Comparative efficacy of once-daily therapy with inhaled corticosteroid, leukotriene antagonist or sustained-release theophylline in patients with mild persistent asthma. Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma. Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma. Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. Effect of inhaled corticosteroids on bronchial hyperresponsiveness in patients with mild asthma. Predicting short term response to anti-inflammatory therapy in young children with asthma.
The purpose of this study was to compare the efficacy and safety of the inhaled budesonide, sustained-release theophylline and montelukast, a leukotriene receptor antagonist, in patients with mild persistent asthma. In this single-center, randomized, parallel-group study that not designed blindly and placebo-controlled manner, 74 patients with mild persistent asthma were treated with either inhaled budesonide 400 microg once daily, oral montelukast 10 mg once daily, or sustained-release theophylline 400 mg once daily for 3 months. In all three treatment groups, improvements were attained in overall asthma control. Asthma symptom scores and supplemental beta2-agonist use were quite the same in all three treatment groups (P>0.05). Although inhaled budesonide group resulted in significantly greater improvements compared with the other two groups in the lung functions (P<0.05), the changes in FEV1 and PEF are within the baseline variability and there was no statistically significant difference among the groups when analyzed by treatment month (P>0.05). Exacerbations of asthma were experienced by 16% of the patients in the montekulast group, by 12.5% of the patients in the theophylline group, and by none of the patients in the budesonide group. The adverse event in each of the three groups was 12%, 16% and 16.7%, respectively. It is concluded that the most important clinical parameters do not point that one of the treatments is more effective than others. Treatment with inhaled corticosteroid is preferred, but sustained-release theophylline and leukotriene antagonists are alternative controller medications in mild persistent asthma. Current guidelines for asthma treatment do not recommend daily maintenance therapy in patients with mild intermittent (step 1) asthma. However, because there is increasing evidence that airway inflammation is present even in this patient group, maintenance anti-inflammatory therapy may be considered. We investigated the clinical impact of regular treatment with the inhaled corticosteroid beclomethasone dipropionate and the leukotriene receptor antagonist pranlukast in the patients concerned. The study was a randomized, controlled, parallel-group, multicenter trial. Eighty-five symptomatic patients with newly diagnosed mild intermittent asthma having normal pulmonary function were assigned beclomethasone or pranlukast for 8 weeks. Then, these medications were stopped for the next 16 weeks. Main outcome measures were asthma symptoms, pulmonary function, and airway inflammation. Treatment with beclomethasone and pranlukast significantly increased forced expiratory volume in 1 second and peak expiratory flow from baseline and decreased asthma symptom scores and sputum eosinophil counts and eosinophil cationic protein contents. After discontinuation of the treatment, symptom scores remained unchanged, but pulmonary function and airway inflammation were aggravated and then returned to the baseline levels. Therefore, maintenance therapy with inhaled corticosteroid or leukotriene receptor antagonist can provide further improvements in asthma symptoms, pulmonary function, and airway inflammation, and discontinuation of the therapy causes worsening of asthma, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with symptomatic mild intermittent asthma. Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma.
                We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma.
                Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 microg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment.
                At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV(1)) in comparison with placebo (P <.05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P <.05) morning and evening peak flow, nighttime beta2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P <.05) with regard to peak flow. Triamcinolone produced suppression (P <.05) of overnight urinary cortisol/creatinine and serum osteocalcin.
                Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree. To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients.
                Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks.
                23 academic asthma centres in United States, Canada, and Europe.
                226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo).
                Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score.
                Last tolerated dose of inhaled corticosteroids.
                Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue.
                Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control. To determine the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.
                We report a pilot study of 49 patients with cystic fibrosis and moderate to severe bronchial obstruction (forced expiratory volume in 1 second < or = 55% of the predicted value); 25 patients were given inhaled corticosteroids for 30 days (1500 micrograms of beclomethasone via spacer), and 24 patients had the same standard treatment but no inhaled corticosteroids.
                Forced vital capacity, forced expiratory volume in 1 second, and airway resistance showed significant improvement in both study groups, but thoracic gas volume and the diffusion capacity of the lung for carbon monoxide improved significantly only in the group given inhaled corticosteroids. When concomitant medications were taken into account, analysis of variance confirmed a significant effect of inhaled corticosteroids on the improvement of thoracic gas volume.
                Inhaled corticosteroids in combination with standard treatment can contribute to the improvement of lung function in patients with cystic fibrosis and moderate to severe bronchial obstruction. Our preliminary data seem encouraging enough to warrant a multicenter, long-term, blind control study. More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children.
                The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control.
                A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements.
                Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm).
                Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups.
                Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations. Outcome data are needed to base recommendations for controller asthma medication use in school-aged children.
                We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA).
                An ICS, fluticasone propionate (100 mug twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated.
                Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV(1)/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast.
                The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA. We studied the effect of inhaled budesonide on bronchial hyperresponsiveness (BHR) in twenty mild asthmatic patients. The study was conducted as a randomized, double-blind, placebo-controlled study. Before entering the study, the patients performed methacholine inhalation challenge (MIC) using a reservoir method to assess BHR. Then, they were randomly allocated to receive budesonide turbuhaler (200 micrograms/dose) or placebo turbuhaler two inhalations, twice daily for eight weeks. During the study, each patient recorded daily asthma score and daily number of puffs of beta 2 agonist and they were assessed at weeks 4 and 8. At the end of the treatment, MIC was repeated again. Patients receiving budesonide showed a significant improvement in airway responsiveness compared with those receiving placebo (p < 0.05). They also showed a significant improvement in asthma severity score and a significant decrease in beta 2 agonist bronchodilator use. This study also suggested that inhaled corticosteroids may be the primary treatment in patients, even with mild asthmatic and well-controlled symptoms. Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.
                To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.
                A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.
                Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.
                Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma.
As monotherapy, inhaled corticosteroids display superior efficacy to anti-leukotrienes in adults and children with persistent asthma; the superiority is particularly marked in patients with moderate airway obstruction. On the basis of efficacy, the results support the current guidelines' recommendation that inhaled corticosteroids remain the preferred monotherapy.