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PubMed1997

[A standard maneuver to measure the concentration of exhaled nitric oxide].

We measured the concentration of nitric oxide (NO) exhaled during a standard maneuver in 55 healthy subjects (nonsmokers: 23 men and 32 women). After two deep breaths, each subject exhaled from total lung capacity through the mouth at 2 L/min into a Teflon tube connected to a chemiluminescence analyzer. The concentration of exhaled NO was defined as the plateau value measured during the latter part of expiration. In nonsmokers, the concentration was 28.7 +/- 12.2 ppb (mean +/- S.D.), which did not differ from that in smokers. The logarithm of the NO concentration (logNO) was normally distributed; it was significantly related to expiratory flow rate, but not to age, height, weight, sex, or the number of cigarettes smoked per day. The 95% confidence interval for the concentration of exhaled NO in healthy nonsmokers was 10.2 to 64.6 ppb.

Adult↗
PubMedDate not supplied

The use of exhaled carbon monoxide for the diagnosis of carbon monoxide poisoning. A case report.

INTRODUCTION: Carbon monoxide (CO) poisoning is difficult to confirm in small rural hospitals that lack easy access to a cooximeter. A small hand held device can be used to assess exhaled CO (ECO) in parts per million. This device is often used in smoking cessation clinics to confirm that a person has abstained from smoking. CASE SUMMARY: A 47-year-old white male became dizzy and had a near syncopal episode while working on his boat in the local marina. He was brought to the ER and was found to have an exhaled CO level of 180 ppm. The presence carboxyhemoglobin (HbCO) was confirmed later by an independent reference laboratory and the result was 26% HbCO. DISCUSSION: The patient's exhaled CO level dropped slower than expected while breathing oxygen delivered by a non-rebreather mask. This could be due to inadequate compliance to oxygen therapy and a fiO2 somewhat less than 1.0. Another limitation of the technique is the calibration gas (50-ppm CO). This concentration may be too low to assess ER patients. Therefore a confirmatory ABG with cooximetry should be obtained if available. Clinicians are cautioned that there is no safe level of HbCO (6). There is a simple formula to convert ECO to HbCO. The use of exhaled CO monitoring may be a promising alternative that is relatively less expensive than cooximetry in the ER setting, but more research is clearly indicated.

Breath Tests↗
PubMed1998

Ambient and exhaled carbon monoxide levels in a high traffic density area in Christchurch.

AIMS: To monitor outdoor and indoor levels of carbon monoxide (CO) in a sample of shops and offices in a high traffic density area of Christchurch and to measure end-exhaled CO levels in the respective shop and office workers in order to assess the potential for adverse health effects. METHODS: Outdoor CO was monitored at two fixed locations near a congested traffic intersection in Riccarton Road, Christchurch. Six shops and three offices were purposefully selected within 300 metres of the monitoring sites. Indoor CO was monitored with a portable ambient gas monitor. Participants in each shop and office underwent end-exhaled breath testing for CO three times daily at approximately 0900, 1300 and 1600 hours for the week their premises was monitored. RESULTS: Outdoor CO levels exceeded the ambient 8-hour guideline of 8 ppm on five of the 37 (14%) monitored days and indoor CO levels exceeded the ambient 8-hour guideline on two days. Thirty-two workers, mean age (SD) 34 (9.9) years, participated in the study. End-exhaled CO levels were all below 7 ppm, within the normal range for non-smokers. There was no consistent relationship between indoor CO levels and outdoor CO levels. CONCLUSIONS: The 8-hour ambient guideline for CO was exceeded on several days but there was no evidence of elevated exhaled CO levels in any of the participants. It is unlikely that such exposures would impact adversely on the health of workers unless they suffered from an underlying cardiovascular disorder.

Adult↗
PubMed1998

[Exhaled and nasal nitric oxide in normal and asthmatic children].

OBJECTIVE: Our aim was to study the concentration of nitric oxide in the exhaled (ENO) and nasal (NNO) air of normal children and asthmatic children who are clinically and functionally stable. PATIENTS AND METHODS: Using a nitric oxide chemiluminescence analyze and a register for CO2, pressure and flow, we studied 73 schoolchildren (6-17 years of age). This included 37 controls and 36 asthmatic children, 21 with mild asthma without antiinflammatory treatment and 15 treated with inhaled corticosteroids. We used the technique of slow exhalation against resistance for (ENO) determination and aspiration with stable flow in nasal cavity while holding the breath for (NNO) determination. RESULTS: The mean ENO was 3.1 ppb (1-6) in the control group, 8.3 ppb (1.7-29.3) in the mild asthma group and 7.7 ppb (2-18.3) in the asthmatics treated with corticosteroids. There were significant differences (p = 0.0001) between the controls and both asthmatic groups. The mean NNO in the controls was 898 ppb and differences between this group and the asthmatic children were found. The ENO and NNO did not change in relation to age or sex. We did not find any relationship between ENO and lung function. There is a significant correlation between ENO and NNO in both asthmatic groups, but not in the control group. CONCLUSIONS: The ENO was higher in asthmatics than in control children. The slow exhalation against resistance technique prevents the contamination of exhaled air with nasal air and this technique can be applied to children over 6 years of age. The NNO was similar in the asthmatic groups and the control group.

Analysis of Variance↗
PubMed2005

Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years.

BACKGROUND: Fractional exhaled nitric oxide (FE NO ) is used in monitoring of asthma. OBJECTIVES: The aim of this multicenter study was to establish normal values of FE NO and assess feasibility in children with a standardized method and equipment approved for clinical use. METHODS: FE NO was measured in healthy subjects of 4 to 17 years according to American Thoracic Society guidelines (single breath online, exhalation flow 50 mL/s) with a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden) in 3 European and 2 US centers. Each child performed 3 acceptable nitric oxide measurements within 6 attempts and completed an extended International Study of Asthma and Allergy in Children questionnaire. RESULTS: Measurement of FE NO was attempted in 522 children. Four hundred five children completed the study according to the protocol. Geometric mean FE NO in 405 children was 9.7 ppb, and the upper 95% confidence limit was 25.2 ppb. FE NO increased significantly with age, and higher FE NO was seen in children with self-reported rhinitis/conjunctivitis or hay fever. The success rate was age-dependent and improved from 40% in the children 4 years old to almost 100% from the age of 10 years. The repeatability of 3 approved measurements was 1.6 ppb (95% CI, 1.49-1.64 ppb). CONCLUSION: FE NO in healthy children is below 15 to 25 ppb depending on age and self-reported atopy. Measurement of FE NO by NIOX is simple and safe and has a good repeatability. Feasibility depends on age and may be difficult in the preschool child.

Adolescent↗
PubMed2006

Exhaled NO and breath condensate.

A growing interest has recently directed toward non invasive methods, such as exhaled nitric oxide (FE(NO)) measurement and exhaled breath condensate (EBC) collection, for the assessment of asthmatic inflammation. FE(NO) is a reliable marker of eosinophilic airway inflammation and it can be measured by means of a standardized technique in children starting from the age of 4. FE(NO) may have useful applications both in asthma diagnosis and monitoring. EBC is obtained cooling exhaled air and its composition is believed to mirror the characteristics of airway lining fluid. The compounds detected in EBC are markers of inflammation and oxidative stress occurring in asthmatic lung. While EBC is still only a research tool, FENO measurement is closer to clinical practice and lately it has been included in some treatment algorithms for asthma.

Asthma↗
PubMed2006

Increased hydrogen peroxide concentration in the exhaled breath condensate of stable COPD patients after nebulized N-acetylcysteine.

BACKGROUND: The oxidative burden in the airways is a hallmark of chronic obstructive pulmonary disease (COPD). AIMS: This prospective, cross-over, placebo (PL)-controlled study was designed to investigate the effect of N-acetyl-l-cysteine (NAC) on hydrogen peroxide (H(2)O(2)), nitrites and nitrates (NO(2)(-)+NO(3)(-)), and thiol (RSH) concentrations in exhaled breath condensate (EBC) in stable COPD patients (n=19, aged 52.6+/-15.6 years, 10 females, mean FEV(1) 95.2+/-23.8%, FEV(1)/FVC 69.1+/-11.4%). METHODS: H(2)O(2), NO(2)(-)+NO(3)(-) and RSH concentrations in EBC were determined with homovanillic acid, NADPH-nitrite reductase assays and Ellman's reaction, respectively. RESULTS: Thirty minutes after nebulization, H(2)O(2) concentration increased if levels after NAC (0.45+/-0.25microM) and PL (0.17+/-0.17microM) were compared in COPD patients (p=0.002). This increased H(2)O(2) level in EBC was no longer observed either after 90min: 0.16+/-0.09microM (PL 0.17+/-0.15microM) or 3h: 0.12+/-0.07microM (PL 0.21+/-0.23microM) (p=0.5 and 0.2, respectively). The levels of NO(2)(-) and NO(3)(-) did not differ between NAC and PL. There was no significant difference in RSH levels between nebulized NAC and PL. After nebulized NAC, however, exhaled RSH increased from 1.42+/-1.69microM (0min) to 2.49+/-2.00microM (30min), and 1.71+/-1.83microM (180min) (p=0.009 and 0.03, respectively, compared with 0min). CONCLUSIONS: These data demonstrate that nebulized NAC transiently increases exhaled H(2)O(2) level, whereas it has no effect on other oxidative parameters.

Acetylcysteine↗
PubMed2003

Nitric oxide exhalation correlates with ventilatory response to exercise in patients with heart disease.

AIMS: It is controversial whether or not pulmonary nitric oxide (NO) production, reflected in the end-tidal alveolar NO concentration, is diminished in patients with heart failure. Since pulmonary perfusion is regulated by NO production, decreased NO production in the pulmonary vasculature is assumed to result in diminished lung perfusion and further increases in ventilation-perfusion mismatch. The aim of this study is to investigate whether exhaled NO correlates with both exercise-induced hyperpnea and exercise tolerance in patients with heart disease. METHODS AND RESULTS: Forty-two patients with heart disease were enrolled (history of prior myocardial infarction (n=19), dilated cardiomyopathy (n=2), hypertensive heart disease (n=5) and prior open-heart surgery (n=16)). During cardiopulmonary exercise testing, exhaled air was collected and end-tidal NO (ETNO) was measured using a chemiluminescent method. Peak ETNO was found to correlate positively with both ventilatory anaerobic threshold (r=0.468) and peak VO(2) (r=0.562). The VE-CO(2) slope, which reflects the ventilatory response to exercise, correlated negatively with peak ETNO (r=-0.588). CONCLUSION: These data indicate that NO exhalation correlates, inversely, with the ventilatory response to exercise and directly with exercise intolerance, although the weakness of the correlation coefficient suggests there may be other possible mechanisms.

Exercise↗
PubMed2006

[Analysis of oxidative stress in exhaled breath condensate from patients with severe pulmonary infections].

OBJECTIVE: Oxidative stress is an intrinsic part of the chain of events leading to inflammation of the airways caused by bacterial infection. The aim of this study was to determine whether analysis of exhaled breath condensate from patients with severe lung infections reveals changes in the redox state at the airway surface. PATIENTS AND METHODS: The study included a total of 48 subjects divided into 4 groups: individuals without respiratory disease (n=14), patients with multilobar pneumonia (n=13), patients who had chronic obstructive pulmonary disease with superinfection (n=14), and mechanically ventilated patients with severe pneumonia (n=7). A sample of exhaled breath condensate was obtained within the first 72 hours of hospital admission and the concentrations of nitrite, nitrate, 8-isoprostane, and myeloperoxidase (MPO) were determined. RESULTS: Significant differences in the concentrations of nitrite, 8-isoprostane, and MPO were observed between patients and individuals without respiratory disease but no differences were found between the 3 patient groups. The concentration of MPO was correlated with the concentrations of 8-isoprostane and nitrate, which were normalized to the nitrite concentration. CONCLUSIONS: Analysis of the concentrations of 8-isoprostane and MPO in exhaled breath condensate allows assessment of oxidative stress in the airways of patients with severe lung infections.

Adult↗
PubMed2003

Assessment of inhaled BDP-dose dependency of exhaled nitric oxide and local and serum eosinophilic markers in steroids-naive nonatopic asthmatics.

The aim of the present study was to assess the dose-dependency from inhaled steroids of changes of airways inflammation [eosinophils count and eosinophil cationic protein (ECP)] measures in induced sputum and in serum, as well as that of exhaled nitric oxide. Twenty steroid-naive patients with nonatopic asthma of mild to moderate degree [forced expiratory volume in 1 s (FEV1) = 70% of predicted] and with negative response to the standard tests for allergy were selected; after a 1-week run-in period they were randomized to receive a 12-week treatment period of inhaled beclomethasone dipropionate dry powder given with the Pulvinal inhaler (Clenil P, Chiesi Farmaceutici S.p.A., Parma, Italy) in two different dose regimens, 400 microg bid (high dose) or 200 microg bid (low dose), over a double blind, parallel groups design. The following outcome measures were assessed in baseline and after 1, 6 and 12 weeks of treatment: FEV1 (l), eosinophils count in sputum (%), is ECP (microg/l), serum eosinophils count (%), serum ECP (microg/l) and exhaled NO (ppb). The results showed that all the considered parameters improved in both groups: the increase over baseline of FEV1 and the decrease of NO were significant at any time in the high-dose group and only at week 12 in the low-dose group (NS between groups), whereas the markers of eosinophilic activity showed more consistent reductions in the high-dose than in the low-dose group when measured in induced sputum (P < 0.05 between groups after 6 and 12 weeks for eosinophils count and after 12 weeks for ECP). Decreases over baseline of markers measured in serum were more rapid in the high-dose group, without differences between groups. A marked trend towards a negative correlation was found between FEV1 and ECP, (r = -0.72, P < 0.05), between FEV1 and eosinophils in sputum (r = -0.31, NS) and between FEV1 and exhaled NO (r = -0.38, NS), all of them only in the high-dose group. The results of the study demonstrate that changes of levels of eosinophilic activity in the airways are dependent from the daily dose of inhaled steroids when measured in induced sputum and that the local assessment can therefore represent a practical and noninvasive method to monitor the extent of airways inflammation.

Administration, Inhalation↗
PubMed2006

Influence of exhaled air on inhalation exposure delivered through a directed-flow nose-only exposure system.

In order to conserve material that is available in limited quantities, "directed-flow" nose-only exposure systems have at times been run at flow rates close to the minute ventilation of the animal. Such low-flow-rate conditions can contribute to a decrease of test substance concentration in inhaled air; near the animal nose, exhaled air and the directed flow of exposure air move in opposite directions. With a Cannon "directed-flow" nose-only exposure system (Lab Products, Maywood, NJ), we investigated the extent to which exposure air plus exhaled air can be inhaled by an animal. A mathematical model and a mechanical simulation of respiration were adopted to predict for a male Fischer 344 rat the concentration of test substance in inhaled air. The mathematical model was based on the assumption of instantaneous mixing. The mechanical simulation of respiration used a Harvard respirator. When the system was operated at an exposure air flow rate greater than 2.5 times the minute ventilation of the animal, the concentration of test substance in the inhaled air was reduced by less than 10%. Under these conditions, the circular jet of air exiting the exposure air delivery tube tended to reach the animal's nose with little dispersion. For exposure air flow rates less than 2 times the minute ventilation, we predict that the interaction of exhaled air and exposure air can be minimized by proportionally reducing the delivery tube diameter. These findings should be applicable to similar "directed-flow" nose-only exposure systems.

Air↗
PubMed2005

Generation of volatile compounds on mouth exposure to urea and sucrose: implications for exhaled breath analysis.

The increase in ammonia and ethanol in the exhaled breath stream following mouthwashes by aqueous solutions of urea and sugar (sucrose), respectively, has been investigated by analysing exhaled breath in real time using selected ion flow tube mass spectrometry, SIFT-MS. It is shown that the measured levels of these compounds in the stream of exhaled breath can be much greater than the endogenous levels originating at the alveolar boundary. Thus, it is concluded that without careful preparation, mouth production of these compounds, and other compounds as yet unidentified, can seriously compromise the quantification of truly endogenous trace compounds present in blood and in the alveolar breath, as required for clinical diagnosis, and can probably introduce additional compounds into the breath stream that could seriously mislead breath analysis. The concentrations of both the urea and sucrose solutions used to enhance the ammonia and ethanol levels were larger than normally present in food and drinks and so in most situations such severe enhancements will not occur.

Ammonia↗
PubMed2005

Ascent exhalations of Antarctic fur seals: a behavioural adaptation for breath-hold diving?

Novel observations collected from video, acoustic and conductivity sensors showed that Antarctic fur seals consistently exhale during the last 50-85% of ascent from all dives (10-160 m, n > 8000 dives from 50 seals). The depth of initial bubble emission was best predicted by maximum dive depth, suggesting an underlying physical mechanism. Bubble sound intensity recorded from one seal followed predictions of a simple model based on venting expanding lung air with decreasing pressure. Comparison of air release between dives, together with lack of variation in intensity of thrusting movement during initial descent regardless of ultimate dive depth, suggested that inhaled diving lung volume was constant for all dives. The thrusting intensity in the final phase of ascent was greater for dives in which ascent exhalation began at a greater depth, suggesting an energetic cost to this behaviour, probably as a result of loss of buoyancy from reduced lung volume. These results suggest that fur seals descend with full lung air stores, and thus face the physiological consequences of pressure at depth. We suggest that these regular and predictable ascent exhalations could function to reduce the potential for a precipitous drop in blood oxygen that would result in shallow-water blackout.

Adaptation, Physiological↗
PubMed2005

Acid-base equilibrium in exhaled breath condensate of allergic asthmatic children.

BACKGROUND: The dysregulation of airway pH control may have a role in asthma pathophysiology. The measurement of exhaled breath condensate (EBC) pH and ammonia levels may be used as a noninvasive method to study acid-base status in the airway of asthmatics. METHODS: Exhaled breath condensate from 29 allergic stable asthmatic children and 13 healthy controls was collected by cooling exhaled air during tidal breathing. Ammonia was measured by high-performance liquid chromatography with fluorescence detection. pH was measured after deaeration of EBC samples by bubbling with argon. The children also underwent FENO measurement. RESULTS: Both pH and ammonia values in EBC were significantly lower in the asthmatics than in the control group [pH: ICS-treated (median and interquartile range) 7.70 (7.62-7.74), steroid-naive 7.53 (7.41-7.68), controls 7.85 (7.80-7.90), P <0.01 and P <0.001, respectively; ammonia: ICS-treated 476.17 microM (282.50-594.80), steroid-naive 253.24 microM (173.43-416.08), controls 788.30 microM (587.29-1310.39), P < 0.05 and P <0.001, respectively]. Both pH and ammonia values were higher in ICS-treated than in steroid-naive asthmatic children. There was a significant correlation between EBC pH and ammonia concentrations. CONCLUSIONS: These data show that EBC pH values of stable asthmatic children are lower compared with those of healthy controls and positively correlated with ammonia concentrations, supporting the hypothesis that airway acidification may have a role in the pathobiology of allergic asthma.

Acid-Base Equilibrium↗
PubMed2005

H. pylori infection increases levels of exhaled nitrate.

BACKGROUND: Helicobacter pylori infection is one of the most common chronic bacterial infections worldwide. Despite the existence of a breath test for the diagnosis of H. pylori infection, no study has described the composition of volatile compounds, especially the levels of nitrate, in the exhaled air of patients with H. pylori infection. MATERIALS AND METHODS: The volatile compounds in the exhaled air of 14 patients suffering from H. pylori gastritis and 11 controls were analyzed using proton transfer reaction-mass spectrometry. Gastric biopsy was used to establish diagnosis of current H. pylori infection. RESULTS: Comparing mass spectra between groups, Mass 28 (hydrogen cyanide, HCN) and Mass 64 (hydrogen nitrate, H2NO3) were found to be significantly elevated in patients with H. pylori infection. CONCLUSIONS: The main result of the present study is that in H. pylori-infected patients, levels of exhaled hydrogen nitrate and hydrogen cyanide are found to be significantly elevated. However, further studies are necessary to find out whether the differences in the detected mass spectrum are specific enough to differentiate patients with H. pylori gastritis from healthy controls.

Adult↗
PubMed2004

Mutual information based CT registration of the lung at exhale and inhale breathing states using thin-plate splines.

The advent of dynamic radiotherapy modeling and treatment techniques requires an infrastructure to weigh the merits of various interventions (breath holding, gating, tracking). The creation of treatment planning models that account for motion and deformation can allow the relative worth of such techniques to be evaluated. In order to develop a treatment planning model of a moving and deforming organ such as the lung, registration tools that account for deformation are required. We tested the accuracy of a mutual information based image registration tool using thin-plate splines driven by the selection of control points and iterative alignment according to a simplex algorithm. Eleven patients each had sequential CT scans at breath-held normal inhale and exhale states. The exhale right lung was segmented from CT and served as the reference model. For each patient, thirty control points were used to align the inhale CT right lung to the exhale CT right lung. Alignment accuracy (the standard deviation of the difference in the actual and predicted inhale position) was determined from locations of vascular and bronchial bifurcations, and found to be 1.7, 3.1, and 3.6 mm about the RL, AP, and IS directions. The alignment accuracy was significantly different from the amount of measured movement during breathing only in the AP and IS directions. The accuracy of alignment including thin-plate splines was more accurate than using affine transformations and the same iteration and scoring methodology. This technique shows promise for the future development of dynamic models of the lung for use in four-dimensional (4-D) treatment planning.

Algorithms↗
PubMed2006

Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation in a disease model.

There is a great deal of interest in developing less invasive markers for monitoring airway inflammation and the effect of possible novel anti-inflammatory therapies that may take time to impact on disease pathology. Exhaled nitric oxide (eNO) has been shown to be a reproducible, noninvasive indicator of the inflammatory status of the airway in the clinic. The aim of the present study was to determine the usefulness of measuring eNO as a marker of the anti-inflammatory impact of glucocorticoid and an inhibitor of kappaB kinase-2 (IKK-2) inhibitor 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), in a pre-clinical model of airway inflammation. Rats were given vehicle, budesonide or TPCA-1 prior to exposure to lipopolysaccharide, previously shown to induce an increase in eNO and airway neutrophilia/eosinophilia. Comparison of the effect of the two compounds on inflammatory components demonstrated a significant correlation between the impact on eNO and inflammatory cell burden in the airway. The current study demonstrates the usefulness of profiling potential disease-modifying therapies on exhaled nitric oxide levels and the way in which an effect on this noninvasive biomarker relates to effects on pathological parameters such as lung cellularity. Information from studies such as the current one would suggest that the measurement of exhaled nitric oxide has potential for monitoring inflammatory status in lung tissue.

Amides↗
PubMed2003

Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations.

Nasal nitric oxide (NO) levels increase greatly during humming compared to silent exhalation. In this study, the physiological and anatomical factors that regulate NO release during humming have been characterised in 10 healthy subjects and in a model of the sinus and the nose. Single-breath humming caused a large initial peak in nasal NO output, followed by a progressive decline. The NO peak decreased in a step-wise manner during repeated consecutive humming manoeuvres but recovered completely after a silent period of 3 min. Topical nasal application of an NO synthase inhibitor reduced nasal NO by >50% but had no effect on the increase evoked by humming. Silently exhaled nasal NO measured immediately after repeated humming manoeuvres was between 5-50% lower than basal silent NO exhalation, suggesting variable continuous contribution from the sinuses to nasal NO. Among the factors known to influence normal sinus ventilation, ostium size was the most critical during humming, but humming frequency was also of importance. In conclusion, humming results in a large increase in nasal nitric oxide, which is caused by a rapid gas exchange in the paranasal sinuses. Combined nasal nitric oxide measurement with and without humming could be of use to estimate sinus ventilation and to better separate nasal mucosal nitric oxide output from sinus nitric oxide in health and disease.

Adult↗