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An international intercomparison of soil gas radon and radon exhalation measurements.

The Environmental Measurements Laboratory hosted the Sixth International Radon Metrology Programme Intercomparison Test and Workshop (IRMP6) from 12-15 June 1995. Thirty participants representing 24 different institutions from 11 countries attended. Laboratory exercises consisted of 220Rn and 222Rn concentration measurements from a source container, and exhalation measurements from a 226Ra-spiked concrete slab and a "normal" concrete slab. Field exercises included soil gas radon measurements and radon exhalation measurements. In this report, we pooled the participants' data and used the ratio of the standard deviation (SD) to the arithmetic mean, expressed as a percentage, to assess participant agreement for each exercise. For the exhalation measurements from the 226Ra-spiked slab, this value is 37%; for soil gas 222Rn, this value is 120%, 36% and 27% for each depth range, 0.4-0.5, 0.6-0.75 and 0.9-1.0 m, respectively; for the surface exhalation measurements, this value is 34%. For the drum 222Rn measurements, the percent SD after removing a linear trend was 13%. These results indicate that sampling errors are greater than instrument errors.

Air Pollutants, Radioactive↗

Interlaboratory comparison of three methods for the determination of the radon exhalation rate of building materials.

In this study three methods for the determination of the radon (222Rn) exhalation rate of building materials are compared. All three are so-called purge-and-trap methods in which the sample is enclosed in a container from which the exhaled radon is continuously purged by a constant flow of nitrogen gas. The outflowing radon is directed through a trapping agent, and the radon exhalation rate is subsequently calculated from the trapped activity. The main differences between the three methods are the trapping agent (silica gel, charcoal), trapping temperature (liquid nitrogen, room temperature), trapping period (30 min to 10 d), analytical method to determine the trapped activity (liquid scintillation counting, gamma ray spectrometry, total gamma counting) and the sample counting times (1 to 16 h). The repeatability and intralaboratory reproducibility are determined for one of the methods and amount to 3.1% and 4.3%, respectively. The intralaboratory reproducibility, derived from five samples with a radon release rate up to 450 microBq s(-1), was found to be 5.6% on average (range 3 to 8%). These figures are close to the combined standard uncertainty of the individual results that vary between 3 to 6%, depending on the method and method variables such as trapping period and the uncertainty of the calibration source. Furthermore, another 10 commercially available building materials were analyzed to investigate the correlation between the applied methods. Using linear regression analysis, it was found that the slope deviated not more than 10% from the one to one correspondence line. The results show that measurements of the exhalation rate can be carried out with a large degree of accuracy provided sufficient care is taken for a well-documented standard method.

Calibration↗

National survey on the natural radioactivity and 222Rn exhalation rate of building materials in The Netherlands.

The present study reports on results of a nation-wide survey on the natural radioactivity concentrations and Rn exhalation rates of the prevailing building materials in the Netherlands. In total 100 samples were taken and analyzed for the activity concentrations of Ra, Ra, Th, and K and for their Rn exhalation rate. The sampled materials consisted of gypsum products, aerated concrete, sand-lime and clay bricks, mortars and concrete, representing about 95% of the stony building materials used in the construction of Dutch homes. The laboratory analyses were performed according to two well-documented standard procedures, the interlaboratory reproducibility of which is found to be within 5% on average. The highest radionuclide concentrations were found in a porous inner wall brick to which fly ash was added. The second highest were clay bricks with average Ra and Ra levels around 40 Bq kg. Concrete and mortar show the highest exhalation rates with a fairly broad range of 1 to 13 microBq (kg s). Low natural radioactivity levels are associated with either natural gypsum (products) or gypsum from flue gas desulphurization units, and low exhalation rates with clay bricks. To evaluate the radiological impact the radioactivity concentrations in each sample were combined into a so-called dose factor, representing the absorbed dose rate in a room with a floor, walls and ceiling of 20 cm of the material in question. For that purpose, calculations with the computer codes MCNP, Marmer and MicroShield on the specific absorbed dose rates were incorporated in the paper. The results of these codes corresponded within 6% and average values were calculated at 0.90, 1.10, and 0.080 nGy h per Bq kg for the U series, the Th series, and K, respectively. Model calculations on the external dose rate, based on the incidence of the various building materials in 1,336 living rooms, are in accordance with measured data.

Air Pollutants, Radioactive↗

Inhalation regional cerebral blood flow: the use of tidal CO2 data to find radionuclide activity associated with exhaled alveolar gas.

When calculating cerebral blood flow by the inhalation regional cerebral blood flow technique, radionuclide activity associated with exhaled alveolar gas is used to represent the arterial input function for each brain region. In this study, tidal CO2 data are used to identify respiratory gas samples that contain alveolar gas. Traditional methods identify alveolar gas samples by searching for maxima and minima in the raw air curve. The raw air curve is determined by sequentially counting radionuclide activity in respiratory gases sampled at the mouth. Traditional methods sometimes erroneously identify and use maxima or minima that do not represent alveolar gas. The use of CO2 data is advantageous since the range of CO2 during exhalation can identify those exhalations that approach the functional reserve capacity and hence represent alveolar gas. The arterial input function is represented by counting intervals from the raw air curve which coincide with exhalation of alveolar gas as identified by CO2 data. This approach for representing the arterial input function is fully automatic, accurate, and reproducible.

Brain↗

Exhaled nitric oxide in paediatric asthma and cystic fibrosis.

Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases.

Adolescent↗

Exhaled nitric oxide is reduced in infants with cystic fibrosis.

BACKGROUND: Exhaled nitric oxide levels are low in patients with cystic fibrosis (CF), despite the chronic inflammation present in the airways. This study aimed to determine whether levels of exhaled nitric oxide were reduced prior to the onset of respiratory symptoms in infants with CF. METHODS: The levels of exhaled nitric oxide were measured using a chemiluminescence analyser in five infants with CF and 11 healthy control subjects, both groups having a mean age of 48.6 days. RESULTS: Mean levels of exhaled nitric oxide were significantly lower in infants with CF than in the control group (4.9 ppb v 12.1 ppb; p=0.01). CONCLUSIONS: This finding may be the key to understanding the inflammatory processes in early cystic fibrosis and may lead to novel treatment approaches.

Breath Tests↗

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations.

BACKGROUND: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. METHODS: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. RESULTS: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Adolescent↗

Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath.

BACKGROUND: The fractional concentration of nitric oxide (NO) in exhaled breath (FeNO) is increased in asthma. There is a general assumption that NO synthase (NOS) 2 in epithelium is the main source of NO in exhaled breath. However, there is no direct evidence to support the assumption and data from animal models suggest that non-inducible NOS systems have important roles in determining airway reactivity, regulating inflammation, and might contribute significantly to NO measured in exhaled breath. METHODS: Bronchial epithelial cells were obtained from healthy, atopic, and asthmatic children by non-bronchoscopic brushing. Exhaled NO (FeNO) was measured directly using a fast response chemiluminescence NO analyser. RNA was extracted from the epithelial cells and real time polymerase chain reaction was used to determine the expression of NOS isoenzymes. NOS2 was examined in macrophages and epithelial cells by immunohistochemistry. RESULTS: NOS1 mRNA was not detectable. NOS3 mRNA was detected in 36 of 43 samples at lower levels than NOS2 mRNA which was detectable in all samples. The median FeNO was 15.5 ppb (95% CI 10 to 18.1). There was a significant correlation between FeNO and NOS2 expression (R = 0.672, p<0.001). All epithelial cells exhibited NOS2 staining, whereas staining in the macrophages was variable and not related to phenotype. CONCLUSIONS: Only NOS2 expression was associated with FeNO in respiratory epithelial cells obtained from children (R = 0.672; p<0.001). This suggests that FeNO variability is largely determined by epithelial NOS2 expression with little contribution from other isoforms.

Adolescent↗

Origin of nitrite and nitrate in nasal and exhaled breath condensate and relation to nitric oxide formation.

BACKGROUND: Raised concentrations of nitrate and nitrite have been found in exhaled breath condensate (EBC) in airway disease, and it has been postulated that this reflects increased nitric oxide (NO) metabolism. However, the chemical and anatomical origin of nitrate and nitrite in the airways has not yet been sufficiently studied. METHODS: The fraction of exhaled NO at an exhalation flow rate of 50 ml/s (FE(NO)) and nitrite and nitrate in EBC, nasal condensate, and saliva were measured in 17 tracheostomised and 15 non-tracheostomised subjects, all of whom were non-smokers without respiratory disease. Tracheal and oral samples were taken from the tracheostomised subjects and nasal (during velum closure) and oral samples from the non-tracheostomised subjects. Measurements were performed before and after sodium nitrate ingestion (10 mg/kg) and use of antibacterial mouthwash (chlorhexidine 0.2%). RESULTS: In tracheostomised subjects oral FE(NO) increased by 90% (p<0.01) while tracheal FE(NO) was not affected 60 minutes after nitrate ingestion. Oral EBC nitrite levels were increased 23-fold at 60 minutes (p<0.001) whereas the nitrite levels in tracheal EBC showed only a minor increase (fourfold, p<0.05). Nitrate was increased the same amount in oral and tracheal EBC at 60 minutes (2.5-fold, p<0.05). In non-tracheostomised subjects oral FE(NO) and EBC nitrite increased after nitrate ingestion and after chlorhexidine mouthwash they approached baseline levels again (p<0.001). Nasal NO, nitrate, and nitrite were not affected by nitrate intake or mouthwash. At baseline, mouthwash with deionised water did not affect nitrite in oral EBC or saliva, whereas significant reductions were seen after antibacterial mouthwash (p<0.05 and p<0.001, respectively). CONCLUSIONS: Besides the salivary glands, plasma nitrate is taken up by the lower airways but not the nasal airways. Nitrate levels in EBC are thus influenced by dietary intake. Nitrate is reduced to nitrite by bacterial activity which takes place primarily in the oropharyngeal tract of healthy subjects. Only oropharyngeal nitrite seems to contribute to exhaled NO in non-inflamed airways, and there is also a substantial contribution of nitrite from the oropharyngeal tract during standard collection of EBC.

Adult↗

Exhaled nitric oxide in sarcoidosis.

BACKGROUND: Increased production of nitric oxide (NO) by the lower respiratory tract is viewed as a marker of airway inflammation in asthma and bronchiectasis. NO is a potentially important immune modulator, inhibiting the release of several key pro-inflammatory cytokines. As sarcoidosis is characterised by granulomatous airway inflammation, we hypothesised that exhaled NO levels might be raised in sarcoidosis and correlate with the morphological extent and functional severity of disease. METHODS: Fifty two patients with sarcoidosis (29 men) of mean age 42 years underwent thin section computed tomography (CT), pulmonary function tests, and measurement of exhaled NO. RESULTS: Exhaled NO levels (median 6.8 ppb, range 2.4-21.8) did not differ significantly from values in 44 control subjects, and were not related to the extent of individual CT abnormalities or the level of pulmonary function impairment. CONCLUSION: Exhaled NO levels are not increased in pulmonary sarcoidosis.

Adult↗

Measurement of exhaled nitric oxide in man.

BACKGROUND: Nitric oxide is released from pulmonary endothelial cells and contributes to the low pulmonary vascular resistance. The resistance pulmonary arteries are in close anatomical proximity to membranous airways, so it is likely that some pulmonary endothelial nitric oxide will enter the airspace to allow its measurement in the exhaled breath. METHODS: Exhaled air was collected from a single full exhalation and during tidal breathing. This was analysed for concentrations of nitric oxide, nitrogen dioxide, and carbon dioxide to give alveolar (FA) and mixed expired (FE) concentrations. Eight normal subjects were studied and laboratory air was similarly analysed using, respectively, chemiluminescent and infrared analysers. RESULTS: There was no relation between FA concentrations and the laboratory air concentrations. From the single breath, the ratio of (Fano/Faco2) x (Feco2/Feno) had a mean value of 0.92 (95% confidence interval 0.7 to 1.14). As this does not differ from unity, nitric oxide is likely to be derived from the same regions of the lungs as carbon dioxide. During tidal breathing the Feno ranged from 8.3 to 20.3 parts per billion. CONCLUSIONS: It is possible to measure endogenous pulmonary nitric oxide production in the exhaled air in man.

Adult↗

Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension.

BACKGROUND: Systemic sclerosis (SSc) may be complicated by pulmonary hypertension (PHT), which can occur both in the setting of fibrosing alveolitis or as lone pulmonary vascular disease. Nitric oxide (NO) is a powerful vasodilator and is produced by various cells in the respiratory tract including pulmonary vascular endothelial cells and can be measured in expired air. A study was undertaken to test the hypothesis that exhaled NO levels would be decreased in patients with SSc with PHT and to assess the utility of this measurement in discriminating between patients with and without PHT, regardless of concurrent fibrosing alveolitis. METHODS: Exhaled NO was measured with a chemiluminescence analyser in 23 patients with SSc (six with PHT, 17 subjects without) and in 67 normal individuals. Doppler echocardiography was used to assess pulmonary artery pressure in subjects with SSc, and lung function tests were performed at the same visit as NO measurements. Thin section CT scans were analysed for the presence of abnormality consistent with fibrosing alveolitis. RESULTS: Patients with SSc with PHT had a greater reduction in arterial oxygen tension (PaO2) and carbon monoxide gas transfer (TLCO) than patients with SSc without PHT. Exhaled NO was significantly higher in patients with SSc without PHT than in normal individuals, and was significantly decreased in patients with SSc with PHT (mean (SD) 20 (6) ppb) compared with 149 (19) ppb in those with SSc without PHT (mean difference 129 (95% CI 112 to 146) ppb) and 80 (7) ppb in normal individuals (mean difference 60 (95% CI 54 to 66) ppb). CONCLUSION: Exhaled NO is decreased in patients with SSc with PHT compared with both normal individuals and patients with SSc without PHT.

Adult↗

Fast vs. slow exhalation before O2 inhalation alters subsequent phase III slope.

We studied 10 symptom-free lifetime non-smokers and 17 smokers all with normal pulmonary function studies. All subjects performed single-breath N2 washout tests by either exhaling slowly ("slow maneuver") from end inspiration (EI) to residual volume (RV) or exhaling maximally ("fast maneuver") from EI to RV. After either maneuver, subjects then slowly inhaled 100% O2 to total lung capacity (TLC) and without breath holding, exhaled slowly back to RV. In the nonsmokers seated upright phase III slope of single-breath N2 test (delta N2/l) was lower (P less than 0.01) for the fast vs. the slow maneuver, but this difference disappeared when the subjects repeated the maneuvers in the supine position. In contrast, delta N2/l was higher for the fast vs. the slow maneuver (P less than 0.01) in smokers seated upright. For the slow maneuver, delta N2/l was similar between smokers and nonsmokers but for the fast maneuvers delta N2/l was higher in smokers than nonsmokers (P less than 0.01). We suggest that the fast exhalation to RV decreases delta N2/l in normal subjects by decreasing apex-to-base differences in regional ratio of RV to TLC (RV/TLC) but increases delta N2/l in smokers, because regional RV/TLC increases distal to sites of small airways obstruction when the expiratory flow rate is increased.

Adult↗

Sputum cell counts and exhaled nitric oxide in patients with gastroesophageal reflux, and cough or asthma.

BACKGROUND: Gastroesophageal reflux (GER) is commonly associated with chronic cough and asthma, but there is little or no information on the nature of any associated airway inflammation. OBJECTIVE: To observe whether the association with GER worsens airway inflammation in patients with chronic cough or asthma. PATIENTS AND METHODS: The airway inflammatory indexes in induced sputum and exhaled air were examined in a cross-sectional study of 11 patients with cough and GER, nine patients with mildly symptomatic asthma and GER, nine patients with mildly symptomatic asthma without GER and nine normal, healthy control subjects. GER was shown objectively by 24 h ambulatory pH recording. RESULTS: The sputum total cell count, the proportion of neutrophils and macrophages, and the fibrinogen level were normal in all four groups, with no significant differences among the groups. The sputum eosinophil and metachromatic cell percentages, and eosinophil cationic protein levels were normal in patients with cough and GER. They were significantly increased in patients with asthma compared with healthy subjects (P<0.01) and patients with cough (P<0.01), but were not different between groups with and without GER. Exhaled nitric oxide levels showed similar results (P<0.01). The correlations between the number of episodes of reflux and the proportion of sputum eosinophils, neutrophils or exhaled nitric oxide were modest but not significant. CONCLUSIONS: GER, when associated with cough or mildly symptomatic asthma, does not cause or aggravate existing airway inflammation as measured by induced sputum cell counts and fibrinogen level, or by exhaled nitric oxide.

Adult↗

Increased nitric oxide in exhaled gas as an early marker of lung inflammation in a model of sepsis.

Nitric Oxide (NO) has been implicated in the pathologic vasodilation of sepsis. Because NO can be measured in the exhaled gas of animals and humans, we hypothesized that increases in exhaled NO would occur in a septic model. Using a blinded design, 10 male Sprague-Dawley rats (300 to 400 g) were anesthetized, paralyzed, tracheotomized, and randomized (5/group) to receive an intravenous injection of either lipopolysaccharide (LPS) (Salmonella typhosa, 20 mg/kg) or placebo (equal volume of saline). Thereafter, exhaled gas was collected and measurements of NO concentration were made using chemiluminescence every 20 min for 300 min during ventilation (RR 40 breaths/min, VT 3 ml; PEEP 0, FIO2 0.21). Another group of 10 animals (5 LPS; 5 control) were treated in the same fashion and then killed at 240 min and an arterial blood sample obtained for blood gas and TNF alpha determinations. Pressure volume (PV) curves were constructed and lungs removed, preserved, and submitted for histologic evaluation. LPS-treated rats had lower mean arterial pressures than the control group, p < 0.0001. No significant differences in static lung compliance and PV curves were found in the two groups. TNF alpha levels were greater in the LPS group (1.40 +/- 0.24 ng/ml) versus control group (0.09 +/- 0.04 ng/ml), p < 0.001. By contrast to the control group, exhaled NO concentration rose in all LPS-treated rats at approximately 100 min and at about 160 min reached a plateau that was 6 times greater than control levels (p < 0.0001). There was greater interstitial, airspace, and total lung injury in the LPS group (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Airway inflammation, exhaled nitric oxide, and severity of asthma in patients with western red cedar asthma.

Examination of induced sputum and measurement of exhaled NO have been advocated as noninvasive methods of assessing the degree of airway inflammation. In this study, we performed follow-up evaluation on 71 subjects with asthma caused by exposure to Western red cedar; 50 subjects had left exposure, whereas the rest continued to work in the same job. Spirometry, methacholine challenge tests, exhaled nitric oxide, and sputum induction were carried out. Of the 50 subjects who left exposure, 12 had no respiratory impairment according to the American Throacic Society guidelines for assessing respiratory impairment in patients with asthma, 17 belonged to Class 1, 12 to Class 2, five to Class 3, and four to Class 4. The percentage of eosinophils in induced sputum showed a significant inverse relationship with FEV1 (r = -0.46, p < 0.001), and a significant positive correlation with levels of exhaled NO (r = 0.42, p < 0.001) and with the class of respiratory impairment (r = 0.52, p < 0.001). Mean percent eosinophils were 1.5 for impairment Class 0, 2.2 for Class 1, 1.7 for Class 2, 6.8 for Class 3, and 16.3 for Class 4. No relationship was found between the levels of exhaled NO and the functional parameters as well as the impairment class. NO levels in ppb were 21 for impairment Class 0, 30 for Class 1, 22 for Class 2, 26 for Class 3, and 49 for Class 4. This study also provides objective evidence that airway inflammation, as indicated by induced sputum, corroborates the rating of respiratory impairment in patients with asthma.

Adult↗

A simple flow-driven method for online measurement of exhaled NO starting at the age of 4 to 5 years.

NO is increased in exhaled air of asthmatic patients, and may be used as a marker of airway inflammation. The online method is a standardized technique for measuring exhaled nitric oxide (ENO). However, this method has proven difficult for some children, who may have trouble maintaining a constant expiratory flow. The aim of this study was to validate a modified technique for online ENO measurement that utilizes a flow regulator to overcome the patient problem of having to actively maintain a constant expiratory flow. We measured ENO levels with two methods in 105 asthmatic and 10 healthy subjects, comparing the standardized (ST) single-breath method with a modified single-breath, flow-driven (FD) method. With the ST method and visual monitoring, the subjects inhaled NO-free air to TLC, and exhaled with a target flow of 50 ml/s. With the FD method, the subjects exhaled from TLC and flow was kept constant (50 ml/s) by the operator, using a flow regulator. The subjects were divided into two groups, one consisting of children aged 4 to 8 yr (n = 74) and the other of children aged 9 to 16 yr (n = 41). In the group aged 4 to 8 yr, 38 children (51%) were unable to perform the ST method, whereas only five children (7%) failed to perform the FD technique. In the group aged 9 to 16 yr, only four children (10%) were unable to perform the ST maneuver, and all successfully performed the FD maneuver. The mean concentrations of ENO in the 73 children who performed both types of maneuver were similar (36.1 +/- 3.4 [mean +/- SEM] ppb with the ST method and 33.8 +/- 3.3 ppb with the FD technique, p = NS) and were highly correlated with one another (r = 0.99, p < 0.0001). ENO values were significantly higher in steroid-naive than in steroid-treated asthmatic children. In conclusion, we describe a modified online method for measuring ENO that is simple, does not require active cooperation to maintain a constant expiratory flow, and can be easily performed by children from 4 to 5 yr of age onward.

Adolescent↗

FeNO measured at fixed exhalation flow rate during controlled tidal breathing in children from the age of 2 yr.

We have outlined a new method to measure exhaled nitric oxide on-line at fixed flow rate during controlled tidal breathing (FeNO [controlled]) in young children aged 2 yr and older. FeNO(controlled) measures NO on-line during operator-controlled tidal breathing. The operator targets the exhaled flow of the child within preset limits of 0.4-0.6 L/s by continuously adjusting an expiratory resistance. FeNO(controlled) is estimated during end exhalation. We have validated this method against the reference method of the single breath on-line (SBOL) maneuvre (FeNO[SBOL]) and compared it with NO in mixed exhaled air collected in a bag (FeNO [mixed]). Sixty-seven children were studied: 16 school children and 51 children aged 2-5 yr; 14 of the young children were healthy, 22 had asthma treated with regular inhaled budesonide, and 15 had mild episodic wheeze treated with inhaled terbutaline as necessary. FeNO (controlled) showed good agreement with FeNO(SBOL) (factor difference 0.7-1.4), whereas FeNO(mixed) showed poor agreement with FeNO(SBOL) (factor difference 0.51-5.37). FeNO(controlled) (mean [95% confidence interval]) was 6 ppb (4-8 ppb) in young children with asthma, 5 ppb (3-7 ppb) in young children with mild episodic wheeze, and 3 ppb (2-4 ppb) in healthy control subjects (asthma versus control subjects: p = 0.006; episodic wheeze versus control subjects: p = 0.057). FeNO(controlled) increased from 4 ppb (2-7 ppb) to 13 ppb (10-18 ppb) (p < 0.0001) when the mean daily maintenance dose of budesonide was tapered in nine young children with asthma. FeNO(controlled) is feasible in young children from age 2 and shows better agreement with FeNO(SBOL) than FeNO(mixed). FeNO(controlled) covaries with asthma disease severity and steroid dose. FeNO(controlled) is therefore suggested as a noninvasive diagnostic tool for monitoring asthma disease activity in young children with asthma from the age of 2 yr.

Adolescent↗