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Gender and age specific differences in exhaled isoprene levels.

The analysis of volatile organic compounds (VOC) in the human breath has attracted a considerable amount of clinical and scientific interest during the last decade. In our study, we turned our attention to gender and age specific differences of exhaled volatile compounds, particularly on isoprene which is one of the most abundant organic molecules found in human exhaled air. A total of 126 test persons were enrolled in the study: 66 females and 60 males. Moreover, the participants were classified into six groups with regard to their age. In a standardized setting all of them had to exhale the endexpiratory breath into a sample bag. The volatile compounds at m/z values from 21 to 229 were analyzed by using proton-transfer-reaction-mass-spectrometry. Isoprene (at m/z 69) was found to be highly significantly (p<0.001) elevated in the exhaled air of male subjects. Furthermore, it could be shown that 19-29 years old subjects exhale significantly lower levels of isoprene than older adults (p=0.002). No significant differences between groups were detected for any other measured mass. In conclusion, the present study demonstrates gender and age specific differences of isoprene levels in the exhaled air. These findings may be of potential clinical relevance regarding the multifaceted roles of isoprene, representing both indicator and effector molecule.

Adult↗

Flow dependency and off-line measurement of exhaled NO in children.

Levels of exhaled nitric oxide (eNO) are flow-dependent, and the choice of an optimal flow rate for off-line and on-line eNO measurement has raised much debate. Recently, a flow rate of 50 ml/s was recommended, but children younger than 5-6 years are not capable of stabilizing their expiratory flow at low flow rates. The power of off-line eNO values to discriminate between normal and atopic children was therefore evaluated at different exhalation flow rates. At flow rates of both 8.3 ml/s and of 350 ml/s, children (8-12 years) sensitive to house dust mite have two-fold higher eNO values (p < 0.001) as compared with children lacking such a sensitivity. The power of eNO to discriminate between normal and atopic subjects was similar at the two flow rates (no difference in AUC of receiver operation curves, p = 0.89). All children from 4.5 to 5 years of age (n = 29) could perform a single off-line exhalation manoeuvre at high (>350 ml/s) but not at low (8.3 ml/s) flow rates. At high exhalation flow rate, eNO was 7.1 +/- 2.4 (mean +/- SD) median, 6.5 p.p.b. with a mean variation coefficient of 5.5%. Depending on their developmental level, about half of the younger children (35-46 months of age) could perform an off-line exhalation manoeuvre at high flow rate with good reproducibility (mean variation coefficient of 6.6%). It is concluded that an exhalation flow rate of 350 ml/s is feasible to determine off-line eNO-values in children from 3.5 years of age, and that this high flow rate does not compromise the power of eNO to detect allergic disease.

Adult↗

Exhaled bronchial cysteinyl leukotrienes in allergic patients.

PURPOSE OF REVIEW: To review the current knowledge of noninvasive monitoring of allergic airway inflammation by analysis of leukotrienes in the exhaled breath condensate. RECENT FINDINGS: Treatment of respiratory allergies involves chronic treatment based on clinical symptoms and pulmonary function tests. Evaluation of local inflammation would be desirable but is currently not feasible because of the difficulty in sampling the airways. Recently, exhaled breath condensate collection and analysis has polarized much interest in the respiratory field. Although some methodological issues are still under scrutiny, airways inflammatory markers can be assayed with this technique. In particular, exhaled breath condensate leukotrienes have been thoroughly investigated in the setting of bronchial asthma and allergic rhinitis in adults and children. Exhaled leukotrienes are increased in patients with asthma and rhinitis during the pollen season, correlate with exacerbations and asthma severity, and are reduced by specific anti-inflammatory treatment and allergen avoidance. SUMMARY: Some issues still prevent the use of exhaled breath condensate in clinical practice but in the research setting it has been proved to be useful for noninvasive monitoring of allergic inflammation in the lung. In particular, exhaled leukotrienes may represent valuable biomarkers for diagnostic and therapeutic purposes in allergic patients.

Cysteine↗

Effect of the hepatocarcinogenic peroxisome proliferator Wy-14,643 in vivo: no increase in ethane exhalation or hepatic conjugated dienes.

Exhalation of ethane and pentane was used to access lipid peroxidation in rats receiving the hepatocarcinogenic peroxisome proliferator Wy-14,643 at 0.1% in the diet. Wy-14,643 treatment from 23 to 345 days did not increase ethane or pentane exhalation. The lack of an increase in ethane exhalation from rats fed Wy-14,643 was not due to resistance to lipid peroxidation or increased metabolism of ethane since rats fed Wy-14,643 were sensitive to CCl4-induced increases in ethane exhalation and cleared exogenous ethane at rates similar to controls. Difference spectra of hepatic lipids extracted from control and Wy-14,643-treated rats showed peaks at 220 and 275 nm but no defined peak at 240 nm, the wavelength at which conjugated dienes in peroxidized lipids absorb. In contrast, injection of CCl4 ip into control rats produced dose-dependent increases in ethane exhalation at 6.25 to 100 microliters/kg and increases in hepatic conjugated dienes and serum liver enzyme activities at 200 to 1000 microliters/kg. The lack of increased ethane and pentane exhalation in combination with no detectable increase in hepatic conjugated dienes argues against increased hepatic lipid peroxidation in rats receiving a hepatocarcinogenic dose of Wy-14,643.

Alkenes↗

Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

The exhalation of ethane is widely used as an indicator of in vivo lipid peroxidation. To test the hypothesis that lipid peroxidative events are involved in the toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), we administered a lethal dose of TCDD (60 micrograms/kg), IP to male Sprague-Dawley rats (160-180 g) and measured by gas chromatography the exhalation of ethane into the atmosphere of a closed all-glass exposure chamber. TCDD-treated rats exhaled only slightly more ethane than control rats at a single time point 7 days following TCDD administration. Since the exhalation of ethane is the net result of the endogenous production of the gas and its metabolic degradation, the latter was quantified by measuring the clearance of exogenous ethane (initial concentration = 100 ppm) introduced to the atmosphere of the exposure chamber. The clearance of ethane in TCDD-treated rats was markedly decreased, reaching a minimum 7 days following TCDD treatment. Apparently, the slight increase in exhaled ethane was due to an inhibition of ethane metabolism caused by TCDD. However, rats obviously intoxicated and having lost considerable body weight might be impaired in their ability to transport ethane. To bypass this problem we injected ethane (0.2 ml) directly into the rats IP. Here also the metabolic clearance in TCDD-treated rats was diminished. In a further experiment, rats treated with dithiocarb at a dose where ethane metabolism was totally inhibited exhaled more ethane than did TCDD-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biological monitoring of occupational exposure to n-hexane by exhaled air analysis and urinalysis.

To compare two methods of biological monitoring for the evaluation of risk of occupational exposure to n-hexane, we analyze the relationship between environmental exposure to this solvent and urinary excretion of 2,5-hexanedione and n-hexane in exhaled air in 69 workers employed in the shoe industry. Environmental exposure to the solvent was monitored with personal diffusive samplers, which were desorbed with carbon sulfide and analyzed by gas chromatography. To measure 2,5-hexanedione, urine was subjected to acid hydrolysis, separation in octadecyl silane columns, elution with 5% aqueous acetonitrile solution and extraction with dichloromethane, followed by gas chromatography. In exhaled air, n-hexane was measured with a sampling system that permitted concentration of aliquots of end-exhaled air (alveolar air) from one or more exhalations in a tube packed with activated charcoal, which was then desorbed with carbon sulfide and analyzed by gas chromatography. Concentrations of n-hexane in breathing zone air were significantly correlated with urinary concentrations of 2,5-hexanedione (r = 0.88) and with exhaled air n-hexane (r = 0.86); in addition, the two biological indicators correlated significantly (r = 0.70). Analyses in both exhaled air and urine were thus considered useful for biological monitoring of the risk of exposure to n-hexane.

Adhesives↗

Ca(2+)-dependent and Ca(2+)-independent exhaled nitric oxide, presence in germ-free animals, and inhibition by arginine analogues.

Nitric oxide (NO) was detected by chemiluminescence in exhaled air from awake humans, anaesthetized rabbits, guinea pigs, germ-free rats and conventional rats. Rabbits exhibited the highest concentrations, followed by guinea pigs, humans and rats. There was no significant difference between germ-free rats and control rats. The authenticity of NO was confirmed in cold-trap experiments. Intravenous administration of inhibitors of NO synthase (0.01-300 mg kg-1) to guinea pigs dose dependently reduced NO concentrations in exhaled air with the following potency order: L-N omega-nitro-arginine-methylester > asymmetric NG,NG-dimethyl-L-arginine-dihydrochloride = L-NG-mono-methyl -arginine = L-N5- (1-iminoethyl)-ornithine = aminoguanidine > L-canavanine. The effect of the NO synthase inhibitors was partly or fully reversed by L-arginine (1 g kg-1 i.v.), and L-arginine per se induced a significant increment of NO in exhaled air. In rats, L-N omega-nitro-arginine-methylester was considerably less potent than in guinea pigs. The concentration of NO in exhaled air increased 3-fold when changing from in situ blood auto-perfusion of rabbit lungs to in situ perfusion with saline medium. Addition of L-N omega-nitro-arginine-methylester to the saline perfusion medium evoked a reduction of NO concentrations in the air from the ventilated perfused lungs. Perfusion of lungs with Ca(2+)-free medium induced significant decrements in NO concentrations in exhaled air, an effect partly reversed upon reintroducing Ca2+ into the medium. In conclusion, NO was detected in exhaled air from humans and animals by chemiluminescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A prospective randomized study to evaluate the effect of leukodepletion on the rate of alveolar production of exhaled nitric oxide during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass is associated with a whole body inflammatory reaction. Exhaled nitric oxide increases in inflammatory lung conditions (eg, asthma) in proportion to the severity of inflammation, and has been proposed as a marker of pulmonary inflammation during cardiopulmonary bypass. This study evaluated the effect of arterial line leukocyte depletion during cardiopulmonary bypass on the rate of alveolar production of exhaled nitric oxide. METHODS: One hundred and ten patients with normal respiratory function, undergoing first time coronary artery bypass grafting, were randomized to two groups. Fifty-five patients had an arterial line leukocyte-depleting filter and 55 controls had a standard arterial line filter. Nitric oxide was sampled through an endotracheal Teflon tube after median sternotomy, but before cardiopulmonary bypass and 30 minutes after cardiopulmonary bypass, using a real time chemiluminescence analyzer, during the phase of the alveolar plateau. RESULTS: There were no significant differences in the precardiopulmonary bypass values of exhaled nitric oxide between the control (2.92 +/- 1.51 ppb/s) and the leukodepletion group (3.11 +/- 1.53 ppb/s) (p = 0.4). After cardiopulmonary bypass, the rate of alveolar production of exhaled nitric oxide increased in both groups, being, however, significantly higher in the control group (4.68 +/- 1.89 vs 3.72 +/- 1.33 ppb/s) (p = 0.02). CONCLUSIONS: Continuous arterial line leukocyte-depletion significantly reduces the rate of alveolar production of exhaled nitric oxide after cardiopulmonary bypass. Changes in the rate of alveolar production of exhaled nitric oxide may be used as a marker of pulmonary inflammation in coronary artery surgery.

Aged↗

Factors controlling measurements of radon mass exhalation rate.

Radon mass exhalation rate of soil samples was measured using an exhalation chamber of 10 dm(3) volume and a Lucas cell. The results show that mass of sample, grain size and water content influence the radon mass exhalation rate. For soil of (226)Ra activity concentration about 2500 Bq kg(-1) and samples within the range from 0.20 kg to 0.50 kg, the radon mass exhalation rate values are higher than those for samples of other masses. The observed radon exhalation rate is an inverse function of the average grain size. At the water content about 6% by weight, the radon mass exhalation rate reaches maximum, then it decreases with both increasing and decreasing of the water content in the sample.

Air Pollutants, Radioactive↗

The measurement of exhaled carbon monoxide in healthy smokers and non-smokers.

The measurement of exhaled carbon monoxide (CO) level may provide an immediate, non-invasive method of assessing smoking status. The aims of this study were to use a portable CO monitor to compare the exhaled CO levels in established smokers and non-smokers. The exhaled CO levels were measured in 322 subjects (243 healthy smokers, 55 healthy non-smokers, 24 passive smokers) who applied to healthy stand during the spring student activity of Firat University in Elaziğ. Exhaled CO concentration was measured using the EC50 Smokerlyser. The mean exhaled CO level was 17.13+/-8.50 parts per million (ppm) for healthy smokers and 3.61+/-2.15 ppm for healthy non-smokers, and 5.20+/-3.38 ppm for passive smokers. There were significant positive correlation between CO levels and daily cigarette consumption, and CO levels and duration of smoking in healthy smokers (r=+0.550, P<0.001, r=+0.265, P<0.001, respectively. Spearman's test). When smokers and non-smokers were looked at as a whole, a cutoff of 6.5 ppm had a sensitivity of 90% and specificity of 83%. In conclusion, exhaled CO level provides an easy, an immediate way of assessing a subject's smoking status.

Adult↗

Increased nitric oxide levels in exhaled air of rat lung allografts.

In organ transplantation nitric oxide has been reported to be involved in allograft rejection. We examined in a rat lung transplantation model whether nitric oxide is overproduced in acute rejection and can be detected in exhaled air. Thirteen rat right lung transplants were separated into three groups: group 1 (n = 5), untreated allografts (Brown-Norway [RT1n] to Lewis [RT1l]); group 2 (n = 4), cyclosporine-treated allografts; and group 3 (n = 4), isografts (Lewis to Lewis). We examined exhaled nitric oxide levels with a chemiluminescence analyzer and chest roentgenograms on days 2 through 5. Histologic samples were obtained on days 3 and 5. On day 5, the recipients were killed and we measured exhaled nitric oxide from the right and left lungs separately. Blood samples were also obtained for measurement of serum nitrite/nitrate. The exhaled nitric oxide level in untreated allografts increased significantly from day 5 (63.9 +/- 39.2 ppb, p = 0.0095) and was significantly higher than that in treated allografts (9.1 +/- 1.6 ppb) (p = 0.0085) and isografts (6.9 +/- 0.5 ppb) (p = 0.0068). The nitric oxide level in untreated allografts (826.5 +/- 416.1 ppb) was 75 times as high as that from the contralateral normal left lungs (11.2 +/- 2.6 ppb) (p = 0.0118). The level of exhaled nitric oxide correlated significantly with the histologic rejection grade (p = 0.0001). There was no significant difference in the serum nitrite/nitrate levels between allografts and isografts. These data suggest that increased exhaled nitric oxide levels might reflect acute rejection in lung transplants.

Animals↗

Effects of mouth cleansing on the levels of exhaled nitrous oxide in young and older adults.

Nitrous oxide (N2O) is produced by denitrification, i.e. by microbial reduction of nitrate (NO3-). Our previous studies have established an analytical method for demonstrating the existence of N2O in exhaled air, and we showed that levels of N2O in exhaled air increase with age after puberty. However, the source of this change and its biological significance are still unclear. The purpose of this study was to examine whether the oral microorganisms are the main source of N2O. We measured exhaled N2O in 35 young adults (aged 19-29 years) and 34 older adults (aged 61-79 years) before and after mouth cleansing. N2O was measured using an infrared-photoacoustic analyzer equipped with an optical filter (UA0985, 2215 cm-1). Participants were classified as producers and non-producers according to the levels of exhaled N2O relative to the level in the atmosphere. N2O production differed significantly between the young adult producers and the older adult producers. Mouth cleansing resulted in an immediate reduction in exhaled N2O in both groups. We only found seven (20.0%) producers in the young, and 32 (94.1%) producers in the older after mouth washing. The differences before and after mouth cleansing were significant in both groups (P < 0.01 in the young and P < 0.05 in the older). The oral cavity is a major source of N2O. However, since approximately half-levels of N2O were still observed in exhaled air after mouth, cleansing, there may exist another N2O source in the human body.

Adolescent↗

[Reproducibility of the technique for measuring nitric oxide in exhaled air in healthy subjects].

UNLABELLED: Exhaled nitric oxide (NO) has become established as the principal non-invasive marker of airway inflammation. Exhaled NO levels reported in the literature vary greatly, with differences sometimes attributable to measurement technique. OBJECTIVE: To determine the reproducibility of the technique used by our department to measure exhaled NO and to know whether results vary with diet and patient characteristics. METHOD: We studied 20 healthy subjects (10 men and 10 women; mean age 28.21 years). Exhaled NO was measured when the patient was fasting(N1), 30 minutes after intake of vegetables (N2) and 30 minutes after intake of meat/fish (N3). For each measure N1, N2 and N3 we took the average of three consecutive measurements separated by 10 minutes. Exhaled NO was assessed by controlled-flow chemoluminescence after adjusting for trapped air and after generating pressure in the oral cavity that was sufficient to close the soft palate(Eco Physics CLD 77 AM analyzer). RESULTS: The mean concentration was 3.40 1.30 ppb for N1, 4.03 1.00 ppb for N2 and 3.71 1.05 ppb for N3. The differences between measurements were not statistically significant(p > 0.05). Nor were differences between the sets of three measurements significant. The mean concentration was 3.13 0.41 ppb for women and 3.72 0.31 ppb for men (ns). No significant differences were related to body mass index 25 (n = 15) or > 25 (n = 5). CONCLUSIONS: The technique our department uses for measuring exhaled NO is reproducible and differences are unrelated to food intake, sex or body mass index.

Adult↗

Exhaled nitric oxide as a marker for serum nitric oxide concentration in acute endotoxemia.

PURPOSE: The main aim of this study was to assess the correlation between exhaled nitric oxide (NO) and serum NO concentrations during the course of endotoxemia. We also assessed whether or not the inducible isoform of NO synthase is responsible for the increase in NO production in endotoxemia animals. MATERIALS AND METHODS: Anesthetized and mechanically ventilated dogs were injected with either saline (control) or Escherichia coli endotoxin (LPS [Lipopolysaccharides]), and the animals were sacrificed 150 minutes later. We measured hemodynamics, exhaled NO, and serum arterial and mixed venous NO concentrations. Western blotting was performed on lung, pulmonary artery, aorta, and kidney tissue samples using anti-inducible NO synthase antibody. RESULTS: Arterial pressure, cardiac output, and pulmonary arterial pressure in the control group remained unchanged, whereas a significant decline in these parameters was observed in the LPS group. Exhaled NO and serum arterial NO concentrations rose significantly within 30 minutes of endotoxin injection and remained higher than baseline values, whereas mixed venous serum NO did not change from baseline values. There was a significant linear relationship between exhaled NO and arterial serum NO concentrations. By comparison, exhaled NO, and arterial and mixed venous serum NO levels remained unchanged in the control group. Western blotting showed no expression of inducible NO synthase (iNOS) isoform in the control or LPS groups. CONCLUSIONS: These results suggest that exhaled NO accurately reflects changes in arterial serum NO concentration and that the source of enhanced NO release in acute endotoxemia is not the iNOS isoform.

Analysis of Variance↗

Exhaled carbon monoxide level as an indicator of cigarette consumption in a workplace cessation program in Taiwan.

BACKGROUND: Smoking cessation programs are critical to the safety and health of workers. Exhaled carbon monoxide (CO) is an effective indicator of smoking in clinics and hospitals. Its application in the community and workplace, however, remains limited. This study assessed whether exhaled CO concentration can be used as an objective indicator of the amount of daily cigarette consumption among smokers in the workplace in Taiwan. METHODS: A total of 150 workers from a chemical manufacturer in Taiwan were included; there were 27 nonsmokers and 123 current smokers. The number of cigarettes smoked daily by each subject was reported, and exhaled CO concentration was measured in each subject using the Micro CO meter (Micro Medical Ltd, Chatham, Kent, UK). RESULTS: Exhaled CO levels were associated with the number of cigarettes consumed daily, with a correlation coefficient of 0.73 (p < 0.01) and an adjusted R-square (simple linear regression model) of 0.44. The mean exhaled CO level of nonsmokers was 4.2 ppm (95% confidence interval, 3.3-5.1). A reading of > 6 ppm had a sensitivity of 84% and specificity of 85% in detecting workplace smoking. CONCLUSION: Exhaled CO level can be used as an objective, noninvasive indicator to determine the smoking status of an individual in the workplace.

Adult↗

[Exhale nitric oxide (NO) and respiratory function measured with body plethysmography in children].

BACKGROUND: Exhaled nitric oxide (NO) may be a marker of airway inflammation. Previous studies in adults have shown that the level of NO in exhaled air is influenced by several factors (breath holding, exercise, etc), or by several disease (asthma, congestive heart failure, diseases of the upper respiratory tract, cystic fibrosis, etc). However, few studies have been performed in children less than 3 years of age. The aim of this study was to determine endogenous NO levels in children with various diseases during lung volume measurements. PATIENTS AND METHODS: Fifty-two children aged 18.3 +/- 9.5 months were studied. The population was divided in two groups, according to the underlying disease: a group of 39 children with cystic fibrosis (n = 7), bronchopulmonary dysplasia (n = 17), asthma (n = 7) or recurrent respiratory tract infections (n = 8) and a second group of 13 children without respiratory disease. Lung function was measured by whole body plethysmography and several respiratory parameters were calculated (functional residual capacity [FRC], compliance and resistances of the respiratory system, trapped volume). NO production was measured on a chemiluminescence analyzer from mixed exhaled air collected into a bag, over a period of 5 minutes. RESULTS: NO production was related to disease: exhaled NO levels were three times higher in bronchopulmonary dysplasia and cystic fibrosis, compared to NO levels in children without respiratory disease. They were higher in asthma. They were not altered in recurrent respiratory tract infections. No correlation was found between respiratory parameters and NO production. However, exhaled NO levels were correlated to trapped volume, which defined dynamic part of pulmonary hyperinflation. CONCLUSION: Levels of endogenous NO in infants were similar to those measured in adults with and without inflammatory respiratory disease. Lung distention influenced exhaled NO production.

Biomarkers↗

Exhaled nitric oxide; relationship to clinicophysiological markers of asthma severity.

Bronchial asthma is an airway disorder associated with bronchial hyperresponsiveness, variable airflow obstruction and elevated levels of nitric oxide (NO) in exhaled air. The variables all reflect, in part, the underlying airway inflammation in this disease. To understand their interrelationships we have investigated the relationship between exhaled NO levels and clinicophysiological markers of asthma severity. Twenty-six steroid naive atopic asthmatics participated in the analysis. All were given diary cards and were asked to record their peak expiratory flow (PEF) rates twice daily together with their asthma symptom scores and beta-agonist use. Diary cards were collected 2 weeks later and measurements of exhaled NO levels, FEV1 and histamine bronchial hyperreactivity (PC20 histamine) were undertaken. Exhaled NO levels were significantly higher in our study population than in normal control subjects and correlated negatively with PC20 histamine (r = -0.51; P = 0.008) and positively with PEF diurnal variability (r = 0.58; P = 0.002), but not with symptom scores, beta-agonist use of FEV1 (%). We conclude that a significant relationship exists between exhaled NO levels and the two characteristic features and markers of asthma severity, namely bronchial hyperreactivity and PEF diurnal variability. The lack of correlation between symptom score and beta-agonist use, of FEV1 (%) predicted and exhaled NO suggests that these measures are reflective of differing aspects of asthma.

Adolescent↗

Increased nitric oxide in exhaled air in patients with rheumatic heart disease.

BACKGROUND: Endogenous production of nitric oxide and its presence in exhaled air was observed in humans. Prior studies have yielded contrasting information about the production of nitric oxide in patients with heart failure. AIMS: The aim of this study was to measure nitric oxide in the exhaled air of patients with chronic rheumatic heart disease with and without pulmonary hypertension. METHODS: Seventy-four patients (6 patients had isolated mitral stenosis; 13 patients had combined mitral stenosis and mitral regurgitation; 1 patient had isolated mitral regurgitation; 54 patients had combined mitral and aortic valve disease) and 27 healthy subjects were entered in the study. The nitric oxide concentration in exhaled air was determined with a chemiluminescence analyser. Echocardiography was performed in all patients to assess the severity of the valve disease and for the measurement of pulmonary artery pressure. RESULTS: The level of exhaled nitric oxide was significantly greater in patients with rheumatic heart disease than in controls. The value of nitric oxide concentration in exhaled air was significantly increased in patients with pulmonary hypertension, as compared with patients who had normal pulmonary artery systolic pressure. CONCLUSION: We found increased nitric oxide in the exhaled air in patients with rheumatic heart disease, especially in those with pulmonary hypertension, compared with healthy patients.

Adult↗