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Effect of beta2-agonist treatment and spirometry on exhaled nitric oxide in healthy children and children with asthma.

We set out to determine the effect of spirometry and bronchodilator therapy on exhaled nitric oxide (FE(NO)) values in children. We hypothesized that there will be no difference on FE(NO) values pre- and postspirometry and following bronchodilator therapy. Sixteen children [(mean = 14.4 +/- 1.2 years; range, 12-18 years; healthy controls (n = 6); asthmatics on inhaled steroids (n = 5); and asthmatics on no steroids (n = 5)] had exhaled nitric oxide (FE(NO)) measurements on 4 consecutive days as follows: pre- and postspirometry (day 1); pre- and postalbuterol metered dose inhaler (MDI) therapy (day 2); pre- and postspirometry and albuterol MDI therapy (day 3); and pre- and postspirometry and placebo MDI (day 4). FE(NO) was measured with a chemiluminescence analyzer, using the single vital capacity exhalation technique at an exhalation flow of 50 mL/sec. There were no statistically significant differences in FE(NO) values pre- and poststudy maneuvers under all experimental conditions in healthy children. However, in healthy children, clinically relevant (>10%) differences from baseline were observed on day 1 (3-18 min) and day 4 at 18 min. In children with asthma, FE(NO) values increased significantly by 11-19% from pretreatment levels at 8 and 18 min, postbronchodilator on day 2, and 12-17% at 8 and 18 min post bronchodilator and spirometry on day 3. Spirometry and treatment with a placebo (day 4) resulted in a decrease in FE(NO) values by 11% at 3 min postbaseline in patients on inhaled steroids. The changes observed were similar in children on vs. off inhaled steroids, and also in well-controlled vs. poorly controlled asthma. We conclude that FE(NO) values should be obtained consistently either pre- and at a specific time postalbuterol treatment or spirometry. Alternatively, changes in FE(NO) values should be interpreted in relationship to the timing of these maneuvers.

Adolescent↗

Passive smoking does not increase hydrogen peroxide (H2O2) levels in exhaled breath condensate in 9-year-old healthy children.

Environmental tobacco smoke, also called passive smoking, was shown to have adverse effects on the health of children. Hydrogen peroxide (H2O2) is proposed as a sensitive marker of oxidative injury and inflammatory processes in the airways, being increased in adult active cigarette smokers. We tested whether passive smoking had an influence on H2O2 exhalation in healthy children. Thirty healthy passive smoking and 24 nonexposed healthy children aged 9 years were included in the study. Exhaled breath condensate (EBC) was obtained by spontaneous tidal volume breathing with EcoScreen (Jaeger, Germany). All subjects underwent flow-volume measurements immediately after EBC collection. Levels of H2O2 were measured fluorimetrically with the homovanillic acid method. Lung function did not differ between the passive smoking and nonexposed children groups. In the passive smoking group, EBC H2O2 concentration (median and range) was 0.32 (0.00-1.20) microM, and did not differ significantly (P >0.05) from that found in the nonexposed group, i.e., 0,22 (0.00-0.68) microM. Exhaled H2O2 did not correlate with spirometric parameters (FEV1, FEV1%FVC, and MEF50%FVC) in either group. We conclude that passive smoking does not increase H2O2 exhalation in healthy children.

Biomarkers↗

The effect of air pollution on exhaled nitric oxide of atopic and nonatopic subjects.

Levels of exhaled nitric oxide (NO) were determined in well-characterized atopic and nonatopic subjects on 4 days with a different level of outdoor air pollution. The two groups matched well regarding spirometric values, i.e., no difference with regard to FEV(1), FVC, and peak flow. On the 4 test days asymptomatic atopic subjects exhaled 1.5- to 2.4-fold higher levels of NO compared with nonatopic subjects. In both groups the increase in exhaled NO in response to air pollution was similar (2.5 times maximal increase, P < 0.01). In conclusion, atopic subjects exhale higher levels of NO compared with nonatopic subjects, but respond to a similar degree to increased levels of air pollution.

Adult↗

Symptom prescription: inducing anxiety by 70% exhalation.

This study investigates the effects of partial exhalation to feelings of anxiety. Thirty five volunteer subjects (14 male, 21 female, mean age 40.6) were first trained in slow diaphragmatic breathing (SDB). Then subjects rated their anxiety levels on a scale from 1 (none) to 5 (extreme) in sequential conditions of SDB, 70% subjective exhalation, and SDB. During the 70% subjective exhalation phase, subjects were instructed to breathe and limit their exhalation to 70% of the inhaled volume during each consecutive breath. The 70% subjective condition significantly (P < .0005) increased subjects' anxiety levels as compared to the initial SDB baseline, while a return to SDB significantly reduced the anxiety levels. The 70% approach appears useful in demonstrating to the client that possible changes in breathing patterns can affect anxiety.

Adult↗

Studies on biochemical effects of nitrogen dioxide: I. Lipid peroxidation as measured by ethane exhalation of rats exposed to nitrogen dioxide.

This research was in order to follow the periodic fluctuation of lipid peroxidation by a new method in rats exposed to nitrogen dioxide. Wistar male rats were examined for lipid peroxidation as demonstrated by ethane exhalation. In rats continuously exposed to 10 ppm nitrogen dioxide for 2 weeks, the amount of ethane exhaled fluctuated in a complex manner during the exposure. Ethane exhalation decreased slightly after the first day of exposure and then increased rapidly. The maximal values were observed after the fourth day of exposure and then decreased gradually to the initial level. Furthermore, the activity of glutathione peroxidase in lungs of rats exposed to 10 ppm nitrogen dioxide varied symmetrically against the change of ethane formation. Similar changes in ethane exhalation were observed in rats exposed to the lowest levels of nitrogen dioxide (0.4, 1.2 and 4.0 ppm) for 4 months. Compared to 10 ppm nitrogen dioxide exposure for 14 days, the characteristics in rats exposed to the low levels (0.4-4.0 ppm) of nitrogen dioxide were: the decline of ethane formation, the delay in alterations, and the tendency toward gradual increase during the longer period exposure.

Animals↗

Validation of 8-isoprostane and prostaglandin E(2) measurements in exhaled breath condensate.

OBJECTIVE: To qualitatively validate radioimmunoassays for 8-isoprostane and prostaglandin (PG) E(2) in exhaled breath condensate. SUBJECTS: Twenty-two subjects with different lung diseases attended the outpatient clinic on one occasion for exhaled breath condensate collection. METHODS: Samples were pooled together and purified by reverse phase high performance liquid chromatography (RP-HPLC). The eluted fractions were assayed for 8-isoprostane-like immunoreactivity and PGE(2)-like immunoreactivity by radioimmunoassays. In addition, simultaneous measurements of exhaled breath condensate unextracted samples with two anti-8-isoprostane and anti-PGE(2) sera with different cross-reactivity were performed. RESULTS: A single peak of 8-isoprostane-like immunoreactivity and PGE(2)-like immunoreactivity co-eluting with 8-isoprostane (retention time: 13 min) and PGE(2) (retention time: 21 min) standards, respectively, was identified by radioimmunoassays. Testing with two different antisera showed similar results for both 8-isoprostane-like immunoreactivity (limits of agreement = 4.5 pg/ml and - 4.1 pg/ml, n = 12) and PGE(2)-like immunoreactivity (limits of agreement = 6.1 pg/ ml and - 6.1 pg/ml, n = 12). CONCLUSION: This study provides evidence for the specificity of the radioimmunoassays for 8-isoprostane and PGE(2) in exhaled breath condensate. This is critical for proposing these markers as a non-invasive way for monitoring airway inflammation.

Breath Tests↗

Validation of leukotriene B4 measurements in exhaled breath condensate.

OBJECTIVE: To qualitatively validate an enzyme immunoassay to measure leukotriene B4 in exhaled breath condensate. Exhaled breath condensate is a new non-invasive method to monitor airway inflammation. SUBJECTS: Twenty-two subjects with different lung diseases attended the outpatient clinic on one occasion for exhaled breath condensate collection. METHODS: Samples were pooled together and purified by reverse-phase high-performance liquid chromatography. The fractions eluted were assayed for leukotriene B4 by enzyme immunoassay. RESULTS: A single peak of leukotriene B4-like immunoreactivity co-eluting with leukotriene B4 standard (retention time: 24 min) was identified by enzyme immunoassay. Reverse phase-high performance liquid chromatography peak of leukotriene B4 was clearly separated from those of 6-trans-leukotriene B4 (retention time: 14 min) and leukotriene B5 (retention time: 18 min) for which the antiserum used in the enzyme immunoassay had the highest cross-reactivity. Leukotriene B4 recovery was 64%. CONCLUSIONS: This study provides evidence for the presence of leukotriene B4 in the exhaled breath condensate and the specificity of the enzyme immunoassay used.

Breath Tests↗

Technique and clinical applications of full-inflation and end-exhalation controlled-ventilation chest CT in infants and young children.

BACKGROUND: The inability of young children to cooperate with breath holding limits the usefulness of chest CT. OBJECTIVE: To describe the technique and utility of a non-invasive method called controlled-ventilation CT (CVCT) for obtaining motion-free full-inflation and end-exhalation images of the lung in infants and young children. MATERIALS AND METHODS: Eighty-seven children (ages 1 week to 5 years, mean 2 years) underwent CVCT of the chest during suspended respiration at full-lung inflation and end-exhalation for a variety of clinical indications. Respiratory pauses were produced using conscious sedation and positive-pressure face-mask ventilation. Forty-one of 87 children had recordings of respiratory motion during CVCT. RESULTS: Respiratory pause lengths increased with age (P < 0.003), were highly reproducible (r = 0.85), and lasted sufficiently long to be practical for full-inflation (24 +/- 9 s) and end-exhalation (12 +/- 5 s) CT scanning. Full-inflation CVCT was useful in evaluating tracheal and bronchial stenosis, bronchial wall thickening, early bronchiectasis, bronchial fistula, extent of interstitial fibrosis, and lung nodules. End-exhalation CVCT was useful in evaluating tracheomalacia and air trapping. CONCLUSION: Controlled-ventilation chest CT is a practical and reliable technique that promises to be clinically useful for a number of clinical indications in infants and young children.

Child, Preschool↗

Exhaled nitric oxide: the effects of age, gender and body size.

Since little is known of the effects of age, gender, and body size on exhaled nitric oxide (NO) production, we have conducted a prospective study to examine these factors in a healthy nonsmoking women (mean age +/- SD 47.7 +/- 15.8, range 20-79 years). Exhaled NO was measured by an automatic chemiluminescence analyzer (Sievers NO Analyser 280) at steady expiration. Men had significantly higher exhaled NO levels than women (p = 0.001). Although exhaled NO levels did not correlate with age (r = 0.12, p = 0.17), it correlated significantly with height (r = 0.23, p = 0.02), weight (r = 0.34, p

Adult↗

Exhaled nitric oxide level during and after heavy exercise in athletes with exercise-induced hypoxaemia.

Endogenous nitric oxide (NO) is an important mediator of vasodilatation, bronchodilatation and lung inflammation. We hypothesised that the exhaled NO level may be modified in some endurance-trained athletes during and after intense exercise. Nine athletes with exercise-induced hypoxaemia (EIH), 12 athletes without EIH and 10 untrained subjects exercised for 15 min at 90% maximal oxygen consumption (VO(2)max). Exhaled NO was measured during exercise, and after 1 h and 22 h of recovery. Exhaled NO concentration ( C(NO)) decreased significantly during exercise in all subjects and returned to basal values after 1 h of recovery with no further modification. Exhaled NO output (V(NO)) rose significantly during exercise, rapidly dropped down following exercise and was similar to resting values after 1 h and 22 h of recovery. The results also showed that C(NO) and V(NO) were significantly lower in the athletes with EIH in comparison with the untrained subjects (V(NO) was 5.32 +/- 0.77 nmol/min versus 3.61 +/- 0.72 nmol/min at rest, 18.52 +/- 1.50 nmol/min versus 15.00 +/- 2.06 nmol/min during heavy exercise, and 5.52 +/- 1.04 nmol/min versus 3.79 +/- 0.76 nmol/min after 22 h recovery, in untrained subjects and EIH athletes, respectively). These findings do not confirm the hypothesis of pulmonary inflammation associated with EIH. However, potential NO epithelial down-regulation may occur and contribute to the development of gas exchange abnormality in some endurance-trained athletes.

Adult↗

Radon exhalation rate of some building materials used in Egypt.

Indoor radon has been recognized as one of the health hazards for mankind. Common building materials used for construction of houses, which are considered as one of the major sources of this gas in indoor environment, have been studied for exhalation rate of radon. Non-nuclear industries, such as coal fired power plants or fertilizer production facilities, generate large amounts of waste gypsum as by-products. Compared to other building materials waste gypsum from fertilizer production facilities (phosphogypsum) shows increased rates of radon exhalation. In the present, investigation solid state alpha track detectors, CR-39 plastic detectors, were used to measure the indoor radon concentration and the radon exhalation rates from some building materials used in Egypt. The indoor radon concentration and the radon exhalation rate ranges were found to be 24-55 Bq m(-3 )and 11-223 mBq m(-2) h(-1), respectively. The effective dose equivalent range for the indoor was found 0.6-1.4 mSv y(-1). The equilibrium factor between radon and its daughters increased with the increase of relative humidity.

Air Pollutants, Radioactive↗

The utility of prolonged respiratory exhalation for reducing physiological and psychological arousal in non-threatening and threatening situations.

To determine whether slowing and altering the respiratory pattern is an effective means for reducing physiological and psychological arousal, subjects participated in one of three treatment conditions in which they reduced their respiration rate to 6 cpm and either inhaled quickly and exhaled slowly, inhaled slowly and exhaled quickly, or spent equal amounts of time inhaling and exhaling. Other subjects participated in a distraction control condition or in a no-treatment control condition. Arousal was measured during a practice period, a threat (electrical shocks) anticipation period, and a threat confrontation period. The results indicated that the breathing manipulations were not effective in reducing arousal during the practice period, but that inhaling quickly and exhaling slowly was consistently effective for reducing physiological (skin resistance) and psychological (subjective cognitive) arousal during the anticipation and confrontation periods.

Adolescent↗

Sex differences in concentrations of exhaled nitric oxide and plasma nitrate.

Nitric oxide (NO) is generally considered as an endogenous vasoprotective agent. Various studies indicate that the female sex hormone estradiol, that contributes to the well known gender differences in cardiovascular disease, may enhance NO-production. Thus we studied sex differences in NO-generation by measuring single breath NO-exhalation and plasma levels of nitrate (NO3), the stable endmetabolite of NO. In this observational trial 22 male and 21 female volunteers, 19 to 38 years of age, were studied on 3 days at weekly intervals. Median concentrations of NO were 20 parts per billion (95% CI: 16 to 32 ppb) in women and 34 ppb (95% CI: 31 to 58 ppb) in men. The median plasma concentrations of NO3 were 14 microM/L (95% CI: 11 to 23 microM/L) in women and 27 microM/L (95% CI: 24 to 47 microM/L) in men. Thus, men exhaled 59% more NO (p < 0.001) and had 99% higher NO3 levels than women (p < 0.0001). Even when exhaled NO concentrations were corrected for body weight, men exhaled 50% more NO than women (p = 0.024). No significant changes in measured endpoints were seen during the menstrual cycle (p > 0.05) in women. In view of the diversity of NO-actions, the finding of marked sex differences in NO-production is basic to the elucidation of gender differences in a number of (patho)-physiologic conditions.

Adult↗

Radon exhalation from the ground; method of measurements and preliminary results.

The paper will present a method for measurements of radon exhalation from the ground. The method is based on a combination of activated charcoal and TLD. This method is superior to the traditional charcoal method, because it yields a mean value for the exhalation rate during the whole in-growth time. Furthermore, by using the activated charcoal/TLD method, the decay time is not critical, because the TLD is irradiated from absorbed radon during the decay time. In this way, the method is usable for remote measurements by mail. The method has been tested in areas with "normal" ground and in areas where high indoor radon concentrations previously have been measured. Exhalation measurements were performed near to houses where the indoor radon concentrations were known, and in most cases there was a strong correlation between exhalation rate and indoor radon concentrations. The method thus seems to be usable for classification of building ground.

Radiation Monitoring↗

Elevated exhalation of hydrogen peroxide and thiobarbituric acid reactive substances in patients with community acquired pneumonia.

BACKGROUND: Bacterial pneumonia involves influx of activated phagocytes into distal airways. These cells release oxidants including H2O2, that may be exhaled or induce peroxidative damage to lung tissues with formation of thiobarbituric reactive substances (TBARs). STUDY OBJECTIVES: To determine whether concentrations of H2O2 and TBARs in exhaled breath condensate (EBC) is elevated and correlate with systemic response to pneumonia during 10 days of hospital treatment. DESIGN: The concentration of H2O2 and TBARs was measured in EBC of 43 inpatients with community acquired pneumonia (CAP) and 20 healthy never smoked subjects over 10 days and were accompanied by monitoring of WBC count, serum concentration of C-reactive protein (CRP) and peroxyl radical-trapping capacity. RESULTS: Patients with CAP exhaled 4.6-, 3.7-, 3.9-, 3.3-times more H2O2 than healthy controls at 1st, 3rd, 5th and 10th day of treatment (P<0.05), respectively. EBC concentrations of TBARs were elevated at 1st and 3rd day. H2O2 and TBARs levels decreased along with treatment course. Correlation (P<0.05) was found between H2O2 levels and CRP and WBC count (r = 0.31) at 1st day and between TBARs and CRP at 5th (r = 0.34) and 10th day (r = 0.46). The mean H2O2 exhalation estimated over ten days of treatment correlated with pneumonic chest X-ray score (r = 0.42), CRP levels (r = 0.46) and WBC count (r = 0.33) at admission (P<0.05). CONCLUSIONS: Pneumonia is accompanied by oxidative stress in airways that moderately correlates with intensity of systemic inflammatory response. Determination of H2O2 in EBC may be helpful for non-invasive monitoring of oxidants production during lower respiratory tract infection.

Adult↗

Application of laser spectroscopy for measurement of exhaled ethane in patients with lung cancer.

There is increasing interest in ethane (C(2)H(6)) in exhaled breath as a non-invasive marker of oxidative stress (OS) and thereby a potential indicator of disease. However, the lack of real-time measurement techniques has limited progress in the field. Here we report on a novel Tunable Diode Laser Spectrometer (TDLS) applied to the analysis of exhaled ethane in patients with lung cancer. The patient group (n=52) comprised randomly selected patients presenting at a respiratory clinic. Of these, a sub-group (n=12) was subsequently diagnosed with lung cancer. An age-matched group (n=12) corresponding to the lung cancer group was taken from a larger control group of healthy adults (n=58). The concentration of ethane in a single exhaled breath sample collected from all subjects was later measured using the TDLS. This technique is capable of real-time analysis of samples with accuracy 0.1 parts per billion (ppb), over 10 times less than typical ambient levels in the northern hemisphere. After correcting for ambient background, ethane in the control group (26% smokers) ranged from 0 to 10.54 ppb (median of 1.9 ppb) while ethane in the lung cancer patients (42% smokers) ranged from 0 to 7.6 ppb (median of 0.7 ppb). Ethane among the non-lung cancer patients presenting for investigation of respiratory disease ranged from 0 to 25 ppb (median 1.45 ppb). We conclude that, while the TDLS proved effective for accurate and rapid sample analysis, there was no significant difference in exhaled ethane among any of the subject groups. Comments are made on the suitability of the technique for monitoring applications.

Aged↗

The biology of exhaled nitric oxide (NO) in ischemia-reperfusion-induced lung injury: a tale of dynamism of NO production and consumption.

The main objective of this paper is to review the potential diagnostic roles of exhaled nitric oxide (NO) in evaluating ischemia-reperfusion-induced lung injury associated with cardiac surgery. We shall start by elaborating on current clinical practice of cardiac surgery and to arrive at the conclusion that clinically important ischemia-reperfusion injury is a common scenario of many forms of these surgical procedures. We shall conclude this part by establishing the clinical need for biomarkers of inflammation in cardiothoracic surgery and by proposing that exhaled NO could be an important new addition to our anaesthetic monitoring repertoire based on our expertise with exhaled breath monitoring. We shall then take a closer look at mechanisms of ischemia-reperfusion injury and will propose the role of reactive oxygen and nitrogen species as mediators and biomarkers of acute lung injury. This analysis will provide a good opportunity to highlight major potential mechanisms of altered NO production and bioactivity of NO. We shall conclude that multiple relevant mechanisms may either lead to increased production of NO or enhance consumption of NO, leaving us with the paradigm that NO maybe used either as a positive or negative biomarker of inflammation. In order to explore this dilemma further, we will investigate the predominant effect of oxidative stress on NO bioactivity in cell culture models of ischemia-reperfusion injury. We will then turn to animal models of ischemia-reperfusion injury to elucidate the ultimate effects of this condition on lung NO production and concentrations of NO in the lung. Finally, we shall complete this journey by highlighting the human relevance of these observations by reviewing our own experience at Harefield Hospital, UK, and that of others, regarding exhaled NO in ischemia-reperfusion injury associated with cardiac surgery and lung transplantation.

Animals↗

A significant proportion of exhaled nitric oxide arises in large airways in normal subjects.

Nitric oxide (NO) of endogenous origin is present in exhaled breath. An increase in exhaled NO concentration (ENO) has been described in bronchial asthma and ENO falls after inhaled steroid therapy. The sources of ENO may include pulmonary blood, the gas exchange region, conducting airways and the nasal cavity. In four healthy volunteers, a catheter was placed in a main bronchus after topical anesthesia in order to sample airway NO (CNO). Exhaled nitric oxide of bronchopulmonary and oropharyngeal origin (ENO(b/o)) was measured while excluding nasal NO and was controlled for expiratory flow. During the same exhalation, ENO(b/o) was compared to CNO at multiple sites in the airway as the catheter was progressively withdrawn. Mean CNO concentration in a position corresponding to a main bronchus was 51.4 +/- 10.8% of ENO(b/o). As the catheter was withdrawn, mean CNO concentration progressively increased both in absolute values and as a proportion of ENO(b/o), until in the oropharynx, it was 96.1 +/- 5.2% ENO(b/o). We conclude that a significant proportion of ENO(b/o) arises in the large airways and trachea in normal subjects and contains a minor oropharyngeal component.

Adult↗