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PubMed2001

Inhaled mannitol shifts exhaled nitric oxide in opposite directions in asthmatics and healthy subjects.

We investigated if healthy subjects could release NO upon hyperosmolar challenge as a defence mechanism, and whether asthmatics with atopy showed an altered response. A plot of NO output versus flow rate was used to calculate the alveolar level and the NO-flux from the airways. The asthmatics had a higher NO output and this was due to an increased NO-flux from the airways, 86+/-30 nl min(-1) compared with control 21+/-2 nl min(-1) (P<0.05). The alveolar NO levels showed no difference. In response to a dry powder of mannitol the exhaled NO concentration decreased in asthmatics by 37+/-7%, but increased in the control by 9+/-4% (P<0.001). The FEV(1.0) decreased 13+/-2% and airway conductance 42+/-7% in asthmatics and in the controls 2+/-1% and 0+/-7%, respectively (P<0.001). We conclude that asthmatics have an altered response to mannitol challenge in regards to exhaled NO. This may result from down regulation of constitutive NO production as a result of high levels of NO flux from the airways.

Administration, Inhalation↗
PubMed1998

Exhaled nitric oxide in preterm infants.

Nitric oxide (NO) is detectable in the exhaled gas of adults during spontaneous respiration and, according to current knowledge, mainly originates from the paranasal sinuses. We studied total NO excretion rates by chemiluminescence in preterm infants whose paranasal sinuses are known to be only partially pneumatized. NO excretion was 7.15 +/- 1.13 nl/min (mean +/- SD, range 6.33-9.36 nl/min) measured from spontaneously exhaled nasal gas (n = 6) and 0.3 +/- 0.05 nl/min (range 0.26-0.36 nl/min) measured from the lower airways in intubated individuals (n = 3). These values are considerably lower than those reported for older children and adults. Body weight-related amounts of NO excretion, however, seem comparable between infants and adults.

Body Weight↗
PubMed1999

Effects of immersion in cool water on lung-exhaled nitric oxide at rest and during exercise.

Lung nitric oxide (NO) has been postulated to relax airway and vascular smooth muscle at rest and during exercise. As a cold environment is a common cause of respiratory distress, lung exhaled NO was measured during skin and core body cooling at rest and during a progressive cycle exercise. Ten healthy male subjects were immersed in water at a water temperature (Tw) which was thermal neutral (35 degrees C) at 30 degrees C Tw, at which only skin temperature is decreased; and at 20 degrees C Tw, at which the core temperature is decreased (0.05 degrees C). At rest, V(O), and V(E) increased while exhaled NO concentration [NO] and the rate of expiration of NO (V(NO)) decreased with decreased Tw. V(O2) and ventilation (V(E)) increased with workload (W) and the values at all Tw were not different, whereas, [NO] decreased with W and the values during exercise were progressively less at all Ws as Tw declined. These results indicate that lung NO output is reduced in a graded fashion during body cooling at rest and during exercise. This suggests that lower lung NO may contribute to airway obstruction in cold environments and NO may contribute to regulation of lung heat and water exchange.

Adult↗
PubMed2001

Radon permeability and radon exhalation of building materials.

High radon concentrations indoors usually depend on the possibilities of radon penetration from the surrounding soil into the buildings. Radon concentrations in dwellings up to 100 kBq/m3 were found in some special regions (i.e. Schneeberg/Saxony, Umhausen/Tyrol), where the soil shows a high uranium content and additionally, a fast radon transport in the soil is possible. To reduce the radon exposure of the inhabitants in these 'radon prone areas' it is necessary to look for building and insulating materials with low radon permeability. We examined several building materials, like cements, concretes and bricks of different constitutions for their diffusion coefficients and their exhalation rates. The insulating materials, like foils and bitumen were tested also on their radon tightness. The measurements were performed with an online radon measuring device, using electrostatic deposition of 218Po ions onto a surface barrier detector and subsequent alpha spectroscopy. The mean diffusion lengths for the investigated building materials range from lower than 0.7 mm (i.e. for plastic foil), up to 1.1 m for gypsum. The diffusion length R was calculated from the diffusion coefficient D with R = square root(D/lambda). If the thickness of the material is more than 3 times the diffusion length, then it is called radon-tight. The mean 222Rn exhalation rates for the building materials varied between 0.05 and 0.4 mBq/m2s. The samples were investigated as stones, plates, blocks, foils, coatings, powders etc., no statement can be made about working at the construction site of a building. Also the fabrication and processing of the materials has to be considered, because the material characteristics may have changed.

Air Pollutants, Radioactive↗
PubMed2002

Analysis of exhaled breath condensate for monitoring airway inflammation.

Several inflammatory mediators have been identified in the exhaled breath condensate (EBC) that is formed by breathing through a cooling system. Analysis of EBC is a noninvasive method that allows repeat measurements of lung inflammation and is potentially useful for monitoring drug therapy. Characterization of the profiles of exhaled markers could help to discriminate between different inflammatory lung diseases; thus, EBC might be a novel, noninvasive approach to monitoring lung diseases. However, several methodological issues, such as standardization of sample collection and validation of analytical techniques, need to be addressed before this method can be applied clinically. Controlled studies are needed to establish the utility of EBC markers for guiding pharmacological treatment in inflammatory lung diseases.

Breath Tests↗
PubMed2002

Photon attenuation, natural radioactivity content and radon exhalation rate of building materials.

High concentrations of natural radionuclides in building materials can result in high dose rates indoors, from both internal and external exposure. In dose calculations, the main radionuclides of interest are 226Ra, 232Th and 40K. Usually much attention is paid to 226Ra due to 222Rn exhalation and the subsequent internal exposure. Other radionuclides of the uranium series such as 238U and 210Pb, emitting low energy photons are not usually determined and an assumption of radioactive equilibrium is made. The above assumption is seldom checked mainly because of the difficulties in the gamma-spectroscopic analysis of low energy photons. For the determination of radionuclides emitting low-energy photons, in samples like building materials where intense self-absorption of the photons exists, a method for self-absorption correction has been developed. The method needs as input the linear attenuation coefficient mu for the material under analysis. This paper presents: 1. Correlations in the form mu = f(rho,E) developed for the estimation of the linear attenuation coefficient mu (cm(-1)), as a function of the material packing density p (g cm(-3)) and the photon energy E (keV), for building materials as well as other materials of environmental importance. 2. Gamma-spectroscopic analysis techniques used for the determination of 238U, 226Ra, 210Pb, 232Th and 40K in environmental samples, together with the results obtained from the analysis of building materials used in Greece, and industrial by-products used for the production of building materials. Among the techniques used, one is based on the direct determination of 226Ra and 235U from the analysis of the multiplet photopeak at approximarely186 keV. 3. Results from radon exhalation measurements of building materials such as cement and fly-ash and building structures conducted in the radon chambers in our Laboratory. Based on the above results, dosimetric calculations are also reported.

Air Pollution, Indoor↗
PubMed2003

Assessment of natural radiation exposure and radon exhalation from building materials in Greece.

In controlling the natural radiation exposure for the residents of dwellings, it is necessary to determine the levels of natural radioactivity (external exposure) and radon exhalation rate (internal exposure) from building materials. Using a high-resolution gamma ray spectrometry system, the activity concentration of natural radionuclides was measured. The radon exhalation rate was measured by hermetically closing the sample in a container and following the radon activity growth as a function of time. Three different methods were applied in order to find the most appropriate, i.e. that with the less uncertainty for the less exposure time. Typical building materials were analyzed in order to examine the external and internal exposures. In addition, the total annual effective dose was evaluated for the residents of a typical Greek dwelling.

Air Pollution, Indoor↗
PubMed1998

Method for analysis of exhaled air by microwave energy desorption coupled with gas chromatography-flame ionization detection-mass spectrometry.

A method for chemical analysis of volatile constituents in exhaled air of mechanically ventilated patients is described. Exhaled substances are adsorbed and concentrated onto activated charcoal, desorbed by microwave energy and transferred into a gas chromatograph for separation without prior cryofocusing. Substances are identified by flame ionisation detection and mass spectrometry. This method yields reproducible results and is well suited for clinical studies.

Acetylene↗
PubMed1998

Effects of thromboxane A2 antagonist on airway hyperresponsiveness, exhaled nitric oxide, and induced sputum eosinophils in asthmatics.

We examined effects of a thromboxane A2 (TXA2) antagonist seratrodast on airway hyperresponsiveness, exhaled nitric oxide (NO), and eosinophils in induced sputum in 14 asthmatics. Subjects were administered 80 mg of seratrodast once a day for 4 weeks. Respiratory conductance (Grs) was measured by the forced oscillation method and airway responsiveness was evaluated as the inhaled dose of methacholine, which induced 35% decrease in Grs. Subjects breathed into a Teflon bag, and NO concentration in the bag was measured by a chemiluminescence analyzer. Induced sputum comprised the entire expectorate produced during a 20 min inhalation of 3% saline, and was analyzed for total and differential cell counts. Airway hyperresponsiveness was significantly decreased by seratrodast. By contrast, no differences in either exhaled NO or percentage of eosinophils in sputum were observed before or after seratrodast. We conclude that seratrodast may attenuate airway hyperresponsiveness, presumably by antagonizing TXA2 released from the inflamed airways.

Anti-Asthmatic Agents↗
PubMed1999

Procedures for the determination of 222Rn exhalation and effective 226Ra activity in soil samples.

Two methods for measuring 222Rn exhalation and effective 226Ra in soil samples were studied. In the first determination, the method employed was based on the adsorption of radon onto activated charcoal and subsequent measurement of the activity of its daughters with an HPGe (high-purity germanium) detector. In the second, vials containing an aqueous suspension of the sample, mixed with an insoluble high efficiency mineral oil scintillation cocktail, were measured using a low-level liquid scintillation counter. Studies of optimum sampling time, efficiency in both procedures, variation of 226Ra efficiency with quenching, as well as the effect of sample amount and granulometry upon the quenching parameter, were carried out. The two methods were applied to the determination of 222Rn exhalation and effective 226Ra in environmental samples.

Charcoal↗
PubMed2006

A fast, simple, and inexpensive method to collect exhaled breath condensate for pH determination.

BACKGROUND: Exhaled breath condensate (EBC) analysis is a noninvasive method for assessing lower airway inflammation. Various methods of collecting EBC have been described. However, they are often time-consuming or involve expensive equipment. OBJECTIVE: To evaluate the efficiency and repeatability of a simple, fast, and inexpensive method of EBC collection for pH determination. METHODS: Twenty-four mild asthmatic patients, 18 moderate-to-severe asthmatic patients, and 26 controls were asked to slowly exhale for 45 seconds into a -80 degrees C cooled metal cylinder covered with protective rubber and attached to a piece of tubing. The EBC was collected using a syringe's plunger. The groups were compared regarding EBC pH. Reproducibility tests were also performed. Induced sputum samples were obtained for inflammatory cell counts. RESULTS: We obtained approximately 50 microL of EBC for pH determination. Mild asthmatic patients had lower mean +/- SD pH values than controls (5.97 +/- 0.48 vs 6.36 +/- 0.34; P = .008), and corticosteroid-treated, moderate-to-severe asthmatic patients had mean +/- SD pH values similar to controls (6.23 +/- 0.38; P > .05). Mean +/- SD sputum eosinophil percentages were higher in both asthmatic groups than in controls (3.42% +/- 5.37% and 4.14% +/- 4.98% vs 0.04% +/- 0.12%; P < .001) and were not correlated with pH values in all groups. The mean intraday coefficient of variation for the method was 4.8% (range, 0.9%-8.8%). No correlation was found in all groups between sputum neutrophils and pH. CONCLUSIONS: We developed a useful device for collecting EBC for pH evaluation that could provide an alternative to other methods when pH is the main variable evaluated.

Adolescent↗
PubMed1999

Comparison of exhaled nitric oxide to spirometry during emergency treatment of asthma exacerbations with glucocorticoids in children.

BACKGROUND: Asthma is characterized as a chronic inflammatory process; however, there is no easily measured marker for airway inflammation. Such a marker, particularly in children, would be very helpful in the management of asthma even in the acute setting. OBJECTIVE: The purposes of this study were to determine whether asthmatic children have (1) elevation of exhaled breath nitric oxide (ENO) during acute exacerbations when presenting to the emergency room, (2) reduction of ENO following glucocorticoid treatment, or (3) improvement in spirometry and clinical examination accompanying reduction of ENO levels. METHODS: Peak ENO levels were measured by chemiluminescence during exhalation into the NO analyzer. Ten asthmatic children (mean age 10 years) who presented to the Pediatric Special Care Unit at National Jewish Medical and Research Center in acute respiratory distress with an asthma exacerbation were studied. The subjects were recruited, after informed consent was obtained from the parent, on the basis of specific inclusion/exclusion criteria. Measurements of ENO in parts per billion (ppb) and spirometry, including percentiles of forced expiratory volume in one second (FEV1%) and peak expiratory flow (PEF%), were performed before and after at least 5 days of glucocorticoid therapy. RESULTS: The mean ENO level in the asthmatic children prior to glucocorticoid treatment was 48 +/- 8ppb, and after glucocorticoid treatment the ENO level was 17 +/- 1ppb; (P < .002). Prior to glucocorticoid treatment, the mean FEV1% value was 68 +/- 3% compared with the postglucocorticoid treatment FEV1% value of 100 +/- 5%; (P < .0001). Prior to glucocorticoid treatment, the mean PEF% value was 81 +/- 7%, compared with the postglucocorticoid treatment PEF% value of 105 +/- 6%; (P < .02). CONCLUSIONS: The mean peak ENO level after glucocorticoid therapy was significantly less than that measured before treatment in children with acute asthma exacerbations. Concomitant with the decrease in ENO levels, there was improvement in the spirometry values and physical examination in the asthmatic children; thus, ENO is a sensitive marker for response to anti-inflammatory treatment in children.

Anti-Asthmatic Agents↗
PubMed1999

Luminol/H2O2 chemiluminescence detector for the analysis of nitric oxide in exhaled breath.

A new instrument for the detection of nitric oxide has been developed and applied to the analysis of exhaled breath. The instrument is based on conversion of NO to NO2, using the oxidant chromium trioxide, followed by detection of chemiluminescence in the reaction of NO2 with an alkaline luminol/H2O2 solution. The presence of H2O2 is found to enhance the sensitivity of NO2 detection by a factor of approximately 20. A bundle of porous polypropylene hollow fiber membranes is used to bring the gaseous sample into contact with the luminol solution. Chemiluminescence occurring within the translucent hollow fibers is detected using a miniature photomultiplier tube. The limit of detection for NO is 0.3 ppbv for S/N = 3, and the 1/e response time is 2 s. A large interference resulting from the 4-6% CO2 concentration in exhaled breath is removed by use of an ascarite scrubber in the air stream. Breath measurements of NO were made using a sampling technique developed by Sensor Medics (Yorba Linda, CA) with simultaneous detection using the luminol/H2O2 and NO + O3 chemiluminescence techniques. The two instruments were found to be in excellent agreement. Nitric oxide levels were in the range 6.0-22.0 ppbv for healthy individuals and 40.0-80.0 ppbv for individuals with asthma or a respiratory infection. This new detector offers the advantages of compact size, low cost, and a simple configuration compared to NO detectors based on NO + O3 chemiluminescence.

Breath Tests↗
PubMed2000

NO chemiluminescence in exhaled air: interference of compounds from endogenous or exogenous sources.

Nitric oxide determination in exhaled air using chemiluminescence analysers is increasingly used, but may be affected by various other components of the air sample. The influence of several compounds originating from endogenous or exogenous sources on NO readings has been studied. Defined amounts of water vapour, carbon dioxide, acetone, heptane, acetonitrile, oxygen, nitrous oxide and enflurane were added to air samples with NO concentrations 0-250 parts per billion. Marked and significant decreases in NO readings, which strongly depend on the concentration of the respective interfering compound, were found for water vapour (0.155% per 1% relative humidity), carbon dioxide (1.97% per 1% CO2 volume/volume (v/v)) and nitrous oxide (0.608% per 1% v/v N2O). While acetone in concentrations up to 8.5% v/v had no measurable effect on NO readings, heptane and acetonitrile led to marked decreases. Oxygen in concentrations of up to 95% (v/v) had no effect on NO determination. NO readings were markedly decreased by >10% per 1% (v/v) of the anaesthetic enflurane. However, due to large variations in NO values, these decreases were not statistically significant. Furthermore, enflurane reacted with the molybdenum converter of the NO(x) analyser in use, resulting in major damage to the instrument. Eliminating, or at least considering, interferences by compounds present in exhaled air is an urgent prerequisite for reliable and precise nitric oxide determination.

Acetone↗
PubMed2000

Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children.

The purpose of the present study was to assess the possible relationships between exhaled nitric oxide (ENO), a circulating marker of eosinophil activation, serum eosinophil cationic protein (SECP), level of airway responsiveness to methacholine and lung function in asthmatic children, as well as to compare these markers between children with and without inhaled steroid therapy. In a cross-sectional study ENO, SECP and bronchial hyperresponsiveness to methacholine were evaluated in a group of 57 asthmatic children (21 without and 36 with regulator inhaled steroid therapy; aged 6-13 yrs). ENO was significantly lower in steroid treated children (p<0.01). No significant differences between steroid treated and untreated children were observed for the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1; PC20), SECP and FEV1. In the whole study population significant increase correlations were observed between PC20 and SECP (r=-0.329, p=0.013) and between ENO and FEV1% of predicted (r=-0.348, p<0.01). In the group not receiving inhaled steroids the inverse relationship between PC20 and SECP was more evident (r=-0.581, p<0.001). In the steroid-treated group a significant inverse relationship was observed between ENO and FEV1 (r=-0.426, p=0.0011). The level of exhaled nitric oxide and the relationships between lung function, bronchial reactivity and markers of inflammation are different between steroid-treated and untreated asthmatic children. This has implications for the monitoring of asthma in childhood.

Adolescent↗
PubMed2001

Exhaled nitric oxide in asthmatic and non-asthmatic children: influence of type of allergen sensitization and exposure to tobacco smoke.

Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3-14 years of age) were studied. Parents completed a questionnaire that sought information on their children's respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin-prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cow's milk. eNO was collected in 1-l mylar bags (exhaled pressure 10 cmH2O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non-atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non-atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7-1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non-atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non-atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2-3.9, p= 0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30-0.29), and with the sum of all wheals (r = 0.47) (p= 0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non-atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1-2.3, p= 0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt-sensitized subjects: 28.0 p.p.b.; Dpt-unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5-3.5, p= 0.000). Non-asthmatic Dpt-sensitized subjects also had significantly higher eNO values than non-asthmatic, non-Dpt-sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1-1.9, p= 0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house-dust mite allergen.

Allergens↗
PubMed2002

Exhaled nitric oxide in healthy children: variability and a lack of correlation with atopy.

Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme nitric oxide synthetase (NOS) and can be easily measured in exhaled air by chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines and endotoxin, NO is elevated in several chronic inflammatory airway diseases. Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway inflammation in daily routine, the role of possibly influencing factors such as age, time of the day, smoking exposure and intra-individual variability have to be clarified. NO concentrations were measured in 107 healthy children aged 4-18 years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were performed and a questionnaire on family history of atopy, personal symptoms of atopic disease and smoke exposure was completed. For intra-individual variability nitric oxide was measured in six children three times daily on 6 consecutive days. Median eNO concentration was 5.7 p.p.b., and increased significantly with age but did not vary with gender. No correlation was found between eNO and smoke exposure, positive skin-prick test, FEV1, MEF25 and time of the day. There was no circadian rhythm found in the six children measured on 6 consecutive days, but the eNO showed an intra-individual coefficient of variation of 25.9%. With the help of a two-compartment model of the lung the alveolar NO concentration was estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the airway part of NO steadily increased with age. When comparing eNO values with standardized measurement techniques, the age of the children and the large intra-subject coefficient of variation have to be taken into account, whereas in healthy children subject-specific factors such as atopic history, gender and skin test reactivity did not affect eNO measurement.

Breath Tests↗
PubMed2004

Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: a pilot study.

Cysteinyl leukotrienes (cys-LTs), LTB4 and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB4 and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756 m). Sputum eosinophil percentage and measurement of cys-LTs, LTB4 and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 +/- 1.1% at T0 and 3.5 +/- 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 +/- 0.5% at T0 and 1.5 +/- 1.0% at T1 (ns). Cys-LTs mean level was 14.24 +/- 4.53 pg/ml at T0 and 4.65 +/- 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 +/- 0.19 pg/ml at T0 and 2.41 +/- 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 +/- 3.18 pg/ml at T0 to 7.36 +/- 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children.

Adolescent↗