Once-daily budesonide inhalation powder (Pulmicort Turbuhaler) maintains pulmonary function and symptoms of asthmatic children previously receiving inhaled corticosteroids.

BACKGROUND: The incidence of pediatric asthma has increased dramatically over the past few decades, with approximately 5% of American children affected by the disease. OBJECTIVES: To compare the efficacy and safety of once-daily budesonide Turbuhaler with placebo in asthmatic children previously treated with orally inhaled corticosteroids. METHODS: This randomized, double-blind, placebo-controlled, multicenter (17 centers) study included 274 male and female children (aged 6 to 17 years) with a history of asthma for at least the previous 6 months. Patients received placebo or budesonide Turbuhaler (200 microg or 400 microg) once daily for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1), AM and PM peak expiratory flow rates (PEFRs), nighttime and daytime asthma symptom severity scores, patient discontinuations, use of beta2-agonists as breakthrough medication, forced vital capacity (FVC), and midexpiratory flow rate between 25% and 75% of FVC (FEF25%-75%). Safety was evaluated by adverse events, physical examinations, vital signs, and laboratory tests. RESULTS: Baseline characteristics were comparable among treatment groups. Percentage of predicted FEV1 at baseline was 76.6 +/- 6.9 for placebo, 77.5 +/- 7.1, and 77.0 +/- 7.8 for the budesonide Turbuhaler 200 microg and 400 microg groups, respectively. Significantly (P < or = 0.024) more placebo patients (24%) discontinued treatment because of disease deterioration or no improvement than budesonide Turbuhaler 200 microg (11%) or 400 microg patients (10%). Patients receiving budesonide Turbuhaler experienced significant improvements in FEV1 compared with patients receiving placebo (P < or = 0.015). Significant (P < or = 0.041) improvements over placebo also were observed in AM and PM PEFRs, FVC, FEF25%-75%, nighttime and daytime asthma symptoms, and amount of beta2-agonist used in both budesonide Turbuhaler groups. Adverse events were generally mild or moderate in intensity and similar among treatment groups. CONCLUSIONS: Once-daily budesonide Turbuhaler is effective and safe in children with persistent asthma previously maintained on at least twice-daily dosing regimens of inhaled corticosteroids.     

Effects of treatment with mometasone furoate dry powder inhaler in children with persistent asthma.

BACKGROUND: Mometasone furoate dry powder inhaler (DPI) has been shown to effectively treat asthma in children. OBJECTIVE: To evaluate the efficacy and safety of 2 dosing regimens of mometasone furoate DPI in the treatment of mild-to-moderate persistent asthma in children previously using inhaled corticosteroids (ICSs). METHODS: A 12-week, multicenter, double-blind, parallel-group, placebo-controlled study evaluated 2 dosing regimens of mometasone furoate DPI (100 microg every evening and 100 microg twice daily) in 296 children 4 to 11 years old with asthma previously using ICSs. The primary efficacy variable was the change in percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline to end point. Secondary efficacy variables included absolute FEV1, forced expiratory flow between 25% and 75% forced vital capacity, morning and evening peak expiratory flow, asthma symptom scores, albuterol use, nocturnal awakenings, response to therapy, and health-related quality of life. RESULTS: Mean changes from baseline at end point in predicted FEV1 were 4.73 and 5.52 percentage points for mometasone furoate DPI, 100 microg every evening and 100 microg twice daily, respectively, the difference of which was not significant, and -1.77 percentage points for placebo (P < or = .002). Significant improvements in secondary efficacy variables were also observed for both mometasone furoate DPI treatments over placebo. Both mometasone furoate DPI doses were well tolerated, and no significant differences were noted among the 3 treatment groups in adverse event reporting. CONCLUSIONS: Both mometasone furoate DPI doses were well tolerated and significantly improved lung function, maintained effective asthma control, and improved quality of life in children with asthma.     

Treatment with 400 microg of inhaled budesonide vs 200 microg of inhaled budesonide and oral montelukast in children with moderate persistent asthma: randomized controlled trial.

BACKGROUND: Montelukast is reported to be beneficial in asthma as add-on therapy to inhaled corticosteroids and may reduce the need for the latter. OBJECTIVE: To evaluate whether a combination of oral montelukast and 200 microg of inhaled budesonide has comparable efficacy to 400 microg of inhaled budesonide alone in children with moderate persistent asthma. METHODS: In this prospective, blinded, hospital-based randomized controlled trial, 71 children with moderate persistent asthma were randomized to receive either montelukast, 5-mg chewable tablet, with 200 microg of inhaled budesonide or only 400 microg of inhaled budesonide daily for 12 weeks. Baseline and serial measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score were performed; the frequency and severity of exacerbations were also recorded. RESULTS: Measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score showed no significant differences between the 2 groups at baseline, during the serial follow-up visits, and at the end of the study. However, children who received montelukast had a greater frequency of exacerbations vs those who did not (33.3% vs 9.1%; P < .01). CONCLUSION: The overall control of asthma with 5 mg of oral montelukast and 200 microg of inhaled budesonide is inferior to that with 400 microg of inhaled budesonide in children with moderate persistent asthma.     

Impact of particulate air pollutants on allergic diseases,allergic skin reactivity and lung function

Elevated levels of particulate matter can exacerbate existing asthma and atopy, while evidence that it can promote the induction of atopy and asthma is limited. A cross sectional study was taken to compare the prevalence of eye, nose, ear and airway allergic symptoms, allergic skin sensitivity and lung function in 290 high school students with a history of high 24 hour average exposure to particulate matter less than 10 microm in diameter (PM10) = 170 microg/m3 versus low PM10 of 36 microg/m3 in central Bangkok. Multivariate analysis revealed an increased risk of eye and airway symptoms in groups exposed to higher PM10 levels (p = 0.003, and 0.05, respectively). Positive skin prick tests and a history of having a lawn at home were associated with nasal symptoms (p = 0.008 and 0.04, respectively). Mean FEF(25-75%) (forced expiratory flow that occurs during the middle 50% of the forced expiratory effort) was significantly lower in those who were exposed to higher PM10 levels (3.89 +/- 1 vs 4.42 +/- 0.9 l/sec, p < 0.001). A significant increase in days of school absence and medical expenses was associated with high PM10 exposure. It is concluded that chronic exposure to high PM 10 levels was significantly associated with increased prevalence of eye and airway symptoms and a decrement of FEF(25-75%) resulting in increase of school absence and medical expense.     

Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects

BACKGROUND: In a cohort of 8 normal and 10 allergic asthmatic volunteers, we previously reported that inhalation of 5 microg of endotoxin (LPS) induced airway inflammation that correlated with CD14 expression that was, in turn, correlated with eosinophil numbers in the airway. Macrophage and neutrophil functions have been reported to be modified by endotoxin in vitro and in vivo, and response to endotoxin is mediated largely by airway phagocytes and related to allergic inflammation. OBJECTIVE: We sought to examine functional and cell-surface phenotype changes in phagocytes recovered from atopic asthmatic subjects after endotoxin challenge. METHODS: Sputum and peripheral blood from 10 allergic asthmatic subjects was recovered after saline and LPS challenge. Assessment of phagocytosis and cell-surface phenotype (CD11b, CD14, and CD64) was performed on phagocytes obtained from sputum (n = 7) and blood samples (n = 10). RESULTS: Phagocytosis of blood and sputum phagocytes was blunted after LPS challenge in a fashion that correlated with the increase in airway neutrophils after LPS challenge. Cell-surface expression of CD14 (membrane-bound CD14) was increased in sputum cells, whereas CD11b was decreased in sputum and circulating phagocytes. Baseline expression of CD11b in blood correlated with the magnitude of the neutrophil response after LPS inhalation, as well as (inversely) with baseline airway eosinophil levels. CONCLUSIONS: Inhalation of endotoxin at levels adequate to induce a neutrophil influx to the airways (but not systemic symptoms) results in decreased phagocytosis in both airway and circulating cells and modifies CD11b expression in a way that implicates its involvement in phagocyte responsiveness to inhaled LPS.     

Once-daily budesonide via Turbuhaler improves symptoms in adults with persistent asthma.

BACKGROUND: Previous studies have demonstrated the efficacy and safety of twice-daily budesonide Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Wilmington, DE) for the treatment of mild to severe asthma. OBJECTIVE: To compare the efficacy and safety of budesonide Turbuhaler administered once daily each morning with placebo in inhaled corticosteroid-naive adults with persistent asthma. METHODS: In this randomized, double-blind, placebo-controlled, multicenter study, 177 adults (aged 18 to 70 years) received placebo or once-daily budesonide Turbuhaler (400 microg) for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1) and AM/PM peak expiratory flow rate (PEFR), and nighttime/daytime asthma symptom scores, patient discontinuations, use of breakthrough medication (albuterol), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), and quality of life assessments. Safety was evaluated based on adverse events, physical examinations, vital signs, and laboratory tests. RESULTS: Demographic and baseline characteristics were comparable between study groups. The mean percentages of predicted FEV1 at baseline were 71.9 +/- 9.8 in patients receiving budesonide Turbuhaler and 70.6 +/- 11.0 in patients receiving placebo. Mean changes from baseline over the 12-week treatment period in FEV1 were significantly (P = 0.007) improved in patients receiving once-daily budesonide Turbuhaler compared with placebo (0.31 L and 0.17 L, respectively). Significant (P < or = 0.037) improvements over placebo also were observed in AM PEFR, nighttime/daytime asthma symptoms, and albuterol use with budesonide Turbuhaler treatment. Adverse events were generally mild or moderate in intensity and similar between study groups. CONCLUSIONS: Budesonide Turbuhaler 400 microg administered once daily in the AM is efficacious and safe for inhaled corticosteroid-naive asthmatic adults.     

Once-daily evening administration of mometasone furoate in asthma treatment initiation.

BACKGROUND: In a previous study, a 200-microg once-daily evening dose of mometasone furoate dry powder inhaler (DPI) was effective in patients with asthma previously taking inhaled corticosteroids. No studies have been conducted to test the effect of a once-daily evening dose in patients previously using only short-acting beta2-adrenergic agonists (SABAs) for symptom relief. OBJECTIVE: To evaluate the effectiveness of mometasone furoate DPI administered once daily in the evening as initial controller therapy in patients previously using SABAs alone for asthma. METHODS: Patients with mild-to-moderate persistent asthma from 18 US centers participated in a 12-week, randomized, double-blind, placebo-controlled study. Patients received either mometasone furoate DPI, 200 microg, or placebo once daily in the evening. The primary efficacy variable was the change in forced expiratory volume in 1 second from baseline to the end point (last evaluable visit). Other measurements included forced vital capacity, forced expiratory flow between 25% and 75%, morning and evening peak expiratory flow, asthma symptoms, use of albuterol, nocturnal awakenings, physicians' evaluation of response to therapy, and time to asthma worsening. RESULTS: At the end point, the mean increase in forced expiratory volume in 1 second relative to baseline for the mometasone furoate DPI group of 0.43 L (16.8%) was significantly greater than that for the placebo group of 0.16 L (6.0%) (P < .01). Morning peak expiratory flow, forced vital capacity, and forced expiratory flow between 25% and 75% also significantly improved with mometasone furoate DPI treatment relative to placebo (P < .01). Once-daily dosing with mometasone furoate DPI was well tolerated. CONCLUSION: Mometasone furoate DPI (200 microg) administered once daily in the evening significantly improves pulmonary function in patients previously using SABAs alone for asthma control.     

Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong

AIMS: To assess the relationship between levels of ambient air pollutants and hospitalization rates for asthma in Hong Kong (HK). METHODS: This is a retrospective ecological study. Data of daily emergency hospital admissions to 15 major hospitals in HK for asthma and indices of air pollutants [sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)), ozone (O(3)), particulates with an aerodynamic diameter of <10 microm particulate matter (PM(10)) and 2.5 microm (PM(2.5))] and meteorological variables from January 2000 to December 2005 were obtained from several government departments. Analysis was performed by the generalized additive models with Poisson distribution. The effects of time trend, season, other cyclical factors, temperature and humidity were adjusted. Autocorrelation and overdispersion were corrected. RESULTS: Altogether, 69 716 admissions were assessed. Significant associations were found between hospital admissions for asthma and levels of NO(2), O(3), PM(10) and PM(2.5). The relative risks (RR) for hospitalization for every 10 microg/m(3) increase in NO(2), O(3), PM(10) and PM(2.5) were 1.028, 1.034, 1.019 and 1.021, respectively, at a lag day that ranged from cumulative lag 0-4 to 0-5. In a multi-pollutant model, O(3) was significantly associated with increased admissions for asthma. The younger age group (0-14 years) tended to have a higher RR for each 10 microg/m(3) increase in pollutants than those aged 15-65 years. The elderly (aged >/=65 years) had a shorter 'best' lag time to develop asthma exacerbation following exposure to pollutants than those aged <65 years. CONCLUSION: Adverse effects of ambient concentrations of air pollutants on hospitalization rates for asthma are evident. Measures to improve air quality in HK are urgently needed.     

Expression of CD35 (CR1) and CD11b (CR3) on circulating neutrophils and eosinophils from allergic asthmatic children

Complement receptors on neutrophils and eosinophils play a role in activation and adhesion. During asthmatic reactions these receptors have been found elevated on circulating granulocytes. In the present study we compared the expression of CD35 (complement receptor type 1) and CD11b (complement receptor type 3) on neutrophils and eosinophils from asthmatic and non-asthmatic children. This was done in whole blood samples using depolarized light scattering for the discrimination of neutrophils and eosinophils. The non-stimulated expression as well as the upregulated expression of receptors by the chemotactic peptide N-formylmethionyl-leucyl-phenyl-alanine (fMLP) were studied. The results showed that without prior stimulation only the expression of CD35 on neutrophils was significantly elevated in children with asthma (P<0.05). After up-regulation with fMLP, the CD11b expression on neutrophils (P<0.005, fMLP: 0.002 microM) and eosinophils (P<0.05, fMLP: 0.02 microM) was significantly higher in asthmatic children than in the controls. These results indicate that the inducible expression of CD11b on neutrophils and eosinophils from allergic asthmatic children is primed in vivo.     

Effects of particulate matter (PM10) on the pulmonary function of middle-school children

It has been reported that the particulate matter under 10 microm (PM10) has deleterious effects on respiratory health. The purpose of this study was to assess the influence of PM10 upon normal children's lung function. The subjects were 368 middle school students in two areas of Incheon Metropolitan City. One (Incheon) is in the central city and the other (Ganghwa) is in the suburbs. Air pollution data in the vicinities of two participating schools were obtained from monthly report of air quality from Korean Ministry of Environment in 2000. Pulmonary function testing (PFT) was done two times, the first one in March and the second one in December with the same students. We analyzed the relationship between the PM10 levels and pulmonary functions (FEV1, FVC) of the children. The monthly average of the PM10 level between the two areas showed no significant difference (55.3 vs. 52.3 microg/m3). In both regions, the difference of the PM10 level between March and December was statistically significant (64 vs. 56 microg/m3 in Incheon, 64 vs. 54 microg/m3 in Ganghwa). The findings of the PFT values in March were significantly lower than those values found in December for both regions. In conclusion, we suggest that PM10 has some adverse effect on the pulmonary function of normal children.     

Association between air pollution and asthma admission among children in Hong Kong

OBJECTIVE: To examine the association of air pollutants with hospital admission for childhood asthma in Hong Kong. METHODS: Data on hospital admissions for asthma, influenza and total hospital admissions in children aged < or =18 years at all Hospital Authority hospitals during 1997-2002 were obtained. Data on daily mean concentrations of particles with aerodynamic diameter <10 microm (i. e. PM10) and <2.5 microm (i. e. PM2.5), nitrogen dioxide (NO2), sulphur dioxide (SO2), and ozone (O3) and data on meteorological variables were associated with asthma hospital admissions using Poisson's regression with generalized additive models for correction of yearly trend, temperature, humidity, day-of-week effect, holiday, influenza admissions and total hospital admission. The possibility of a lag effect of each pollutant and the interaction of different pollutants were also examined. RESULTS: The association between asthma admission with change of NO2, PM10, PM2.5 and O3 levels remained significant after adjustment for multi-pollutants effect and confounding variables, with increase in asthma admission rate of 5.64% (3.21-8.14) at lag 3 for NO2, 3.67% (1.52-5.86) at lag 4 for PM10, 3.24% (0.93-5.60) at lag 4 for PM2.5 and 2.63% (0.64-4.67) at lag 2 for O3. Effect of SO2 was lost after adjustment. CONCLUSION: Ambient levels of PM10, PM2.5) NO2 and O3 are associated with childhood asthma hospital admission in Hong Kong.     

Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma

BACKGROUND: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.     

佐剂性关节炎大鼠肺功能变化与Th1/Th2细胞、调节性T细胞的相关性研究

目的:探讨细胞因子、Th1/Th2细胞及调节性T细胞(Treg)、转录因子Foxp3在佐剂性关节炎(AA)大鼠肺功能损害中的作用机制。方法:将24只Wistar大鼠随机分为正常对照(NC)组和模型(Model)组,每组12只,向Model组大鼠右后足跖皮内注射弗氏完全佐剂0.1mL致炎,复制成AA模型。致炎48d后,观察两组大鼠足跖肿胀度(E)及关节炎指数(AI),HE染色观察肺组织病理学改变,计算两组大鼠肺系数(LI)、肺泡炎积分,免疫组化染色法检测Foxp3、TGF-β1蛋白表达情况。通过小动物肺功能仪检测肺功能,ELISA法测定细胞因子的变化,流式细胞术(FCM)测定Treg的表达。结果:与NC组相比,Model组大鼠E、AI、LI、1s内平均呼气流量(FEV1/FVC%)、肺泡炎积分、血清TNF-α、Th1/Th2、肺组织TGF-β1、CD4+ CD25- T细胞的表达水平明显升高,且两者差异有统计学意义(P<0.05或P<0.01);用力肺活量(FVC)、25%肺活量的最大呼气流量(FEF25)、50%肺活量的最大呼气流量(FEF50)、75%肺活量的最大呼气流量(FEF75)、最大呼气中期流量(MMF)、用力最大呼气流量(PEF)、肺动态顺应性(Cldyn)、血清IL-10、CD4+ Treg、CD4+ CD25- Treg、肺组织Foxp3蛋白表达水平显著降低(P<0.01)。Spearman相关分析结果显示,AA大鼠肺功能参数分别与E、AI、TNF-α、IL-10、Th1/Th2及CD4+ Treg、CD4+CD25+Treg、CD4+ CD25- T细胞、Foxp3、TGF-β1表达呈相关性,且相关有统计学意义(P<0.05或P<0.01)。结论:大鼠在致炎后对抗原刺激呈高敏反应状态,Th1/Th2状态失衡、CD4+ CD25- T细胞转化成CD4+ CD25+ Treg受阻,免疫调节功能紊乱,释放大量细胞因子和炎症介质,导致局部关节的病变和肺组织损害,从而发生AA肺功能降低。     

Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler.

BACKGROUND: Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma. OBJECTIVE: Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS. METHODS: During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1. RESULTS: Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages. CONCLUSIONS: Once-daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma.     

Nasal inflammation and personal exposure to fine particles PM2.5 in asthmatic children

BACKGROUND: Outdoor and indoor air pollutants are suspected to induce harmful effects on respiratory health, raising the question of their involvement in allergic asthma and rhinitis. OBJECTIVE: The potential effect of short-term personal exposure to particulate matter with a diameter of less than 2.5 microm (PM2.5) on nasal inflammation was examined in children living in the Paris area. METHODS: Forty-one children with allergic asthma and 44 healthy children participated in this study. They were monitored during 48 hours for their personal exposure to PM2.5. At the end of the measurement period, children underwent one nasal lavage. Nasal lavage fluid was investigated for cellular (neutrophils and eosinophils) and soluble (albumin, urea, elastase, alpha1-antitrypsin, IL-6, and IL-8) mediators. RESULTS: Pollutant concentrations did not differ between the 2 groups. In asthmatic subjects, but not in healthy children, personal PM2.5 levels were correlated to nasal percentage of eosinophils and to albumin, urea, and alpha1-antitrypsin concentrations after adjustment for confounders (age, sex, house dust mites, pollens, cat, environmental tobacco smoke through urinary cotinine, barometric pressure, and respiratory infection). CONCLUSION: The association observed with the percentage of eosinophils supports recent speculations on fine particle involvement in allergic phenotype overexpression. CLINICAL IMPLICATIONS: This study highlights the link between personal fine particle exposures and nasal inflammation in asthmatic allergic children living in urban areas. Because the view of united airways is still not completely understood, the question of pulmonary inflammation in such a situation deserves further investigation.     

Resource costs for asthma-related care among pediatric patients in managed care.

BACKGROUND: In 1998, the economic burden of asthma in the United States was estimated to be 12.7 billion dollars. Yet few studies have examined the relationship between the total costs of asthma-related care and measures of asthma morbidity. Understanding the relationship between total costs of asthma-related care and morbidity can assist in designing the most cost-effective asthma care strategies to improve patient outcomes and minimize total costs. OBJECTIVE: To investigate correlates of asthma costs for children with mild-to-moderate persistent asthma and, specifically, to characterize how closely the percentage of predicted forced expiratory volume in 1 second (FEV1) and symptom days were correlated with costs of illness. METHODS: A total of 638 parents and children with mild-to-moderate persistent asthma in 4 managed care delivery systems in 3 different US geographic regions were enrolled. Symptom burden and annual resource utilization were determined from reports of physician visits, hospitalizations, emergency department visits, medication use, and parental missed workdays. Spirometry was conducted on children who were 5 years and older. To characterize the relationship between symptom days and the percentage of predicted FEV1 with costs, we specified a multivariate regression model. RESULTS: The median total annual asthma-related cost for the group was 564 dollars (interquartile range [IQR], 131 dollars-1602 dollars). Indirect costs represented 54.6% of total costs. Medicines accounted for 52.6% of direct costs. The mean percentage of predicted FEV1 was 101.6% (range, 39.3%-183.5%; IQR, 91.6%-111.3%), with 91.4% of patients with a percentage of predicted FEV1 of more than 80%. Based on multivariate modeling, increasing asthma severity, use of peak expiratory flow rate meters, younger age, low-income status and nonwhite race, and longer duration of asthma were significantly associated with increasing cost. Symptom days (P < 0.001) predicted annual costs better than percentage of predicted FEV1 (P < 0.16) in this group of children. CONCLUSIONS: For the large number of children with mild-to-moderate persistent asthma and normal or near-normal lung function, symptom days are predictive of health care costs. For these insured children receiving care from 3 large managed care providers, low-income status and nonwhite race were the strongest correlates for increased asthma-related costs.     

Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma

BACKGROUND: Inhaled corticosteroids (ICS) are recommended therapy for persistent asthma, although side effects can limit appropriate use. Ciclesonide, a novel ICS, is activated in the lung, thereby reducing systemic activity and side effects. This 12-week, double-blind, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma. METHODS: After a 2-week baseline period in which current ICS treatment was continued, 329 patients were randomized to receive ciclesonide 160 microg (n = 107) or 640 microg (n = 112) (ex-actuator doses, equivalent to 200 and 800 microg ex-valve, respectively), or placebo (n = 110) once daily in the morning. Efficacy was monitored by asthma symptom scores, rescue medication use, morning and evening peak expiratory flow (PEF) measurements, spirometry, and probability of study completion without experiencing lack of efficacy. RESULTS: Morning PEF remained stable with either ciclesonide dose but decreased with placebo; the differences were significant (P < 0.0001) for both ciclesonide doses vs placebo. The forced expiratory volume in 1 s and forced vital capacity decreased significantly with placebo (P < 0.005), but were unchanged with ciclesonide. Lack of efficacy was significantly greater for patients switched to placebo (63%) than it was for those treated with ciclesonide 160 microg (30%) (P < 0.0001 vs placebo) or ciclesonide 640 microg (31%) (P < 0.0001 vs placebo). There were no significant differences between the two tested doses of ciclesonide with respect to efficacy and safety. Serum and 24-h urine cortisol were unaffected by ciclesonide treatment. Both doses of ciclesonide were well tolerated with no cases of oral candidiasis. CONCLUSION: Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma.     

Effects of ambient air pollution on symptom severity and medication use in children with asthma.

BACKGROUND: Exposure to air pollutants has been investigated as a possible cause of asthma attacks in children. OBJECTIVE: To investigate the short-term effects of air pollutants on a panel of 133 children with asthma who enrolled in the Childhood Asthma Management Program. METHODS: During screening, the children completed daily diary cards for an average of 58 days to indicate their medication use and asthma severity. We used ordinal logistic regression to compare the odds of a more serious relative to a less serious asthma attack, and we used a Poisson model to analyze medication use. In both analyses we accommodate dependence in the data and different periods of observation for study subjects. RESULTS: Our results indicate that a 10-microg/m3 increase in particulate matter less than or equal to 2.5 microm (PM2.5) lagged 1 day was associated with a 1.20 times increased odds of having a more serious asthma attack [95% confidence interval (CI), 1.05 to 1.37] and a 1.08-fold increase in medication use (95% CI, 1.01 to 1.15). A 10-microg/m3 increase in particulate matter less than or equal to 10 microm (PM10) increased the odds of a more serious asthma attack (odds ratio = 1.12; 95% CI, 1.04 to 1.22) and also increased medication use (relative risk = 1.05; 95% CI, 1.00 to 1.09). CONCLUSIONS: Increases in PM2.5 and PM10 are significantly associated with an increased risk of more severe asthma attacks and medication use in Seattle area children with asthma. We also found associations with carbon monoxide, but we believe that carbon monoxide is a marker for exposure to combustion byproducts.     

Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of moderate persistent asthma using fluticasone propionate as an active comparator.

BACKGROUND: Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability. OBJECTIVES: To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research Triangle Park, NC) was used as an active control. DESIGN: A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial. SETTING: Sixty centers in 20 countries. PATIENTS: Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment. INTERVENTIONS: Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 microg twice daily) and one of FP (250 microg twice daily >12 weeks). RESULTS: FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total daily 800-microg dose of MF-DPI conferred no significant additional benefit >400 microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively. CONCLUSIONS: A total daily dose of 400 microg of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 microg of FP Diskhaler.