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PubMed2006

IgE sensitisation in relation to flow-independent nitric oxide exchange parameters.

BACKGROUND: A positive association between IgE sensitisation and exhaled NO levels has been found in several studies, but there are no reports on the compartment of the lung that is responsible for the increase in exhaled NO levels seen in IgE-sensitised subjects. METHODS: The present study comprised 288 adult subjects from the European Community Respiratory Health Survey II who were investigated in terms of lung function, IgE sensitisation (sum of specific IgE), smoking history and presence of rhinitis and asthma. Mean airway tissue concentration of NO (CawNO), airway transfer factor for NO (DawNO), mean alveolar concentration of NO (CalvNO) and fractional exhaled concentration of NO at a flow rate of 50 mL s(-1) (FENO 0.05) were determined using the extended NO analysis. RESULTS: IgE-sensitised subjects had higher levels (geometric mean) of FENO 0.05 (24.9 vs. 17.3 ppb) (p < 0.001), DawNO (10.5 vs. 8 mL s(-1)) (p = 0.02) and CawNO (124 vs. 107 ppb) (p < 0.001) and positive correlations were found between the sum of specific IgE and FENO 0.05, CawNO and DawNO levels (p < 0.001 for all correlations). Sensitisation to cat allergen was the major determinant of exhaled NO when adjusting for type of sensitisation. Rhinitis and asthma were not associated with the increase in exhaled NO variables after adjusting for the degree of IgE sensitisation. CONCLUSION: The presence of IgE sensitisation and the degree of allergic sensitisation were related to the increase in airway NO transfer factor and the increase in NO concentration in the airway wall. Sensitisation to cat allergen was related to the highest increases in exhaled NO parameters. Our data suggest that exhaled NO is more a specific marker of allergic inflammation than a marker of asthma or rhinitis.

Adult↗
PubMed1998

[Exposure of relatives of patients after stationary radioiodine therapy by inhalation of 131I in their homes].

AIM: From a model of iodine metabolism exhalation coefficients shall become derived to calculate 131I exhalation by patients after a radioiodine treatment. The validity of these exhalation coefficients shall be reviewed by whole body activity measurements of relatives of patients, who inhaled the radioiodine exhaled by the patients in their homes. The exposure of relatives to patients of a nuclear medical ward after release by exhalation of iodine-131 is investigated. METHODS: Iodine 131I-activity of 17 relatives to patients who had to undergo a radioiodine therapy became measured in a whole body counter only a few days after release of the patient from the nuclear medical ward. The results of the measurements have been compared with the results of calculations according to the model of iodine metabolism. RESULTS: The calculated values of incorporated radioiodine in the relatives of the patient at time of measurement (Amodel) correlate with the measured whole body activity (AGK) according to the regression: Amodel = AGK -47.3 (r2 = 0.959). This relation holds if 2.1 micrograms of iodine become exhaled per day of the 60 micrograms of iodine which are the daily intake of iodine by food. The exposure of all relatives did never exceed 100 microSveff. Using the same model parameters the effective dose equivalent of the relatives to our patients rises up to 6.5 mSv under ambulant radio therapy condition. CONCLUSION: The daily exhalation of 131I is able to be calculated by a mathematical model of iodine metabolism. After staying of patients at least 3 days in a nuclearmedical ward the exposure of relatives of patients in their home does not exceed the value of 100 microSveff by inhalation of iodine-131. This are 10% of the limit of 1 mSveff according to the Recommendations of the Commission on Radiological Protection (ICRP 60). Radioiodine therapy outside of a hospital and "iodine therapy tourisme" of German patients to other countries cannot be accepted.

Air Pollution, Indoor↗
PubMedDate not supplied

[Environmental and biological control in a population exposed to isoflurane in the operating room].

OBJECTIVE: To measure the level of occupational exposure to isoflurane in the operating room, and to determine the relation between isoflurane concentration in atmospheric and exhaled air. PATIENTS AND METHODS: One hundred seventy-eight samples were obtained from 60 male and female subjects who work in the operating room of our hospital. To monitor workplace exposure we used passive diffusion samplers. Biological monitoring (isoflurane in exhaled air) was accomplished with standard adsorption tubes to collect exhaled air samples. Gases were thermically separated and analyzed by gas chromatography. RESULTS: Atmospheric isoflurane concentrations ranged between 1.14 and 157.23 mg/m3 (geometric mean 16.23 mg/m3). Exhaled isoflurane concentrations ranged from 0.15 to 26.09 mg/m3 (geometric mean 2.85 mg/m3). Atmospheric and exhaled isoflurane concentrations were strongly related (r = 0.82; p < 0.0001). Linearity was determined by the following equation: log of exhaled isoflurane concentration = -0.69 + 0.95 log of atmospheric isoflurane concentration. CONCLUSIONS: The concentrations of isoflurane in atmospheric and exhaled air found in our study exceed the maximum levels for halogenated gases recommended by the National Institute for Occupational Safety and Health, although they do not exceed the levels stipulated by Swiss authorities. In order to adequately assess operating room antipollution measures, atmospheric and biologic monitoring of isoflurane and other inhaled anesthetic gas concentrations is necessary.

Adult↗
PubMed2006

[How do pleasant and unpleasant odours change the breathing pattern?].

BACKGROUND: Pleasant odours are thought to stimulate whereas unpleasant odours are thought to shorten it. This common breathing behaviour should be tested with short pure odour stimuli. The question was: Is there an influence on exhalation as well? METHOD: 53 normosmic subjects (33 female, 20 male, mean 22,3 years) had to breathe through one nostril. The other nostril was closed using a foam nose tip with a tube connected to a manometer to record the respiratory pressure. The signal was digitally converted and visualised with LabView-software. Odours were presented in front of the nose with a flow-olfactometer OM 2S by Kobal. Hydrogen sulphide (H2S) as an unpleasant pure odour and phenylethylalcohol (PEA) as a pleasant pure odour were used in weak, moderate and strong concentration. The stimulus duration was 200 ms. The onset of stimulus was triggered manually in late exhalation during regular breathing pattern. The interstimulus interval was at least 3 min. A trial consisted of 16 stimuli (4 weak, 2 moderate, 2 strong of both odours). From the recording the duration and the areas below the respiration curves of inhalation and exhalation were calculated. The changes of these four respiratory parameters were estimated using the ratio of the first breathing cycle after stimulus to the average from the five regular breathing cycles prior to stimulation. Only changes of more than +/- 20 % were defined as an olfactory evoked respiratory response (OERR). RESULTS: Short PEA stimuli evoked about three times more frequently an increase than a decrease of duration of inhalation. The area below the inhalatory curve was enlarged. The subjects inhaled the pleasant odour more deeply and for longer. Short H2S-stimuli evoked three times more frequently a decrease of duration of exhalation than an increase. Due to the forced exhalation an increase of the area below the exhalatory curve was observed in these cases. Changes of inhalation did not show any trend. The subjects exhaled quickly to breathe fresh air in the following cycle. Every subject showed some OERR. 52 subjects responded to both odours. One subject responded to PEA only. The individual frequency of OERRs in a trial ranged from 16 % to 84 %. CONCLUSIONS: In all normosmic subjects some OERRs are evoked by repeated H2S- and PEA-stimuli. Strong stimuli do not increase the rate of OERRs. Therefore, the use of perithreshold stimuli is recommended for respiration-olfactometry.

Adult↗
PubMed1981

Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test.

[1-Methyl-14C], [3-Methyl-14C] and [7-Methyl-14C] caffeine were used to investigate demethylation in control rats, and in rats pretreated with phenobarbital or 3-methylcholanthrene, by a 14CO2-exhalation test. Compared to controls, pretreatment with phenobarbital did not enhance demethylation of any of the labelled caffeines. In contrast, induction by 3-methylcholanthrene, presumably of cytochrome P-448, resulted in highly significant increases in peak 14CO2 exhalation rates, 14CO2 disappearance constants and areas under the exhalation rate - time curves. Based on these results, [7-methyl-14C] and [3-methyl-14C] caffeine were chosen for assessing the feasibility of a caffeine breath test in man, using 5 normal volunteers and 2 patients with compensated liver cirrhosis. 14CO2 exhalation curves in cirrhotics were clearly different from those in normal volunteers, being characterised by a slower rise and a lower specific activity of exhaled 14CO2. Since the variability of the levels of the specific activity in subjects with normal livers suggested the influence of extraneous factors, a second group of normal volunteers, smokers and nonsmokers, was investigated. With either labels, the average 14CO2 exhalation rate was doubled in smokers. From these studies in rats and preliminary results in man it is concluded that specifically labelled caffeine is a suitable and promising substrate for studying demethylation by breath analysis. Presumably, caffeine represents a safe and sensitive indicator of the activity of the cytochrome P-448 system.

Adult↗
PubMed2006

The impact of breathing pattern and lung size on the alcohol breath test.

Highly soluble gases exchange primarily with the bronchial circulation through pulmonary airway tissue. Because of this airway exchange, the assumption that end-exhaled alcohol concentration (EEAC) is equal to alveolar alcohol concentration (AAC) cannot be true. During exhalation, breath alcohol concentration (BrAC) decreases due to uptake of ethanol by the airway tissue. It is therefore impossible to deliver alveolar gas to the mouth during a single exhalation without losing alcohol to the airway mucosa. A consequence of airway alcohol exchange is that EEAC is always less than AAC. In this study, we use a mathematical model of the human lung to determine the influence of subject lung size on the relative reduction of BrAC from AAC. We find that failure to inspire a full inspiration reduces the BrAC at full exhalation, but increases the BrAC at minimum exhalation. In addition, a reduced inhaled volume and can lead to an inability to provide an adequate breath volume. We conclude that alcohol exchange with the airways during the single-exhalation breath test is dependent on lung size of the subject with a bias against subjects with smaller lung size.

Artifacts↗
PubMed1985

Uptake and excretion of [14C]methyl bromide as influenced by exposure concentration.

Methyl bromide is a widely used soil fumigant and poses potential inhalation hazard to workers. Uptake of methyl bromide and pathways for excretion of 14C were investigated in male Fischer-344 rats after nose-only inhalation of 50, 300, 5700, or 10,400 nmol (1.6 to 310 ppm) of [14C]methyl bromide/liter of air for 6 hr. Fractional uptake of methyl bromide decreased at the highest concentrations, 5700 and 10400 nmol/liter, with 37 and 27% of the inhaled methyl bromide absorbed, respectively, compared to 48% at the lower levels. This resulted in the same total amount of methyl bromide being absorbed at the two higher exposure concentrations (650 mumol/kg body wt). Total methyl bromide adsorbed was 9 or 40 mumol/kg body wt after exposure to 50 or 300 nmol/liter, respectively. Elimination of 14C was linearly related to the amount of methyl bromide absorbed as determined from urine, feces, expired CO2, and parent compound collected for 66 hr after the end of exposure. Exhaled 14CO2 was the dominant route of excretion, with from 1.2 to 110 mumol (50% of amount absorbed) exhaled, and was described by a two-component negative exponential function; 85% was exhaled with a t 1/2 of 4 hr, and the remaining 15% was exhaled with a t 1/2 of 17 hr. The rate of exhalation of 14CO2 was not affected by the amount of [14C]methyl bromide absorbed. From 0.4 to 54 mumol was excreted in urine (20% of amount absorbed). The half-time for excretion of 14C in urine was approximately 10 hr, and the rate of excretion was not dependent on the amount of [14C]methyl bromide absorbed. Little 14C was exhaled as methyl bromide (less than 4% of the dose) or excreted in feces (less than 2%). At the end of 66 hr, 25% of the 14C absorbed remained in the rats. Liver, kidneys, adrenals, lungs, thymus, and turbinates (maxilloturbinates, ethmoturbinates, and nasal epithelial membrane) contained the highest concentrations of 14C. Results indicated that uptake of inhaled methyl bromide could be saturated. Any [14C]methyl bromide equivalents absorbed, however, would be excreted by concentration-independent mechanisms.

Air Pollutants, Occupational↗
PubMed1988

The induction of autoxidative tissue damage by iron nitrilotriacetate in rats and mice.

Iron nitrilotriacetate (FeNTA) is a potent initiator of lipid peroxidation, and, when injected intraperitoneally into mice, it greatly increased ethane and pentane exhalation within 30 min. The time course and dose-response of the exhalation of ethane were studied and compared with the increase in tissue malondialdehyde (MDA) production. Production of MDA was greater in mouse kidney than liver and correlated better with the exhalation of ethane. In rats FeNTA also increased ethane exhalation and MDA, but the rat was less susceptible than the mouse to FeNTA toxicity. MDA production was greater in rat liver than kidney and both correlated well with ethane exhalation (r = 0.97 and 0.98, respectively). Renal proximal tubular damage was observed histologically 35 min after mice were given FeNTA, but in rats the lesion appeared 24 hr after dosage. Histopathological assessment of kidney damage at these times showed fair correlation with ethane exhalation in mice (r = 0.73) and rats (r = 0.62), respectively. Activities of kidney brush-border marker enzymes were decreased in mice, 35 min after FeNTA administration, and showed a similar trend in rats. Some rats also showed periportal necrosis of the liver, 24 hr after FeNTA administration. The very rapid onset of autoxidative damage suggests that FeNTA itself is the causative agent rather than subsequently formed, less reactive complexes, such as transferrin. The site of damage in the kidney tubule is consistent with the region of concentration of filtered FeNTA. It is suggested that FeNTA supports the formation of superoxide ion from dissolved oxygen and may be responsible for the subsequent formation of hydroxyl radical which initiates lipid peroxidation. The species difference between rat and mouse may be due to the greater resistance of the rat kidney to FeNTA-induced autoxidative damage.

Alkanes↗
PubMed1989

The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats.

The pharmacokinetics of 1,1,1-trichloroethane (TRI) was studied in male Sprague-Dawley rats in order to characterize and quantify TRI uptake and elimination oby direct measurements of the inhaled and exhaled compound. Fifty or 500 ppm TRI was inhaled for 2 hr through a one-way breathing valve by unanesthetized rats of 325-375 g. Repetitive samples of the separate inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently both during and following TRI inhalation and analyzed for TRI by gas chromatography. Respiratory rates and volumes were continuously monitored during and following exposure and were used in conjunction with the pharmacokinetic data to characterize profiles of uptake and elimination. TRI was very rapidly absorbed from the lung, in that substantial levels were present in arterial blood at the first sampling time (i.e., 2 min). Blood and exhaled breath concentrations of TRI increased rapidly after the initiation of exposure, approaching but not reaching steady state during the 2-hr exposures. The blood and exhaled breath concentrations were directly proportional to the exposure concentration during the exposures. Percentage uptake of TRI decreased 30-35% during the first hour of inhalation, diminishing to approximately 45-50% by the end of the exposure. Total cumulative uptake in the 50 and 500 ppm groups over the 2-hr inhalation exposures was determined to be 6 and 48 mg/kg body wt, respectively. By the end of the exposure period, 2.1 and 20.8 mg, respectively, of inhaled TRI was eliminated from rats inhaling 50 and 500 ppm TRI. A physiological pharmacokinetic model for TRI inhalation was utilized to predict blood and exhaled breath concentrations for comparison with observed experimental values. Overall, values predicted by the physiological pharmacokinetic model for TRI levels in the blood and exhaled breath were in close agreement with measured values both during and following TRI inhalation.

Administration, Inhalation↗
PubMed2006

Breath tests and airway gas exchange.

Measuring soluble gas in the exhaled breath is a non-invasive technique used to estimate levels of respiratory, solvent, and metabolic gases. The interpretation of these measurements is based on the assumption that the measured gases exchange in the alveoli. While the respiratory gases have a low blood-solubility and exchange in the alveoli, high blood-soluble gases exchange in the airways. The effect of airway gas exchange on the interpretation of these exhaled breath measurements can be significant. We describe airway gas exchange in relation to exhaled measurements of soluble gases that exchange in the alveoli. The mechanisms of airway gas exchange are reviewed and criteria for determining if a gas exchanges in the airways are provided. The effects of diffusion, perfusion, temperature and breathing maneuver on airway gas exchange and on measurement of exhaled soluble gas are discussed. A method for estimating the impact of airway gas exchange on exhaled breath measurements is presented. We recommend that investigators should carefully control the inspired air conditions and type of exhalation maneuver used in a breath test. Additionally, care should be taken when interpreting breath tests from subjects with pulmonary disease.

Breath Tests↗
PubMed2000

Baseline airway hyperresponsiveness and its reversible component: role of airway inflammation and airway calibre.

Airway hyperresponsiveness (AHR), in which airway inflammation has been reported to be a key factor, is an important component of asthma. However the precise role of inflammation in AHR is still unclear. In this report, airway inflammatory changes were assessed using hypertonic saline-induced sputum examination and exhaled nitric oxide analysis, and the relation between AHR to methacholine, airway calibre forced expiratory volume in one second (FEV1) and airway inflammatory indices examined. Furthermore, the changes in these variables were also examined by means of 8 weeks' open uncontrolled inhaled steroid administration (800 microg x beclomethasone x day(-1)). Asthmatic subjects had higher eosinophil counts and bradykinin concentration in induced sputum and higher exhaled NO levels, and showed AHR to methacholine. Baseline AHR significantly correlated with FEV1 but not with indices of inflammation in sputum or exhaled air. Steroid inhalation therapy was associated with a reduction in eosinophil and bradykinin concentration in sputum and NO levels in exhaled air and an improvement in FEV1 and AHR. The changes in FEV1 and AHR were significantly related to changes in markers in sputum and exhaled air (p<0.01 for each). These results suggest that baseline airway hyperresponsiveness can be predicted from the airway calibre but not from inflammatory parameters in sputum or exhaled air. In contrast, the reversible component of airway hyperresponsiveness appeared to be associated with the reduction in airway inflammation.

Administration, Inhalation↗
PubMed2002

Biological monitoring of midwives' exposure to N(2)O using the Bio-VOC breath sampler.

The use of exhaled breath as a biological monitoring tool is still not widely used. Although there are now commercially available kits, there are limited data on biological guidance values for all but a few substances for breath monitoring. The study investigated the possibility of using an indirect breath sampler to measure the levels of nitrous oxide in the exhaled breath of midwives at a midpoint during their shift. Levels of nitrous oxide in the exhaled breath were measured at (0-727 ppm) with a mean level of 64 ppm. The correlation between the established personal environmental monitoring and exhaled breath monitoring was generally poor as was the correlation between duration of nitrous oxide exposure and levels in the exhaled breath. Clearly the use of exhaled breath as a tool for biological monitoring is more appropriate than other invasive procedures. The breath sampler used has been a readily acceptable tool for occupational hygiene monitoring in a busy hospital ward.

Adult↗
PubMed2002

Relationship between environmental exposure to toluene, xylene and ethylbenzene and the expired breath concentrations for gasoline service workers.

This study evaluated the relationship between the breath concentrations of, and personal exposure to, toluene, xylene and ethylbenzene of thirty workers from ten gasoline stations. Personal exposure air samples and workplace samples were collected simultaneously. Each subject provided a sample of exhaled breath after his or her personal exposure air was sampled. Twenty-five personal air, 17 workplace and 30 breath samples were collected in this study. Results indicated that breath concentrations of toluene and xylene were significantly correlated with personal monitoring concentrations. Furthermore, multiple regression analysis showed that exhaled toluene levels were highly influenced by personal toluene concentrations and the amount of personal gasoline sold (r2 = 0.762), while exhaled xylene levels depended on wind speed and personal xylene exposure concentrations (r2 = 0.665). Exhaled ethylbenzene levels were too low to present a relationship between concentrations and personal exposure levels. The exhaled toluene, xylene and ethylbenzene concentrations ranged from 4.3 to 41.8, 0.9 to 13.9, and 0.2 to 6.5 ppb, and the corresponding personal monitoring concentrations ranged from 60.3 to 572.3, 16.4 to 156.6, and 10.7 to 136.6, respectively. The average number of symptoms per person, according to neurotoxic questionnaire 16 (abbreviated as Q16) was 4.1 and six workers showed over six symptoms in Q16. This study suggests that exhaled toluene and xylene levels are suitable for use as biological exposure indices even at the ppb-level of exposure. Gasoline service workers are exposed to high levels of volatile organic compounds (VOCs) and the potential threats to their neurological systems deserve further investigation.

Adult↗
PubMed2001

Hydrogen peroxide in breath condensate during a common cold.

BACKGROUND: Hydrogen peroxide (H2O2) in exhaled air condensate is elevated in inflammatory disorders of the lower respiratory tract. It is unknown whether viral colds contribute to exhaled H2O2. AIM: To assess exhaled H2O2 during and after a common cold. METHODS: We examined H2O2 in the breath condensate of 20 normal subjects with acute symptoms of a common cold and after recovery 2 weeks later and, similarly, in 10 subjects without infection. H2O2 was measured with a fluorimetric assay. RESULTS: At the time of infection exhaled H2O2 (median, ranges) was 0.20 microM (0.03-1.2 microM), and this decreased to 0.09 microM (< 0.01-0.40 microM) after recovery (p = 0.006). There was no significant difference in lung function (forced vital capacity and forced expiratory volume in 1 sec) during and after colds. In the controls, exhaled H2O2 did not change over a 2-week period. CONCLUSIONS: H2O2 in exhaled air condensate is elevated during a common cold, and returns to normal within 2 weeks of recovery in healthy subjects. Hence, symptomatic upper respiratory tract infection may act as a confounder in studies of H2O2 as a marker of chronic lower airway inflammation.

Adult↗
PubMed2001

Toxicokinetics of methyl tert-butyl ether and its metabolites in humans after oral exposure.

Methyl tert-butyl ether (MTBE) is widely used as an additive to gasoline, to increase oxygen content and reduce tailpipe emission of pollutants. Widespread human exposure to MTBE may occur due to leakage of gasoline storage tanks and a high stability and mobility of MTBE in ground water. To compare disposition of MTBE after different routes of exposure, its biotransformation was studied in humans after oral administration in water. Human volunteers (3 males and 3 females, identical individuals, exposures were performed 4 weeks apart) were exposed to 5 and 15 mg 13C-MTBE dissolved in 100 ml of water. Urine samples from the volunteers were collected for 96 h after administration in 6-h intervals and blood samples were taken in intervals for 24 h. In urine, MTBE and the MTBE-metabolites tert-butanol (t-butanol), 2-methyl-1,2-propane diol, and 2-hydroxyisobutyrate were quantified, MTBE and t-butanol were determined in blood samples and in exhaled air in a limited study of 3 male volunteers given 15 mg MTBE in 100 ml of water. MTBE blood concentrations were 0.69 +/- 0.25 microM after 15 mg MTBE and 0.10 +/- 0.03 microM after 5 mg MTBE. MTBE was rapidly cleared from blood with terminal half-lives of 3.7 +/- 0.9 h (15 mg MTBE) and 8.1 +/- 3.0 h (5 mg MTBE). The blood concentrations of t-butanol were 1.82 +/- 0.63 microM after 15 mg MTBE and 0.45 +/- 0.13 microM after 5 mg MTBE. Approximately 30% of the MTBE dose was cleared by exhalation as unchanged MTBE and as t-butanol. MTBE exhalation was rapid and maximal MTBE concentrations (100 nmol/l) in exhaled air were achieved within 10-20 min. Clearance of MTBE by exhalation paralleled clearance of MTBE from blood. T-butanol was cleared from blood with half-lives of 8.5 +/- 2.4 h (15 mg MTBE) and 8.1 +/- 1.6 h (5 mg MTBE). In urine samples, 2-hydroxyisobutyrate was recovered as major excretory product, t-butanol and 2-methyl-1,2-propane diol were minor metabolites. Elimination half-lives for the different urinary metabolites of MTBE were between 7.7 and 17.8 h. Approximately 50% of the administered MTBE was recovered in urine of the volunteers after both exposures, another 30% was recovered in exhaled air as unchanged MTBE and t-butanol. The obtained data indicate that MTBE-biotransformation and excretion after oral exposure is similar to inhalation exposure and suggest the absence of a significant first-pass metabolism of MTBE in the liver after oral administration.

Adult↗
PubMed1995

The promotion of patent airways and inhibition of antigen-induced bronchial obstruction by endogenous nitric oxide.

1. The aim of the present study was to investigate the role of nitric oxide (NO), histamine and leukotrienes in bronchial obstruction. For this, guinea-pigs immunised against ovalbumin were studied under anaesthesia during challenge with antigen or agonists. 2. Challenge with nebulised antigen (0.1-1 mg) elicited dose-dependent increases in insufflation pressure which were abolished by combined administration of histamine and leukotriene antagonists. 3. Challenge with nebulised antigen (0.1-1 mg) also elicited dose-dependent increases in the concentration of endogenous nitric oxide in the exhaled air. After an initial peak, exhaled NO concentrations returned to pre-challenge levels. 4. The increase in insufflation pressure and in exhaled NO caused by ovalbumin challenge was inhibited by combined administration of histamine and leukotriene antagonists. 5. In non-immunised guinea-pigs, challenge of the airways with nebulised histamine (10-1000 nmol) or leukotriene C4 (LTC4, 30-300 pmol) elicited dose-dependent increases in insufflation pressure and in concentrations of endogenous NO in exhaled air. 6. The increase in exhaled NO correlated with the increase in insufflation pressure in response to ovalbumin, histamine and LTC4. An inhibitor of endogenous NO synthesis, N omega-nitro-L-arginine methylester (L-NAME, 30 mg kg-1 i.v.) abolished NO exhalation, and markedly augmented the airway responses to ovalbumin, histamine, or LTC4. 7. The potentiation by L-NAME of the increase in insufflation pressure in response to ovalbumin or histamine was prevented by exogenous NO (20 p.p.m.) in the inhaled air. 8. The results indicate that endogenous NO has an inhibitory effect on bronchial obstruction. Increased NO release during allergen challenge is likely to be due to actions of histamine and leukotrienes.

Airway Obstruction↗
PubMed2005

Dose reconstruction in deforming lung anatomy: dose grid size effects and clinical implications.

In this study we investigated the accumulation of dose to a deforming anatomy (such as lung) based on voxel tracking and by using time weighting factors derived from a breathing probability distribution function (p.d.f.). A mutual information registration scheme (using thin-plate spline warping) provided a transformation that allows the tracking of points between exhale and inhale treatment planning datasets (and/or intermediate state scans). The dose distributions were computed at the same resolution on each dataset using the Dose Planning Method (DPM) Monte Carlo code. Two accumulation/interpolation approaches were assessed. The first maps exhale dose grid points onto the inhale scan, estimates the doses at the "tracked" locations by trilinear interpolation and scores the accumulated doses (via the p.d.f.) on the original exhale data set. In the second approach, the "volume" associated with each exhale dose grid point (exhale dose voxel) is first subdivided into octants, the center of each octant is mapped to locations on the inhale dose grid and doses are estimated by trilinear interpolation. The octant doses are then averaged to form the inhale voxel dose and scored at the original exhale dose grid point location. Differences between the interpolation schemes are voxel size and tissue density dependent, but in general appear primarily only in regions with steep dose gradients (e.g., penumbra). Their magnitude (small regions of few percent differences) is less than the alterations in dose due to positional and shape changes from breathing in the first place. Thus, for sufficiently small dose grid point spacing, and relative to organ motion and deformation, differences due solely to the interpolation are unlikely to result in clinically significant differences to volume-based evaluation metrics such as mean lung dose (MLD) and tumor equivalent uniform dose (gEUD). The overall effects of deformation vary among patients. They depend on the tumor location, field size, volume expansion, tissue heterogeneity, and direction of tumor displacement with respect to the beam, and are more likely to have an impact on serial organs (such as esophagus), rather than on large parallel organs (such as lung).

Body Burden↗
PubMed1999

Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma.

BACKGROUND: It is desirable to prescribe the minimal effective dose of inhaled steroids to control asthma. To ensure that inflammation is suppressed whilst using the lowest possible dose, a sensitive and specific method for assessing airway inflammation is needed. METHODS: The usefulness of exhaled nitric oxide (NO), sputum eosinophils, and methacholine airway responsiveness (PC20) for monitoring airway inflammatory changes following four weeks of treatment with an inhaled corticosteroid (budesonide via Turbohaler) were compared. Mild stable steroid naive asthmatic subjects were randomised into two double blind, placebo controlled studies. The first was a parallel group study involving three groups receiving either 100 micrograms/day budesonide (n = 8), 400 micrograms/day budesonide (n = 7), or a matched placebo (n = 6). The second was a crossover study involving 10 subjects randomised to receive 1600 micrograms budesonide or placebo. The groups were matched with respect to age, PC20, baseline FEV1 (% predicted), exhaled NO, and sputum eosinophilia. RESULTS: There were significant improvements in FEV1 following 400 micrograms and 1600 micrograms budesonide (11.3% and 6.5%, respectively, p < 0.05). This was accompanied by significant reductions in eosinophil numbers in induced sputum (0.7 and 0.9 fold, p < 0.05). However, levels of exhaled NO were reduced following each budesonide dose while PC20 was improved only with 1600 micrograms budesonide. These results suggest that exhaled NO and PC20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in sputum. There were dose dependent changes in exhaled NO, sputum eosinophils, and PC20 to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 micrograms daily. CONCLUSION: Monitoring the number of eosinophils in induced sputum may be the most accurate guide to establish the minimum dose of inhaled steroids needed to control inflammation. This, however, requires further studies involving a larger number of patients.

Administration, Inhalation↗