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PubMed2003

Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma.

OBJECTIVE: Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed. STUDY DESIGN: FE(NO), spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout. RESULTS: Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FE(NO) levels were similar between the three treatments. FE(NO) levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FE(NO) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly. CONCLUSIONS: Budesonide therapy was more effective than nedocromil in reducing FE(NO). Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FE(NO) may be a complementary tool to current practice guidelines in assessing asthma control and medication response.

Anti-Asthmatic Agents↗
PubMedDate not supplied

Evaluation of methodological and biological influences on the collection and composition of exhaled breath condensate.

The purpose of this inter-species comparison (calves and pigs) was to identify methodological and biological influences on the collection and composition of exhaled breath condensate (EBC). A total of 352 EBC samples were collected, whilst variables of ventilation were registered in parallel. Partial pressure of carbon dioxide (pCO2) and pH were analysed in non-degassed EBC samples. The concentration of total protein in EBC was measured colorimetrically. In both species, lung function was evaluated before and after EBC collection. Statistical analyses were performed to study the effect of EBC collection on lung function and to identify the influence of ventilatory variables on the collection and composition of EBC. Collection of EBC did not affect lung function. Despite the volume of EBC collected per unit time being primarily dependent on ventilation per unit time, species-specific conditions during the EBC collection process resulted in different dependences of EBC collection from other variables of ventilation (i.e. maximal airflow during expiration or expired tidal volume kg-1 body weight). The concentration of protein ml(-1) EBC increased with the expired volume per min and with peak expiratory flow. Although the pCO2 in fresh EBC was significantly negatively dependent on the duration of collection, comparable pHs (5.6 - 6.2) were measured in EBC of both calves and pigs. The obtained data may help one standardize EBC collection in different species.

Animals↗
PubMed2003

Steroid-naive adolescents with mild intermittent allergic asthma have airway hyperresponsiveness and elevated exhaled nitric oxide levels.

Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25-75%, and FVC values not significantly different from controls, (p > 0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20 > or = 400 microg or accumulative dose < or = 1220 microg) and moderate in 32.7% (MCh PD20 400-1400 microg or accumulative dose 1220-4620 microg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 +/- 5.3 ppb and 4.4 +/- 0.7 ppb, respectively; p < 0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e., > 2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25-75% values and MCh PD20 (r = 0.358; p < 0.01) or MCh accumulative dose (r = 0.355; p < 0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p > 0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.

Adolescent↗
PubMed2003

Correlation of exhaled nitric oxide levels and airway inflammation markers in stable asthmatic patients.

Monitoring of inflammation is an important factor in asthma management. The gold standard for measuring direct airway inflammation is bronchial biopsy specimens taken from proximal airways through a fiberoptic bronchoscope. As a noninvasive procedure, the use of exhaled nitric oxide (FENO) for monitoring airway inflammation has been reported in many studies. The aim of this study was to evaluate the correlation of FENO with direct measurements of airway inflammation in biopsy specimens and pulmonary function tests (PFT). Histopathologic features were observed on bronchial biopsy specimens obtained from nine stable mild-moderate asthmatics. Each subject had measurements of PFT, FENO levels, blood eosinophil count, and bronchoscopy with bronchial biopsies and bronchoalveolar lavage. Five subjects with forced expiratory volume in 1 second >80% had methacholine challenge test. None of the subjects had prior anti-inflammatory therapy for asthma. No correlation was found between PFT, blood eosinophil count, and FENO levels. There was a negative correlation between PC20 and FENO. Though there was no correlation between bronchial biopsy eosinophil, monocyte and lymphocyte counts, and FENO, we found a weak positive correlation between total inflammatory cell count in bronchial biopsies and FENO levels. A negative significant correlation was found between FENO levels and epithelial desquamation (p<0.05, r=-0.7). These results suggest that, FENO levels reflect the increased number of activated inflammatory cells in airways and the negative correlation with epithelial desquamation reflects the role of epithelium in NO syntheses. FENO should not be interpreted as a specific inflammation marker for asthma.

Adult↗
PubMed2004

Exhaled nitric oxide predicts asthma exacerbation.

The fraction of exhaled nitric oxide (FeNO) is elevated in asthmatics compared to normal subjects. Many studies have demonstrated that FeNO correlates with other markers of airway inflammation. The purpose of this study was to assess the clinical utility of routine monitoring of FeNO in determining its ability to predict future asthma exacerbations compared with other standard clinical measures of spirometry, peak flows, quality of life score, medication usage, and symptoms. A convenience sample of 22 patients with moderate and severe-persistent asthma in the University of New Mexico Adult Asthma Clinic were evaluated during a routine clinic visit and then noted whether they had an exacerbation within 2 weeks of the initial appointment. Those with an exacerbation had a higher mean FeNO (29.67 ppb +/- 14.48) compared to those who did not (12.92 ppb +/- 5.17), p = 0.002. A nominal logistic regression model to determine those variables that predict asthma exacerbation found that FeNO was the only significant predictor, p = 0.03. Thus, FeNO appears to be a clinically useful tool to assess disease control in this population.

Adult↗
PubMed2006

A longitudinal study of ammonia, acetone and propanol in the exhaled breath of 30 subjects using selected ion flow tube mass spectrometry, SIFT-MS.

Selected ion flow tube mass spectrometry, SIFT-MS, has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 males, 11 females) over a 6 month period. Volunteers provided breath samples each week between 8:45 am and 1 pm (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ammonia, acetone and propanol. It was found that the concentration distributions of these compounds in breath were close to log-normal. The median ammonia level estimated as a geometric mean for all samples was 833 parts per billion (ppb) with a multiplicative standard deviation of 1.62, the values ranging from 248 to 2935 ppb. Breath ammonia clearly increased with increasing age in this volunteer cohort. The geometric mean acetone level for all samples was 477 parts per billion (ppb) with a multiplicative standard deviation of 1.58, the values ranging from 148 to 2744 ppb. The median propanol level for all samples was 18 ppb, the values ranging from 0 to 135 ppb. A weak but significant correlation between breath propanol and acetone levels is apparent in the data. The findings indicate the potential value of SIFT-MS as a non-invasive breath analysis technique for investigating volatile compounds in human health and in the diseased state.

1-Propanol↗
PubMedDate not supplied

The mathematical analysis of breath alcohol profiles generated during breath exhalation.

The mathematical analysis of time domain data provides a useful tool for evaluating biological and instrumental systems. Breath alcohol profile measurements generated during exhalation constitute biological signals that can be subjected to a variety of mathematical treatments. The present paper discusses the application of a variety of mathematical procedures to breath alcohol profiles. These mathematical procedures include model approximation, data smoothing, integration, differentiation, and fourier transformation. The different mathematical procedures provide insight into the physiology of breath alcohol measurement and suggest forensic as well as instrumental applications.

Breath Tests↗
PubMed2004

Screening of exhaled breath by low-resolution multicomponent FT-IR spectrometry in patients attending emergency departments.

Interest in noninvasive methods for disease diagnosis is increasing. In this study, we tested the utility and potential of a portable Fourier transform infrared (FT-IR) multicomponent analyzer in the emergency rooms (ERs) of two Finnish hospitals. Major detected breath volatiles in this population were ethanol, carbon monoxide, methane, and acetone, in addition to carbon dioxide and water. The analysis of breath revealed an ethanol concentration of over 25 ppm (0.1 g/L in blood) in 56 out of 589 patients (9.5%). During nightshifts the proportion was 30% for all and 63% for trauma patients. Five-hundred eighty-four patients had measurable carbon monoxide in their breath. A breath carbon monoxide of over 4 ppm (4.4 micro g/L) differentiated smokers from nonsmokers. Methane over 2 ppm (1.3 micro g/L) was detected in the breath of 32% of the participants. Methane concentration was higher among aged patients. Two-hundred ninety-eight participants had detectable acetone in their breath. Elevated exhaled acetone [10-76 ppm (23-75 micro g/L)] was detected in 10 patients. The FT-IR method proved functional in the ER setting. A major advantage over blood sampling was fast and easy analysis performed by nonlaboratory personnel.

Acetone↗
PubMed2001

A new 'online' method to measure increased exhaled isoprene in end-stage renal failure.

BACKGROUND: Isoprene is the most abundant hydrocarbon present in breath, and recent reports indicate that breath concentrations increase following haemodialysis. The purpose of this study was to establish whether selected ion flow tube mass spectrometry (SIFT-MS), a newly established technique in breath analysis, may be used to quantify breath isoprene in haemodialysis patients in the clinical setting. SIFT-MS is compared and contrasted with the established gas chromatography mass spectrometric technique for this purpose. METHODS: Three consecutive exhalations from 19 haemodialysis patients (12 males, seven females) undergoing a morning dialysis shift were analysed just prior to commencing treatment. Within 5 min of completing their usual dialysis regimen, using polysulphone membranes, the breath of each patient was analysed again. Additional contemporary samples were obtained from 17 normal controls. Breath isoprene was quantified using SIFT-MS, a method previously validated quantitatively using neat isoprene. RESULTS: Successful measurements of breath isoprene were obtained for each subject within 2 min, with minimum disruption to a busy dialysis environment. The coefficient of variation of triplicate measurements of breath isoprene was <10%. Prior to dialysis, the mean (+/-SD) breath isoprene concentration (138+/-63 parts per billion (ppb)) was significantly greater than for normal controls (89+/-36 ppb; P=0.016). Immediately following treatment, breath isoprene increased significantly to 184+/-95 ppb (P=0.023). CONCLUSIONS: SIFT-MS permits the accurate and rapid measurement of breath isoprene in haemodialysis patients in the clinical setting. The previously reported increase in breath isoprene following dialysis treatment is confirmed. SIFT-MS is the ideal analytical tool to investigate this phenomenon further.

Acute Kidney Injury↗
PubMed2004

Theory of radon exhalation into accumulators placed at the soil-atmosphere interface.

A theoretical analysis is provided for the phenomenon of radon diffusion into cylindrical accumulators (inverted cups), which are commonly used for the measurement of radon exhalation rates from the earth's surface. Analytical solutions to the diffusion equations in the soil and the cup spaces are obtained by a two-dimensional (2-D) analysis that takes into account the perturbation in the horizontal and vertical radon concentration profiles brought about by the presence of the cup. The mixed nature of the boundary conditions at the soil surface and the cup-soil interface is handled by dual integral equation techniques. The treatment includes steady-state and time-dependent situations with and without ventilation. Formulae are derived for the effective time constant of radon build-up in the cup and for the back diffusion correction factors in different experimental situations. It is found that the effective time constant of radon build-up is much larger than the radon decay constant and it increases for smaller cups. The back diffusion correction factors to be employed in one-time measurement methods also increase as the cup dimensions decrease. The present work provides an analytical basis of an earlier numerical treatment for the growth curve analysis of the same problem. Although the results are based on the assumptions of somewhat ideal nature for mathematical tractability, they provide upper bound estimates of the phenomenon of back diffusion. Some practical applications of the results for extracting diffusion length of radon in materials are also suggested.

Atmosphere↗
PubMed1980

Hazard of a ruptured exhalation mushroom diaphragm.

In most breathing circuits, ventilation of a patient requires some device to occlude the expiratory limb during inflation. Usually one or another modification of a mushroom exhalation valve is employed. Such valves are found in the Bourns Bear 1 ventilator, the Bennett MA-1 and MA-2 ventilators, and the Emerson postoperative ventilator, as well as in the Frumen valve for manual ventilation. Recently, the authors observed a defect that might cause permanent occlusion, raising the patient's airway pressure to the level of the limiting safety pop-off and effectively applying a prolonged Valsalva maneuver without ventilation. The defect responsible for this malfunction was a half-centimeter laceration in the mushroom valve. Although the defect occurred on a Bourns Bear 1 ventilator, the authors were able to reproduce it on other ventilators of different manufacturers.

Cough↗
PubMed1993

Effects of dense, high-volume, artificial surfactant aerosol on a heated exhalation filter system.

OBJECTIVE: To evaluate a supplemental heated filter system during mechanical ventilation with continuous nebulization of an artificial surfactant by a new, high-volume nebulizer. DESIGN AND METHODS: A new nebulizer system, containing artificial surfactant, provided half of a 20-L minute ventilation and the remainder of this minute ventilation was provided by a commonly used mechanical ventilator. Ventilation sources were joined in the inspiratory limb of the breathing circuit, which was connected to a test lung system. A supplemental filter system was placed upstream of the ventilator's heated filter in the expiratory limb of the circuit. Circuit pressures at the inlet of the supplemental filter (P1), between the filters (P2), and after the ventilator expiratory filter (P3) were monitored and recorded. Nebulizer canisters containing artificial surfactant were replaced every 4 hrs. The performance of four supplemental filters in continuous use was examined. Another four filters were each used over 4 hrs, steam autoclaved, and reused. SETTINGS: The ventilator was set at a rate of 20 breaths/min, with a tidal volume of 0.5 L, a flow rate of 40 L/min, and positive end-expiratory pressure of 10 cm H2O. The nebulizer provided an equal volume and flow rate so that the delivered tidal volume was 1.0 L with a flow rate of 80 L/min. RESULTS: Ventilator failure and/or excessive airway pressure caused by increased filter resistance occurred at a mean of 7.3 +/- 1.3 (SD) hrs of continuous ventilation. Mean P1-peak increased from 67.5 +/- 8.2 to 94.0 +/- 10.7 cm H2O (p < .001) and P1-baseline increased from 9.3 +/- 1.0 to 53.5 +/- 17.1 cm H2O (p = .014). Filters that were autoclaved after 4 hrs of ventilation and reused lasted a total of 7.0 +/- 1.3 hrs. Mean P1-peak increased from 68.9 +/- 4.9 to 84.8 +/- 19.1 cm H2O and P1-baseline increased from 9.5 +/- 1.7 to 30.8 +/- 14.2 cm H2O (p < .05). CONCLUSIONS: The supplemental filter system was able to protect the ventilatory exhalation sensors for approximately 7 hrs at a minute ventilation of 20 L/min. Steam sterilization did not extend the supplemental filter life.

Aerosols↗
PubMed1986

Measurement of 220Rn in exhaled breath of Th plant workers.

The concentration of 220Rn in the exhaled breath of workers currently employed in a Th plant was measured using a double filter system. The results are expressed in terms of the equivalent activity of 224Ra freely emanating 220Rn at the mouth. Measurements performed on 176 subjects, without isolating them from day-to-day work, showed 220Rn levels having a median of 0.74 Bq, with the group consisting of sweepers and helpers showing the highest average level (1.68 Bq). Measurements performed on 15 selected workers, after isolating them from work for a minimum duration of 48 h yielded 220Rn levels which were consistently lower than those obtained in the first measurements. This is attributed to the material undergoing short term elimination from the body. It was also found from the latter measurements that the group consisting of workers engaged in radioactive work for more than 24 y has an average 220Rn level of 2.65 Bq which is significantly higher than that (1.27 Bq) found in the group that has worked for less than 12 y. A conversion factor of 0.09 deduced by earlier investigators is assumed to be valid for estimating the actual 224Ra burdens from the 220Rn data.

Body Burden↗
PubMed2002

Hypotension during septic shock does not correlate with exhaled nitric oxide in anesthetized rat.

Sepsis is characterized by hypotension, acidosis, and increased nitric oxide (NO) production. The role of NO in the development of sepsis-related hypotension is still unclear. The relationship among exhaled nitric oxide (ENO), arterial blood pressure (BP), and pH after administration of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFalpha) was investigated in anesthetized rats. Forty-three adult male Sprague-Dawley rats were randomized into five groups: group 1 (C, n = 8) received normal saline; group 2 (LPS-I, n = 8) received Escherichia coli (LPS) 10 mg/kg intravenously (i.v.); group 3 (LPS-h, n = 10) received 100 mg/kg LPS i.v.; group 4 (n = 9) was treated with 100 mg/kg i.v. aminoguanidine (AG) 1 h after receiving 100 mg/kg i.v. LPS; group 5 (TNFalpha, n = 8) received 1 microg recombinant rat TNFalpha i.v.. ENO, BP, and pH were measured every 30 min for 4 h whereas arterial blood gases and pH were measured every hour. LPS administration induced a dose-related increase in ENO and a dose-related decrease in BP and pH. AG blocked the increase in ENO after LPS but had minimal effect on BP and pH. TNFalpha administration increased ENO without changing BP and pH. In LPS-treated rats, no significant correlation was found between ENO and BP (r2 = 0.13, P= ns). However, there was a significant correlation between pH and BP (r2 = 0.7, P < 0.01). Our results suggest that, in this animal model, ENO may not be a key mediator in the development of systemic hypotension during sepsis, while acidosis may significantly contribute to it.

Acidosis↗
PubMed1986

Concentrations of 20 volatile organic compounds in the air and drinking water of 350 residents of New Jersey compared with concentrations in their exhaled breath.

Twenty volatile organic compounds were measured in the personal air and drinking water of 350 New Jersey residents in the fall of 1981. Two consecutive 12-hour integrated personal air samples and two tap water samples were collected from each participant. At the end of the 24-hour monitoring period, each participant supplied a sample of exhaled breath. Simultaneous outdoor samples were collected in 100 residential locations in two cities. Eleven compounds were present much of the time in air, but only four (the trihalomethanes) in water; wide ranges of exposures (three to four orders of magnitude) were noted for most compounds. Ten of 11 compounds displayed significant correlations between air exposures and breath concentrations; the 11th (chloroform) was correlated with drinking water exposures. It was concluded that breath measurements are a feasible, cost-effective, and highly sensitive way to determine environmental and occupational exposures to volatile organic compounds.

Air Pollutants↗
PubMed2005

Is exhaled nitric oxide measurement a useful clinical test in asthma?

PURPOSE OF REVIEW: Exhaled nitric oxide measurements (FENO) are easy to perform and are repeatable. Given the strong correlations between FENO and bronchial biopsy and induced sputum eosinophilia, as well as airway hyper-responsiveness, FENO may now be advocated as a surrogate for these tests in certain circumstances. They provide the opportunity to assess pathological rather than physiological changes in asthma. This review highlights recent advances in applying this technology to the diagnosis and ongoing assessment of asthma in the clinical and epidemiological settings. RECENT FINDINGS: Epidemiological data confirm that whereas FENO measurements reflect the presence and severity of airway inflammation, levels do not correlate strongly with symptoms or lung function abnormalities. Although reference values and thresholds for an abnormal test still need to be agreed internationally, there are now sufficient data for clinicians to use the test meaningfully in clinical practice. Studies confirm the relatively high diagnostic accuracy of FENO measurements compared with conventional tests to distinguish asthma from nonasthma. Further, dose-response relationships for changes in FENO with inhaled steroids have been confirmed, and provide the basis for using FENO to assess asthma control and, potentially, to determine antiinflammatory treatment requirements. SUMMARY: The measurement of FENO is evolving to provide a complementary role alongside existing pulmonary function tests. Further work is required to establish reference values and possibly prediction equations in relation to age and height. Its role in determining optimum steroid requirements in chronic asthma and to identify steroid responsiveness in chronic obstructive pulmonary disease are two important areas for future research.

Adult↗
PubMed2004

Exhaled tidal volume overestimation in mechanically ventilated patients with large cardiogenic oscillation.

OBJECTIVES: In postcardiac surgery patients, we often noticed that monitored tidal volumes exceeded the ventilator settings. We investigated whether cardiogenic oscillation causes overestimation of tidal volume. DESIGN: Prospective, observational, clinical study. SETTING: Surgical intensive care unit in a national heart institute. PATIENTS: Eight postcardiac surgery patients (age 13-70). INTERVENTIONS: Patients were paralyzed and received flow-triggered volume-controlled ventilation with a tidal volume of 10 mL/kg. In random order, two types of ventilator (Bird 8400 STi and Servo-300) and two respiratory rates (5 and 10 breaths/min) were applied to each patient via a disposal ventilatory circuit and heat-and-moisture exchanger. For each ventilator, we adjusted the flow-triggering sensitivity to prevent autotriggering due to cardiogenic oscillation: 10 L/min for the Bird 8400 STi and green zone for the Servo-300. MEASUREMENTS AND MAIN RESULTS: The magnitude of cardiogenic oscillation during mechanical ventilation was defined as peak expiratory flow fluctuation at end-expiration. We recorded tidal volume using the monitoring devices on the ventilators and calculated the discrepancy from the set tidal volume. Cardiogenic oscillation was significantly greater with the Bird 8400STi (4.0 +/- 1.8 L/min) than with the Servo-300 (1.7 +/- 0.8 L/min). With the Bird 8400 STi, the discrepancy between monitored tidal volume and set tidal volume ranged from 15 to 260 mL when the respiratory rate was 5 breaths/min and from -9 to 75 mL at 10 breaths/min; there was a linear correlation between the overestimation of tidal volume and the magnitude of cardiogenic oscillation. In contrast, with the Servo-300, the discrepancy was relatively small (-36 to 14 mL). CONCLUSIONS: In mechanically ventilated patients with large cardiogenic oscillation, exhaled tidal volume is overestimated on at least one model of ventilator.

Adolescent↗