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Effect of two anaesthetic regimens on airway nitric oxide production in horses.

There is evidence that halothane inhibits nitric oxide synthase in vitro, but the effect of intravenous anaesthetic agents is less clear. This study was undertaken to compare the rate of exhaled nitric oxide production (VNO) in spontaneously breathing horses anaesthetized with halothane or an intravenous regimen. Seven adult horses were studied twice in random order. After premedication with romifidine 100 microg kg(-1), anaesthesia was induced with ketamine 2.2 mg kg(-1) and maintained with halothane in oxygen (HA) or by an intravenous infusion of ketamine, guaiphenesin and romifidine (IV). Inhaled and exhaled nitric oxide (NO) concentrations, respiratory minute ventilation (VE), pulmonary artery pressure (PPA), fractional inspired oxygen concentration (FIO2), end-tidal carbon dioxide concentration (E'CO2), cardiac output (Q) and partial pressures of oxygen and carbon dioxide in arterial blood (PaO2, PaCO2) were measured. Exhaled nitric oxide production rate was significantly lower (40 min, P<0.01; 60 min, P<0.02) during HA [40 min, 1.4 (SD 1.4) pmol l(-1) kg(-1) min(-1); 60 min, 0.7 (0.7) pmol l(-1) kg(-1) min(-1)] than during IV [40 min, 9.3 (9.9) pmol l(-1) kg(-1) min(-1); 60 min, 12.5 (13.3) pmol l(-1) kg(-1) min(-1)). Mean pulmonary artery pressure was significantly higher (40 min, P<0.01; 60 min, P<0.001) during HA [40 min, 5.9 (1.1) kPa; 60 min, 5.9 (0.9) kPa] compared with IV (40 min, 4.4 (0.4) kPa; 60 min, 4.4 (0.5) kPa]. NO is reduced in the exhalate of horses anaesthetized with halothane compared with an intravenous regimen. It is suggested that increased mean pulmonary artery pressure during halothane anaesthesia may be linked to the differences in NO production.

Anesthetics, Inhalation↗

Domestic pollution and respiratory illness in a Himalayan village.

Summer and winter surveys of a village in Ladakh have been used to study respiratory illness and domestic pollution from fires in an arid high altitude region of northern India. The prevalence of chronic cough with chronic phlegm rose steeply with age, and was greater among women than men. The percentage of villagers with a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio of less than 65% also rose with age, to include 24% of men and 32% of women over 50 years in the summer survey. Lung function was significantly worse in those reporting chronic cough, independently of age and sex (p less than 0.001). Carbon monoxide (CO) measurements were used to assess domestic pollution from fires. Amongst the small minority of smokers (all men) CO in exhaled air was higher than in non-smoking men. In non-smoking men and the women, levels of exhaled CO were very significantly higher in winter than in summer, as were the levels of CO measured in the houses. There was a fall in FEV1 (but not FVC) between summer and winter (p less than 0.0001), and an association was found between individual change from summer to winter in exhaled air CO and the individual change in FEV1 (p less than 0.01). A significant negative association was found between the winter value of CO in exhaled air and FEV1/FVC ratio in women (p less than 0.05), although a similar association in men was non-significant. No significant associations were found between winter pollution levels and the presence of chronic symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Uptake of 10 polar organic solvents during short-term respiration.

Respiratory uptake was investigated for 10 polar organic solvents with high blood/air partition coefficients (lambda(blood/air)): ethyl acetate (lambda(blood/air), 77), methyl iso-butyl ketone (90), methyl acetate (90), methyl propyl ketone (150), acetone (245), iso-pentyl alcohol (381), iso-propyl alcohol (848), methyl alcohol (2590), ethylene glycol monobutyl ether (EGBE, 7970), and propylene glycol monomethyl ether (PGME, 12380). Test-air concentrations (Cinh) were 25 to 200 ppm. Four healthy male volunteers inhaled the test air for 10 min at rest and then room air for 5 min. The percentage of solvent in the end-exhaled air and in the mixed-exhaled air increased after the start of the test-air respiration, and reached a quasi-steady-state level within a few min. The speeds of these increases at the start of the test-air respiration became lower as lambda(blood/air) increased. The mean uptakes (U) for the last five min of the test air respiration were 67.3, 52.9, 60.4, 53.0, 52.6, 63.0, 60.3, 60.8, 79.7, and 81.3%, respectively, for ethyl acetate, methyl iso-butyl ketone, methyl acetate, methyl propyl ketone, acetone, iso-pentyl alcohol, iso-propyl alcohol, methyl alcohol, EGBE and PGME. Thus, U values of the alcohols were higher than those of the ketones and lower than the glycol ethers. The overall view, except for esters, showed that U increased with lambda(water/air) increases. This tendency can be explained by a hypothesis that solvent absorbed in the mucus layer of the respiratory tract is removed by the bronchial blood circulation. U values of ethyl acetate and methyl acetate were higher than those of methyl iso-butyl ketone and methyl propyl ketone, though the lambda(blood/air) values of these esters were nearly equal to those of the ketones. For the respiration of the esters, their metabolites, ethyl alcohol and methyl alcohol, were detected in the exhaled air. The exhalation percentage of the metabolites increased after the start of test-air respiration and reached a quasi-steady-state level of 2 and 3%, respectively, by the 5th min. These data suggest that removal of the solvent via metabolism in the wall tissue of the respiratory tract plays an important role for the esters.

Administration, Inhalation↗

Quantitative and qualitative differences in the metabolism of 14C-1,3-butadiene in rats and mice: relevance to cancer susceptibility.

1,3-Butadiene (butadiene) is a potent carcinogen in mice, but not in rats. Metabolic studies may provide an explanation of these species differences and their relevance to humans. Male Sprague-Dawley rats and B6C3F1 mice were exposed for 6 h to 200 ppm [2,3-14C]-butadiene (specific radioactivity [sa] 20 mCi/mmol) in a Cannon nose-only system. Radioactivity in urine, feces, exhaled volatiles and 14C-CO2 were measured during and up to 42 h after exposure. The total uptake of butadiene by rats and mice under these experimental conditions was 0.19 and 0.38 mmol (equivalent to 3.8 and 7.5 mCi) per kg body weight, respectively. In the rat, 40% of the recovered radioactivity was exhaled as 14C-CO2, 70% of which was trapped during the 6-h exposure period. In contrast, only 6% was exhaled as 14C-CO2 by mice, 3% during the 6-h exposure and 97% in the 42 h following cessation of exposure. The formation of 14C-CO2 from [2,3-14C]-labeled butadiene indicated a ready biodegradability of butadiene. Radioactivity excreted in urine accounted for 42% of the recovered radioactivity from rats and 71% from mice. Small amounts of radioactivity were recovered in feces, exhaled volatiles and carcasses. Although there was a large measure of commonality, the exposure to butadiene also led to the formation of different metabolites in rats and mice. These metabolites were not found after administration of [4-14C]-1,2-epoxy-3-butene to animals by i.p. injection. The results show that the species differences in the metabolism of butadiene are not simply confined to the quantitative formation of epoxides, but also reflect a species-dependent selection of metabolic pathways. No metabolites other than those formed via an epoxide intermediate were identified in the urine of rats or mice after exposure to 14C-butadiene. These findings may have relevance for the prediction of butadiene toxicity and provide a basis for a revision of the existing physiologically based pharmacokinetic models.

Administration, Inhalation↗

PBPK modeling of the percutaneous absorption of perchloroethylene from a soil matrix in rats and humans.

Perchloroethylene (PCE) is a widely used volatile organic chemical. Exposures to PCE are primarily through inhalation and dermal contact. The dermal absorption of PCE from a soil matrix was compared in rats and humans using real-time MS/MS exhaled breath technology and physiologically based pharmacokinetic (PBPK) modeling. Studies with rats were performed to compare the effects of loading volume, concentration, and occlusion. In rats, the percutaneous permeability coefficient (K(P)) for PCE was 0.102 +/- 0.017, and was independent of loading volume, concentration, or occlusion. Exhaled breath concentrations peaked within 1 h in nonoccluded exposures, but were maintained over the 5 h exposure period when the system was occluded. Three human volunteers submerged a hand in a container of PCE-laden soil for 2 h and their exhaled breath was continually monitored during and for 2.5 h following exposure. The absorption and elimination kinetics of PCE were slower in these subjects than initially predicted based upon the PBPK model developed from rat dermal kinetic data. The resulting K(P) for humans was over 100-fold lower than for the rat utilizing a single, well-stirred dermal compartment. Therefore, two additional PBPK skin compartment models were evaluated: a parallel model to simulate follicular uptake and a layered model to portray a stratum corneum barrier. The parallel dual dermal compartment model was not capable of describing the exhaled breath kinetics, whereas the layered model substantially improved the fit of the model to the complex kinetics of dermal absorption through the hand. In real-world situations, percutaneous absorption of PCE is likely to be minimal.

Administration, Cutaneous↗

Selective iNOS inhibition prevents hypotension in septic rats while preserving endothelium-dependent vasodilation.

UNLABELLED: Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) mediates hypotension and metabolic derangements in sepsis. We hypothesized that selective iNOS-inhibition would prevent hypotension in septic rats without inhibiting endothelium-dependent vasodilation caused by the physiologically important endothelial NOS. Rats were exposed to lipopolysaccharide (LPS) for 6 h and the selective iNOS-inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL), the nonselective NOS-inhibitor N:(G)-nitro-L-arginine methyl ester (L-NAME), or control. Mean arterial pressure (MAP) and vasodilation to acetylcholine (ACh, endothelium-dependent), sodium nitroprusside (SNP, endothelium-independent), and isoproterenol (ISO, endothelium-independent beta agonist) were determined. Exhaled NO, nitrate/nitrite-(NOx) levels, metabolic data, and immunohistochemical staining for nitrotyrosine, a tracer of peroxynitrite-formation were also determined. In control rats, L-NAME increased MAP, decreased the response to ACh, and increased the response to SNP, whereas L-NIL did not alter these variables. LPS decreased MAP by 18% +/- 1%, decreased vasodilation (ACh, SNP, and ISO), increased exhaled NO, NOx, nitrotyrosine staining, and caused acidosis and hypoglycemia. L-NIL restored MAP and vasodilation (ACh, SNP, and ISO) to baseline and prevented the changes in exhaled NO, NOx, pH, and glucose levels. In contrast, L-NAME restored MAP and SNP vasodilation, but did not alter the decreased response to ACh and ISO or prevent the changes in exhaled NO and glucose levels. Finally, L-NIL but not L-NAME decreased nitrotyrosine staining in LPS rats. In conclusion, L-NIL prevents hypotension and metabolic derangements in septic rats without affecting endothelium-dependent vasodilation whereas L-NAME does not. IMPLICATIONS: Sepsis causes hypotension and metabolic derangements partly because of increased nitric oxide. Selective inhibition of nitric oxide produced by the inducible nitric oxide synthase enzyme prevents hypotension and attenuates metabolic derangements while preserving the important vascular function associated with endothelium-dependent vasodilation in septic rats.

Acetylcholine↗

The effect of a bellows leak in an Ohmeda 7810 ventilator on room contamination, inspired oxygen, airway pressure, and tidal volume.

We investigated the effect of a small bellows leak (bellows full at end-expiration) on inspired oxygen fraction (Fio(2)), exhaled tidal volume (Vt), airway pressure, and room contamination in an oxygen-driven anesthesia ventilator (Ohmeda 7810, Madison, WI). CO(2) concentration at the ventilator exhalation valve, Fio(2), Vt, and airway pressure were measured (n = 3) while ventilating a CO(2)-producing test lung at 8 breaths/min and an inspiratory/expiratory ratio of 1:2, with and without a bellows leak (4-mm-long tear). Set Vt was 400, 600, 800, and 1000 mL. Fresh gas flow (FGF) was 0.3 L/min O(2) and (a) 5.0 L/min air, (b) 2.0 L/min air, and (c) 0.2 L/min nitrogen. There was no clinical difference in Fio(2), Vt, PIP (peak inspiratory pressure) and PEEP (positive end-expiratory pressure), with and without a 4-mm bellows tear, at all FGFs and Vt settings. CO(2) at the ventilator exhalation valve was always nonzero with a bellows leak, indicating that CO(2)-laden circuit gas was contaminating the drive gas via the bellows leak. A 4-mm bellows tear in an Ohmeda 7810 ventilator allows anesthetic gases to contaminate ambient air but does not cause clinically significant changes in Fio(2), exhaled Vt, PIP, or PEEP.

Air Pressure↗

Errors in measurement of oxygen uptake due to anesthetic gases.

Errors in measurement of exhaled gas volume, mixed expired oxygen and carbon dioxide concentrations, and inspired oxygen concentration and the presence of exhaled anesthetic agents cause errors in on-line calculated oxygen uptake that increase geometrically with increasing inspired oxygen concentration. No one has quantified the decrease in the magnitude of the error that might be realized if directly measured nitrogen concentration were included in the calculation. We used a computer model to evaluate this improvement, assuming an oxygen uptake of 200 ml/min and normal ventilatory parameters. Using a Monte Carlo technique, we generated 100 sets of data points, with random errors averaging 0.5% around the expected gas concentrations, and compared the accuracy of oxygen uptake calculated with and without inclusion of directly measured inspired and expired nitrogen concentrations. When the inspired oxygen fractions were 0.2, 0.5, and 0.8, the calculated oxygen uptakes +/- % standard deviation were 200 +/- 4.3, 200 +/- 12, and 196 +/- 21 when directly measured nitrogen was included versus 200 +/- 3.5, 196 +/- 16, and 205 +/- 71 when it was not. The procedure was repeated, assuming 50 ml/min of anesthetic excretion and the calculated oxygen uptakes were 200 +/- 4.6, 202 +/- 12, and 195 +/- 17 versus 212 +/- 3.8, 251 +/- 17, and 398 +/- 64. Including direct measurement of inhaled and exhaled concentrations of nitrogen or another insoluble inert tracer gas allows accurate measurement of oxygen uptake, even in the presence of exhaled anesthetic gases. It also decreases the error in oxygen uptake determination by a factor of nearly six when the inhaled oxygen fraction is 0.8.

Anesthetics↗

Efficacy of preoxygenation with tidal volume breathing. Comparison of breathing systems.

BACKGROUND: Preoxygenation before tracheal intubation is intended to increase oxygen reserves and delay the onset of hypoxemia during apnea. Various systems are used for preoxygenation. Designed specifically for preoxygenation, the NasOral system uses a small nasal mask for inspiration and a mouthpiece for exhalation. One-way valves in the nasal mask and the mouthpiece ensure unidirectional flow. This investigation compares the efficacy of preoxygenation using the standard circle system with the NasOral system and five different resuscitation bags. METHODS: Twenty consenting, healthy volunteers were studied in the supine position for 5-min periods of tidal volume breathing using the circle absorber system, the NasOral system, and five resuscitation bags in a randomized order. Data were collected during room air breathing and at 30-s intervals during 5 min of oxygen administration. Inspired oxygen, end-tidal oxygen, and end-tidal nitrogen were measured by mass spectrometry. RESULTS: At 2. 5 min of oxygenation, end-tidal oxygen plateaued at 88.1 +/- 4.8 and 89.3 +/- 6.4% (mean +/- SD) for the circle absorber and NasOral systems, respectively. This was associated with inverse decreases in end-tidal nitrogen. At no time did these end-tidal oxygen or nitrogen values differ from each other. Three of the resuscitation bags (one disk type and two duck-bill type with one-way exhalation valves) delivered inspired oxygen more than 90%, and the end-tidal oxygen plateaued between 77 and 89% at 2 min of tidal volume breathing. The other two resuscitation bags (both duck-bill bags without exhalation valves) delivered inspired oxygen less than 40%, and the end-tidal oxygen values ranged between 21.8 +/- 5.0 and 31.9 +/- 8.7%. CONCLUSIONS: The circle absorber and NasOral systems were equally effective in achieving maximal preoxygenation during tidal volume breathing. Resuscitation bags differed markedly in effectiveness during preoxygenation; those with duck-bill valves without one-way exhalation valves were the least effective. Thus, the use of these bags should be avoided for preoxygenation.

Adult↗

Simple method to measure total expiratory time constant based on the passive expiratory flow-volume curve.

OBJECTIVE: In intubated, mechanically ventilated patients, inspiration is forced by externally applied positive pressure. In contrast, exhalation is passive and depends on the time constant of the total respiratory system. The expiratory time constant is thus an important determinant of mechanical ventilation. The aim of this study was to evaluate a simple method for measuring the expiratory time constant in ventilated subjects. DESIGN: Prospective study using a lung simulator and ten dogs. SETTING: University hospital. SUBJECTS: Commercially available lung simulator and ten greyhound dogs. INTERVENTIONS: Different expiratory time constants were set on the lung simulator. In the dogs, the endotracheal tube was clamped to increase airways resistance by 22.5 cm H2O/(L/sec) and the lungs were injured with hydrochloric acid to decrease total respiratory compliance by 16 mL/cm H2O. This procedure resulted in a wide range of expiratory time constants. MEASUREMENTS AND MAIN RESULTS: Pneumotachography was used to measure flow and volume. The ratio of exhaled volume and peak flow was calculated from these signals, corrected for the limited exhalation time yielding the "calculated expiratory time constant" and compared with the actual expiratory time constant. The typical error was +/- 0.19 sec for the lung simulator and +/- 0.15 sec for the dogs. CONCLUSIONS: The volume and peak flow corrected for limited exhalation time is a good estimate of the total expiratory time constant in passive subjects and may be useful for the titration of mechanical ventilation.

Airway Resistance↗

Radon mitigation by depressurization of concrete walls and slabs.

A special laboratory, the Radioisotope Unit Radon Analysis Laboratory, has been built for the study of radon mitigation in high-rise buildings. Reduction of radon exhalation rate from concrete walls as a result of depressurizing the interior of the wall was studied by embedding tunnels in a wall and pumping away the radon in the wall. The reduction in exhalation rate was quantified against the applied depressurization, the separation of the tunnels, the depth of the tunnel, and the thickness of the wall. Results show that radon exhalation rate from a wall embedded with tunnels can be reduced significantly by applying depressurization. For example, the radon exhalation rate from a wall of 20 cm thickness containing tunnels separated by 0.7 m can be reduced by 60% at a depressurization of 67 kPa (20 in Hg). This paper summarizes the effect of depressurization and suggests practical ways of applying the technique in radon mitigation in high-rise commercial buildings.

Air Pollution, Indoor↗

Triglyceride oxidation in cystic fibrosis: a comparison between different 13C-labeled tracer substances.

BACKGROUND: For indirect evaluation of pancreatic lipase activity in cystic fibrosis, different 13C-labeled triglycerides may be used. METHODS: Triglyceride oxidation in patients with cystic fibrosis was investigated after administration of different 13C-labeled triglycerides by comparing 13CO2 breath exhalation. In the comparative study, five patients with cystic fibrosis (age, 8-15 years; body weight, 22.5-39.8 kg) were treated with Pangrol (individual dosages: 1-3 capsules per morning meal; Berlin-Chemie, Berlin, Germany). [1,1,1-13C3]Glyceryl tripalmitate and [1,1,1-13C3]glyceryl trioleate were administered as a single oral pulse at 8:00 A.M. (dosage, 4 mg/kg each) with the standard diet Fresubin (dosage, 10 ml/kg; Fresenius, Bad Homburg, Germany). Alternately, the same subjects were given the synthetic mixed triglyceride 1,3-distearyl, 2[13C]octanoyl glycerol (dosage, 12.5 mg/kg) contained in the standard diet Nutri-Mix (dosage, 10 ml/kg; Nutricia, Zoetemeer, The Netherlands). Breath samples were taken in 15- and 30-minute intervals over 8 hours. The 13CO2 enrichment was measured by continuous-flow isotope ratio mass spectrometry. RESULTS: After administration of the 13C-labeled tripalmitin-triolein mixture and the mixed triglyceride, mean maximum 13CO2 enrichments were 4.70 and 7.37 delta over baseline, occurring at 7.0 and 3.5 hours, respectively. The corresponding percentage cumulative 13CO2 exhalations were 12.25% and 29.19%, respectively, and differed significantly in the five paired subjects (p = 0.003). CONCLUSIONS: After using different 13C-labeled triglycerides the resultant 13CO2 exhalation reflected the triglyceride hydrolysis and subsequent oxidation. It is concluded that the different cumulative 13CO2 exhalations were mainly caused by the rate-limiting step of triglyceride hydrolysis to free fatty acids and 2-monoglycerides and by fat deposition. Noninvasive 13C breath tests using different 13C-labeled triglycerides can be used for evaluation of pancreatic lipase activity before and during enzyme supplementation.

Adolescent↗

Species-specific modulation of the nitric oxide pathway after acute experimentally induced endotoxemia.

OBJECTIVE: The derangement of the nitric oxide pathway is an important contributing factor to the pathogenesis of septic shock. The aim of this study was to investigate potential differences in modulation of such a pathway in two experimental models of endotoxemia. DESIGN: Prospective, randomized, placebo-controlled animal investigation. SETTING: Cardiovascular research laboratory. SUBJECTS: Male, anesthetized, and mechanically ventilated New-Zealand rabbits (n = 24) and Sprague-Dawley rats (n = 24). INTERVENTIONS: After pretreatment with 1400W (1 mg kg(-1) subcutaneously), an inhibitor of inducible nitric oxide synthase, animals received an intravenous bolus of Escherichia Coli lipopolysaccharides (5 mg kg(-1)). After 4 hrs, lungs, myocardial left ventricles, and aortas were collected. MEASUREMENTS AND MAIN RESULTS: Blood mean arterial pressure, pH, and nitrite/nitrate were monitored. Nitric oxide in the exhaled air was measured by chemiluminescence. Tissue activity of both constitutive nitric oxide synthase and inducible nitric oxide synthase was determined by measuring the conversion of [3H]L-arginine to [3H]L-citrulline. In lipopolysaccharide-treated animals, both mean arterial pressure (after 60 to 90 mins) and blood pH (after 4 hrs) decreased with respect to baseline values. 1400W prevented lipopolysaccharide-induced hypotension only in rats (p <.01). Exhaled nitric oxide decreased in lipopolysaccharide-treated rabbits by 120 mins (from 12.6 +/- 0.6 to 8.4 +/- 0.6 ppb, p <.01) and remained low until the end of the experiment (p <.01 vs. baseline). Conversely, exhaled nitric oxide increased in lipopolysaccharide-treated rats by 120 mins (from 0.4 +/- 0.1 to 5.3 +/- 1.7 ppb, p <.01) and reached a plateau by 210 mins (19.8 +/- 3.1 ppb, p <.01 vs. baseline). 1400W prevented the lipopolysaccharide-induced increase in exhaled nitric oxide and blood nitrite/nitrate in rats (p <.05). Inducible nitric oxide synthase activity increased in endotoxemic rabbit heart (0.19 +/- 0.05 vs. 0.07 +/- 0.02 pmol L-citrulline/min/mg protein in the control group, p <.05) and in all rat tissues, being more striking in the lungs (25.00 +/- 0.01 vs. 0.19 +/- 0.04 pmol L-citrulline/min/mg protein in the control group, p <.001). CONCLUSIONS: The nitric oxide pathway is differently modulated between endotoxemic rabbits and rats.

Amidines↗

Heterogeneity of FeNO response to inhaled steroid in asthmatic children.

BACKGROUND: Nitric oxide in exhaled air is regarded as an inflammation marker, and may be used to monitor the anti-inflammatory control from inhaled corticosteroids (ICSs). However, this response to ICSs exhibits a heterogeneous pattern. OBJECTIVE: The study aimed to describe the independent variables associated with the heterogeneity in the response of exhaled nitric oxide to ICSs. METHODS: Exhaled nitric oxide (FeNO), lung function, bronchial hyper-responsiveness (BHR), specific IgE to common inhalant allergens, blood eosinophils, other atopic manifestations and variants in nitric oxide synthethase 1 (NOS1) gene were studied in a double-blind, placebo-controlled crossover comparison of budesonide (BUD) Turbohaler 1600 mcg daily vs. placebo in asthmatic schoolchildren. RESULTS: Forty children were included in the study from a screening of 184 asthmatic children with moderately persistent asthma, well controlled on regular BUD 400 mcg daily: 20 children with normal FeNO and 20 with raised FeNO. FeNO, BHR and forced expiratory volume in 1 s improved significantly after BUD 1600 mcg (BUD1600). However, FeNO after ICS treatment exhibited a Gaussian distribution and FeNO was significantly raised in 15 children. Allergy and BHR, but none of the other independent variables under study were significantly related to FeNO after BUD1600. CONCLUSION: Exhaled nitric oxide exhibited a heterogeneous response to ICS in asthmatic schoolchildren. Allergy and BHR were driving FeNO level independently of high-dose steroid treatment. This should be considered when using FeNO for steroid dose titration and monitoring of ICS anti-inflammatory control in asthmatic children.

Administration, Inhalation↗

Reliability and validity of the lung volume measurement made by the BOD POD body composition system.

The BOD POD Body Composition System uses air-displacement plethysmography to measure body volume. To correct the body volume measurement for the subject's lung volume, the BOD POD utilizes pulmonary plethysmography to measure functional residual capacity (FRC) at mid-exhalation as that is the subject's lung volume during the body volume measurement. Normally, FRC is measured at end-exhalation. The BOD POD FRC measurement can be corrected to an end-exhalation volume by subtracting approximately one-half of the measured tidal volume. Our purpose was to determine the reliability and validity of the BOD POD FRC measurement at end-exhalation. Ninety-two healthy adults (half female) underwent duplicate FRC measurements by the BOD POD and one FRC measurement by a traditional gas dilution technique. The latter method was used as the reference method for the validity component of the study. The order of the FRC measurements by the two methods was randomized. The test-retest correlation coefficients for the duplicate BOD POD FRC measurements for the male and female subjects were 0.966 and 0.948, respectively. The mean differences between the BOD POD FRC trial #1 measurement and gas dilution FRC measurement for the male and female subjects were -32 and -23 ml, respectively. Neither difference was statistically significant. The correlation coefficients for these two measurements in the male and female subjects were 0.925 and 0.917, respectively. Based on these results, we conclude that the BOD POD FRC measurement in healthy males and females is both reliable and valid.

Adolescent↗

A compartmental model for the prediction of breath concentration and absorbed dose of chloroform after exposure while showering.

In order to predict the exhaled breath concentration of chloroform in individuals exposed to chloroform while showering, an existing physiologically based pharmacokinetic (PB-PK) model was modified to include a multicompartment, PB-PK model for the skin and a completely mixed shower exposure model. The PB-PK model of the skin included the stratum corneum as the principal resistance to absorption and a viable epidermis which is in dynamic equilibrium with the skin microcirculation. This model was calibrated with measured exhaled breath concentrations of chloroform in individuals exposed while showering with and without dermal absorption. The calibration effort indicated that the expected value of skin-blood partitioning coefficient would be 1.2 when the degree of transfer of chloroform from shower water into shower air was 61%. The stratum corneum permeability coefficient for chloroform was estimated to be within the range of 0.16-0.36 cm/hr and the expected value was 0.2 cm/hr. The estimated ratio of the dermally and inhaled absorbed doses ranged between 0.6 and 2.2 and the expected value was 0.75. These results indicate that for the purposes of risk assessment for dermal exposure to chloroform, a simple steady-state model can be used to predict the degree of dermal absorption and that a reasonable value of skin permeability coefficient for chloroform used in this model would be 0.2 cm/hr. Further research should be conducted to compare the elimination of chloroform via exhaled breath when different exposure routes are being compared. The model results from this study suggest that multiple measurements of exhaled breath concentrations after exposure may be necessary when making comparisons of breath concentrations that involve different exposure routes.

Baths↗

Metabolism of histamine in myotonic dystrophy a dual pattern of inactivation of intestinal histamine.

The catabolism of orally and subcutaneously administered 14C histamine was studied in myotonic dystrophy patients. No definite abnormalities were observed as for subcutaneously administered histamine. The catabolism of orally administered histamine followed two distinct patterns: In patients with a relatively low endogenous urinary conjugated histamine excretion at the time of testing, small quantities of radioactivity were excreted in the stools (mean 0.25 per cent), whereas the quantity of exhaled 14CO2 was in the control range (mean 14.4 per cent), and the exhalation curve diphasic as in controls. In patients with a relatively high urinary conjugated histamine excretion, the catabolic pattern differed: There was a relatively high faecal excretion of radioactivity (mean 20.1 per cent), whereas the exhalation of 14CO2 was markedly reduced (i.e. mean 0.5 per cent, versus a mean control level of 8.9 per cent). Diphasicity of the exhalation curve was not present in these patients. It has previously been demonstrated that a patient with myotonic dystrophy may shift between being a normal and a high conjugated histamine excretor. It is thus possible that all patients with myotonic dystrophy may pass through phases with abnormal catabolism of intestinal histamine.

Administration, Oral↗

Gadolinium chloride inhibition of pulmonary nitric oxide production and effects on pulmonary circulation in the rabbit.

Nitric oxide is an important regulator of pulmonary vascular resistance. Pulmonary nitric oxide formation is detectable in exhaled air and the synthesis is partly stretch-dependent. Gadolinium chloride (GdCl3) reduces pulmonary nitric oxide formation, possibly by interference with stretch-activated cellular calcium influx, but the effect on pulmonary circulation is not known. We therefore measured exhaled nitric oxide and pulmonary vascular resistance in anaesthetised rabbits, and compared the effects of GdCl3 with those of an nitric oxide-synthase inhibitor (L-N omega-nitro-arginine methyl ester, L-NAME). Both GdCl3 and L-NAME reduced nitric oxide in exhaled air and increased pulmonary vascular resistance. However, the increase in pulmonary vascular resistance was more pronounced with GdCl3 than with L-NAME. A 50% reduction of exhaled nitric oxide caused by either GdCl3 or L-NAME was accompanied by a 90% or 17% increase in pulmonary vascular resistance respectively. Inhaled nitric oxide (40 ppm) reduced pulmonary vascular resistance after L-NAME, but not after GdCl3 infusion. Infusion of glyceryltrinitrate reduced pulmonary vascular resistance after GdCl3 infusion. GdCl3 caused hypoxaemia, probably due to vasoconstriction since lung weight was unaltered. Thus GdCl3 can induce a marked increase in pulmonary vascular resistance, which partly may be caused by inhibition of pulmonary nitric oxide formation. Intact stretch-activated calcium channels may be important for maintenance of normal pulmonary vascular function.

Animals↗