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Exhaled NO during graded changes in inhaled oxygen in man.

BACKGROUND: Nitric oxide (NO) is present in the exhaled air of animals and humans. In isolated animal lungs the amount of exhaled NO is decreased during hypoxia. A study was undertaken to determine whether changes in arterial oxygen tension affect levels of exhaled NO in humans. METHODS: Sixteen healthy subjects were randomised to inhale different gas mixtures of oxygen and nitrogen in a double blind crossover study. Eight gas mixtures of oxygen and nitrogen (fractional inspired oxygen concentration (FiO2) 0.1 to 1.0) were administered. Exhaled NO was measured with a chemiluminescence detector from end expiratory single breath exhalation. RESULTS: A dose-dependent change in exhaled NO during graded oxygen breathing was observed (p = 0.0012). The mean (SE) exhaled NO concentration was 31 (3) ppb at baseline, 39 (4) ppb at an FiO2 of 1.0, and 26 (3) ppb at an FiO2 of 0.1. CONCLUSIONS: The NO concentration in exhaled air in healthy humans is dependent on oxygen tension. Hyperoxia increases the level of exhaled NO, which indicates increased NO production. The mechanism behind this phenomenon remains to be elucidated.

Administration, Inhalation↗

Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma.

BACKGROUND: Eosinophils in induced sputum and exhaled nitric oxide (NO) are currently used as non-invasive markers in the assessment of airway inflammation in asthma. As both sputum eosinophils (%) and exhaled NO are raised in asthmatic subjects not receiving inhaled steroids and decreased following corticosteroid therapy, a relationship between them is plausible. METHODS: Exhaled NO was measured by chemiluminescence analyser, sputum induction by 3.5% saline inhalation, and bronchial responsiveness was measured as PC20FEV1 methacholine in 35 stable asthmatic patients using beta 2 agonist alone and the correlation between these non-invasive markers of airway inflammation was studied. RESULTS: There were significant correlations between exhaled NO and PC20 (r = -0.64), exhaled NO and sputum eosinophils (%) (r = 0.48), and also between sputum eosinophils (%) and PC20 (r = -0.40). CONCLUSION: The correlation between exhaled NO and PC20 suggests that exhaled NO or the mechanisms leading to its increase may contribute to airway hyperresponsiveness in asthma. Furthermore, the relationship between sputum eosinophils (%), exhaled NO, and PC20 highlight the potential use of eosinophils (%) in induced sputum and exhaled NO to monitor the severity of asthma.

Adult↗

Exhaled nitric oxide during exercise: site of release and modulation by ventilation and blood flow.

To define the site of release and factors modulating exhaled nitric oxide (NO) during exercise in humans, we measured exhaled NO output during exercise, during exercise after balloon occlusion of the nasopharynx (to exclude nasal NO), and at rest with isocapneic hyperventilation or dobutamine infusion. Exhaled NO output increased from rest to exercise (57 +/- 10 to 171 +/- 30 nl.min-1.m-2; P < 0.003; n = 8). Exclusion of nasal NO reduced exhaled NO at rest and during exercise. Calculated nasal contribution at rest (53 +/- 5%) decreased during exercise (29 +/- 6%; P < 0.05), whereas nonnasal contribution increased (47 +/- 5 to 71 +/- 6%; P < 0.05). Isocapneic hyperventilation at rest increased exhaled NO output (51 +/- 8 to 94 +/- 22 nl.min-1.m-2; P = 0.05). Dobutamine infusion did not increase exhaled NO output. We conclude that nasal exhaled NO decreases (and nonnasal exhaled NO increases) with exercise. We also conclude that, under the conditions of this study, increased exhaled NO output during exercise is more closely related to increased ventilation than to increased blood flow.

Adult↗

Allergen-induced late asthmatic reactions are associated with elevation of exhaled nitric oxide.

The concentration of nitric oxide (NO) is increased in the exhaled air of asthmatic patients and may reflect cytokine-mediated inflammation in the airways. We investigated whether allergen-induced inflammation causes an elevation in the level of exhaled NO. Of 25 patients who underwent allergen challenge, 16 developed dual early and late responses, whereas eight had a single early response. In the patients with a dual response, the maximal fall in FEV1 during the late response was 26.8 +/- 4.2% at 9 h and there was a significant increase in the level of exhaled NO (maximal increase of 59.4 +/- 9.8%) 10 h after challenge. There was a significant relationship between the size of the late response and the increase in exhaled NO (r = 0.75, p < 0.01). In patients who have a single early response, there was no significant increase in exhaled NO, with the exception of a single time point at 21 h. In five patients given a control challenge with methacholine there was no change in exhaled NO. There was no increase in exhaled NO after inhaled histamine in any of the patient groups. We conclude that the late asthmatic response to allergen is associated with elevated exhaled NO concentrations and that this provides further evidence that exhaled NO may reflect allergic inflammation in asthmatic airways, and may be a useful marker in monitoring asthma and its response to anti-inflammatory treatments. Whether endogenously produced NO plays a pathophysiologic role in the late response remains to be determined.

Adult↗

Exhaled nitric oxide in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and a neutrophilic inflammation. Exhaled nitric oxide (NO) may be a marker of disease activity in a variety of lung diseases. We measured exhaled NO in patients with documented COPD and investigated whether the concentration of exhaled NO is related to the severity of disease as defined by lung function. We also investigated whether concentration of exhaled NO was different in COPD patients who received inhaled steroids compared with steroid-naive patients. We studied 13 current smokers with COPD, eight exsmokers with COPD, 12 patients with unstable COPD (exacerbation or severe disease), and 10 smokers with chronic bronchitis without airflow limitation. Exhaled NO levels were significantly higher in patients with unstable COPD (12.7 +/- 1.5 ppb) than in other groups (p < 0.01). Exhaled NO levels were significantly higher in smokers with COPD than in smokers with chronic bronchitis (4.3 +/- 0.5 versus 2.5 +/- 0.5 ppb, p < 0.05), and were even higher in patients with COPD who had stopped smoking (6.3 +/- 0.6 ppb, p < 0.01). Exhaled NO levels showed a significant negative correlation with their lung function assessed by % predicted FEV1 values (r = -0.6, p < 0.001). Exhaled NO levels in patients treated with inhaled steroids were significantly higher compared with steroid-naive patients (8.2 +/- 1.2 ppb versus 5 +/- 0.4 ppb, p < 0.05), but the first group included more severe patients as assessed by lung function. We conclude that exhaled NO could serve as a useful, practical marker for monitoring disease activity in COPD.

Administration, Inhalation↗

Endogenous nitric oxide release by vasoactive drugs monitored in exhaled air.

Direct measurements of endogenous nitric oxide (NO) release is of great interest but difficult to perform in vivo. We hypothesized that endogenous NO release from vasoactive substances would be detectable in exhaled air. Exhaled NO was measured after intravenous injections of various endothelium-dependent and endothelium-independent vasoactive drugs, in anesthetized pigs and humans. In pigs, a dose-dependent release of exhaled NO was observed for acetylcholine (ACh), bradykinin, substance P, endothelin (ET)-1, and nitroglycerine. Each compound had an individual and highly reproducible release pattern. Bradykinin-induced NO release was enhanced by angiotensin converting enzyme inhibition. ET receptor antagonism markedly reduced the response in exhaled NO to ET-1, whereas atropin abolished the NO response to ACh. NO synthase inhibition abolished basal levels of exhaled NO as well as the responses in exhaled NO to all compounds except nitroglycerine. In humans, ACh evoked a dose-dependent increase of NO levels in exhaled air. NO release by endogenous vasoactive agonists can be measured online in the exhaled air of pigs and humans. These novel findings may be useful when characterizing NO release from compounds that interfere with NO synthesis or drugs that act as donors of NO. Moreover, the possibility of using exhaled NO as an indicator of pulmonary endothelial dysfunction merits further studies.

Acetylcholine↗

Clinical aspects of exhaled nitric oxide.

There has been intense research into the role nitric oxide (NO) plays in physiological and pathological mechanisms and its clinical significance in respiratory medicine. Elevated levels of exhaled levels of exhaled NO in asthma and other inflammatory lung diseases lead to many studies examining NO as potential markers of airway inflammation, enabling repeated noninvasive and standardized monitoring of airway inflammation. In airway inflammation, NO is not merely a marker but may have anti-inflammatory and pro-inflammatory effects. Significant correlation has been found between exhaled NO and skin test scores in steroid naive asthmatic patients, allowing to discriminate patients with and without airway responsiveness. Exhaled NO is significantly elevated in acute asthma, or steroid-resistant severe asthma, or when the maintenance dose of inhaled steroids is reduced, and quickly reduced down to the levels in patients with stable asthma after steroid treatment. Exhaled NO has been successfully used to monitor anti-inflammatory treatment with inhaled corticosteroids in asthma. Exhaled NO is extremely sensitive and rapid marker of the dose-dependent effect of steroid treatment, or asthma deterioration, which is increased to any changes in lung function, provocative concentration causing a 20% fall in forced expiratory volume, sputum eosinophilia or asthma symptoms. Exhaled NO is not increased in stable chronic obstructive pulmonary disease (COPD), but patients with unstable COPD, or bronchiectasis have high NO levels. Exhaled and nasal NO are diagnostically low in cystic fibrosis and primary pulmonary dyskinesia. Analysis of exhaled air, including nitric oxide, is feasible and could provide a noninvasive method for use in monitoring and management of lung diseases.

Asthma↗

Evaluation of the measurement of leukotriene B4 concentrations in exhaled condensate as a noninvasive method for assessing mediators of inflammation in the lungs of calves.

OBJECTIVE: To determine whether measurement of an inflammatory mediator in exhaled condensate could provide a noninvasive method for evaluating lungs of calves. ANIMALS: 84 calves < or = 2 months old. PROCEDURE: Concentration of leukotriene B4 (LTB4) was evaluated in the exhaled condensate of healthy calves and calves with experimentally induced respiratory tract infections. For collection of samples of exhaled condensate, the total amount of exhaled air was directed into a cooled double-jacketed tube. Each tube was sealed and stored at -80 C. The LTB4 concentration was measured, using an ELISA. RESULTS: In exhaled condensates of clinically healthy calves, normally distributed and highly reproducible LTB4 concentrations (mean +/- SD, 116.1 +/- 55.4 pg/ml) were measured. After experimentally induced infection with Pasteurella multocida serovar D, LTB4 in exhaled condensate increased significantly (mean, 179% increase), compared with basal concentrations before infection; this increase in LTB4 was significantly correlated with deterioration in lung function. In 2 of 4 calves experimentally infected with bovine respiratory syncytial virus, the LTB4 concentration in exhaled condensate increased (300 to 400% increase), compared with baseline values, which was associated with development of bronchial hyperresponsiveness after infection. CONCLUSIONS AND CLINICAL RELEVANCE: Collection of exhaled condensate is tolerated well by calves and is an acceptable method for obtaining fluid from exhaled air originating from the lungs. This method provides alternatives for diagnosing and evaluating treatment of naturally acquired and experimentally induced diseases of the lungs and airways in calves.

Animals↗

Studies on the attraction of Simulium damnosum s.l. (Diptera: Simuliidae) to its hosts. I. The relative importance of sight, exhaled breath, and smell.

Four traps used in capturing hunting female S. damnosum s.l. are discribed: the slat trap, the enclosure trap, the fan trap, and the sticky trap. In forest a man hidden inside a trap, but removing his exhaled breath through a long hose, attracted 4 times as many flies as did an unbaited trap. When the man exhaled normally into the trap the number of flies taken rose again by a further factor of 4. Carbon dioxide gas, emitted from inside the trap attracted some two-thirds as many flies as a man exhaling normally inside the trap. In both forest and Sudan-savanna environments the catches of a man stationed on an open stretch of land and fully exposed to view while his exhaled breath was removed through a long hose, were not substantially lower than those of a man in a similar situation who exhaled normally. In forest a motionless man, partly hidden among vegetation, attracted fewer flies than a moving man who was fully exposed to view (a) when both men removed their exhaled breath through long hoses, and (b) when they exhaled normally. In the forest a trap baited with CO2 gas (250 cc per min) caught more flies than a similar, unbaited trap, but the preformance of CO2-baited traps, as compared with that of human collectors, was highly variable. Catches in CO2-baited traps were uniformly low in the Sudan-savanna. In forest, removal of olfactory substances from the human skin, by vigorous washing and application of petroleum jelly, or by wearing impermeable clothing, greatly reduced the numbers of flies attracted. No such reduction was observed in Sudan savanna. In the forest, cloths, worn by men for several days and then used as bait, attracted about 10 times as many flies as did similar, unworn cloths. Addition of CO2 gas produced a 4-fold increase in the attractiveness of worn cloths and an 18-fold increase in that of unworn cloths. No corresponding experiments were done in the savanna. Fan traps could become contaminated by human handling during the assembly and setting-up procedures. They were thus rendered attractive to flies. In the Sudan-savanna, the catches of men positioned in front of warm rock surfaces were lower than those of men stationed on coller, sandy surfaces. This suggests that body heat may be an additional attractant factor. The results suggest that "forest" S. damnosum s.l. (presumably S. squamosum) females rely heavily on smell as an attractant and, to a lesser extent, on sight and exhaled breath. Smell appears to be the only obligatory attractant, and it can act by itself. This raises the possibility that a trap might be developed which incorporates only smell stimuli as bait. For "savanna" S. damnosum s.l. (presumably S. damnosum s.s.) neither smell nor exhaled breath appear to be important attractants, and some other factor, perhaps sight, appears to be the dominant attractant in this zone.

Air↗

Measurement of exhaled hydrogen peroxide from rabbit lungs.

Exhaled H2O2 is considered an indicator of lung inflammatory and oxidative stress. Moreover, H2O2 may be involved in signal transduction processes. It is not fully elucidated to what extent (i) H2O2 escapes from the intravascular compartment, and (ii) pulmonary H2O2 generation and nasopharyngeal H2O2 generation contribute to exhaled H2O2. We investigated H2O2 concentrations in breath condensate from isolated buffer-perfused and ventilated rabbit lungs, and from both intubated and spontaneously breathing rabbits with a horseradish peroxidase/2',7'dichlorofluorescin assay. For the perfused lungs, a H2O2 concentration of 58 +/- 19 nM was found. Addition of H2O2 to the buffer fluid resulted in only minute appearance in the exhaled air (<0.001%). Levels of exhaled H2O2 in intubated rabbits and perfused lungs were virtually identical. Nearly ten-fold higher levels were detected in spontaneously breathing rabbits. Decreasing the inspired oxygen concentration from 21% to 1% resulted in a tendency toward decreased H2O2 exhalation in perfused lungs. In contrast, phorbol-12-myristate-13-acetate (PMA) prompted a approximately 4-fold increase in H2O2 exhalation. We conclude that the horseradish peroxidase/2',7'dichlorofluorescin assay is a feasible technique to measure H2O2 in exhaled breath condensate in rabbits. When collecting exhaled air via the tracheal tube, the signal represents pulmonary H2O2 generation with the contribution of the remaining body being negligible.

Animals↗

Effect of atmospheric nitric oxide (NO) on measurements of exhaled NO in asthmatic children.

The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive means for measuring airway inflammation. However, several measurement conditions may influence exhaled NO levels, and ambient NO may be one of these. We measured exhaled NO levels in 47 stable asthmatic children age 5 to 17 years and in 47 healthy children, gender and age matched. Exhaled [NO] in expired air was measured by a tidal breathing method with a chemiluminescence analyzer, sampling at the expiratory side of the mouthpiece. NO steady-state levels were recorded. In order to keep the soft palate closed and avoid nasal contamination, the breathing circuit had a restrictor providing an expiratory pressure of 3-4 cm H2O at the mouthpiece. To evaluate the effect of [NO] in ambient air, measurements were randomly performed by breathing ambient air or NO-free air from a closed circuit. Breathing NO-free air, exhaled [NO] in asthmatics (mean +/- SEM) was 23.7 +/- 1.4 ppb, significantly higher (P < 0.001) than in healthy controls (8.7 +/- 0.4 ppb). Exhaled NO concentrations measured during ambient air breathing were higher (49 +/- 4.6 ppb, P < 0.001) than when breathing NO-free air (23.7 +/- 1.4 ppb) and were significantly correlated (r = 0.89, P < 0.001) with atmospheric concentrations of NO (range 3-430 ppb). These findings show that 1) exhaled [NO] values of asthmatic children are significantly higher than in healthy controls, and 2) atmospheric NO levels critically influence the measurement of exhaled [NO]. Therefore, using a tidal breathing method the inhalation of NO-free air during the test is recommended.

Adolescent↗

Single-breath exhaled nitric oxide in preschool children facilitated by a servo-controlled device maintaining constant flow.

Fractional concentration of exhaled nitric oxide (FENO), an index of airway inflammation, is optimally measured in adults and school-age children using a single-breath online (SBOL) exhalation at constant flow. However, preschool-aged (<6 years old) children have difficulty exhaling at constant flow, and alternative methods are needed. We employed a servo-controlled variable resistance device (servo device) that controls expiratory flow while allowing the child to vary expiratory pressure. To validate this device, 8 children (aged 6-12 years) performed SBOL exhalations with and without the servo device at expired flow rates between 20-50 ml/sec. We then studied 32 young children aged 24-71 months with the servo device alone at exhalation flows of 30, 40, and 50 ml/sec. Test difficulty (TD) with each method was rated by questioning the older children, or as observed by the physician obtaining the data in the younger children (0 = no difficulty, 1 = mild difficulty, 2 = moderate difficulty, and 3 = unable to perform test). In the older children, SBOL exhalations with and without the servo device demonstrated equivalent flow-dependence of FENO values. Test difficulty was low (0.125-0.625) at all flow rates, with excellent agreement between the two methods (P < 0.001). Twenty-eight young children (<6 years old) were able to complete measurements at all three flow rates evaluated. The 4 subjects who were not able to successfully complete all the measurements were between 2-3 years old (mean 2.75 +/- SD). Exhaled NO (mean +/- SD; ppb) was 8.8 (+/-6.2), 10.6 (+/-6.7), and 13.2 (+/-8.8) ppb at flows of 50 ml/sec, 40 ml/sec, and 30 ml/sec, respectively. Mean values of SD scores were 1.00, 1.14, and 1.43 at flows of 50, 40, and 30 ml/sec, respectively (P = NS). In conclusion, exhaled NO measurement by the SBOL method was facilitated in preschool children by the use of a servo-controlled variable resistance device. This device may allow these measurements to be applied to aid in the diagnosis and treatment of asthma in the preschool child, where spirometry is generally impossible.

Age Factors↗

A simple method to sample exhaled NO not contaminated by ambient NO from children and adults in epidemiological studies.

We previously showed that contamination of exhaled air by ambient NO could be avoided by 1 min of breathing and final inhalation of clean air (clean air procedure) prior to exhaled air sampling in balloons. This approach is, however, unsuitable for sampling large groups in epidemiological studies, because it is time consuming and laborious. We therefore discarded the initial part of exhaled air, which may contain ambient NO, in prebags of 250, 540, 775, 1000, and 2000 ml. The subsequent part of exhaled air was sampled in balloons and the NO content was measured. Inflation of a prebag of 500 ml to prevent ambient NO contamination proved to be effective only at low ambient NO levels (<20 ppb). Larger sizes of the prebag (1000 ml for adults and 775 ml for children) are, however, required so that contamination of the air sample at higher levels of ambient NO (up to 115 ppb) is excluded. Using different prebags of gradually increasing size, it was shown that the initial part of exhaled air (<500 ml) contained relatively high amounts of NO that gradually decreased, but attained a constant level in the subsequent air volumes. Using rather large prebags of 2000 and 1000 ml, respectively, in adults and children yielded exhaled NO levels even below those obtained the clean air procedure was applied in combination with a prebag of 540 ml. As this reduction also occurs at ambient NO levels of nearly zero, we suggest that this reduction was due to interference by the water vapor arising from the lowest part of the lungs. In conclusion, the use of a prebag to discard the initial volume of exhaled air ensures accurate measurement of exhaled endogenous NO in large-scale epidemiological studies not biased by ambient NO.

Adult↗

Effects of inhaled corticosteroids on exhaled leukotrienes and prostanoids in asthmatic children.

BACKGROUND: Lipid mediators play an important pathophysiologic role in atopic asthmatic children, but their role in the airways of atopic nonasthmatic children is unknown. OBJECTIVE: We sought (1) to measure leukotriene (LT) E 4 , LTB 4 , 8-isoprostane, prostaglandin E 2 , and thromboxane B 2 concentrations in exhaled breath condensate in atopic asthmatic and atopic nonasthmatic children; (2) to measure exhaled nitric oxide (NO) as an independent marker of airway inflammation; and (3) to study the effect of inhaled corticosteroids on exhaled eicosanoids. METHODS: Twenty healthy children, 20 atopic nonasthmatic children, 30 steroid-naive atopic asthmatic children, and 25 atopic asthmatic children receiving inhaled corticosteroids were included in a cross-sectional study. An open-label study with inhaled fluticasone (100 microg twice a day for 4 weeks) was undertaken in 14 steroid-naive atopic asthmatic children. RESULTS: Compared with control subjects, exhaled LTE 4 ( P <.001), LTB 4 ( P <.001), and 8-isoprostane ( P <.001) levels were increased in both steroid-naive and steroid-treated atopic asthmatic children but not in atopic nonasthmatic children (LTE 4 , P=.14; LTB 4 , P=.23; and 8-isoprostane, P=.52). Exhaled NO levels were increased in steroid-naive atopic asthmatic children ( P <.001) and, to a lesser extent, in atopic nonasthmatic children ( P <.01). Inhaled fluticasone reduced exhaled NO (53%, P <.0001) and, to a lesser extent, LTE 4 (18%, P <.01) levels but not LTB 4 , prostaglandin E 2 , or 8-isoprostane levels in steroid-naive asthmatic children. Conclusions Exhaled LTE 4 , LTB 4 , and 8-isoprostane levels are increased in atopic asthmatic children but not in atopic nonasthmatic children. In contrast to exhaled NO, these markers seem to be relatively resistant to inhaled corticosteroids.

Administration, Inhalation↗

Assaying all of the nitrogen oxides in breath modifies the interpretation of exhaled nitric oxide.

Exhaled nitric oxide (NO) assays measure the quantity of NO that emanates from the airway, not the amount of NO that is formed. Consumptive processes-including oxidation reactions-decrease the amount of gas phase NO available for exhalation. Higher oxides of nitrogen (HiNO(x)) are resulting reaction products, and are easily measured in exhaled breath condensate (EBC). We performed concurrent sampling of exhaled breath for gas phase NO and EBC HiNO(x) in controls and stable asthmatics. We identified that, mole for mole, asthma patients hourly exhale more HiNO(x) than they do NO, with a HiNO(x)/NO ratio of 1.21 (0.54-3.4). This is the reverse of the ratio found in controls, in whom the HiNO(x)/NO ratio was 0.75 (0.44-0.93), p=0.04. The sum of the hourly molar exhalation of NO and HiNO(x) was significantly higher in asthmatics (333 nmol/h (221-543) than controls (179 (138-231), p<0.001). We conclude that exhaled oxides of nitrogen are more informative when measured together as opposed to in isolation. We suggest that inflammation can be better evaluated with HiNO(x) and NO measured concurrently, and that the level of oxidation in the lung can be evaluated by comparing the easily measured ratios of HiNO(x) to NO in the exhaled breath.

Adolescent↗

Exhaled carbon monoxide in childhood asthma.

OBJECTIVES: Oxidative stress and inflammation induce the expression of heme oxygenase-1, which produces carbon monoxide (CO), and nitric oxide synthase, which produces nitric oxide (NO). Exhaled CO and NO levels are elevated in asthmatic patients and are decreased after corticosteroid treatment, suggesting that they may be useful as noninvasive markers of airway inflammation. STUDY DESIGN: We measured forced expiratory volume in the first second, PC(20), and exhaled CO and NO levels in 29 children (18 boys, mean age 11.5 +/- 0.53 years) with asthma of different severity and 40 nonsmoking children without asthma (21 boys, mean age 8.1 +/- 0.35 years). We also studied whether upper respiratory tract infections were associated with elevated exhaled CO. RESULTS: Exhaled CO levels (ppm) were significantly higher (2.17 +/- 0.21) in children with persistent asthma compared with those in children with infrequent episodic asthma (1.39 +/- 0.18, P <.05) and healthy children (1.01 +/- 0.12, P <.001). The CO levels in children with infrequent episodic asthma and the normal control group, however, were not different. In contrast, exhaled NO levels (ppb) were higher in children with persistent asthma (24.2 +/- 5.9, P <.001) and infrequent episodic asthma (14.5 +/- 3.73, P <.05) than in normal subjects (5.1 +/- 0.24), but no significant difference was seen between the 2 asthmatic groups. In healthy children with upper respiratory tract infections (n = 12), exhaled CO concentrations were significantly elevated (2.16 +/- 0.33) during the acute symptomatic phase. No correlation was found between exhaled CO and forced expiratory volume in the first second or PC(20). CONCLUSIONS: Noninvasive measurement of exhaled CO may provide complementary data for assessment of asthma control in children. However, elevated CO levels are nonspecific and may be found in association with an acute viral illness.

Asthma↗

Smoking in pregnancy, exhaled carbon monoxide, and birth weight.

OBJECTIVE: To examine the relation of cigarette consumption and exhaled carbon monoxide levels during pregnancy and to assess the effect of these smoking measures on birth weight. METHODS: Cigarette consumption and exhaled carbon monoxide levels were recorded at the first prenatal visit and the 36-week visit from women who smoked early in pregnancy. Analysis of variance was used to compare birth weights for differing levels of cigarette consumption and exhaled carbon monoxide. Correlation and regression analyses were used to estimate the effects of the smoking measures at both prenatal visits on birth weight. RESULTS: Cigarette consumption and exhaled carbon monoxide levels at both visits were associated significantly with birth weight. After the first prenatal visit, a reduction in cigarette consumption of at least nine cigarettes per day or in exhaled carbon monoxide of 8 parts per million (ppm) was associated with gains in birth weight of 100 g or more. The proportion of low birth weight (LBW) infants increased significantly with increasing levels of cigarette consumption and with increasing concentrations of exhaled carbon monoxide. CONCLUSION: Substantial reductions in cigarette consumption or in exhaled carbon monoxide levels after the first prenatal visit are needed to achieve gains in birth weight. Not smoking, or having an exhaled carbon monoxide level less than 5 ppm minimizes the likelihood of having an LBW infant.

Adult↗

Levels of exhaled nitric oxide before and after surgical and transcatheter device closure of atrial septal defects in children.

OBJECTIVES: We have shown that exhaled nitric oxide levels decrease after surgical closure of congenital left-to-right cardiac shunts. It remains unclear whether the change in exhaled nitric oxide levels reflects endothelial injury caused by the use of cardiopulmonary bypass or the decrease in pulmonary blood flow attendant on shunt closure. Transcatheter atrial septal defect closure permits shunt closure without the use of cardiopulmonary bypass. Therefore we compared changes in exhaled nitric oxide levels after surgical and transcatheter device closure of atrial septal defects. METHODS: We enrolled sequentially 30 children undergoing atrial septal defect closure. Fifteen patients (age range, 0.4-16 years; median age, 6.5 years) underwent surgical atrial septal defect closure with cardiopulmonary bypass, and 15 patients (age range, 4-17 years; median age, 8.4 years) had device closure of the atrial septal defect in the catheterization laboratory. We measured nitric oxide levels in end-tidal expiratory gas with a rapid-response chemiluminescent analyzer before and after atrial septal defect closure. RESULTS: After surgical repair of the atrial septal defect, exhaled nitric oxide decreased by 21%, from 10.9 +/- 4.4 to 8.4 +/- 3.3 ppb (P <.005), whereas after transcatheter defect closure, exhaled nitric oxide increased by 23%, from 7.6 +/- 2.6 to 9.3 +/- 3.7 ppb (P <.005). Hemoglobin levels in patients undergoing surgical intervention were significantly lower (P =.0001) postoperatively. CONCLUSIONS: We confirmed that exhaled nitric oxide, despite a fall in hemoglobin, decreases after surgical closure of atrial septal defects. In contrast, exhaled nitric oxide levels increase after transcatheter closure. Exhaled nitric oxide levels may reflect bypass-induced endothelial cell injury and are independent of changes in pulmonary blood flow.

Adolescent↗