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PubMed2007

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease.

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.

Birth Weight↗
PubMed2006

A longitudinal study of ethanol and acetaldehyde in the exhaled breath of healthy volunteers using selected-ion flow-tube mass spectrometry.

Selected-ion flow-tube mass spectrometry (SIFT-MS) has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 male, 11 female) over a 6-month period. Volunteers provided breath samples each week between 8:45 and 13:00 (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ethanol and acetaldehyde, which were simultaneously quantified by SIFT-MS using H3O+ precursor ions. The mean ethanol level for all samples was 196 parts-per-billion (ppb) with a standard deviation of 244 ppb, and the range of values for breath samples analysed is 0 to 1663 ppb. The mean acetaldehyde level for all samples was 24 ppb with a standard deviation of 17 ppb, and the range of values for breath samples analysed is 0 to 104 ppb. Background (ambient air) levels of ethanol were around 50 ppb, whereas any background acetaldehyde was usually undetectable. Increased ethanol levels were observed if sweet drink/food had been consumed within the 2 h prior to providing the breath samples, but no increase was apparent when alcohol had been consumed the previous evening. The measured endogenous breath ethanol and acetaldehyde levels were not correlated. These data relating to healthy individuals are a prelude to using breath analysis for clinical diagnosis, for example, the recognition of bacterial overload in the gut (ethanol) or the possibly of detecting tumours in the body (acetaldehyde).

Acetaldehyde↗
PubMed2005

Direct and rapid analysis of ambient air and exhaled air via electrostatic precipitation of aerosols in an atomizer furnace and Zeeman spectrometry.

Techniques that allow the elements present in the air to be determined in a simple and rapid manner are very attractive. Direct aerosol sampling techniques avoid the need to pretreat the filter via wet digestion in order to remove any sources of contamination, and they decrease the precipitation time significantly. Analyzers based on this technique can also determine the concentrations of elements in the air automatically in situ. This paper is concerned with the development of a novel analytical system that is based on electrostatically precipitating aerosols from the air into a graphite furnace. The equipment includes a Zeeman spectrometer with high frequency modulation polarization (MGA-915), and an electrostatic precipitation system incorporated into the analyzer. The high sensitivity of the system developed here means that it can be used to determine element concentrations in the air exhaled by humans, as well as those in ambient air.

Aerosols↗
PubMed2006

Exhaled air temperature as a function of ambient temperature in flying and resting ducks.

Exhaled air temperature (T (exh)) has a paramount effect on respiratory water loss during flight. For migratory birds, low T (exh) potentially reduces water loss and increases flight range. However, only three studies provide empirical data on T (exh) during flight. The aim of this study was to record T (exh) of birds during rest and flight at a range of controlled ambient temperatures (T (amb)). One wigeon and two teal flew a total of 20 times in a wind tunnel at T (amb) ranging from 1 degrees to 24 degrees C. T (exh) during flight did not differ between the two species and was strongly correlated with T (amb) (T (exh)=1.036 T (amb) + 13.426; R2=0.58). In addition, body temperature had a weak positive effect on T (exh). At a given T (amb), T (exh )was about 5 degrees C. higher during flight than at rest.

Animal Migration↗
PubMed2004

Sampling airway surface liquid: non-volatiles in the exhaled breath condensate.

Exhaled breath condensate (EBC) samples contain molecules that have no appreciable vapor pressure; such molecules likely derive from droplets of airway fluid. We analyzed EBC gathered from a total of 62 healthy volunteers in order to quantify the volume of airway liquid that was the source of the non-volatiles; saliva was analyzed as a reference secretion. EBC urea averaged 0.52 +/- 0.12 micromol/L (n = 18), an 8,600-fold dilution from predicted blood urea nitrogen levels. Protein averaged 2.3 +/- 0.3 microg/ml (n = 31), three orders of magnitude less than in saliva (1.4 +/- 0.1 mg/ml, n = 15). EBC ammonia was 6.6 +/- 0.6 mmol/L (1/15 that of saliva) and EBC ammonium ion was 0.90 +/- 0.19 micromol/L, concentrations that are incompatible with an 8,600-fold dilution from a biological source. Thus, urea-derived dilution factors may be used to interpret EBC non-volatile molecules, but not EBC volatiles.

Albumins↗
PubMedDate not supplied

Age does not affect airway pH and ammonia as determined by exhaled breath measurements.

Measurement of airway pH has been used as a diagnostic and monitoring tool in a variety of pulmonary diseases in adults. These diseases occur across a wide age range. Few investigations have addressed the effects of aging on airway pH and ammonia. The aim of this study was to determine whether exhaled breath condensate (EBC) measurements of pH and ammonia differ in older and younger populations of normal subjects. Twenty-three normal younger individuals (median age-24 years) and 25 normal older participants (median age-72 years) were investigated by measuring EBC for pH and ammonia using recommended methodologies. EBC ammonia and pH values were not significantly different between younger and older individuals. Thus, we conclude that EBC ammonia and pH do not appear to be affected by age.

Adolescent↗
PubMed2004

Exhaled nitric oxide as a marker of airway inflammation for an epidemiologic study in schoolchildren.

BACKGROUND: Exhaled nitric oxide (eNO) levels are increased in airway inflammatory disorders, such as asthma. OBJECTIVE: We sought to determine whether eNO could serve as a noninvasive marker of allergic airway inflammation for an epidemiologic study in schoolchildren. METHODS: Two hundred seventy-eight schoolchildren aged 10 to 12 years answered a modified American Thoracic Society questionnaire, and eNO levels and pulmonary function were measured. In 246 subjects serum nonspecific IgE levels and levels of IgE specific to house dust mite, cat, cedar, and mold were also measured. Correlation analysis was used to examine eNO levels, nonspecific IgE levels, antigen-specific IgE levels, and pulmonary function. In addition, we compared these variables between subjects with (recurrent wheezers) and without (nonwheezers) recurrent wheeze. Finally, multiple logistic regression analysis was used to find possible predictors for recurrent wheezers. RESULTS: eNO showed significant positive correlations with nonspecific IgE (r=0.62, P <.001) and mite-specific IgE (r=0.74, P <.001) and weak positive correlations with specific IgE to cat and cedar. Only eNO showed a weak but significant inverse correlation with pulmonary function (%FEV(1), P=.035; FEV(1)/forced vital capacity, P=.018). eNO, nonspecific IgE, and mite-specific IgE levels in recurrent wheezers were greater (P <.001), and %FEV(1) was less (P=.06) when compared with values seen in nonwheezers. Finally, eNO was determined by means of multiple logistic regression analysis to be the best predictor for recurrent wheezers compared with other variables (odds ratio, 11.2; 95% CI, 1.33-94.0). CONCLUSION: eNO can be used in epidemiologic studies as a noninvasive marker of allergic airway inflammation in schoolchildren.

Asthma↗
PubMed2006

Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide.

BACKGROUND: Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined. OBJECTIVE: To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation. METHODS: A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (F(ENO)). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria. RESULTS: Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of F(ENO) and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEV(1) and increase in F(ENO) persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%). CONCLUSION: Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and F(ENO). CLINICAL IMPLICATIONS: Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high F(ENO).

Adolescent↗
PubMed2006

Why inhaling salt water changes what we exhale.

We find that inhaling salt water diminishes subsequently exhaled biomaterial in man and animals due to reversible stabilization of the airway lining fluid (ALF)/air interface as a novel potential means for control of the spread of airborne infectious disease. The mechanism of this phenomenon relates to charge shielding of mucin or mucin-like macromolecules that consequently undergo gelation; this gelation alters the physical properties of the ALF surface and reduces its breakup. Cations in the nebulized solution and apparent surface viscoelasticity of the ALF (more than any other ALF intrinsic physical property) appear to be responsible for the reduced tendency of the ALF to disintegrate into very small droplets. We confirm these effects in vivo and show their reversibility through nebulization of saline solutions to anesthetized bull calves.

Administration, Inhalation↗
PubMed2006

Environmental exposures and exhaled nitric oxide in children with asthma.

OBJECTIVE: To evaluate the relation of environmental factors with exhaled nitric oxide (FENO) concentrations among asthmatic children. STUDY DESIGN: Cross-sectional analysis of 170 tobacco smoke-exposed children, ages 6 to 12 years, who have doctor-diagnosed asthma using measures of FENO, medication use, and exposures to settled indoor allergens and tobacco smoke. RESULTS: In multivariable analysis, child's age, uncarpeted flooring, not owning a cat, higher income, dust mite exposure, and being sensitized to any allergens were associated with higher FENO concentrations. Children who were sensitized to indoor allergens had an adjusted geometric mean FENO of 15.4 ppb (95% CI, 13.1, 18.2) compared with 10 ppb (95% CI, 8.2, 12.2) for unsensitized children. There was no statistically significant association of serum cotinine, hair cotinine, or reported corticosteroid therapy with FENO. CONCLUSIONS: FENO is higher among children who are sensitized to indoor allergens and exposed to dust mites. The results hold promise for the use of FENO as a tool to manage childhood asthma by using both pharmacologic and environmental treatments.

Air Pollution, Indoor↗
PubMed2006

Noxious compounds in exhaled air, a potential cause for ocular manifestations of H. pylori gastrointestinal infection.

Helicobacter pylori infection is one of the most common chronic bacterial infections worldwide. In the past few years, a variety of extradigestive disorders have been associated with H. pylori infection. This infection has also been linked to some ophthalmic disorders, including glaucoma, central serous chorioretinopathy, uveitis and blepharitis. Several possible theories to explain pathogenetic mechanism underlying the observed associations have been provided. H. pylori infection causes elaboration of some noxious compounds, including ammonia, hydrogen nitrate and hydrogen cyanide, in exhaled breath of infected individuals. Herein we hypothesize that chronic exposure of ocular surface to these compounds may explain some ophthalmic and also respiratory manifestations of the chronic gastrointestinal infection.

Air Pollutants↗
PubMed2006

Free 3-nitrotyrosine in exhaled breath condensates of children fails as a marker for oxidative stress in stable cystic fibrosis and asthma.

3-Nitrotyrosine (3-NT) is considered as a marker of oxidative stress, which occurs during inflammation. Since 3-NT levels in exhaled breath condensate (EBC) are very low, we applied a specific and sensitive gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) method and high performance liquid chromatography (HPLC) with electrochemical detection for the analysis of free 3-NT in EBC. A total of 42 children (aged 5-17 years) were enrolled in this study, including children with asthma (n=12), cystic fibrosis (n=12), and healthy controls (n=18). Additionally, 14 healthy non-smoking adults (aged 18-59 years) were included. An EcoScreen system was used for the collection of EBC samples. Free 3-NT levels in EBC ranged from 0.54-6.8 nM. Median (interquartile range) concentrations (nM) were similar in all groups: 1.46 (0.97-2.49) in healthy adults, 2.51 (1.22-3.51) in healthy children, 1.46 (0.88-2.02) in children with asthma, and 1.97 (1.37-2.35) in CF children, respectively (p=0.24, Kruskall-Walis test). No difference was found between the children with airway disease and age-matched healthy controls. In healthy subjects, there was no effect of age on 3-NT concentrations. HPLC analyses provided similar concentration ranges for EBC 3-NT when compared with GC-NICI-MS. Our study has clearly demonstrated that free 3-NT in EBC fails as a marker for oxidative stress in children with stable CF and asthma.

Adolescent↗
PubMed2004

Long-term oral n-acetylcysteine reduces exhaled hydrogen peroxide in stable COPD.

Oxidative stress caused by airway inflammation is increased in chronic obstructive pulmonary disease (COPD) and may account for the progressive deterioration of structure and function of the respiratory tract observed in this disease. Antioxidant defences of the respiratory tract may be overwhelmed by the oxidant burden in COPD and possibly restored with antioxidant therapy. The level of hydrogen peroxide (H(2)O(2)) concentration in exhaled air condensate (EAC) is a valuable tool for assessing and monitoring oxidative stress. This study aimed to verify the effect of 2-month oral N-acetylcysteine (NAC) treatment compared to placebo on the H(2)O(2) content in EAC of 55 clinically stable COPD patients (48 males), mean age 65.93+/-9.3 years. After clinical examination, pulmonary function tests, and collection of EAC for the basal (T0) assay of H(2)O(2), patients were randomly allocated to group A (usual therapy plus oral NAC 600 mg b.i.d. for 2 months) or group B (usual therapy plus placebo b.i.d. for 2 months). H(2)O(2) assay in EAC was repeated at 15 (T15), 30 (T30), and 60 (T60) days after the start of therapy in each group. All patients were non-smokers or ex smokers for at least 5 years and the two groups were comparable in terms of demographic, respiratory function, and EAC data at baseline. The H(2)O(2) level in EAC of group A was significantly decreased at T15 (1.00+/-0.38 SD microM; p=0.003), T30 (0.91+/-0.44 microM; p=0.007), and T60 (0.83+/-0.41 microM; p=0.000) compared to T0 (1.28+/-0.61 microM). No significant decrease in H(2)O(2) of group B was found at any time point. We conclude that oral NAC 600 mg b.i.d. for 2 months rapidly reduces the oxidant burden in airways of stable COPD patients.

Acetylcysteine↗
PubMed2005

Validation of a new method to measure hydrogen peroxide in exhaled breath condensate.

Inflammatory processes in the lung can or will elicit oxidative stress. The degree of oxidative stress can be determined by measuring hydrogen peroxide (H(2)O(2)) concentration in exhaled breath condensate (EBC) but the methods to measure H(2)O(2) are all rather time consuming and only reliable and/or accurate in the hand of skilled technicians in a dedicated laboratory. We tested a new commercial device (Ecocheck), developed to offer a less time-consuming method to measure H(2)O(2). We validated this new method according the NCCLS EP10-A2 protocol. The validation shows that the imprecision in the low range is high (28.4%) and declines with higher concentrations of H(2)O(2) (up to 6.6%). The Ecocheck is "an easy to use" measuring device for routine measurements getting quick results without the need for skilled technicians to determine H(2)O(2) concentrations.

Adult↗
PubMed2006

Relationship between exhaled nitric oxide levels and compliance with inhaled corticosteroids in asthmatic children.

Levels of exhaled nitric oxide (eNO) are elevated in subjects with asthma and fall in response to oral or inhaled steroids. This study explored the possibility the measurement of eNO levels could be used to identify subjects who were not adhering to their treatment regimen. Twenty children with asthma attending the respiratory clinic were recruited. Each attended on four occasions 1 month apart when eNO levels were measured. A data logger attached to a pressurised metered dose inhaler was used to objectively monitor use of inhaled corticosteroids (ICSs). The correlation between day and dose compliance with eNO was assessed. The data demonstrated a weak but non-significant correlation between eNO and both day (r = 0.055, P = 0.67) and dose (r = 0.153, P = 0.23). A recorded value of eNO less than 12 was associated with day compliance rates of 3-97%. Of the 19 recorded eNO values greater than 12 ppb almost 80% were from subjects with a day compliance of less than 50% during the preceding month. Of the four values greater than 12 ppb and day compliance > 60% one subject had a poor inhaler technique, one had a mild viral exacerbation and one appeared to be associated with increase pollen exposure. The measurement of eNO may prove to be a useful tool in helping to manage children with asthma but further work is required to define its precise role. Elevated eNO levels in asthmatic children taking ICSs are likely to reflect poor compliance but confounding factors such as disease activity and inhaler technique need to be carefully considered.

Administration, Inhalation↗
PubMed2006

Determinants of variability of protein content, volume and pH of exhaled breath condensate.

Collection of exhaled breath condensate (EBC) is a simple and noninvasive method to obtain information on the respiratory system. Different mediators can be determined in EBC. However, determinants of variability are not well described. The aim of this study was to evaluate variability of pH, volume and protein concentration of EBC between individuals and between sampling times. Therefore, EBC was collected from 20 healthy volunteers on two different days. Median pH for all samples, measured 5 min after collection without deaeration, was 6.17. Median volume was 1.70 ml and median total protein concentration was 1.02 microg/ml. Coefficients of variation were 5.17%, 21.84% and 37.93%, respectively. No intra- or interday variability could be found, except for the first collection time. Between individuals, significant differences were observed for all three mediators. Age, height and gender can explain part of this variation. In conclusion, no significant difference between sampling times on the same day or on different days was obtained for pH, volume and total protein concentration, provided that subjects are experienced in collecting EBC.

Adolescent↗
PubMed2006

Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased exhalation and target tissue regeneration.

The aims of the present study were to characterize the subchronic toxicity of chloroform by measuring tissue injury, repair, and distribution of chloroform and to assess the reasons for the development of tolerance to subchronic chloroform toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and kidney injury were measured by plasma ALT and BUN, respectively, and by histopathology. Tissue regeneration was assessed by (3)H-thymidine incorporation into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at selected time points. The levels of chloroform were measured in blood, liver, and kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was evident after 1 day with all three doses and sustained until 7 days followed by complete recovery. Mild to moderate liver injury was observed from 1 to 14 days with all three dose levels followed by gradual decrease. Significantly higher regenerative response was evident in liver and kidney at 7 days, but the response was robust in kidney, preventing progression of injury beyond first week of exposure. While the kidney regeneration reached basal levels by 21 days, moderate liver regeneration with two higher doses sustained through the end of the dosing regimen and 3 days after that. Following repeated exposure for 7, 14, and 30 days, the blood and tissue levels of chloroform were substantially lower with all three dose levels compared to the levels observed with single exposure. Increased exhalation of (14)C-chloroform after repeated exposures explains the decreased chloroform levels in circulation and tissues. These results suggest that toxicokinetics and toxicodynamics (tissue regeneration) contribute to the tolerance observed in SW mice to subchronic chloroform toxicity. Neither bioactivation nor detoxification appears to play a decisive role in the development of this tolerance.

Animals↗
PubMed2006

Cytokines in exhaled breath condensate of children with asthma and cystic fibrosis.

BACKGROUND: Inflammatory mediators in exhaled breath condensate (EBC) indicate ongoing inflammation in the lungs and might differentiate between asthma and cystic fibrosis (CF). OBJECTIVES: To evaluate the presence, concentration, and short-term variability of TH1- and TH2-mediated cytokines (interferon-gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], interleukin 10 [IL-10], IL-5, IL-4, and IL-2) in EBC of children with asthma or CF and in controls and to analyze the discriminating ability of inflammatory markers in EBC between children with asthma or CF and controls. METHODS: Expired air was conducted through a double-jacketed glass tube cooled by circulating ice water. In 33 asthmatic children, 12 children with CF, and 35 control children, EBC was collected during tidal breathing. Cytokines were measured using flow cytometry. RESULTS: Interleukin 2, IL-4, IFN-gamma, and IL-10 were detected in 16%, 16%, 11%, and 9%, respectively, of all samples in asthma and CF. Interleukin 5 and TNF-alpha were not detected in children with CF. Cytokine concentrations did not differ significantly in children with asthma vs CF. In controls, IFN-gamma, TNF-alpha, and IL-10 were detected in 9%, 14%, and 3%, respectively; IL-2, IL-4, and IL-5 were not detected in controls. CONCLUSIONS: Cytokines such as IFN-gamma, TNF-alpha, IL-10, IL-5, IL-4, and IL-2 can be detected in EBC of children with asthma or CF. However, the concentrations found are close to the detection limits of the assay used. These findings emphasize the importance of developing more sensitive techniques for the analysis of EBC and of standardizing the EBC collection method.

Adolescent↗