAIN OUTCOME MEASURES: The systolic PAP was estimated by Doppler echocardiography. PAP, ECG, NO and ABG were monitored at baseline, after 2-week placebo and MPA periods, and after 3- and 6-week placebo and MPA washout periods. RESULTS: The mean PaCO2 at baseline was 5.4 +/- 0.6 kPa (mean +/- SD). The average decrease of PaCO2 on MPA was -0.8 +/- 0.3 kPa (P < 0.001) and 0.3 +/- 1.0 kPa (P = 0.007) at the 3-week washout. The mean systolic PAP at baseline was 44.3 +/- 14.5 mm Hg. MPA did not change PAP until the 6-week washout, when the average increase of + 6.9 +/- 19.8 mm Hg (P = 0.002) was observed. No changes occurred in PaO2, exhaled NO or the ECG axes. The PR interval was shorter only on MPA (15.9 +/- 27.0 ms, P = 0.020) whereas the QRS duration remained shorter up to 3-week washout (3.9 +/0 5.5 ms, P = 0.008 and 4.0 +/- 14.3 ms, P = 0.032). The systolic and diastolic BP and the heart rate did not change. CONCLUSIONS: Despite prolonged decrease in PaCO2, short-term MPA had no effect on exhaled NO and did not decrease systolic PAP in postmenopausal women with respiratory impairment. MPA shortened the PR interval and the QRS duration, the latter effect being sustained at least up to 3 weeks.

Aged↗

Exhaled nitric oxide in patients with PiZZ phenotype-related alpha1-anti-trypsin deficiency.

There is no report of exhaled NO (eNO) in subjects with different phenotypes of alpha1-anti-trypsin (AAT) deficiency. Exhaled nitric oxide was evaluated by means of single-breath chemiluminescence analysis (fractional exhaled concentration at the plateau level [plFE(NO)]) in 40 patients with AAT deficiency. Patients were divided according to the protease inhibitor (Pi) phenotype: PiMZ/MS, n = 25; PiSZ n = 6; PiZZ, n = 9. Nineteen healthy subjects served as controls. Levels of eNO in PiZZ patients were also compared with those of subjects, without AAT deficiency (PiMM), matched for diagnosis, sex, age, smoking habit and forced expiratory volume in 1 sec (FEV1). In AAT deficiency subjects airway hyper-responsiveness to methacholine (PD20 FEV1) was also assessed. plFE(NO) was significantly lower in the PiZZ group (4.5+/-1.4 ppb) than in matched PiMM subjects (8.2+/-3.8 ppb), in healthy controls (9.3+/-2.8 ppb) and in patients of other phenotypes. Dynamic lung volumes and DL(CO) were significantly lower in PiZZ than in other AAT-deficient patients. Bronchial hyper-responsiveness was not different among AAT phenotypes. These results suggest that eNO may be significantly reduced in PiZZ as compared to healthy control subjects and to AAT subjects with other phenotypes, independent of the level of airway obstruction. Whether, at least potentially, eNO may be considered as an early marker of lung involvement in AAT deficiency must be confirmed with studies on larger number of subjects.

Adult↗

An efficient and reproducible method for measuring hydrogen peroxide in exhaled breath condensate.

We investigated the sensitivity and reproducibility of a test procedure for measuring hydrogen peroxide (H202) in exhaled breath condensate and the effect of storage of the condensate on the H2O2 concentration, and compared the results to previous studies. Twenty stable COPD patients breathed into our collecting device twice for a period of 10 min. The total exhaled air volume (EAV) and condensate volume were measured both times and the H2O2 concentration of the condensate was determined fluorimetrically. The concentration was measured again after freezing the reaction product at -70 degrees C for a period of 10, 20 and 40 days. We collected 2-5 ml condensate in 10 min. The EAV and condensate volumes were strongly correlated. There was no significant difference between the mean H2O2 concentration of the first and second test. We obtained a detect on limit for the H2O2 concentration of 0.02 micromoll(-1). The H2O2 concentration appeared to remain stable for a period up to 40 days of freezing. Compared to previous studies we developed a more efficient breath condensate collecting device and obtained a lower H2O2 detection limit. The measurement of exhaled H2O2 was reproducible. In addition, storage of the samples up to 40 days showed no changes in H2O2 concentration.

Aged↗

Exhaled nitric oxide in asthma: from bench to bedside.

With more than 600 publications, exhaled nitric oxide (NO) has been extensively investigated as a noninvasive marker of airway inflammation in a research setting. This clinical rostrum presents a synopsis of the latest research about this novel marker in asthma and suggests how it might move from bench to bedside. Specifically, we review the evidence citing the applicability of exhaled NO in diagnosing asthma, monitoring the response to therapy, evaluating current symptom control, and predicting exacerbations of asthma. These studies support a role for exhaled NO in the evaluation and treatment of asthma in the clinical arena.

Adrenal Cortex Hormones↗

Exhaled and nasal nitric oxide in mechanically ventilated preterm and term newborns.

AIM: Nitric oxide (NO) is an important mediator required for neonatal pulmonary circulatory adaptation and for pulmonary defence. Both deficient and excessive NO production have been proposed to play a role in neonatal lung disease. This study aimed to establish a method that allows direct measurement of exhaled and nasal NO concentrations in newborn infants who require intubation and ventilation. METHODS: A rapid-response chemiluminescence NO analyser was used. Gas was sampled from the endotracheal intubation tube, and tidal volumes and flow rates were measured. The nasal NO was sampled from the non-intubated nostril. The accuracy of the method was validated using a lung model. NO levels from six preterm and six term/near-term newborns were studied. Measurements were performed on a daily basis during the first week. RESULTS: An expiration >0.2 s in duration with a flow rate >1.7 ml s(-1) could be accurately analysed for the presence of >1 parts per billion of NO. The very preterm infants with neonatal lung disease had a different postnatal NO output pattern from the lower and upper airways compared with the ventilated term/near-term infants. CONCLUSION: A novel method for measurement of exhaled NO of an intubated newborn is presented. The possible association of exhaled NO concentration with the development of chronic lung disease remains to be studied.

Breath Tests↗

Determination of known exhalation valve damage using a negative pressure user seal check method on full facepiece respirators.

A negative pressure user seal check (NPUSC) method was evaluated for its ability to adequately detect known exhalation valve leakage into a respirator. Three valves with different types of damage were included. Twenty-six test subjects, wearing full facepiece respirators, were asked to perform a NPUSC. Their responses as to whether they passed or failed the user seal check were compared to fit testing results from two quantitative fit test methods: ambient aerosol and controlled negative pressure. In addition, equipment developed at the University of Cincinnati was used to measure in-mask pressures that are generated during the performance of NPUSCs. This technique was employed to assess the ability of respirator wearers to properly conduct user seal checks. The data were analyzed to determine if the user seal check procedure is an effective method for detecting known exhalation valve damage. All test subjects reported passing the user seal check with the undamaged valve. With the warped valve installed, 95 percent of test subjects reported passing the user seal check. With the slit valve installed, 73 percent of test subjects reported passing. With the dirty valve installed, 65 percent reported passing. All fit factors, measured with the damaged valves, were below the Occupational Safety and Health Administration-recognized pass/fail criteria except one fit test with the respirator equipped with the slit valve. Results from the in-mask pressure measurements confirmed whether or not the subject properly conducted a user seal check, but did not detect respirator leakage. In conclusion, the performance of a NPUSC rarely helped to identify damaged exhalation valves. These results support the need for respirator inspection prior to donning with periodic fit testing and the performance of user seal checks as necessary components of an adequate respiratory protection program.

Equipment Failure↗

Influence of ventilatory settings and sampling position on measurements of simulated exhaled nitric oxide levels.

Chronic lung disease is a common adverse outcome of prematurely born infants and is associated with an early inflammatory response, which persists over weeks. As a consequence, it is possible that exhaled nitric oxide levels might be raised in affected infants. The majority of such infants will be ventilated in the first weeks of birth and thus it is important to determine the influence of mechanical ventilation on nitric oxide levels. As a consequence, our aim was to determine whether, during mechanical ventilation, simulated exhaled nitric oxide levels were influenced by changes in ventilator settings or the sampling catheter position. A lung model was created consisting of a rubber bag inside a 11 jar. An endotracheal tube (ETT) was fixed securely within the neck of the bag. Nitric oxide was delivered into the bag at a constant rate to simulate production and sampled from within the ETT and the bag. The sampled nitric oxide was analysed using a Sievers chemiluminescence analyser. The ETT was attached to a neonatal ventilator and a nitric oxide scavenger placed in the ventilator's inspiratory limb to ensure nitric oxide free gas was delivered. Comparison of different sampling positions revealed that the highest peak nitric oxide level within the ETT was at the tip. Increasing peak inflating pressure and ventilator rate resulted in a decrease in the peak nitric oxide levels. Increasing the inspired oxygen concentration also was associated with a reduction in the peak nitric oxide levels, the effect being more pronounced when larger volume lung models were examined. The results emphasized that the conditions of measurement must be standardized in infants receiving respiratory support, if exhaled nitric oxide results are to be appropriately interpreted.

Air↗

Exhaled breath analysis as a measure of workplace exposure to benzene ppm.

Exposures to benzene vapour were measured in a group of coal tar distillation workers and the concentration of benzene in the air that they exhaled was determined at the beginning of the following work period. Time-weighted average benzene concentrations were principally in the range 0.02-0.9 ppm. Benzene vapour was detectable in the breath of all subjects 16 h after exposure, and a progressive build-up over the working week was found. Nevertheless the relationship between exposure and concentration in exhaled breath was found to be poor. This suggests that at concentrations below about 1 ppm, the analysis of exhaled breath is not a reliable method of measuring previous exposure to benzene.

Benzene↗

Evaluation of exhalation valves.

Certification tests currently employed by some industrialized nations to certify respirators require that when challenged with air flow at a constant suction head of 25 mmH2O, the leakage into the facepiece from the exhalation valve(s) should not exceed 30 ml min(-1). However, the test alone might not reflect the leakage rate under different levels of vacuum. To study the characteristics of leakage through exhalation valves, a leakage meter was built to measure the leakage rate of four brands of exhalation valves. Seven valves of each brand were tested for leakage rate at pressure drops ranging from 15 to 45 mmH2O (or extended to 75 mmH2O for some valves). Two types of leaks, i.e. fiber insertion and arch dent on the valve seat, were used to investigate the effect of leak shape on the characteristic leak flow as a function of pressure drop. A leakage data point represented a mean value of five measurements. The results showed that the leakage rate could increase or decrease with increasing pressure drop inside the respirators, indicating that the current method of conducting leakage tests, at a constant suction head of 25 mmH2O, does not guarantee better protection than when the respirators are used at a lower suction head. Moreover, based on the sample valves tested in this study, it was found that valve leakage was mostly caused by defects in the valve seats. Both fiber-insertion and arch-dent leaks had either increasing or decreasing characteristic curves, depending on the size of the leak and the material of the valve membrane.

Data Collection↗

Human individuals vary in attractiveness for host-seeking black flies (Diptera: Simuliidae) based on exhaled carbon dioxide.

The attractiveness of 5 male subjects was compared to determine if female black flies were attracted more readily by certain individuals and, if so, to determine the bases of such differences. During 2 yr, in experiments contrasting different groupings of the subjects, 1 subject was consistently the most attractive, whereas another was consistently the least attractive. Attractiveness of the remaining 3 subjects was intermediate. Removing exhaled breath resulted in a decrease of attractiveness to approximately 15% of previous levels and removed differences among subjects. Replacing breath exhalations with subject-specific CO2 levels restored subject attractiveness to approximately 90% of original levels. Exhaled breath from which CO2 had been removed with a soda-lime filter and then augmented with bottled CO2 was consistently more attractive than CO2 alone at the augmentation rate, indicating the role of other breath components. A human form plus breath odor was more attractive than a human form and a human form plus body odor. Results lend credibility to popular notions that some people are more attractive for black flies than are others and indicate that these differences may be accounted for by individual production rates of breath CO2.

Animals↗

Increased hydrogen peroxide in the exhaled breath of uraemic patients unaffected by haemodialysis.

BACKGROUND: Uraemia is accompanied by conditions favouring the rise of H2O2 activity in body fluids. This results from the increased release of H2O2 by polymorphonuclear leukocytes and decreased plasma glutathione peroxidase activity. The purpose of this study was to determine if patients on chronic haemodialysis (HD) exhale more H2O2 than healthy individuals, and if dialysis affects breath H2O2 content. METHODS: We studied 29 chronic HD patients (mean age 49 +/- 11 years) and 40 healthy persons (mean age 44 +/- 9 years). H2O2, which is volatile, was measured fluorimetrically with the homovanillic acid method in the exhaled breath condensate (EBC) of the study cohort. EBC was collected immediately before and after the HD session and also at 20 and 60 min of HD treatment (n = 14) and once in controls. Peak expiratory flow (PEF), white blood cell (WBC) count, PaO(2) and circulatory cyclic guanosine monophosphate (cGMP), Il-6 and Il-8 concentrations were measured concomitantly. Finally, H2O2 diffusion through the dialyser cuprophane membrane was determined in an in vitro experiment. RESULTS: At baseline, EBC H2O2 concentration was 22 times higher in HD patients than in controls (2.92 +/- 4.64 vs 0.16 +/- 0.13 microM, P < 0.001). Although the maximum decrease in PEF (431 +/- 52 vs 398 +/- 56 l/min, P < 0.01) and WBC count (6.72 +/- 1.02 vs 3.82 +/- 1.51 x 10(3)/ microl, P < 0.01) occurred at 20 min after the start of HD, no significant changes in breath H2O2 levels were noted throughout the session. Plasma IL-6 and IL-8 levels remained unchanged whereas cGMP rose 1.3 times at 60 min (P < 0.01). In vitro, H2O2 rapidly diffused through the cuprophane membrane. CONCLUSION: Chronic HD patients exhale more H2O2 than healthy subjects. Although no change of breath H2O2 concentration was observed during HD, as H2O2 easily diffuses through the dialyser membrane, it is not possible to rule out that HD stimulates H2O2 generation.

Adult↗

Exhaled flow monitoring can detect bronchial flap-valve obstruction in a mechanical lung model.

Flap-valve obstruction to expiratory flow (V) in a major bronchus can result from inspissated secretions, blood, or foreign body. During inhalation, increasing airway caliber preserves inspired V past the obstruction; during exhalation, decreasing airway diameter causes airflow obstruction and even frank gas trapping. We reasoned that the resultant sequential, biphasic exhalation of the lungs would be best detected by measuring exhaled V versus time. Accordingly, we designed an airway obstruction element in a mechanical lung model to examine flap-valve bronchial obstruction. A mechanical lung simulator was ventilated with a pressure-limited flow generator, where f = 10/min, tidal volume = 850 mL, and respiratory compliance = 40 mL/cm H2O. Airway V (pneumotachometer) and pressure (P) were digitally sampled for 1 min. Then, the circumference of the diaphragm in a respiratory one-way valve was trimmed to generate unidirectional resistance to expiratory V. Measurement sequences were repeated after this flap-valve was interposed in the right "main-stem bronchus." Integration of airway V versus time generated changes in lung volume. During flap-valve obstruction of the right bronchus, the V-time plot revealed preservation of peak expired flow from the normal lung, followed by retarded and decreased flow from the obstructed right lung. Gas trapping of the obstructed lung occurred during conditions of decreased expiratory time and increased expiratory resistance. Airway P could not differentiate between bronchial and tracheal flap-valve obstruction because P decreased abruptly in both conditions. The flow-volume loop displayed less distinctive changes than the flow-time plot, in part because the flow-volume loop was data (flow) plotted against its time integral (volume), with loss of temporal data. In this mechanical lung model, we conclude that bronchial flap-valve obstruction was best detected by the flow-time plot, which could measure the sequential emptying of the lungs.

Airway Obstruction↗

Exhaled nitric oxide level decreases after cardiopulmonary bypass in adult patients.

OBJECTIVE: To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. DESIGN: Prospective, single-center, observational study. SETTING: University hospital operating room, intensive care unit. PATIENTS: Sixteen adult patients undergoing cardiac surgery with CPB. INTERVENTIONS: None except cardiac surgery with CPB. MEASUREMENTS AND MAIN RESULTS: Exhaled NO was measured continuously by the chemiluminescence method and was expressed as the peak and mean NO concentrations, and the NO output (VNO). These parameters were calculated by averaging four sequential tidal NO values. The data were obtained serially from before CPB to 16 hrs after CPB. Lung function was evaluated by monitoring lung compliance, pulmonary artery pressure, and alveolar-arterial oxygen difference (P(A-a)O2). The cardiac index did not change except for a significant increase at 16 hrs compared with 6 hrs after CPB. Peak NO, mean NO, and VNO decreased from 15.4 +/- 2.0 ppb (before CPB) to 8.2 +/- 0.8 ppb (6 hrs after CPB), from 5.7 +/- 0.7 ppb to 2.8 +/- 0.6 ppb, and from 29.2 +/- 3.1 nL/min to 15.7 +/- 2.2 nL/min, respectively. These changes were associated with the increases in pulmonary artery pressure and alveolar-arterial oxygen difference, and the decrease in lung compliance. VNO recovered to the level measured before CPB 16 hrs after CPB, which was consistent with the physiologic recovery in pulmonary hypertension, lung compliance, and gas exchange. CONCLUSION: Measurement of exhaled NO as VNO, which was associated with lung dysfunction, may be an indicator of lung injury in adult patients after cardiopulmonary bypass.

Adult↗

Radium-226 body burden in U miners by measurement of Rn in exhaled breath.

Uranium miners were made to inhale Rn-free medical O2 and exhale through a 5.2-1 A1 chamber before reporting to work. The chamber was sealed and isolated from the sampling circuit. An electrostatic plate collected the freshly formed Rn-decay products. The subsequent programmed alpha counting of the plate yielded a Rn concentration in the exhaled breath. Assuming that the exhaled breath represents a certain fraction of the Rn produced inside the body, the body burden of 226Ra was calculated. Standardisation of this procedure and the data collected on 310 miners are discussed. The procedure is simple and applicable for routine measurements. The miner needs to be in the laboratory for only 10 min. The system is also portable for field application. For routine use, the minimum detectable concentration is 3.87 Bq X m-3 which corresponds to a body burden of 0.26 kBq in a typical miner, if one assumes the Rn release fraction from the body as 84%. The system offers a more convenient and sensitive alternative to whole-body counting of workers for 226Ra.

Body Burden↗

The variation of radon exhalation rates from building surfaces of different ages.

Standardized activated charcoal canisters (according to the U.S. EPA) have been used to collect radon exhaled from concrete surfaces covered with thin plaster (categorically different from thick plaster) of 32 buildings of different ages (0.5-31 y) in Hong Kong. Concrete surfaces covered with thin plaster is the commonest wall configuration in Hong Kong. The canisters are analyzed using gamma spectroscopy to obtain the radon exhalation rates. The results show that the radon exhalation rate decreases with the building age.

Air Pollution, Indoor↗

Radon exhalation rates and gamma doses from ceramic tiles.

This study was carried out to assess the possible radiological hazard resulting from the use of zircon in glaze applied to tiles used in buildings. The 226Ra content of various stains and glazing compounds was measured using gamma spectroscopy and the 222Rn exhalation rates for these materials were measured using adsorption on activated charcoal. The radon exhalation rates were found to be close to or less than the minimum detectable values for the equipment used. This limit was much lower than the estimated exhalation rates, which were calculated assuming that the parameters controlling the emanation and diffusion of 222Rn in the materials studied were similar to those of soil. This implied that the 222Rn emanation coefficients and/or diffusion coefficients for most of the materials studied were very much lower than expected. Measurements on zircon powders showed that the 222Rn emanation coefficient for zircon was much lower than that for soil, indicating that only a small fraction of the 222Rn produced by the decay of 226Ra was able to escape from the zircon grains. The estimated increase in radon concentration in room air and the estimated external gamma radiation dose resulting from the use of zircon glaze are both much lower than the relevant action level and dose limit.

Adsorption↗