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Effect of vitamin E on exhaled ethane in cigarette smokers.

STUDY OBJECTIVES: We hypothesized that micronutrient antioxidant intake may be one factor determining the development of significant COPD. Vitamin E was administered to smokers to determine if exhaled ethane was reduced and if ethane correlated with measures of lung function. STUDY DESIGN: Longitudinal placebo lead-in trial with posttreatment observation period. SETTING: Tucson Veterans Affairs Medical Center. PARTICIPANTS: Twenty-nine current stable smokers having no interest in smoking cessation. INTERVENTIONS: Spirometry, exhaled breath ethane measurements, and vitamin E and [-carotene plasma levels followed by 3 weeks of placebo with repeat plasma vitamin levels and ethane measurements; next, 3 weeks of vitamin E (dl-a-tocopherol), 400 IU po bid followed by plasma vitamin levels and breath ethane measurements; finally, 3 weeks without vitamins followed by breath ethane and plasma vitamin levels. RESULTS: Vitamin E treatment did not reduce ethane significantly. Exhaled ethane levels (mean + SD: pm/min/kg) were as follows: baseline, 7.39 + 5.39; after run-in period, 6.86 + 4.09; after vitamin E, 6.36+/-3.02; and final, 7.23+/-4.63. After vitamin E therapy, a significant negative correlation existed between exhaled ethane and FEV1/FVC. Pack-years of smoking at baseline and after vitamin E were significantly associated with ethane exhaled. Initial lung function was not significantly negatively associated with vitamin E-induced changes in exhaled ethane but a negative trend was found. CONCLUSIONS: Vitamin E alone, unlike the combination of vitamins C, E, and beta-carotene, failed to reduced exhaled ethane in cigarette smokers. Exhaled ethane was correlated with pack-years of smoking. Smokers whose ethane values were found to fall the most tended to have better preserved lung function.

Adult↗

Atopy influences exhaled nitric oxide levels in adult asthmatics.

STUDY OBJECTIVE: To examine whether atopy influences exhaled nitric oxide (NO) levels in adults with established asthma. SETTING: Specialist respiratory unit in a university teaching hospital. PATIENTS: Twenty-eight asthmatics (mean FEV(1), 85.7%) receiving short-acting inhaled bronchodilators and a range of inhaled steroids (0 to 4,000 microg/d). INTERVENTIONS: Subjects were studied on two occasions, 5 to 7 days apart, between September and March. MEASUREMENTS AND RESULTS: On the first day, FEV(1), exhaled NO, and histamine challenge were performed. On the second day, exhaled NO, total IgE, and skin-prick testing to six common allergens were conducted. Exhaled NO was measured with the single exhalation method. We found exhaled NO levels to correlate positively with total IgE (r = 0.43, p = 0.02) and number of positive skin-prick tests (p = 0. 002). By contrast, there was no significant correlation between exhaled NO and FEV(1) or the provocative concentration causing a 20% fall in FEV(1). Subanalyses of steroid-treated and steroid-naive patients in this group revealed the same findings. CONCLUSION: Exhaled NO levels in asthmatics correlate more closely with atopy than with bronchial hyperreactivity and lung function.

Administration, Inhalation↗

Exhaled carbon monoxide and nitric oxide in COPD.

STUDY OBJECTIVES: To investigate whether exhaled carbon monoxide (CO) and nitric oxide (NO) could be used as noninvasive in vivo biomarkers of oxidative stress in the lungs of patients with COPD. DESIGN: Single-center cross-sectional study. PATIENTS: Ten healthy nonsmokers, 12 smokers, 15 stable ex-smokers with COPD, and 15 stable current smokers with COPD. INTERVENTIONS: Subjects attended the outpatient clinic on one occasion for pulmonary function tests and exhaled CO and NO measurements. MEASUREMENTS AND RESULTS: Mean (+/- SEM) CO levels in ex-smokers with COPD were higher (7.4 +/- 1.9 ppm; p < 0.05) than in nonsmoking control subjects (3.0 +/- 0.3 ppm) but were lower than in current smokers with COPD (20.0 +/- 2.6 ppm; p < 0.001). There was no correlation between exhaled CO and NO. There was no correlation between CO and lung function tests in any group of patients. Exhaled NO was higher in ex-smokers with COPD (12.0 +/- 1.0 parts per billion [ppb]; p < 0.001) than in healthy nonsmokers (6.5 +/- 0.6 ppb) and in current smokers with COPD (7.6 +/- 1.1 ppb; p < 0.01) compared to healthy smokers (3.3 +/- 0.4 ppb). Ex-smokers with COPD had higher exhaled NO levels than did current smokers with COPD (p < 0.001) There was a negative correlation between exhaled NO and FEV(1) in both ex-smokers with COPD (r = -0.60; p < 0.02) and current smokers with COPD (r = -0.59; p < 0.02). CONCLUSION: The measurement of exhaled CO and NO may represent a new method for the noninvasive monitoring of airway inflammation and oxidant stress in COPD ex-smokers. Exhaled CO and NO are strongly affected by cigarette smoking, which limits their usefulness as biomarkers in current smokers.

Biomarkers↗

Clinical significance of the increased peak levels of exhaled nitric oxide in patients with bronchial asthma.

We measured exhaled nitric oxide (NO) with a chemiluminescence method to elucidate the clinical significance of the increased concentration of exhaled NO in patients with bronchial asthma. Exhaled NO was measured in 25 patients with bronchial asthma and in 10 healthy control subjects. The concentration of exhaled NO in asthmatics was significantly higher than in the controls (250.4 +/- 30.4,59.9 +/- 9.6 ppb, respectively, p < 0.01). Symptomatic patients (unstable asthmatics) had a higher exhaled NO concentration than did the asymptomatic patients (stable asthmatics) (384.2 +/- 32.5,143.6 +/- 18.8 ppb, respectively, p < 0.01). The exhaled NO concentration was significantly correlated with the peak expiratory flow rate (r = 0.671, p < 0.01) and eosinophil ratio in induced sputum (r = 0.772, p < 0.05), but it was not correlated with the parameters of bronchial hyperactivity (Dmin and PD35 Grs). We conclude that the increased concentration of exhaled NO in patients with bronchial asthma reflects the state of airway inflammation, and we suggest that the measurement of exhaled NO is a useful, non-invasive and simple method for the management of bronchial asthma.

Adult↗

Exhaled nitric oxide levels in exacerbations of asthma, chronic obstructive pulmonary disease and pneumonia.

OBJECTIVE: Nitric oxide is known to be present in the exhaled air of normal subjects and at higher concentrations in asthmatics. The aim of this study was to measure exhaled nitric oxide levels in patients admitted to hospital with acute exacerbations of asthma, or chronic obstructive pulmonary disease, or with pneumonia. METHODS: Within 24 hours of admission exhaled nitric oxide levels were measured by a chemiluminescent analyzer in 11 patients with acute sever asthma, 19 patients with acute exacerbation of chronic obstructive pulmonary disease, and in 12 patients with pneumonia. In asthmatics measurements were made on 3 occasions, at day 1, 4, and 28 and were related to changes in peak expiratory flow rate. RESULTS: On admission median exhaled nitric oxide levels (range) were significantly higher in asthmatics 22 (9.3-74) parts per billion in comparison to patients with chronic obstructive pulmonary disease 10.3 (2.7-34) parts per billion; p < 0.01, pneumonia 7 (4-17) parts per billion; p<0.001, and normal subjects 8.7 (5-13.3) parts per billion; p < 0.001. Following treatment the asthmatics had a significant reduction in their exhaled nitric oxide levels from 22 (9.3-74) parts per billion on day 1 to 9.7 (5.7-18.3) parts per billion on day 28; p = 0.005. Peak expiratory flow rate measurements increased from 200 (120-280) l/min on day 1 to 280 (150-475) l/min on day 4; p < 0.05 and to 390 (150-530) l/min on day 28; p < 0.01. A strong negative correlation existed between peak expiratory flow rate measurements and exhaled nitric oxide levels in asthmatics on day 28 (r = -0.70; p = 0.017). CONCLUSION: Acute exacerbations of asthma are associated with increased levels of exhaled nitric oxide in contrast to exacerbations of chronic obstructive pulmonary disease and acute pneumonia. Exhaled nitric oxide may be a useful indirect marker of asthmatic airway inflammation. The differing time course of response of nitric oxide to peak flow measures suggests that these two measures are reflecting differing airway events.

Adolescent↗

An assessment of the role of exhaled carbon monoxide in acute asthmatic exacerbations in hospitalised patients.

Exhaled carbon monoxide is a useful marker of airway inflammation in untreated asthma. Whether exhaled CO is clinically useful in steroid treated patients in a hospital setting is uncertain. We therefore studied exhaled CO as a marker of asthma severity in clinical practice. Non-smoking "acute" asthmatics (hospitalised; n=33), "stable" asthmatics (n=35), and healthy controls (n=22) were recruited. Exhaled CO, peak expiratory flow (PEF) and FEV1 were measured daily (hospitalised cases) or once only (stable outpatients). Inpatients were managed without knowledge of the results. Exhaled CO levels in acute asthmatics (initial levels), stable asthmatics and controls were similar (median=2.0 ppm, h=5.05, p=0.08). In acute asthmatics, initial exhaled CO did not correlate with duration of hospitalisation, doses of intravenous corticosteroids, doses of nebulised salbutamol, PEF (% predicted) or FEV1 (% predicted). In stable asthmatics, exhaled CO did not correlate with corticosteroid dosage, PEF (% predicted) or FEV1 (% predicted). In the setting of acute hospitalised asthma patients, exhaled CO may not add any further to clinical management. This may in part be due to prior treatment with corticosteroids.

Acute Disease↗

Nitric oxide in exhaled air is a new marker of airway inflammation.

The measurement of exhaled NO has excited considerable interest, as it may provide a simple noninvasive means of measuring airways inflammation. There is now persuasive evidence that levels of NO are increased in association with airway inflammation and are decreased with anti-inflammatory treatment. Correlation of exhaled NO with more direct measurements of inflammation in the airways, such as induced sputum, bronchoalveolar lavage and bronchial biopsies, is needed. The great advantage of exhaled NO is that the measurement is completely noninvasive. It can, therefore, be performed repeatedly, and also in children and patients with severe airflow obstruction, where more invasive techniques are not possible. However, the measurement is not specific, and exhaled NO is increased in inflammation due to asthma, bronchiectasis, and respiratory tract infections. This means that absolute values are less important than serial measurements in individual patients. The value of this approach has been demonstrated in asthmatic patients, where the dose of inhaled steroid is changed, resulting in increased levels when the dose is reduced and lower levels when the dose is increased. Because exhaled NO is reduced by anti-inflammatory treatments, it may be of use in monitoring whether therapy is adequate. The technique may also have application in the monitoring of the anti-inflammatory effects of new antiasthma drugs, such as selective phosphodiesterase inhibitors, leukotriene antagonists and synthesis inhibitors, and immunomodulators. Because the measurement is precise and reasonably reproducible, it may facilitate the measurement of dose-response effects with anti-inflammatory treatments, which is difficult at present. The analysers for exhaled NO that are currently available are expensive, but in the future it is likely that technological advances will make it possible to miniaturize these analysers, so that they are portable and may even be used at home in conjunction with peak flow meters. -his may lead to their application in epidemiological research, which may be a useful screening measurement for community studies. Although we have discussed exhaled nitric oxide, other volatile substances may also be detected in exhaled air. Thus, ethane and pentane, which are volatile products of lipid peroxidation, and hydrogen peroxide, may be used to detect oxidant stress in the respiratory tract and may also be useful as markers of inflammation. There is little doubt that this is a rapidly expanding area of research.

Biomarkers↗

Exhaled nitric oxide levels in school children in relation to IgE sensitisation and window pane condensation.

BACKGROUND: A positive relation between exhaled nitric oxide (NO) levels and allergen exposure has been found in some studies whereas there is less information on how non-allergen environmental factors influences exhaled NO. OBJECTIVE: To study the relationship between exhaled NO levels in schoolchildren in relation to IgE sensitisation and allergenic and non-allergenic environmental factors. METHOD: This study comprised 374 schoolchildren (13-14 years of age) who performed exhaled NO-measurements and skin prick tests. Exposure to allergens, respiratory infections, environmental tobacco smoke and home window pane condensation, the latter an indicator of high humidity and poor ventilation was evaluated through questionnaires. RESULTS: In IgE-sensitised children sensitisation to pets was a more important determinant of exhaled NO than sensitisation to pollen. Higher NO levels were found in cat-sensitised children with a cat or other furred pets at home compared to cat-sensitised children without pets (geometric mean, 24.0 vs. 13.9 ppb, P=0.03). Significantly higher exhaled NO levels were found in non-sensitised children that reported having a cold (5.7 vs. 3.8 ppb, P<0.001) or lived in homes with window pane condensation (7.1 vs. 4.4 ppb, P=0.01) than in non-sensitised children without a cold and window pane condensation, respectively. These associations were not found in children that were sensitised to inhalation allergens. CONCLUSION: Allergen exposure seems to be the most important determinant for exhaled NO levels in IgE-sensitised children whereas in non-sensitised children NO levels were associated with respiratory infections and home window pane condensation.

Adolescent↗

Exhaled nitric oxide in a population-based study of asthma and allergy in schoolchildren.

Exhaled nitric oxide (NO) reflects inflammation in the lower airways and is well adapted for use in children. The aims of this study were to investigate the distribution of the fraction of expired NO (FENO) in school children and to compare FENO and spirometry in relation to the International Study of Asthma and Allergies in Childhood questionnaire. The study was performed in 959 randomly selected 13-14-year-old school children in Uppsala, Sweden. Exhaled NO was measured at an inhalation rate of 0.1 l/s (FENO0.1) and a spirometric test was performed and data from these measurements were related to questionnaire data. Exhaled NO was measured according to American Thoracic Society recommendations, except the use of a mouth wash and an exhalation flow rate of 0.1 l/s. The distribution of the mean FENO0.1 values was skewed, with a preponderance of very low levels and a widespread tail of values ranging up to 102 parts per billion (ppb). Boys exhibited significantly higher mean FENO0.1 values than girls, 5.2 (4.7-5.7) vs 4.4 (4.0-4.8) ppb (geometric mean and 95% CI), P <0.01). Children who reported wheezing in the last year had higher FENO0.1 values than children that had not, 8.5 (7.1-10.2) vs 4.3 (4.0-4.6) ppb, P <0.001). The same association was found to most symptoms indicating hay fever and eczema. In contrast to this, only weak or inconsistent associations were found between asthma and spirometric indices. Exhaled NO levels were found to be independently related to male gender, wheeze and rhinoconjuctivitis but not to current eczema. In conclusion, exhaled NO was closely associated with reported asthma and allergy symptoms whereas spirometric indices such as percent predicted forced expiratory volume in 1 s were not. As most asthma cases in a population are mild, the findings suggest that exhaled NO is a sensitive marker of asthma and allergy.

Adolescent↗

Inflammatory response to sputum induction measured by exhaled markers.

BACKGROUND: Sputum induction is increasingly used to study both cellular and biochemical composition of the airways. However, there is a significant rise in the percentage of neutrophils at 8 h after inhalation with hypertonic saline. OBJECTIVE: The aim of this study was to assess whether markers of inflammation in exhaled air and exhaled air condensate change after sputum induction in normal and asthmatic subjects. METHODS: We measured leukotriene B(4) (LTB(4)) and a marker of oxidative stress, 8-isoprostane, (by enzyme immunoassay) in exhaled air condensate and exhaled nitric oxide (NO; by chemiluminescence analyzer) in 15 healthy subjects (8 females, mean age 35 +/- 4 years, FEV(1) 97.4% predicted) and in 8 mild asthmatic subjects (5 males, mean age 34 +/- 2 years, FEV(1) 70.5% predicted). RESULTS: LTB(4) was significantly higher compared with baseline at 6 h but did not remain increased at 24 h after sputum induction (134.3 +/- 30.15 and 75.4 +/- 14.32 vs. 64.6 +/- 11.6 pg/ml at baseline; p < 0.02 and p > 0.05, respectively) in healthy subjects. An inverse correlation between LTB(4) and exhaled NO at 6 h after sputum induction was observed in healthy subjects (r = -0.66, p < 0.03). No increase in LTB(4) levels was observed in asthmatic patients. Baseline 8-isoprostane levels were higher in asthmatic patients than in healthy subjects (47.3 +/- 37.1 vs. 17.5 +/- 8.8 pg/ml; p < 0.01). A trend towards increased levels of 8-isoprostane could be observed at 6 and 24 h after inhalation in healthy subjects (26.2 +/- 3.7 and 26.7 +/- 3.9 pg/ml; p = 0.09 and p = 0.07, respectively). In healthy subjects, exhaled NO was significantly higher compared with baseline at 6 h and remained increased 24 h after sputum induction (7.96 +/- 3.5 vs. 5.61 +/- 1.86 ppb; p < 0.01 and p < 0.05, respectively). Exhaled NO levels were increased in asthmatic patients but did not further increase after sputum induction. CONCLUSIONS: Sputum induction with hypertonic saline causes an inflammatory response which should be considered when using the technique to monitor airway inflammation.

Adult↗

[Exhaled nitric oxide (NO) in asthma patients with acute exacerbation].

In recent years there has been an upsurge in interest in exhaled markers of inflammation, and nitric oxide (NO) in particular. The aim of the study was to evaluate the exhaled NO in monitoring anti-inflammatory therapy in asthma patients with acute exacerbation. The study was conducted in the group of 12 asthma patients, during acute asthma exacerbation treated with oral corticosteroids. NO was measured in exhaled air by means of chemiluminescence (model 280i nitric oxide analyzer, Sievers Instruments, Inc, USA. During 15 days of study a significant decrease in exhaled NO was observed. In our study the improvement of this inflammation marker correlated with clinical markers of disease control (the need for rescue beta 2-agonist use). The significant decrease in exhaled NO was started long before than increase in spirometric parameters. Treatment of airway inflammation in asthma with systemic and inhaled corticosteroids reduces levels of NO in exhaled air. Measurement of exhaled NO is non-invasive, safe and causes no inconvenience to the patients' method to monitoring of anti-inflammatory therapy.

Acute Disease↗

Exhaled nitric oxide measurements in normal and asthmatic children.

The aim of this study was to determine whether we could measure exhaled nitric oxide (NO) levels in children, and whether the same pattern of exhaled NO concentrations was observed in asthmatic and normal children as had been seen in adults. Using a chemiluminescence NO analyzer, we measured NO in exhaled air both directly and through a T-piece allowing us to measure carbon dioxide (CO2), mouth pressure, and expiratory flows. In 39 normal children the mean peak exhaled NO was 49.6 parts per billion (ppb) (SD 37.4) when all expired gas passed directly through the NO analyzer, and 29.7 ppb (SD 27.1) when expiration occurred through a T-piece. The results were significantly higher in 15 asthmatic subjects on bronchodilator therapy only [126.1 ppb (SD 77.1) direct (P < 0.001), and 109.5 ppb (SD 106.8) via T-piece (P < 0.001)]. In 16 asthmatics on regular inhaled corticosteroids the mean peak exhaled levels were significantly lower 48.7 ppb (SD 43.3) direct (P < 0.001) and 45.2 ppb (SD 45.9) via T-piece (P < 0.01). There was no difference between the normal children and the asthmatic children on regular inhaled corticosteroids (P = 0.9 direct, P = 0.2 via T-piece). There were no significant differences in carbon dioxide levels, mouth pressure, duration of expiration and expiratory flows between the different groups, and no difference between carbon dioxide levels, mouth pressure and duration of expiration between the two methods (direct and T-piece). In 6 asthmatic children mean peak exhaled levels on NO fell from a median peak level of 124.5 ppb to 48.6 ppb when measured before and 2 weeks after commencement of inhaled corticosteroid treatment. The measurement of exhaled NO levels may be useful as a noninvasive means of monitoring children with asthma.

Adolescent↗

Off-line exhaled nitric oxide measurements in children.

The concentration of exhaled nitric oxide (eNO) is a useful marker of asthmatic bronchial inflammation. eNO can now be measured away from the laboratory (off-line), even in children. Short exhalation maneuvers (8 sec) and small samples (1 L) of exhaled gas are probably sufficient in children, but more information is needed about the effect of different measurement conditions. As a preliminary step before conducting epidemiological studies in schoolchildren, we investigated the effects of expiratory flow, dead space, and expiratory time on eNO concentrations collected in 1-L mylar collection bags. We studied 101 cooperative subjects (62 males) aged 5-18 years (30 healthy volunteers, 51 asthmatics, and 20 children with various other respiratory diseases) in our pulmonary function laboratory. On-line and off-line eNO were compared in a single session, and analyzed with a Sievers NOA 280 nitric oxide analyzer. For both methods of collecting expired gas, subjects did a single exhalation without breath-holding against an expiratory pressure 10 cm H(2)O. We investigated the effects of expiratory flow, dead space, and exhalation time on eNO; we also compared on-line and off-line eNO measurements, and the repeatability of both techniques at a given flow rate. Expiratory flows of 58 mL/sec provided more reproducible data than lower flows (coefficient of repeatability 1.1 ppb for 58 mL/sec vs. 2.8 for 27 mL/sec vs. 5.7 for 18 mL/sec). eNO concentrations were about 25% higher in off-line than in on-line recordings if the initial 250 mL of exhaled gas were not eliminated, and 37% higher if exhalation lasted longer (16 sec vs. 8 sec). Eliminating 250 mL of dead space and shortening the filling time to 8 sec yielded off-line eNO values close to those on-line (geometric mean off-line eNO 14.4 ppb, 95% confidence interval: 12.2-17.0) vs. on-line eNO 13.8 ppb (95% confidence interval: 11.6-16.5). On-line and off-line results were highly correlated (r = 0.996, P = 0.000) and had similar coefficients of variation (on-line eNO 2.6%, off-line 2.8%). Neither agreement nor repeatability of eNO measurements were affected by disease status or baseline FEV(1) (% predicted values). Once standardized, the off-line eNO technique using 1-L gas collection bags will provide results similar to those recorded on-line.

Adolescent↗

Exhaled carbon monoxide in mechanically ventilated critically ill patients: influence of inspired oxygen fraction.

OBJECTIVE: To assess the feasibility of exhaled carbon monoxide (CO) measurements in mechanically ventilated critically ill adult patients and to determine the influence of inspired oxygen fraction on this measurement. DESIGN: Prospective physiologic study. SETTING: Medical ICU in a community hospital. PATIENTS: The study was performed on nine mechanically ventilated patients with varying diagnoses. MEASUREMENTS AND RESULTS: Carbon monoxide concentration was determined with an infrared CO analyzer on exhaled breath collected at the outlet of the ventilator. We assessed the stability of exhaled carbon monoxide concentration over a 4-hour period and determined its course during a 7-hour period after inspired oxygen fraction had been abruptly increased from baseline to 1. Carbon monoxide was detected in exhaled breath in each patient at a higher concentration than in inspired gas (0.64 +/- 0.1 ppm vs 0.25 ppm, approximately). Exhaled carbon monoxide did not vary during a 4-hour period in five hemodynamically stable patients. When inspired oxygen fraction was increased from baseline (0.52 +/- 0.04) to 1, exhaled carbon monoxide concentration increased abruptly from baseline (0.63 +/- 0.13 ppm) to a peak value of 1.54 +/- 0.16 ppm within 15 min and returned slowly to baseline values within 7 h. CONCLUSION: CO was easily detected in the exhaled breath of mechanically ventilated patients and CO lung excretion was markedly but transiently dependent on inspired oxygen fraction. Other studies are warranted in order to determine the different factors that might influence CO lung excretion in critically ill patients.

Aged↗

Carbon isotope ratios in exhaled CO(2) can be used to determine not just present, but also past diets in birds.

We show that an animal's past and present diet can be distinguished through the delta(13)C of exhaled CO(2). The exhaled delta(13)C of 12 pigeons fed solely corn (a C(4) plant) for 30 days was -13.63 per thousand (+/-0.30). We then fed six pigeons wheat (a C(3) plant) and continued to feed the other six corn. After 48 h the exhaled delta(13)C from the corn-fed pigeons was unchanged; that from the wheat-fed pigeons was -20.5 per thousand. We then fasted three of the wheat-fed pigeons for 3 days, after which their exhaled delta(13)C was -14.96 per thousand, while it was -13.57 per thousand in corn-fed pigeons, and -22.22 per thousand in pigeons that continued on wheat. Thus, we could infer diet from the (13)C/(12)C ratios of exhaled CO(2). Significantly, breath samples from fasted pigeons also revealed that they had eaten corn when their lipid stores were formed. We also showed that the change in the (13)C/(12)C of exhaled CO(2) had a half-life of approximately 3.5 h, and a time constant of approximately 6.7 h. Thus one can infer past and present diet from exhaled delta(13)C alone, if the initial breath sample is followed by a fasted breath sample, without harming the animal or having to recapture it successively.

Analysis of Variance↗

Endogenous pulmonary nitric oxide production measured from exhaled air is increased in patients with severe cirrhosis.

BACKGROUND/AIMS: Endogenous pulmonary nitric oxide production may be increased in severe cirrhosis and contribute to pulmonary vasodilation. This study assessed pulmonary nitric oxide production by measuring nitric oxide in the exhaled air in patients with severe cirrhosis and examined the relationship between exhaled nitric oxide and pulmonary hemodynamics in these patients. METHODS: Nitric oxide concentrations and production were measured in the exhaled air in six Child-Pugh class C patients with cirrhosis and 21 non-smoking healthy controls. Systemic and pulmonary hemodynamics were measured in patients only. RESULTS: Nitric oxide concentration (32.0 +/- 1.7 (mean +/- SEM) vs. 8.9 +/- 1.0 ppb) and production (9.2 +/- 1.3 vs. 3.1 +/- 0.3 nmol/min) in exhaled air were significantly higher in patients than in controls. Patients had high cardiac output (8.5 +/- 0.9 l/min), low pulmonary and systemic vascular resistance (57 +/- 10 and 767 +/- 93 dyn.s.cm-5, respectively) under baseline conditions. A significant negative correlation was found between pulmonary vascular resistance and exhaled nitric oxide production (r=0.943, p=0.05) but not between cardiac output or systemic vascular resistance and nitric oxide measured in exhaled air. CONCLUSIONS: Endogenous pulmonary nitric oxide production measured from exhaled air is increased in patients with cirrhosis and liver failure. Increased in patients with cirrhosis and liver failure. Increased nitric oxide production may also contribute to cirrhosis-induced pulmonary vasodilatation.

Female↗

Exhaled markers in the monitoring of airways inflammation and its response to steroid's treatment in mild persistent asthma.

The measure of inflammatory cytokines in the exhaled breath condensate has been recently proposed for use in monitoring asthma and the therapeutic response to steroids. The aim of the present study was to investigate the usefulness of measuring exhaled IL-6, IL-4 and pH in mild persistent asthma. Furthermore the effects on these markers of inhaled steroids were assessed. The study enrolled 28 asthmatic (15 males, 38+/-12 years) and 15 healthy subjects (5 males, 35+/-6 years). IL-6, IL-4 and pH were measured in the exhaled breath condensate of the subjects studied. Significantly higher concentrations of IL-6 and IL-4 were observed in the breath condensate of asthmatic patients (7.1+/-1.1 and 64.4+/-8.3 pg/ml) compared to controls (2.7+/-0.6 and 31.7+/-3.5 pg/ml), p<0.001. Furthermore, exhaled IL-4 fell significantly after treatment with inhaled steroids for 6 months (47.9+/-3.2 pg/ml, p<0.001) while exhaled IL-6 did not (6.4+/-1.0 pg/ml, p=0.8). The exhaled pH turned out to be lower in asthmatic subjects than in controls (7.39+/-0.11 vs. 7.85+/-0.14; P<0.001) but trended towards control levels after steroid treatment (7.65+/-0.16, P<0.001). We conclude that the measurement of exhaled IL-4 and pH in mild asthmatic subjects could be a useful way of monitoring their airway inflammation as well as their response to the treatment.

Administration, Inhalation↗

Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma. BHR-Study Group.

Exhaled nitric oxide (NO) has attracted increasing interest as a non-invasive marker of airway inflammation. The purpose of this study was to determine whether exhaled nitric oxide in subjects with asthma varied according to their atopic status and to examine its correlation with airway hyperresponsiveness and lung function measurements. Forty patients with asthma and 13 controls participated in the study. Nitric oxide was measured on three occasions with intervals of at least 3 days, using a chemiluminescence method. Airway responsiveness was assessed with methacholine challenge and lung function measurements were made. All subjects recorded peak expiratory flow and kept a symptom diary during a 17-day period. There was no significant difference in lung function measurements, peak expiratory flow or symptom score between the two asthma groups. Atopic patients with asthma had a significantly higher mean amount of exhaled NO than non-atopic subjects with asthma (162 +/- 68 vs. 113 +/- 55 nl min-1; P = 0.03) and the control group (88 +/- 52 nl min-1; P = 0.004). No significant difference was found in the amount of exhaled NO between non-atopic patients with asthma and the controls. In atopic subjects with asthma the mean exhaled NO was significantly correlated to the dose-response slope for methacholine (r = -0.52; P = 0.02), while no such correlation was found in the non-atopic group. In conclusion; in this study, atopic subjects with asthma had higher levels of exhaled NO than non-atopic subjects. Atopic status should be taken into account when measuring levels of exhaled NO in subjects with asthma.

Adolescent↗