Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial. Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial. A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children. Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study). Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Children with mild asthma: do they benefit from inhaled corticosteroids? Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease. Effectiveness and safety of inhaled corticosteroids in controlling acute asthma attacks in children who were treated in the emergency department: a controlled comparative study with oral prednisolone.
International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FE(NO)) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.
                In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FE(NO) measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.
                Forty-six patients in the FE(NO) group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 microg per day for the FE(NO) group (95 percent confidence interval, 263 to 477) and 641 microg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 microg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FE(NO) group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a nonsignificant reduction of 45.6 percent (95 percent confidence interval for mean difference, -78.6 percent to 54.5 percent) in the FE(NO) group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).
                With the use of FE(NO) measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.
                Copyright 2005 Massachusetts Medical Society. Current asthma guidelines recommend adjusting antiinflammatory treatment on the basis of the results of lung function tests and symptom assessment, neither of which are closely associated with airway inflammation.
                We tested the hypothesis that titrating corticosteroid dose using the concentration of exhaled nitric oxide in exhaled breath (Fe(NO)) results in fewer asthma exacerbations and more efficient use of corticosteroids, when compared with traditional management.
                One hundred eighteen participants with a primary care diagnosis of asthma were randomized to a single-blind trial of corticosteroid therapy based on either Fe(NO) measurements (n = 58) or British Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4 months and then every 2 months for a further 8 months. The primary outcome was the number of severe asthma exacerbations. Analyses were by intention to treat.
                The estimated mean (SD) exacerbation frequency was 0.33 per patient per year (0.69) in the Fe(NO) group and 0.42 (0.79) in the control group (mean difference, -21%; 95% confidence interval [CI], -57 to 43%; p = 0.43). Overall the Fe(NO) group used 11% more inhaled corticosteroid (95% CI, -17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was lower in the Fe(NO) group (557 vs. 895 microg; mean difference, 338 microg; 95% CI, -640 to -37; p = 0.028).
                An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines. Clinical trial registered with www.controlled-trials.com (ISRCTN08067387). Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma.
                We evaluated whether titrating steroids on FENO improved asthma management in children.
                Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a FENO group (n=39) in which treatment decisions were made on both FENO and symptoms, or to a symptom group (n=46) treated on symptoms only. Children were seen every 3 months over a 1-year period.
                Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyperresponsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose.
                Changes in steroid dose from baseline did not differ between groups. In the FENO group, hyperresponsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p=0.04). FEV1 in the FENO group improved, and the change in FEV1 was not significantly different between groups. The FENO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. FENO increased in the symptom group; the change in FENO from baseline differed between groups (p=0.02).
                In children with asthma, 1 year of steroid titration on FENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation. Inhaled corticosteroids (ICS) may provide benefit in the therapy of acute asthma. The purpose of this study was to test the hypothesis that ICS are as effective as oral corticosteroids (OCS) in the management of acute childhood asthma.
                A randomized, masked, placebo-controlled study was conducted in children aged 6 to 16 years seeking emergent care for an acute exacerbation of asthma. Patients were randomized into one of two groups: group 1 (OCS), oral prednisone, 2 mg/kg (maximum of 60 mg/d) for 7 days, and placebo pressurized metered-dose inhaler with valved holding chamber, four inhalations bid; and group 2 (ICS), flunisolide, four inhalations (1 mg) bid for 7 days, and daily placebo tablets. Spirometry (FEV(1)) was performed at baseline, day 3, and day 7 of the study. A symptom diary and twice-daily peak expiratory flow were recorded.
                A total of 58 subjects receiving ICS (n = 27) or OCS (n = 28) were enrolled. Baseline asthma severity, race, gender, and age were balanced between the two groups. chi(2) showed no significant difference in symptom severity between the two groups at any time during the study. FEV(1) percentage of predicted was lower in the ICS group on day 3 (65% vs 78%, p = 0.03) and on day 7 (77% vs 95%, p = 0.002).
                ICS were found to be useful in the management of acute asthma in children; however, spirometry data suggested a more rapid resolution of asthma with OCS. Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy. Exhaled nitric oxide (NO) is elevated in untreated patients with asthma but not in patients treated with inhaled glucocorticoids. This may reflect an inhibitory effect of glucocorticoids on the induction of the enzyme NO synthase in the respiratory tract. We have now studied the effect of an inhaled glucocorticoid (budesonide 800 micrograms twice daily via a dry powder delivery system for 3 wk) on exhaled NO in 11 patients with mild asthma in a double-blind crossover randomized-order placebo-controlled study. Exhaled NO was reduced from a baseline value of 203 +/- 29 parts per billion (ppb) to 120 +/- 26 ppb after 3 wk of treatment (p < 0.01), whereas there was no change after a matched placebo (169 +/- 20 at baseline compared with 184 +/- 16 ppb after 3 wk). A significant and progressive fall in exhaled NO was found from 1 to 3 wk. There was no significant change in FEV1 after inhaled steroids (although mean FEV1 was 92% predicted normal at baseline), although there was a reduction in airway responsiveness to methacholine (approximately 2.5 doubling dilutions). These results add further support to the view that the elevated levels of exhaled NO in asthma may derive from induction of an inducible isoform of NO synthase and indicate that exhaled NO may be a useful way of monitoring the anti-inflammatory effects of glucocorticoids and other anti-inflammatory treatments in asthma. In children with mild asthma, who show hardly any abnormalities in pulmonary function, objective measurement of the effect of inhaled corticosteroids is difficult. The short term effect of fluticasone propionate (FP) in these children was evaluated, using both subjective and objective parameters. A total of 68 children (5-10 yrs old) were randomly assigned to either FP 250 microg or placebo twice daily as metered-dose inhaler via spacer during 12 weeks. Symptom scores, use of rescue medication, wheezing, parent global evaluation and pulmonary function tests including forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) and bronchial responsiveness (provocation dose of methacholine causing a 20% fall in FEV1 (PD20)) were evaluated. FP-treated versus placebo-treated children showed significant changes in percentage symptom-free days, use of beta2-mimetics, morning and evening PEF, FEV1 % pred and wheezing. No significant improvements were found in parent global evaluation, absolute values of FEV1 nor PD20. These findings show that inhaled corticosteroids are effective in children with mild asthma. This effect can be assessed by both objective and subjective parameters. Early start of inhaled corticosteroids should be considered even when pulmonary function is normal. Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.
                In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.
                Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.
                Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD. Inhaled corticosteroids have a greater antiinflammatory potency and fewer systemic effects than intravenous, intramuscular, or oral corticosteroids. However, their role in acute asthma has not been established. We prospectively investigated the efficacy and safety of inhaled corticosteroids in controlling moderately severe acute asthma attacks in children who were treated in the emergency department.
                Children who were treated in the emergency department with moderately severe asthma attacks after receiving treatment with inhaled terbutaline were allocated by double-blind design to receive 1 dose of either 1600 micro(g) budesonide turbohaler or 2 mg/kg prednisolone. The pulmonary index score and peak expiratory flow rate were measured hourly for the first 4 hours. After discharge the children were treated with the same initial doses given 4 times daily, followed by a 25% reduction in dose every second day for 1 week. Parents recorded asthma symptoms and use of beta-2 agonists on a daily diary card. Serum cortisol concentration was measured at the end of weeks 1 and 3.
                Twenty-two children (11 in each group) with similar baseline parameters completed the study. There was a similar improvement in pulmonary index score and peak expiratory flow rate in the 2 groups. Children treated with budesonide showed an earlier clinical response than those given prednisolone, who also showed a decrease in serum cortisol concentration.
                In children with moderately severe asthma attacks who were treated in the emergency department, a short-term dose schedule of inhaled budesonide turbohaler, starting with a high dose and followed by a decrease over 1 week, is at least as effective as oral prednisolone, without suppressing serum cortisol concentration.
Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain.