Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double-blind, multicenter study.

BACKGROUND: For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines. OBJECTIVE: To compare montelukast, a once-daily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting beta-agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year. METHODS: A randomized, double-blind, double-dummy, multicenter study was conducted. Adult patients with moderate-to-severe persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 microg/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 microg/d) or montelukast (10 mg/d) for 48 weeks. RESULTS: Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated. CONCLUSIONS: Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.     

The effectiveness of high-dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children.

BACKGROUND: International guidelines recommend the use of systemic steroids for the treatment of acute asthma attack if it has not been resolved within 24 to 36 hours of home management with regular beta2 mimetic inhalation. Such therapy for infrequent exacerbations is unlikely to have serious systemic effects. Unfortunately, many patients receiving frequent courses are potentially at risk for corticosteroid-induced side effects such as adrenal suppression, depression of linear growth, and osteoporosis. OBJECTIVE: To decrease the use of frequent oral corticosteroid courses in children, this study was designed to evaluate the efficacy of high-dose inhaled steroids in comparison with oral steroids, in the therapy of acute asthma exacerbations in children. METHODS: Sixty children who have experienced an acute exacerbation of asthma unresponsive to home management with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize, were randomized to be treated with either high-dose inhaled budesonide (1,600 microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000 microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow 25% to 75% (FEF25%-75%) were evaluated. RESULTS: The mean number of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid-receiving group (group II). There was a statistically significant difference between the two groups, in favor of group I (P = .038). No statistically significant difference was detected between the two groups with respect to the increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P = .790, .959, .819, respectively). CONCLUSIONS: Short-term high-dose budesonide therapy can be considered an alternative for children who are experiencing an acute asthma attack that is unresponsive to home management with regular use of an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.     

Effectiveness of montelukast in the treatment of cough variant asthma.

BACKGROUND: Antileukotriene agents have been shown to be beneficial in chronic asthma. Although patients with cough variant asthma have cough with minimal wheezing and dyspnea, airway hyperresponsiveness from chronic inflammation is believed to be the underlying mechanism. OBJECTIVE: To evaluate the effectiveness of montelukast, a leukotriene receptor antagonist, in the treatment of cough variant asthma. METHODS: Fourteen patients with cough variant asthma participated in a randomized, double-blind, placebo-controlled trial with a 7- to 10-day baseline period and a 4-week treatment period with montelukast, 10 mg, or placebo daily. Inclusion criteria were (1) chronic cough with a duration of at least 4 weeks with minimal or no wheezing or dyspnea and (2) forced expiratory volume in 1 second of 50% to 85% of predicted and reversibility of 12% with use of an inhaled beta-agonist or forced expiratory volume in 1 second greater than 85% and positive methacholine challenge results. Patients fulfilled the minimum criteria for cough frequency and symptom scores for randomization. RESULTS: Eight patients received montelukast and 6 received placebo. The primary efficacy variable, mean percentage change from baseline in cough frequency, was significantly improved by the second week, and by the fourth week the mean percentage change from baseline was 75.7% for the treatment group and 20.7% for the placebo group. CONCLUSIONS: The leukotriene receptor antagonist montelukast seems to be effective in the treatment of cough variant asthma. Larger studies are recommended to confirm this effect.     

Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent asthma treated with montelukast: a 16-week single-blind randomized study

Pharmacological therapy with inhaled steroids (IS) is currently considered the gold-standard of treatment for mild-persistent asthma. Leukotriene receptor antagonist drugs (LTRAs) play an important role associated with IS, allowing dose tapering and maintaining control of asthma symptoms. The aim of this study was to determine the effectiveness of montelukast (MON) to allow tapering of the inhaled dose of budesonide (BUD) in patients with mild-moderate persistent asthma. This 16-wk single-blind randomized study included 40 asthmatic patients divided in 2 treatment groups. After a run-in period (4 wk), in which all patients inhaled 400 microg of BUD twice daily (bid), group A (20 patients) received MON (oral, 10 mg/day) combined with inhaled BUD (400 microg/bid), while group B (20 patients) was treated with BUD for the whole period of the study. In both groups, at every 4 wk the dose of BUD was halved. After 12 wk of treatment the mean value of forced expiratory volume during the first sec (FEV1, as % of predicted value) was significantly greater in group A compared with group B (94 +/- 7.5 vs 83.1 +/- 6.9; p<0.005). The mean values of peak expiratory flow (PEF), the percentages of asthmatic exacerbations, and the use of beta2-short-acting agonist (SABA) were similar in the 2 groups at 4, 8, and 12 wk. In conclusion, in patients with mild-moderate persistent asthma, MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease.     

The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial

BACKGROUND: Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids. OBJECTIVE: To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks). METHODS: Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV(1) and methacholine PC(20). After this, an additional 4-month trial evaluated asthma control. RESULTS: Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV(1) improvement) and nonresponders (相似文献   

Administration of budesonide once daily by means of turbuhaler to subjects with stable asthma.

BACKGROUND: Optimal management of chronic, mild-to-moderate asthma with inhaled steroids may include use of the lowest possible doses, as recommended in guidelines, and a reduction in the frequency of daily administration for greater convenience. Lower doses and once daily treatment with inhaled steroids must be rigorously evaluated in controlled clinical trials. OBJECTIVES: The objective of this study was to assess the efficacy and safety of once daily treatment with budesonide in subjects with stable asthma. METHODS: Once daily budesonide was assessed in 309 adult subjects, including those who were and were not using an inhaled steroid at baseline. The subjects were stratified by inhaled steroid use and randomly assigned to one of 3 treatments: 200 microgram budesonide, 400 microgram budesonide, or placebo administered by means of Turbuhaler once daily in the morning for 6 weeks. Beyond this point, treatment was continued unchanged for another 12 weeks (maintenance) in those receiving 200 microgram budesonide once daily and placebo. In those who received 400 microgram budesonide once daily, the dose was reduced to 200 microgram once daily at week 6 and held constant for the remaining 12 weeks (400/200 microgram group). Primary efficacy endpoints were mean change from baseline in FEV1 and morning peak expiratory flow. RESULTS: Once daily budesonide was well tolerated and resulted in significant improvements in all efficacy endpoints, even though baselines were well stabilized. Baseline lung function was elevated with little room for improvement; however, mean increases in FEV1 during the maintenance period were 0.10 L and 0.11 L in the 200 microgram and 400/200 microgram groups, respectively, versus a decrease of -0.09 L in the placebo arm (P <.001). Results for peak expiratory flow were similar. Significant improvements in secondary endpoints, including symptoms, beta-agonist use, and quality of life, also developed with budesonide 200 and 400 microgram once daily. CONCLUSION: Inhaled budesonide, in doses as low as 200 microgram, may be an appropriate introductory or maintenance dose in subjects with stable, mild-to-moderate asthma.     

Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients

BACKGROUND: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma. OBJECTIVE: To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR). METHODS: After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 micro g/day), were randomly assigned to one of two treatments - placebo (n = 98) or montelukast 10 mg once daily (n = 93) - for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and beta-agonist use. RESULTS: After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 +/- 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 +/- 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 +/- 28.5 L/min (P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group. CONCLUSION: These data suggest that montelukast reduces the need for inhaled corticosteroids while maintaining asthma control over a 24-week period. Therefore, montelukast may be useful for long-term treatment in patients with asthma who require high doses of inhaled corticosteroids.     

Changes in serum eotaxin and eosinophil cationic protein levels, and eosinophil count during treatment of childhood asthma.

BACKGROUND AND PURPOSE: Increased serum levels of eotaxin are related to the severity of asthma in adults. There are limited data on the effects of oral corticosteroids and inhaled corticosteroid therapy on serum levels of eotaxin and eosinophil cationic protein (ECP) and peripheral blood eosinophil counts (ECs) in pediatric asthma patients. We investigated prospectively the changes in eotaxin and ECP serum levels and peripheral blood ECs after administering oral corticosteroids and then inhaled corticosteroids plus long-acting beta2 agonist treatment in pediatric patients. METHODS: Serum samples of 20 pediatric patients with mild-to-moderate asthma were collected before treatment, after 5-7 days of oral prednisolone treatment, and after 1-2 months of inhaled fluticasone plus salmeterol treatment. Peak expiratory flow was used as the outcome index. RESULTS: Serum eotaxin levels remained the same after oral prednisolone treatment, but decreased after subsequent inhalation treatment compared with the end of oral steroid treatment (64.7 +/- 22.6 vs 85.7 +/- 36.8 pg/mL, p<0.001). The EC and serum ECP levels declined soon after oral steroid treatment, rebounding to initial levels during inhalation treatment. The decrease in ECP level was positively correlated with the decrease in ECs with oral steroid treatment (r(2) = 0.28, p=0.016). There was no correlation between changes in eotaxin levels and peak expiratory flow. CONCLUSIONS: Our data suggest that the serum eotaxin level, not peripheral blood EC or serum ECP level, declines during inhaled fluticasone plus salmeterol treatment and might serve as a surrogate marker of T helper 2 residual activity in pediatric asthma.     

Multicolored simplified asthma guideline reminder (MSAGR) for better adherence to national/global asthma guidelines.

BACKGROUND: Clinicians in general have not widely and consistently used asthma guidelines in their practices around the world. This study identifies reasons for the poor adherence to asthma guidelines by primary care physicians (PCPs), and simultaneously introduces multicolored simplified asthma guideline reminder (MSAGR) as a practical tool to enhance adherence to asthma guidelines. METHODS: Sixty-nine PCPs were given a simple, one-page, fill-in-the-blank questionnaire on the classification of asthma severity as defined in National Asthma Education and Prevention Program guidelines, using patients' symptoms, peak expiratory flow rate (PEFR)/forced expiratory volume in 1 second (FEV1) value, PEFR variability, and step therapy based on asthma severity. Also, they were given a questionnaire on barriers to using asthma guidelines and MSAGR for evaluation. In one targeted community, free copies of MSAGR were made available to PCPs, and data on emergency room visits and hospitalization of asthmatic patients were analyzed. RESULTS: Of the PCPs, 16% correctly classified mild, intermittent asthma, 13% mild, persistent asthma, 8% moderate, persistent asthma, and 8% severe, persistent asthma based on the combined patient's symptoms, PEFR or FEV1 value and PEFR variability as defined in National Asthma Education and Prevention Program guidelines. One hundred percent of the PCPs chose inhaled beta2-agonists as quick relief medication. Fifty percent of the PCPs chose inhaled steroids, leukotriene antagonists, oral theophylline, and long acting beta-agonists in various combinations for different severity of asthma. Eighty percent of the physicians failed to select the appropriate dosages of inhaled steroids for different severities of asthma. Ninety-five percent of PCPs reported that MSAGR made using the guidelines easier for them. In the targeted community, asthma-related emergency room visits decreased 22.5% and hospitalizations by 26.9%. CONCLUSIONS: This is the first study that identified the reasons for poor adherence to asthma guidelines by PCPs, and introduced MSAGR as a practical "low-tech" tool to promote better adherence to asthma guidelines. MSAGR presents patient-specific recommendations, based on asthma guidelines in a user-friendly format that can save the physician time in real-world primary care settings, where such information is often needed instantly. The overwhelming majority of PCPs strongly agreed that MSAGR helped them recall the classification of asthma severity in a timely manner, to inquire about various triggers, and to use step therapy accurately and confidently. In one targeted community, MSAGR helped clinicians in primary care settings to achieve better asthma outcomes and to reduce both emergency room visits and hospitalizations.     

Nocturnal asthma: effect of treatment with oral sustained-release terbutaline, inhaled budesonide, and the two in combination

The purpose of this study was to compare effect of treatment with an oral long-acting beta 2-agonist (sustained-release terbutaline, Bricanyl depot), an inhaled steroid (budesonide, Pulmicort), and the combined treatment in patients with nocturnal asthma. Thirty-seven patients completed the study. During a 1-week run-in period with inhaled terbutaline monotherapy, the mean nocturnal asthma score was 1.0 (+/- 0.1) (corresponding to one awakening every night), and the mean overnight fall in peak expiratory flow rate was 27.7% (+/- 2.0). The patients were randomly entered into double-blind, crossover periods of 3 weeks each: (1) sustained-release terbutaline, 10 mg twice daily (b.i.d.), (2) sustained-release terbutaline, 10 mg b.i.d., and two puffs (400 micrograms) of budesonide, b.i.d., and (3) two puffs (400 micrograms) of budesonide, b.i.d. The combined treatment resulted in significantly lower overnight fall in peak expiratory flow rate (6.9% +/- 1.4 compared to 9.4% +/- 2.0 during sustained-release terbutaline and 10.4% +/- 1.9 during budesonide) and less nocturnal awakenings (nocturnal asthma score 0.15 +/- 0.05, 0.43 +/- 0.09, and 0.26 +/- 0.06, respectively) than either single treatment alone (p less than 0.05). The differences between the single treatments were not significant. We thus found that an inhaled steroid is as effective as a long-acting oral beta 2-agonist in controlling nocturnal asthma and that the combination is better. The observed differences were, however, small, and other studies would be required to evaluate the clinical significance of the present finding.     

Serum eosinophil cationic protein (ECP) as a mediator of inflammation in acute asthma, during resolution and during the monitoring of stable asthmatic patients treated with inhaled steroids according to a dose reduction schedule

Objective and Design: The main objective was to establish the level of serum ECP in a group of adult asthmatic patients with acute exacerbation and the following resolution and in another group of adult, stable asthmatic patients during reduction of inhaled steroids.¶Subjects and Treatment: Acute group: Twenty-one asthmatic patients admitted to the asthma clinic with acute deterioration of their asthma were set on oral steroids which were reduced to 0 within one week. Reduction group: Forty-four stable asthmatic patients on maintenance inhaled steroids were included and, on the basis of their peak expiratory flow (PEF) values, adjustments in the doses of steroids were made. Control group: Twenty stable asthmatics on a constant dose of inhaled steroids were enrolled as controls.¶Methods: All patients registered daily PEF measurements and spirometry was performed at each visit. Blood samples were drawn and analysed for eosinophil cationic protein (ECP), myeloperoxidase (MPO), eosinophils and neutrophils.¶Results: ECP was low and within the normal range for all three groups at study entry. (Acute group = 8.4 7g/l, reduction group = 3.7 7g/l and control group = 4.6 7g/l). Nevertheless, the value in the acute group was significantly higher than in the control group (p = 0.005). The levels in the acute group decreased significantly (p = 0.004) after one week on oral steroids. No significant changes in ECP were observed in the reduction group or in the control group during the follow-up period. The lung function was low in the acute group at inclusion, forced expiratory volume in one second (FEV₁) = 47.1% of predicted, and increased significantly during the treatment period (p = 0.006). The patients in the reduction- and control group showed small variations in lung function during the whole study, FEV₁ >70% and PEF > 80% of predicted, respectively. No correlation between atopy and ECP was found in the patients irrespective of the stage of disease.¶Conclusions: This study suggests that the resolution of acute asthma exacerbations during treatment could be followed using ECP determinations. In stable asthmatics on inhaled steroids and with normal ECP levels, a dose reduction could be indicated. A longer period after tapering off steroids is proposed to confirm the benefit of ECP measurements for controlling asthma.     

Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth

BACKGROUND: Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated. OBJECTIVE: The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight. METHODS: Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births. RESULTS: A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed. CONCLUSION: These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.     

Body composition and growth in asthmatic children treated with inhaled steroids.

BACKGROUND: Prolonged treatment with inhaled steroids is recommended for long-term control of asthma in children; however, it can interfere with growth and body composition. OBJECTIVE: The aim of this study is to answer the question whether 6 months treatment with inhaled steroids causes body fat accumulation and growth velocity reduction. METHODS: Hospital-based, open study of body composition [by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and skinfolds] and growth of 26 asthmatic children, treated for 6 months with inhaled steroids [budesonide (BUD) 400 microg/day (group 1) or fluticasone proprionate (FP) 200 microg/day (group 2)], sodium cromoglycate and beta2-agonist (salbutamol) compared with a control group of 16 asthmatic children treated only with sodium cromoglycate and beta2-agonist. RESULTS: On average, total and regional fat mass, adjusted for pubertal stage and gender, and growth velocity were similar in all three groups of patients and were not influenced by treatment (% mean change +/- 1 SD of fat mass during treatment in BUD 0.1 +/- 3.0%, FP -1.1 +/- 3%, and control -2.8 +/- 3.5%; ANOVA P > or = .05); however seven patients, two in group 1 (1 preschool child), three in group 2 (2 preschool children) and two in the control group (two prepubertal boys aged 8.5 and 9.5 year), during treatment, showed a growth velocity standard deviation score below the third percentile. CONCLUSION: A 6-month treatment with inhaled BUD and FP does not induce body fat accumulation; however, in a few preschool children the treatment was associated with growth velocity below the third percentile. Our results suggest the need for constant monitoring of growth in all asthmatic children on chronic treatment with inhaled steroids. Further studies devoted to the effects of inhaled steroids use in preschool children are needed.     

Step-down and step-up therapy in moderate persistent asthma

BACKGROUND: A step-down therapy may be more beneficial for the management of asthma than a step-up therapy. METHODS: Eighty-two asthmatic patients with moderate persistent asthma were enrolled in the study and randomized into three groups. One group of patients received 400 microg/day of beclomethasone dipropionate (BDP) for 4 weeks and then 800 microg/day for another 4 weeks (step-up group). The other two groups of patients received 1,200 microg/day of BDP for 4 weeks with or without short-term oral steroid (prednisolone, 0.5 mg/day for 1 week) and then 800 microg/day for another 4 weeks (step-down group). Severe exacerbation of asthma, asthma symptoms, respiratory function and rescue use of inhaled beta(2)-agonists were monitored. If asthma was well controlled, the dose of BDP was decreased every 3 months and if asthma was exacerbated, the dose of BDP was increased until 8 months after the initial treatment. RESULTS: Twenty-two patients during the run-in period, 4 patients in the step-up group, 2 patients in the step-down group treated with a high dose of BDP and no patients in the step-down group with oral steroids during first 4 weeks dropped out because of severe exacerbation of asthma. Although asthma symptoms and respiratory function significantly improved 8 weeks after the therapy in all groups, more significant and prompt improvements of these parameters were observed in patients of the step-down group than in patients of the step-up group after the first 2 weeks of treatment. Furthermore, step-down therapy with short-term oral steroid resulted in the lowest maintenance doses of BDP at 8 months of the three groups. CONCLUSIONS: These results suggest that step-down therapy starting with a high dose of inhaled steroid and short-term oral steroid is more effective in gaining prompt control of asthma and reducing the severe exacerbation of asthma and the maintenance dose of inhaled steroids than a step-up therapy starting with a low dose of inhaled steroids in patients with moderate persistent asthma.     

Adherence rate to inhaled corticosteroids and their impact on asthma control

Background:  Poor asthma control is associated to high morbidity. The objective of this study was to assess the association between adherence rates to beclomethasone dipropionate (BDP) and the degree of asthma control.
Methods:  A cohort concurrent study was carried out for 12 months with 122 asthmatic patients, aged 3–12 years, randomly selected in a pediatric pulmonology outpatient clinic, who received BDP free of charge. Adherence rates were verified by pharmacy records. Clinical control was assessed through a scoring system comprised four variables (nocturnal and morning symptoms, limitation of physical activities and exacerbations). Total score was 16 points. Patients whose score was below or equal to two were considered controlled (group 1), and patients whose score was above or equal to three were considered uncontrolled (group 2). For patients able to perform spirometry, we considered as controlled the patients with forced expiratory volume in 1 s (FEV₁) equal to or above 80% of the predicted value, and as uncontrolled the patients with FEV₁ below 80%.
Results:  Fewer than half (40.3% maximum) of the 122 patients maintained asthma control. Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, ( P  < 0.001) in the 4th month, 90.0% and 48.0% ( P  < 0.001) in the 8th month and 84.4% and 47.0% in the 12th month ( P  < 0.001), respectively.
Conclusion:  In all periods, there were statistically significant differences in adherence rates for maintaining or not maintaining the asthma control. Optimal asthma control entailed adherence rate higher than 80%. Strategies for reducing asthma morbidity should include a regular monitoring of adherence to inhaled steroids.     

"Real-world" effectiveness of daily controller medicine in children with mild persistent asthma.

BACKGROUND: Unmeasured confounders and selection bias can significantly influence the results of retrospective observational analyses of asthma therapy. OBJECTIVE: To evaluate the efficacy of oral montelukast and inhaled fluticasone propionate in a randomized, prospective 12-month "real-world" observational analysis of children with mild persistent asthma. METHODS: Children (n = 104) between 6 and 15 years of age with mild asthma as determined by forced expiratory volume in 1 second, symptoms, and evaluation by an experienced pediatric allergist or pulmonologist, who were not currently receiving controller therapy, were randomly assigned to fluticasone or montelukast on an alternating basis. Subjects were asked to complete a questionnaire at 6 and 12 months; otherwise, medical care was identical to that of similar managed care patients. Outcome parameters were evaluated after 12 months by claims database analysis. An acute asthma attack requiring emergent care was the primary outcome parameter. Measures of adherence, symptoms, and asthma control, as measured by the pediatric Asthma Therapy Assessment Questionnaire, were secondary outcome parameters. RESULTS: Demographics, spirometry, symptoms at enrollment, emergent care visits, asthma hospitalizations, routine office visits, and symptoms at study completion were not significantly different between study groups. Adherence, as evaluated by the number of controller fills, was significantly (P = 0.0003) better for montelukast (7.65 +/- 3.01) than fluticasone (5.46 +/- 3.01). Similar numbers of subjects in each study group required beta-agonists and oral prednisone. CONCLUSIONS: These results suggest that oral montelukast and inhaled fluticasone have similar real-world efficacies in the treatment of children with mild asthma, possibly as a result of the significantly better adherence with oral montelukast therapy compared with inhaled fluticasone.     

Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant

BACKGROUND: This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate (BDP) formulated in hydrofluoroalkane-134a (HFA-BDP) and the standard chlorofluorocarbon propellants (CFC-BDP). Because HFA-BDP has improved lung deposition compared with CFC-BDP, this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP. METHODS: In this multicenter, randomized, parallel-group blinded study, asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were randomized to receive one of 6 possible treatments: 100 microg/d, 400 microg/d, or 800 microg/d of HFA-BDP or 100 microg/d, 400 microg/d, or 800 microg/d of CFC-BDP for 6 weeks. Changes in spirometry, daytime asthma symptom and nighttime asthma-related sleep disturbance scores, morning and evening peak expiratory flows, and daily use of inhaled beta-agonist for symptom control on diary cards were assessed over 6 weeks of treatment. RESULTS: Three hundred twenty-three patients were randomized to the 6 treatment groups, which had similar demographics and baseline lung function. There were significantly larger changes from baseline at week 6 in FEV(1) percent predicted with increasing doses of both HFA-BDP and CFC-BDP. The FEV(1) percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP. By using the Finney bioassay method, it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV(1) percent predicted as HFA-BDP (95% confidence interval, 1.1-11.6). All treatment groups except the 100 microg/d CFC-BDP group tolerated study drug well. Ten (17%) of 59 patients in this group reported an acute asthma episode, increased asthma symptoms (6 of the 8 reports of increased asthma symptoms were classified as severe), or both, and 8 patients withdrew from the study (3 for adverse events related to asthma). CONCLUSIONS: Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control. Moreover, the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP.     

Efficacy of montelukast during the allergy season in patients with chronic asthma and seasonal aeroallergen sensitivity.

BACKGROUND: Montelukast has proven efficacy in the treatment of chronic asthma and seasonal allergic rhinitis, but it has not been evaluated in the subpopulation of asthmatic patients with seasonal asthma symptoms. OBJECTIVE: To determine the effectiveness of montelukast treatment in improving the control of asthma symptoms during the allergy season in patients with active asthma and seasonal aeroallergen sensitivity. METHODS: Adults with a history of chronic asthma who are also symptomatic during the allergy season and with skin test sensitivity to seasonal aeroallergens were enrolled in a randomized, parallel-group, multicenter study with a 1-week, single-blind, placebo run-in period followed by 3 weeks of double-blind treatment during the spring of 2004. After the run-in period, eligible patients were randomly assigned to receive either oral montelukast (10 mg) or placebo. Daytime and nighttime asthma symptom scores, beta-agonist use, and morning and evening peak expiratory flow rates were recorded daily using an electronic diary. The primary end point was mean change from baseline to week 3 in the daytime asthma symptom score. RESULTS: Of 455 randomized patients, 433 completed the study. Compared with placebo, treatment with montelukast resulted in a significant improvement from baseline in the daytime asthma symptom score (-0.54 vs -0.34; P = .002) and in beta-agonist use, nighttime symptoms, and peak expiratory flow rates. Few patients in the montelukast and placebo groups discontinued study participation because of asthma (1.3% and 3.0%, respectively). CONCLUSION: In patients with chronic asthma and seasonal aeroallergen sensitivity, montelukast treatment provided significant asthma control during the allergy season compared with placebo.     

Efficacy and safety of fluticasone propionate 250 microg administered once daily in patients with persistent asthma treated with or without inhaled corticosteroids.

BACKGROUND: Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously. OBJECTIVE: We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS). METHODS: In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning. RESULTS: At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001). CONCLUSIONS: FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.