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PubMed2003

Exhaled nitric oxide increases following admission for intravenous antibiotics in children with cystic fibrosis.

BACKGROUND: Lack of standardisation for the measurement of exhaled nitric oxide (NO) (FENO) has resulted in conflicting data in cystic fibrosis (CF). The aim of this study was to assess whether FENO is a useful non-invasive marker of lung disease in CF by assessing the effect of intravenous (IV) antibiotics on FENO. METHODS: FENO was measured on line, according to recently published ERS/ATS guidelines, using a chemiluminescence analyser together with pulmonary function in 14 CF children prior to and following a course of IV antibiotics. RESULTS: There was a significant improvement in mean (S.E.M.) % FEV1 from 60.0 (6.3) to 68.0 (5.4) (P < 0.05) and mean (S.E.M.) % FVC from 66.3 (5.5) to 75.1 (4.9) (P < 0.01). FENO increased significantly from median (range) 5.8 (2.0-14.3) to 9.2 ppb (0.8-25.1) (P < 0.05). There was no correlation between FE(NO) and lung function. Subgroup analysis on those with chronic Pseudomonas aeruginosa infection (n = 6) demonstrated no significant change in FENO. CONCLUSIONS: Using a flow of 50 ml/s, FENO increases following admission for IV antibiotic treatment in children with CF but does not correlate with lung function. It is not a useful marker of lung diseases in CF, which has implications for clinical practice.

Anti-Bacterial Agents↗

PubMed2005

[Limitations of the technique to determine hydrogen peroxide levels in exhaled breath condensate from patients with adult respiratory distress syndrome].

OBJECTIVE: Exhaled breath condensate represents an alternative to bronchoalveolar lavage for the analysis of markers of inflammation and oxidative stress in patients with adult respiratory distress syndrome (ARDS). However, analysis of hydrogen peroxide (H2O2) yields variable results that do not correlate with severity of the clinical presentation. In an attempt to explain this variability, the aim of the present study was to assess the possible limitations of the most commonly used technique for analyzing H2O2 in breath condensate. PATIENTS AND METHODS: H2O2 levels were analyzed using the Gallati technique (linear range between 0.3 and 10 microM, r=0.99; P<.05) in serial samples of condensate taken from the expiratory tube of a mechanical ventilator in 6 patients with ARDS. RESULTS: The volume of condensate obtained correlated to minute ventilation (r=0.96; P<.05). In 11 out of 23 samples, a spectrophotometer reading was obtained at 450 nm despite the absence of the characteristic color of the reaction and in some of these samples a spontaneous reading was obtained that was indicative of contamination. The absorbance spectrum of these samples did not contain the characteristic peak for H2O2 at 450 nm and pretreatment of some samples with catalase did not affect the absorbance at 450 nm. CONCLUSIONS: The spectrophotometric method commonly used to measure H2O2 levels in breath condensate lacks specificity in ARDS due to the presence of variable levels of contaminants in the samples, which lead to false positives.

Breath Tests↗

PubMed2005

[Exhaled breath condensate: standardized collection of samples from healthy volunteers].

Expired breath condensate collection is a noninvasive technique for obtaining a sample in which to analyze substances that reflect the functional status of the lung and other tissues. Twenty healthy volunteers provided 3 expired breath samples: the second was collected 20 minutes after the first and the third 48 hours after the first. The air and condensate volumes were assessed. The mean (SD) volume of condensate in exhaled air over a period of 15 minutes was 1.8 (0.5) mL (95% confidence interval [CI], 1.5-2 mL) and the coefficient of variation was 29%. Analysis of variance in the 3 samples demonstrated no significant differences. The mean volume of air inhaled over 15 minutes was 119 (25) L (95% CI, 112-125 L). These results indicate that it takes at least 15 minutes and the inhalation of some 120 L of air to collect a condensate volume that exceeds 1.5 mL, sufficient to allow distribution in aliquots to analyze fundamental physical and chemical properties (conductivity, pH) and certain relevant biomarkers.

Adult↗

PubMed2003

NOS1 polymorphism is associated with atopy but not exhaled nitric oxide levels in healthy children.

Exhaled nitric oxide (FENO) is raised in atopy. The mechanism for this is unclear. The aim of this study was to investigate whether the number of AAT repeats in intron 20 of the NOS1 gene, recently associated with variations in FENO in adults with asthma and cystic fibrosis, was associated with the raised FENO in healthy atopic children. Eighty-seven healthy children (44 girls, 42 atopic, age range 6-18 years) underwent measurements of FENO, spirometry, airway responsiveness and skin prick testing. Genotyping was carried out to determine the number of AAT repeats. There was no association between the number of AAT repeats and FENO in either the whole sample of healthy children (n = 87) or in the subsample of healthy atopics (n = 42). However, a greater number of atopic children had two high repeat alleles compared with non-atopic children (33.3% vs. 13.6%, respectively, p = 0.03). This suggests that variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FENO.

Adolescent↗

PubMed2024

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 μg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 μg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

Humans↗

PubMed2003

Total and allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites.

Although elevated levels of serum immunoglobulin E (IgE) are considered the hallmark of atopic diseases, their clinical value in evaluating subjects with allergic disorders is under debate. To evaluate possible relationships between serum IgE levels and a variety of clinical parameters, 83 mild asthmatic children [10.98-year-old (2.95)], sensitized to house dust mites (HDM) Dermatophagoides pteronyssinus (Dp) or D. farinae (Df), were enrolled. As compared with normal control reference values detected in our laboratory, children with allergic asthma had higher blood eosinophil counts (expressed both as percentage and as absolute number) and higher fractional exhaled nitric oxide (FeNO) levels but similar values in pulmonary function parameters. In the allergic asthmatic population, serum levels of total, Dp-specific or Df-specific IgE correlated positively with eosinophil counts (Rho > or = 0.30, p < 0.01, each correlation) and FeNO levels (Rho > or = 0.33, p < 0.01, each correlation) but not with pulmonary function parameters (p > 0.1, each correlation). Finally, significant correlations, although moderate, were found in the allergic asthmatic population between eosinophil counts and FeNO levels (Rho > or = 0.42, p < 0.001, each correlation). Thus, in atopic children sensitized to HDM with mild intermittent asthma, IgE levels in blood appear to reflect systemic (blood eosinophils) and organ-specific (FeNO) markers of allergic inflammation but not pulmonary volumes or the degree of airflow limitation.

Adolescent↗

PubMed2005

Exhaled nitric oxide and bronchial wall thickening in asthmatics during and after acute exacerbation: evidence of bronchial wall remodeling.

To assess whether bronchial wall thickening during asthma exacerbations is due to active inflammation in severe asthmatics, we measured bronchial wall thickness and exhaled nitric oxide (FeNO) following treatment. Nine asthmatics were compared with seven controls with high-resolution computed tomography, spirometry, and FeNO measurements. The asthmatic bronchial wall area percent and FeNO was greater than controls. Following treatment, the FEV1 markedly improved, FeNO decreased modestly, and bronchial wall area percent did not change significantly. Bronchial wall thickening persisted after treatment of acute asthma exacerbation despite improvement in spirometry and decline in FeNO, possibly due to chronic airway remodeling.

Acute Disease↗

PubMed2005

Correlation of exhaled nitric oxide, spirometry and asthma symptoms.

Asthma is the most common chronic disease of childhood. Asthma severity is monitored by spirometry. However, this does not directly measure airway inflammation. Exhaled nitric oxide (FeNO) is a proposed method to measure airway inflammation non-invasively. Previous studies have shown that FeNO correlates with endobronchial biopsies and symptoms in patients with asthma. We monitored daily asthma symptoms compared to monthly spirometry and FeNO. Total monthly symptom scores correlated with both forced expiratory volume at 1 sec (FEV1) and FeNO. FeNO had a strong correlation than FEV1. FeNO and FEV1 were not correlated. We propose that FeNO should be used as an additional monitoring tool for asthma.

Adolescent↗

PubMed2006

Validation study of fractional exhaled nitric oxide measurements using a handheld monitoring device.

We tested reproducibility of exhaled nitric oxide (FE(NO)) and inter-operator handling when measured with a handheld device, NIOX MINO. We enrolled 20 volunteers using a priori goals of acceptable reproducibility to be mean within-subject standard deviation less than 3 parts per billion (ppb) for FE(NO) measurements less than 30 ppb, and mean coefficient of variation less than 10% for FE(NO) measurements more than 30 ppb. Seventeen subjects with measurements less than 30 ppb displayed a mean standard deviation of 1.15, and 3 subjects with FE(NO) more than 30 ppb had a mean coefficient of variation of 2.4%. We conclude that NIOX MINO demonstrates excellent reproducibility for all ranges of FE(NO).

Adolescent↗

PubMedDate not supplied

Non-invasive estimation of arterial blood pH using exhaled CO/CO2 analyser, microwave radar and infrared thermography for patients after massive haemorrhage.

In order to conduct non-contact estimation of arterial blood pH after massive haemorrhage, we calculated the arterial pH based on linear-regression analysis of exhaled gas concentrations (CO and CO2) and vital signs (heart rate, respiratory rate, and surface temperature) measured using non-contact methods in hypovolemic animals.

Acidosis↗

PubMed2006

Free radicals in exhaled breath condensate in cystic fibrosis and healthy subjects.

Many markers of airway inflammation and oxidative stress can be measured non-invasively in exhaled breath condensate (EBC). However, no attempt has been made to directly detect free radicals using electron paramagnetic resonance (EPR) spectroscopy. Condensate was collected in 14 children with cystic fibrosis (CF) and seven healthy subjects. Free radicals were trapped by 5,5-dimethyl-1-pyrroline-N-oxide. EPR spectra were recorded using a Bruker EMX spectrometer. Secondly, to study the source of oxygen centered radical formation, catalase or hydrogen peroxide was added to the condensate. Radicals were detected in 18 out of 21 condensate samples. Analysis of spectra indicated that both oxygen and carbon centered radicals were trapped. Within-subject reproducibility was good in all but one subject. Quantitatively, there was a trend towards higher maximal peak heights of both oxygen and carbon centered radicals in the children with CF. Catalase completely suppressed the signals in condensate. Addition of hydrogen peroxide resulted in increased radical signal intensity. Detection of free radicals in EBC of children with CF and healthy subjects is feasible using EPR spectroscopy.

Adolescent↗

PubMed2006

Inspiratory flow rates during hard work when breathing through different respirator inhalation and exhalation resistances.

There has been a long-standing debate regarding the adequacy of airflow rates used in respirator certification testing and whether these test flow rates underestimate actual values. This study investigated breath by breath inspiratory peak flow rate, minute ventilation, and instantaneous flow rates of eight young, healthy volunteers walking on a treadmill at 80-85% of maximal aerobic capacity until exhaustion while wearing an air-purifying respirator with one of eight combinations of inhalation and exhalation resistance. An analysis of variance was performed to identify differences among the eight conditions. Scheffe's post hoc analysis indicated which means differed. The group of conditions with the highest average value for each parameter was identified and considered to represent a worst-case scenario. Data was reported for these conditions. A Gaussian distribution was fit to the data and the 99.9% probability levels determined. The 99.9% probability level for the peak and instantaneous flow rates were 374 L/min and 336 L/min, respectively. The minute ventilation distribution was not Gaussian. Less than 1% of the recorded minute ventilations exceeded 135 L/min. Instantaneous flow rates exceeded the National Institute for Occupational Safety and Health's respirator test standards of 64, 85, and 100 L/min constant flow 91%, 87%, and 82% of the time, respectively. The recorded minute ventilations exceeded the 40 L/min minute ventilation test standard (for tests with a sinusoidal flow pattern) 100% of the time. This study showed that young, healthy respirator wearers generated peak flow rates, minute ventilations, and instantaneous flow rates that consistently exceeded current test standards. Their flow rates should be higher than those of a respirator wearer performing occupational work and could be considered upper limits. Testing respirators and respirator cartridges using a sinusoidal breathing pattern with a minute ventilation of 135 L/min (peak flow rate approximately 424 L/min) would encompass 99% of the recorded minute ventilations and 99.9% of the predicted peak and instantaneous flow rates from this study and would more accurately reflect human respiration during strenuous exercise.

Adult↗

PubMed2004

Exhaled nitric oxide in relation to the clinical features of childhood asthma.

BACKGROUND: Exhaled nitric oxide (ENO) has been shown to be a noninvasive marker of eosinophilic inflammation in asthmatic children. Few studies have evaluated the relationship between ENO levels and the clinical features of children with asthma. The aim of this study was to examine children attending a routine asthma clinic and evaluate the relationship between ENO levels and clinical parameters including decision making. METHODS: Asthmatic children (n= 133, aged 5 to 14 years) attending a hospital asthma clinic were studied. ENO levels were measured and compared between subgroups of subjects according to recent symptoms, asthma control and treatment, and the clinician's decision (blinded to ENO levels) regarding further management. RESULTS: ENO levels (median [IQR] ppb) were significantly elevated in children who had recent symptoms compared to those without recent symptoms (14.6 [6.5 to 45.3] vs. 6.0 [3.2 to 17.4], difference between medians 8.6, 95% confidence interval [CI] (1.8 to 13.9, p=0.004). ENO levels differed significantly between the controlled and uncontrolled subgroups (8.5 [4.2 to 26.4] vs. 26.4 [5.0 to 62.0], difference between medians 17.9, 95% CI 0.1 to 22.8, p=0.03) and between the three treatment decision subgroups (up, down, or unchanged; p < 0.001). CONCLUSIONS: ENO levels are strongly related to the clinical features of childhood asthma and the clinical decision making process. To fully evaluate the role of ENO in the clinical management of asthma, this "proof of concept" study paves the way for prospective randomized trials of the inclusion of ENO levels in the decision making process in childhood asthma.

Adolescent↗

PubMed2004

Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naïve atopic asthmatic children.

BACKGROUND: Measurement of fractional exhaled nitric oxide (FENO) is a noninvasive, simple, well-tolerated, and reproducible marker of airway inflammation. Asthmatic children with normal respiratory function could be affected by airway inflammation. The aim of this study was to assess the correlation between FENO and bronchial hyperesponsiveness (BHR) to methacholine, and between FENO and lung function in atopic children with intermittent asthma. METHODS: Thirty-seven children (21 male), aged 7.2-14.4 years (median: 10.9 years), suffering from mild intermittent atopic asthma with a physician-diagnosed history of wheezing and/or chest tightness were studied. None had taken anti-asthmatic therapy for at least three months before the study. No child had symptoms of respiratory tract infection in the month before the study. All subjects underwent FENO measurement, pulmonary function testing and the methacholine provocation tests. RESULTS: The mean percentages of FEV1 and FEF25-27 were 91.9+/-10.5 and 88.3+/-11.8, respectively. The mean FENO was 62.2+/-39.2 ppb and PC20 methacholine was 0.93 mg/ml+/-0.54. Significant correlations were identified between FENO and FEV1 (p<0.0059, r=0.468) and between FENO and FEF25-75 (p<0.0098, r=0.439). There was no correlation between FENO and logPC20 (p=0.14). CONCLUSIONS: A single FENO measurement is probably of scarce prognostic and predictive value and it is not surprising to find discordance with BHR. We suggest that FENO measurement could represent a good marker of airway inflammation also in naïve atopic children with intermittent asthma. Repeated measurements over time are probably necessary to understand better the clinical implications of the data obtained in this study.

Adolescent↗

PubMed2006

A longitudinal study of methanol in the exhaled breath of 30 healthy volunteers 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 male, 11 female) over a six-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 methanol in breath. The median methanol level determined using the H(3)O(+) precursor ions for all samples was 461 parts-per-billion (ppb), the concentrations for all the samples ranging from 32 to 1684 ppb. The distribution of breath methanol concentration is seen to be log-normal for this healthy population; the geometric mean was 450 ppb, close to the median value, and the multiplicative (geometric) standard deviation was 1.62. Breath methanol is not correlated with age, breath ethanol or ethanol consumed in the previous 24 h, but there was an inverse correlation with body mass index (BMI) for the cohort of volunteers recruited for this study. Observed breath methanol levels are well compatible with the previously published blood methanol levels. Some tentative suggestions are made concerning the origin of endogenous methanol.

Adult↗

PubMed2005

Calibration of an electrostatic chamber for thoron measurements in exhaled breath.

An electrostatic chamber system used for measuring thoron in the exhaled breath of thorium workers is calibrated using a standard thoron source and a scintillation cell counting system. A formulation based on both a streamlined flow model and a well-mixed flow model in the chamber has been made to estimate thoron concentration in breath from the observed alpha counts. The experimental measurements of the ratio of the outlet and the inlet thoron concentrations across the chamber strongly validate the well-mixed flow model for thoron, as against the streamlined flow model. The progeny collection efficiency on the electrode has been found to be 70%. The study points out a major error by a factor of approximately 25 in the calibration factor reported in an earlier work. From the present study, the minimum detectable limit of the activity of (224)Ra, freely emanating thoron at mouth works out to be 0.36 Bq as against 0.014 Bq reported earlier for the same system.

Air Pollutants, Radioactive↗

PubMed2004

Time-frequency detection and analysis of wheezes during forced exhalation.

The objective of the present work was to detect and analyze wheezes by means of a highly sensitive time-frequency algorithm. Automatic measurements were compared with clinical auscultation for forced exhalation segments from 1.2 to 0 liters/second (l/s). Sensitivities between 100% and 71%, as a function of flow level related to wheezing segments detection, were achieved. Time-frequency wheeze parameters were measured for the flow range from 1.2 to 0.2 l/s. Wheezes were detected in both analyzed groups; asthmatics (N = 16) and control subjects (N = 15). Significant differences between groups were found for the mean number of wheezes detected at basal condition (p = 0.0003). Frequency parameter differences were also significant (0.0112 < p < 0.0307). All these parameters were also studied after applying a bronchodilator drug (Terbutaline). Significant differences between patient groups were found when studying the changes in the number of wheezes for each patient (p = 0.0195). Finally, limited bandwidth parameters, which measure the bronchodilator response, were also studied.

Algorithms↗

PubMed2005

Determinants of increased exhaled nitric oxide in patients with suspected asthma.

Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FENO in clinical use selects patients primarily according to their atopic or asthmatic status. The aim of this study was to investigate the determinants of increased FENO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FENO of 132 patients referred because of symptoms suggestive of asthma were studied, and the explanatory factors tested included atopy according to prick skin tests, clinical asthma according to lung function tests, sputum eosinophilia and bronchial hyperresponsiveness (BHR). Slightly elevated FE(NO) levels were significantly explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P=0.04), but for high levels of FE(NO) (> or =3 SD of predicted), clinical asthma (OR: 16.3; 95% CI: 5.4-49.7; P <0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0; P >0.0001) were the characteristics with the highest prediction, followed by atopy and BHR. A significant interaction between asthma and atopy was observed relating to the effect on high FENO, but further analyses stratified by atopy showed significant associations between asthma and high FENO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FENO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FENO, irrespective of atopy. The results suggest that FENO is primarily a marker of airway eosinophilia, and that only high values of FENO may be useful to identify patients with atopic or nonatopic asthma.

Adolescent↗