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Concentrations of exhaled nitric oxide in asthmatics and subjects with allergic rhinitis sensitized to the same pollen allergen.

BACKGROUND: Some studies have reported that the levels of exhaled nitric oxide (ENO) in asthmatics are similar to those in subjects with allergic rhinitis, and it has been postulated that atopic status might be the determinant of enhanced nitric oxide production in asthma. OBJECTIVES: The aim of this study was to determine differences in ENO levels between asthmatics and subjects with allergic rhinitis sensitized to the same allergen, and to correlate these levels with airway responsiveness. METHODS: Nineteen patients with asthma and 18 subjects with allergic rhinitis monosensitized to Parietaria pollen were enrolled in the study. ENO values and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured during the pollen season. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV1 (PC20). ENO was measured with the single-exhalation method. RESULTS: The geometric mean (95% confidence interval) ENO values were significantly higher in asthmatics than in subjects with allergic rhinitis: 72.4p.p.b. (54.9-93.3p.p.b) vs. 44.7p.p.b. (30.9-64.6p.p.b., P = 0.03). In asthmatics, a significant correlation was found between ENO and PC20 AMP values (p = -0.57, P=0.02), whereas no correlation was detected between ENO and PC20 methacholine (p = -0.35, P = 0.14). CONCLUSIONS: Our results suggest that atopy is not the only determinant of increased ENO levels detected in subjects with asthma, and that responsiveness to AMP may be a more sensitive marker for assessing airway inflammation in asthma compared to methacholine.

Adenosine Monophosphate↗

Influenza vaccination: changes in exhaled nitric oxide levels and sputum cytology.

OBJECTIVE: Influenza vaccination is routinely recommended for patients with chronic lung disease, but has been reported to cause a small increase in airway reactivity. The use of simple, non-invasive methods of assessing changes in airway inflammation could potentially allow improved understanding of the cellular mechanisms underlying such changes. METHODOLOGY: We studied a group of 44 hospital workers before and after routine influenza vaccination, using spirometry, and exhaled nitric oxide (eNO) as a marker of pulmonary inflammation (Group A). In addition, methacholine challenge and sputum induction were also performed in a subgroup (subgroup B, n = 7) at baseline and at 7 days after vaccination. RESULTS: Spirometry did not change in either group. In Group A there was a small but significant rise in mean peak eNO from 47.32 +/- 4.5 (mean NO p.p.b. +/- SEM) to 53.2 +/- 4.9 between days 0 and 7 (P < 0.05). A non-significant rise in eNO was seen in subgroup B. In subgroup B, when the differential cell counts in induced sputum were compared between baseline and sampling 1 week later, there was a significant rise in the percentage of lymphocytes, from 3.9 (1.8-9.8: median %total (range)) to 11.9 (6.0-18.5, P < 0.02) and a non-significant increase in shed respiratory epithelial cells from 3.1 (0.6-5.8) to 13.0 (1-30.3, P=0.06). There was a corresponding significant fall in the percentage of macrophages. Methacholine challenge in subgroup B showed no change in reactivity in these normal subjects. CONCLUSION: Influenza vaccination causes a small increase in exhaled NO, and is accompanied by increased sputum lymphocytosis and respiratory epithelial shedding. An influx of inflammatory cells may help to explain the induction of increased airway reactivity that has been described in other studies.

Adult↗

Exhaled nitric oxide partitioned into alveolar, lower airways and nasal contributions.

During the last year exhaled nitric oxide (NO) has been proposed as a marker of airway inflammation. More knowledge of the production and transfer of this molecule are needed in order for NO analysis to become a clinical tool. This was the aim of the study. Exhaled NO values from multiple flow rates were used to model alveolar NO, transfer rate and tissue concentration of NO in the airways. Three flows rates, 0.005, 0.1 and 0.51 sec(-1) were found to be optimal. The NO transfer rate of the airways was 9 +/- 2 ml sec(-1), the tissue source was 75 +/- 28 ppb and the alveolar fraction of NO was 2 +/- 1 ppb in 10 healthy subjects (mean +/- CI95%). In conclusion, we have shown that it is possible to get more information about the distribution of NO in the lungs and the airways than only a single value from one expiratory flow rate can give. Further studies will reveal if this airway modelling can be useful in disease of the respiratory system.

Biomarkers↗

Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia.

Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF-concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4-7 days while HGF values in breath condensate remained elevated even after 4-6 weeks. These results might imply local product on of HGF in the lungs and a long repair and healing process after pneumonia.

Adult↗

Activity related increase of exhaled nitric oxide in Crohn's disease and ulcerative colitis: a manifestation of systemic involvement?

Nitric oxide (NO) is an important mediator of inflammation in several pathological conditions. Patients with lung diseases, like asthma, have higher levels of exhaled NO (eNO) in active disease in comparison with healthy volunteers. Aspirated colonic gas in patients with ulcerative colitis (UC) showed more than 100 times higher levels of NO in comparison with normal subjects. Crohn's disease (CD) and UC are associated with a variety of systemic manifestations, although lung diseases as an extra-intestinal expression of inflammatory bowel disease (IBD) are not well investigated. In some studies, clinical and subclinical pulmonary abnormalities are described in active IBD as well as in the stable situation. The aim of the present study is to evaluate whether eNO is increased in patients with active IBD and to investigate whether there exists a correlation between (1) the eNO levels and the disease activity, and (2) the spirometry and the disease activity in a subgroup of patients. In 31 patients with CD (mean age 36.8 +/- 12.9 years) and 24 patients with UC (mean age 38.0 +/- 14.7 years) the Crohn's Disease Activity Index (CDAI) and Colitis Activity Index (CAI) were measured, respectively. Exhaled NO was measured with a chemiluminescence analyzer, according to standardized criteria. In a subgroup of CD patients, spirometry was also performed according to standardized criteria. The mean CDAI in CD patients was 192.4 +/- 94.3 and their mean eNO value was 13.5 +/- 4.6 ppb. For UC the mean CAI was 6.2 +/- 4.8 and the mean eNO value was 15.8 +/- 6.2 ppb. In a matched control group of 27 healthy, non-smoking volunteers (mean age of 33.7 +/- 13.2 years) the eNO was 10.2 +/- 2.5 ppb (P < 0.05 compared to CD and P < 0.01 compared to UC). There was a disease-activity-related increase of the eNO level in patients with IBD. For patients with UC the correlation coefficient (r = 0.63, P < 0.001) was more pronounced than for CD (r = 0.39, P < 0.05). In 17 patients with CD, spirometry was available at the time of the eNO measurement. We found a significant negative correlation between the CDAI and the FEV1 and FVC in these patients (r = -0.559, P = 0.02 and r = -0.634, P = 0.006, respectively). We conclude that eNO is increased in active IBD and correlates with the activity of the disease; furthermore, we found a negative correlation between spirometry and disease activity in patients with CD. These observations strengthen the arguments that IBD is a systemic disease. Further research is needed to try to explain the significance of an increased eNO in IBD.

Acute Disease↗

Reduction of variability of exhaled nitric oxide in healthy volunteers.

Exhaled nitric oxide (eNO) is elevated in patients with asthma in contrast to healthy subjects, although the variability is high. In this study, we tried to reduce the variability of eNO in healthy subjects. We measured eNO using ERS guidelines with a fixed exhalation flow of 250 ml/s in 117 (72 women, 45 men) non-smoking healthy subjects and correlated this to antropometric data and standard lung function measurements. Using a model previously defined by Hyde et al., we selected parameters that were likely to have a high correlation with eNO. ENO was log-normally distributed. The normal values for eNO are significantly (P < 0.001) different for men and women: in women mean ln eNO levels (SD) were 1.49 (0.34), in men 1.74 (0.41) (back-transformed value 4.43 resp. 5.73 ppb). Using multiple regression analysis, only In D(m,CO), InTLC and In sG(aw) showed a significant positive correlation with In eNO in men, although only 20% of the variability of eNO could be explained. In women no correlation was observed and only 5% ofthe variability was explained. The high variability of eNO could only partly be explained in men, which makes the use of reference equations not very helpful.

Adult↗

[John Snow (1813-1858): experimental studies on rebreathing of anesthetic gases in exhaled air].

As early as in 1850 (only 4 years after the first clinical performance of ether anaesthesia by W. T. G. Morton on 16 October 1846) John Snow recognised that ether and chloroform were exhaled unchanged with the expired air. To reuse these unchanged vapours in the following inspiration and thereby prolonging the narcotic effect of a given amount of anaesthetic vapour, he converted his ether inhaler into a To-and-Fro Rebreathing System: The apparatus was equipped with a facemask without an expiratory valve and a large reservoir bag containing pure oxygen; an aqueous solution of caustic potash was used as CO2 absorbent. In several experiments, performed on himself, Snow succeeded to demonstrate that rebreathing of the exhaled vapours was possible following carbon dioxide absorption, and that it resulted in a pronounced prolongation of the narcotic effects of the volatile anaesthetics. Furthermore, Snow performed experiments on animals using a closed system for evaluating the carbon dioxide production during anaesthesia. It is all the more worthwhile to introduce Snow's publications on these topics, as, despite their extraordinary theoretical and practical significance, they remained nearly unnoticed. Even in the fundamental articles by D. Jackson and R. Waters, both being the respected protagonists of the rebreathing technique in anaesthesia, the Snow papers remained uncited.

Anesthesia, Closed-Circuit↗

Exhaled carbon monoxide levels after a course of oral prednisone in children with asthma exacerbation.

BACKGROUND: Fractional exhaled nitric oxide (FE(NO)) and exhaled carbon monoxide (ECO) have been proposed as markers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to assess the effect of oral prednisone treatment on FE(NO) and ECO levels in a group of 30 asthmatic children with asthma exacerbation. METHODS: Thirty asthmatic children with asthma exacerbation were treated with oral prednisone for 5 days (1 mg/kg/day). Before and after prednisone therapy, ECO was measured by means of a chemical analyzer and FE(NO) was measured by means of a chemiluminescence analyzer. ECO and FE(NO) were also measured in a group of healthy nonatopic children. RESULTS: Before therapy, both ECO values and FE(NO) values were higher in asthmatic children (ECO, 3.2 +/- 0.2 ppm; FE(NO) online, 74.9 +/- 6.2 ppb; FE(NO) offline, 20.2 +/- 1.4 ppb) than in healthy controls (ECO, 2.0 +/- 0.2 ppm [P <.01]; FE(NO) online, 10.1 +/- 0.8 [P <.0001]; FE(NO) offline, 5.9 +/- 0.4 ppb [P <.0001]). An overlap in ECO values was found between healthy controls and asthmatic children. After prednisone therapy, there was a significant reduction in FE(NO) values (FE(NO) online, 40.6 +/- 4.6 ppb [P <.0001]; FE(NO) offline, 11.1 +/- 0.8 ppb [P < 0.0001]) and a slight but nonsignificant decrease in ECO values (2.7 +/- 0.2 ppm [P = not significant]) in the asthmatic group. No significant correlation between ECO values and FE(NO) values was found in either the asthmatic children or the controls. CONCLUSIONS: After a course of prednisone therapy, in children with asthma exacerbation there is a significant decrease in FE(NO) but no significant change in ECO levels. This possibly suggests that ECO is less sensitive than FE(NO) to inhibition by corticosteroids.

Administration, Oral↗

Traffic-related air pollution affects peak expiratory flow, exhaled nitric oxide, and inflammatory nasal markers.

The authors used a longitudinal observational design, with repeated measures, to study the association between traffic-related air pollutants (i.e., nitric oxide, nitrogen dioxide, carbon monoxide, and Black Smoke) and respiratory symptoms. Subjects (N = 82) attended an elementary school in either Utrecht (i.e., urban children) or Bilthoven (i.e., suburban children). These two geographic areas differed with respect to levels of Black Smoke (means = 53 microg/m3 and 18 microg/m3, respectively). Levels of nitric oxide, nitrogen dioxide, carbon monoxide, and Black Smoke were consistently higher in Utrecht than in Bilthoven (mean daily ratios were 8, 1.5, 1.8, and 2.7, respectively). The authors compared mean levels of short-term effects of the aforementioned air pollutants on suburban and urban children. Urban children had higher mean levels (p = .05) of interleukin-8 (32%), urea (39%), uric acid (26%), albumin (15%), and nitric oxide metabolites (21%) in nasal lavage than did suburban children. Peak expiratory flow, exhaled nitric oxide levels, and nasal markers were associated with levels of particulate matter with diameters less than or equal to 10 microm, Black Smoke, nitrogen dioxide, and nitric oxide. With respect to per-unit increases in air pollution, urban children had more increased peak expiratory flow, higher levels of exhaled nitric oxide, and more increased release of uric acid, urea, and nitric oxide metabolites than suburban children. In summary, urban children had increased levels of inflammatory nasal markers, and their responses were more pronounced than were the suburban children's responses to the same increments of air pollution.

Adolescent↗

Transient decrease of exhaled nitric oxide after acute exposure to passive smoke in healthy subjects.

Nitric oxide (NO) is produced and detected in the exhalate from the respiratory tract where it plays important regulatory functions. Exhaled nitric oxide (eNO) concentrations are reduced in active cigarette smokers between cigarettes and in nonsmoking subjects during short-term exposure to environmental tobacco smoke. In this study, the authors evaluated eNO before and after an acute exposure to environmental tobacco smoke in healthy, nonsmoking subjects (n = 12). Baseline eNO levels were measured by chemiluminescence at baseline (1 hr before exposure), shortly after the end of exposure, and 10 and 30 min after the end of exposure. Mean room air NO concentration increased from 3 ppb to 4 ppm (range, 560 ppb-8.5 ppm) during the exposure period. Carboxyhemoglobin levels were assessed before and after the exposure with spectrophotometry. All subjects had decreased eNO with exposure to environmental tobacco smoke (mean +/- standard error of the mean: 16.65 +/- 1.35 ppb to 13.86 +/- 1.33 ppb; p < .001). These concentrations remained significantly decreased at 10 min and recovered within 30 min. No modifications in airway resistance or increase in carboxyhemoglobin levels were observed. Exposure to environmental tobacco smoke transiently--but consistently--decreased eNO concentration in healthy, nonsmoking subjects, suggesting that second-hand smoke can directly affect NO in the airway environment.

Acute Disease↗

Reduction of mercuric ion and exhalation of mercury in acatalasemic and normal mice.

A significant difference in the amount of exhaled mercury per hour between normal and acatalasemic mice was observed in 7 of 11 experiments for different periods of time. The total amount of mercury exhaled from acatalasemic mice was significantly higher than those of normal mice. The results confirm that the reduction of mercuric ion to metallic mercury occurs by recycling of mercury in the tissues and reoxidized metallic mercury to mercuric ion by catalase. Mercuric ion was reduced to metallic mercury in the presence of superoxide anion in vitro. The reduction rate of mercuric ion to metallic mercury in the presence of both superoxide anion and cytochrome C or nitro blue tetrazolium was higher than that in the presence of superoxide anion alone, and the reduction of mercuric ion by NADPH or NADH was also observed. The reduction of mercuric ion to metallic mercury by liver homogenates of acatalasemic mice was higher than that of normal mice.

Acatalasia↗

Detection of ketosis in dairy cows by analysis of exhaled breath.

In four healthy cows an elevation of ketone bodies was induced by reduction of feed intake. Two cows became clearly ketotic while the other two cows showed only slight increases in ketone body concentrations in serum and milk. Acetone concentrations in exhaled breath were measured by gas chromatography combined with mass spectrometry. These values were correlated with concentrations of serum beta-hydroxybutyric acid (r = 0.81) and milk acetoacetate+acetone (r = 0.70). It is concluded that the ketotic state of dairy cows can be detected by analysis of exhaled breath. This offers a potential non-invasive method of determining the metabolic state of dairy cows.

3-Hydroxybutyric Acid↗

Exhaled nitric oxide levels are not correlated with eczema severity in Chinese children with atopic dermatitis.

Asthma is a common atopic disease associated with atopic dermatitis (AD) and allergic rhinitis (AR). Exhaled nitric oxide level (eNO) has been found to be an interesting noninvasive marker of disease severity in children with asthma. However, it is uncertain if eNO may be confounded by any coexisting AD or AR. In this study, eNO in Chinese children with moderate-to-severe AD and no asthma symptoms (n = 53) was measured online by a chemiluminescence analyzer. Severity of AD was assessed using the objective SCORing-Atopic-Dermatitis score and coexisting allergic rhinitis with the Allergic-Rhinitis-Score (ARS). Patients with active symptoms of asthma or inhaled/intranasal corticosteroids were excluded. There was no difference in eNO between genders and no correlation between eNO and AD severity regardless of ARS or bronchial reactivity status. ENO appears to be a noninvasive marker whose level is independent of the two atopic diseases of AD and AR in children old enough to perform exhalation maneuver.

Adolescent↗

Exhaled nitric oxide in mylar balloons: influence of storage time, humidity and temperature.

BACKGROUND: Mylar balloons are used to collect exhaled air for analysis of fractional nitric oxide concentration (FENO). AIM: We studied the effect of storage conditions on the stability of nitric oxide (NO) in mylar balloons. METHODS: Exhaled air samples and calibration gases were stored in mylar balloons at 4, 21 and 37 degrees C, with or without silica gel. NO was measured after 0, 6, 9, 24 and 48 h. Scheffe F-tests were used to compare NO values. RESULTS: NO remained stable in balloons for 9 h at all temperatures, without silica gel. NO increased between 9 and 48 h, but only with low initial FENO. Silica gel increased variability. CONCLUSIONS: FENO in mylar balloons is stable for at least 9 h. The storage temperature is not critical, but silica gel increases variability.

Breath Tests↗

A review of the USEPA's single breath canister (SBC) method for exhaled volatile organic biomarkers.

Exhaled alveolar breath can provide a great deal of information about an individual's health and previous exposure to potentially harmful xenobiotic materials. Because breath can be obtained non-invasively and its constituents directly reflect concentrations in the blood, its use has many potential applications in the field of biomarker research. This paper reviews the utility and application of the single breath canister (SBC) method of alveolar breath collection and analysis first developed by the US Environmental Protection Agency (USEPA) in the 1990s. This review covers the development of the SBC technique in the laboratory and its application in a range of field studies. Together these studies specifically show how the SBC method (and exhaled breath analysis in general) can be used to clearly demonstrate recent exposure to volatile organic compounds, to link particular activities to specific exposures, to determine compound-specific uptake and elimination kinetics, and to assess the relative importance of various routes of exposure (i.e. dermal, ingestion, inhalation) in multi-pathway scenarios. Specific investigations covered in this overview include an assessment of exposures related to the residential use of contaminated groundwater, exposures to gasoline and fuel additives at self-service gas stations, swimmers' exposures to trihalomethanes, and occupational exposures to jet fuel.

Biomarkers↗

Abnormal exhaled ethane concentrations in scleroderma.

Scleroderma (systemic sclerosis) is a chronic multisystem autoimmune disease in which oxidative stress is suspected to play a role in the pathophysiology. Therefore, it was postulated that patients with scleroderma would have abnormally high breath ethane concentrations, which is a volatile product of free-radical-mediated lipid peroxidation, compared with a group of controls. There was a significant difference (p<0.05) between the mean exhaled ethane concentration of 5.27 pmol ml(-1) CO(2) (SEM=0.76) in the scleroderma patients (n=36) versus the mean exhaled concentration of 2.72 pmol ml(-1) CO(2) (SEM=0.71) in a group of healthy controls (n=21). Within the scleroderma group, those subjects taking a calcium channel blocker had lower ethane concentrations compared with patients who were not taking these drugs (p=0.05). There was a significant inverse association between lung diffusion capacity for carbon monoxide (per cent of predicted) and ethane concentration (b=-2.8, p=0.026, CI=-5.2 to -0.35). These data support the presence of increased oxidative stress among patients with scleroderma that is detected by measuring breath ethane concentrations.

Breath Tests↗

Effects of variation in exposure to airborne acetone and difference in work load on acetone concentrations in blood, urine, and exhaled air.

Using a physiologically based pharmacokinetic (PBPK) model, the effects of variation of exposure concentration of acetone on three biological indicators--acetone concentrations in blood, urine, and exhaled air--were investigated. The effect of the difference in work load was also examined. It was confirmed that the model could be used to estimate acetone concentrations during fluctuating exposure by comparing simulated acetone concentrations with the corresponding values observed in field surveys. By inputting the exposure situations into the PBPK model, the variabilities of the biological indicators were simulated. The variation of acetone exposure was expressed by seven 1-hour time-weighted averages (CEXPs). The arithmetic means of the CEXPS were 200 and 750 ppm. The geometric standard deviations (GSDs) were 1.5, 2.0, and 3.0, representing low, moderate, and high variations, respectively. Work loads were set at 15 and 50 W. Consequently, there were 12 exposure situations. The acetone concentrations in venous blood (CB) and exhaled alveolar air (CA) at 1 minute after the end of the work shift were selected as biological indicators of exposure because they were predicted to decrease rapidly at the end of exposure and become relatively stable after 1 minute. The acetone concentration in urine excreted during the last 2 hours of the work shift (CU) was also used as a biological indicator. Simulation was repeated 100 times with randomly permuting CEXPs for each situation. The mean values of CB, CU, and CA showed almost no variation regardless of the difference in the GSD of CEXPs. The coefficients of variation increased with the GSD of CEXPs but were less than 0.2. Consequently, these variables were acceptable as biological indicators of daily average exposure for the same work load. However, the difference in work load greatly changed the mean values of CB, CU, and CA, thus making it difficult to use these variables as indicators of daily average exposure for different work loads.

Acetone↗

Time-dependent changes in orally exhaled nitric oxide and pulmonary functions induced by inhaled corticosteroids in childhood asthma.

Exhaled nitric oxide levels are elevated in asthmatic children and decrease after inhaled steroid treatment. We evaluated the time-dependent changes in fractional exhaled nitric oxide concentration (FENO) and pulmonary function parameters following inhaled steroid therapy. Thirty-nine steroid-naive atopic patients (age 11.92+/-0.48 years) with mild intermittent asthma and 22 age-matched healthy controls were enrolled in the study; pulmonary functions and FE(NO) levels were measured. Low doses of inhaled steroids were prescribed to all asthmatic patients who were reevaluated in a second visit (between 10 and 40 days after the beginning of the treatment). At the enrolment, asthmatic patients had similar forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) values (p > 0.05) but reduced forced expiratory flows at 25-75% of the vital capacity (FEF(25-75%)) values, as compared to controls (p < 0.05). In addition, FE(NO) levels were significantly higher in asthmatics with respect to control subjects (30.8+/-3.0 and 4.0+/-0.5 ppb, respectively; p < 0.01). All asthmatics had FE(NO) levels higher than 8.8 ppb (i.e., > 2 standard deviations of the mean in controls). After steroid treatment, patients showed significant improvement of FEV1, FVC, and FEF(25-75%) (p = 0.0001; each comparison) and a reduction of FE(NO) levels (p = 0.0001). A weak significant correlation was found between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.33, p = 0.04) or in FEF(25-75%) (r = 0.4, p = 0.01) after treatment. When changes in FE(NO) levels and in pulmonary function parameters were corrected for days of treatment, significant correlations were still present between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.57, p = 0.0004) or percent increase in FEF(25-75%) (r = 0.45, p = 0.006). Sixteen of the 39 asthmatic patients were evaluated on two occasions after the beginning of treatment, at days 10 and 40. The significant reduction in FE(NO) levels (p < 0.01) and the significant increase in FEV1 and FEF(25-75%) values observed (p < 0.05) after 10 days did not further improve at day 40. These data show that it is possible to demonstrate early effects of low-dose inhaled steroids in asthmatic children using objective measurements of airway caliber and inflammation.

Administration, Inhalation↗