Oral β2-Agonist Use by Preschool Children with Asthma in East and Central Harlem,New York

Although studies have documented underuse of controller medications and overuse of short-acting inhaled β₂-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral β₂-agonist use in pediatric practice has not been studied since inhaled short-acting β₂-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physician's diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks—only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral β₂-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting β₂-agonist. Use of oral β₂-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral β₂-agonist for treatment of children in a low-income community with high prevalence of asthma.     

Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma

The objective of this study was to compare the efficacy and safety of the second controller medications (long-acting beta2-agonist, leukotriene receptor antagonist and sustained-release theophylline) used in addition to inhaler corticosteroid treatment in moderate persistent asthma. A total of 64 patients with asthma, in the moderate persistent asthma category, were divided into three groups. Patients, all of whom were concurrently using inhaled corticosteroid (Budesonide 400 microg twice daily), were treated for 3 months with either inhaled formoterol 9 microg twice daily (first group), oral zafirlukast 20 mg twice daily (second group), or sustained-release theophylline 400 mg once daily (third group). All of the patients were subjected to assessments on the subject of peak expiratory flow (PEF) variability, forced expiratory volume in 1 sec (FEV1), asthma symptom scores (daytime and night-time), supplemental terbutalin use, asthma exacerbations and adverse events. Over the 3-month treatment period. In all of the three groups, significant improvements were recorded in the lung function, asthma symptom scores and supplemental terbutalin use criteria, as a result oftreatments applied. Formoterol treatment resulted in significantly greater and earlier improvements compared with the other two groups in several criteria: PEF variability (17.9 +/- 2.5; 21.9 +/- 3.2; 23.7 +/- 3.3; P < 0.001); asthma symptom score (daytime) (1.6 +/- 0.5; 1 +/- 0.5; 2.0 +/- 0,5; P < 0.05); asthma symptom score (night-time) (1.2 +/- 0.4; 2.2 +/- 0.5; 16 +/- 0.6; P < 0001); and supplement alter butalin use (1.2 +/- 0.3; 1.8 +/- 0.5; 1.7 +/- 0.5; P < 0.05). However, at the end of the treatment, in all of the three groups studied, improvements were attained in overall asthma control and there was no statistical difference among the groups. Although there were no side effects which required the discontinuation of the treatment, it was observed that the maximum side effect was in the second group (20%, 31.6% and 20%, respectively). In conclusion, in patients who still have symptoms on treatment with inhaled corticosteroids, the addition of a long-acting beta2-agonist, leukotriene antagonists or sustained-release theophylline to the treatment is a logical approach, and, in addition to inhaled corticosteroids, any one of these second controller medications may be chosen in patients with moderate asthma.     

妊娠期支气管哮喘治疗进展

临床研究已证明妊娠期重度及控制不佳的支气管哮喘(简称哮喘)与母亲及胎儿严重并发症相关.对于妊娠期哮喘患者,接受药物治疗比存在哮喘症状和哮喘发作更安全.所有程度的持续妊娠哮喘患者都应当应用吸入糖皮质激素作为控制药物,首选布地奈德.白三烯受体拮抗剂可以缓解支气管痉挛、减轻症状、改善肺功能.长效β2受体激动剂对于正在应用吸入糖皮质激素的患者可作为首选的添加药物.吸入短效β2受体激动剂可以作为缓解药物.对于正在接受维持量或接近维持量治疗,无不良反应、临床疗效好的妊娠哮喘患者可以继续进行变应原免疫治疗.     

Effects of on-demand beta2-agonist inhalation in moderate-to-severe asthma. A randomized controlled trial

BACKGROUND: The appropriate use of short-acting beta2-agonist inhalation in asthma has been the subject of controversy in recent years. Limited information is available for the group of moderate to severe asthmatics with high intake of bronchodilator inhalants and continuous anti-inflammatory protection. OBJECTIVE: To investigate the effects of beta2-agonist reduction in marked asthma treated with multiple asthma medications. DESIGN: Randomized, controlled single-blind, cross-over trial. SETTING: Outpatient clinic at a university medical centre. SUBJECTS: A total of 80 adult patients with moderate-to-severe asthma. INTERVENTIONS: In a 1-year study patients were assigned to on-demand vs. regular beta2-agonist inhalation treatment. MAIN OUTCOME MEASURES: Asthmatic episodes (primary outcome), symptoms, peak expiratory flow rates (PEF) and drug use were recorded daily. Bronchodilator and airway responsiveness, lung function indices and quality of life were assessed during five clinic visits. Also, practicability of beta2-agonist tapering in multimedicated asthmatics was analysed. RESULTS: More than 80% of moderate-to-severe asthmatics were able to reduce their beta2-agonist intake by >/=50%. Puffs per day of active therapy decreased from 7.9 in regular to 3.3 in on-demand treated patients (P = 0.0001). The type of beta2-agonist used (salbutamol/fenoterol) had no significant impact on the study findings. Almost all parameters of control of asthma improved during the on-demand treatment period. CONCLUSION: On-demand inhalation of short-acting beta2-agonists in moderate-to-severe asthma is safe, and even in severe asthma a reduction from regular to on-demand beta2-agonist inhalation is possible, with improved asthma control.     

Asthma medication use among adults with current asthma by work-related asthma status,Asthma Call-back Survey, 29 states, 2012–2013

Objective: Asthma severity is defined as the intensity of treatment required to achieve good control of asthma symptoms. Studies have shown that work-related asthma (WRA) can be associated with poorer asthma control and more severe symptoms than non-WRA. Associations between asthma medications and WRA status were assessed using data from the 2012–2013 Asthma Call-back Survey among ever-employed adults (≥18 years) with current asthma from 29 states. Methods: Persons with WRA had been told by a physician that their asthma was work-related. Persons with possible WRA had asthma caused or made worse by their current or previous job, but did not have physician-diagnosed WRA. Asthma medications were classified as controller (i.e., long-acting β-agonist, inhaled corticosteroid, oral corticosteroid, cromolyn/nedocromil, leukotriene pathway inhibitor, methylxanthine, anti-cholinergics) and rescue (i.e., short-acting β-agonist). Demographic and clinical characteristics were examined. Associations between asthma medications and WRA status were assessed using a multivariate logistic regression to calculate adjusted prevalence ratios (PRs). Results: Among an estimated 15 million ever-employed adults with current asthma, 14.7% had WRA and an additional 40.4% had possible WRA. Compared with adults with non-WRA, those with WRA were more likely to have taken anti-cholinergics (PR = 1.80), leukotriene pathway inhibitor (PR = 1.59), and methylxanthine (PR = 4.76), and those with possible WRA were more likely to have taken methylxanthine (PR = 2.85). Conclusions: Results provide additional evidence of a higher proportion of severe asthma among adults with WRA compared to non-WRA. To achieve optimal asthma control, adults with WRA may require additional intervention, such as environmental controls or removal from the workplace exposure.     

Misunderstanding of Asthma Controller Medications: Association with Nonadherence

Objective. Nonadherence to regular inhaled anti-inflammatory medication use is a frequent contributor to poor control of persistent asthma and may result from misunderstanding of the preventive role of such medications. This study's aims are to 1) test the hypothesis that misunderstanding is associated with decreased adherence to its daily use and 2) identify factors associated with increased risk of misunderstanding. Study Design. A sample of parents of children with asthma insured by Medicaid and enrolled in managed care programs in Northern California, Washington, and Massachusetts were interviewed by telephone. This analysis focused on the subset that reported having an inhaled anti-inflammatory medication and whose medication use and symptom frequency in the 2 weeks before the interview suggested persistent asthma. Misunderstanding of the role of inhaled anti-inflammatory medication was defined as identifying it as being for treatment of symptoms after they begin and not for prevention of symptoms before they start. Results. A total of 1663 parents of children with asthma (63% response rate) were interviewed. Of those, 571 subjects (34%) reported use of an inhaled anti-inflammatory medication and met our criteria for persistent asthma. Among those with persistent asthma, 23% (131 parents) misunderstood the role of their child's inhaled anti-inflammatory. Misunderstanding of inhaled anti-inflammatory medication was associated with decreased adherence to its daily use (odds ratio [OR] 0.18, 95% confidence interval [CI], 0.11-0.29). The risk for misunderstanding was lower if the patient had seen a specialist (OR 0.42, 95% CI, 0.24-0.75) or had graduated high school (OR = 0.54, 95% CI, 0.34-0.84). Conclusion. Misunderstanding of the role of inhaled anti-inflammatory medication is associated with reduced adherence to its daily use.     

Misunderstanding of Asthma Controller Medications: Association with Nonadherence

Objective.?Nonadherence to regular inhaled anti-inflammatory medication use is a frequent contributor to poor control of persistent asthma and may result from misunderstanding of the preventive role of such medications. This study's aims are to 1) test the hypothesis that misunderstanding is associated with decreased adherence to its daily use and 2) identify factors associated with increased risk of misunderstanding. Study Design.?A sample of parents of children with asthma insured by Medicaid and enrolled in managed care programs in Northern California, Washington, and Massachusetts were interviewed by telephone. This analysis focused on the subset that reported having an inhaled anti-inflammatory medication and whose medication use and symptom frequency in the 2 weeks before the interview suggested persistent asthma. Misunderstanding of the role of inhaled anti-inflammatory medication was defined as identifying it as being for treatment of symptoms after they begin and not for prevention of symptoms before they start. Results.?A total of 1663 parents of children with asthma (63% response rate) were interviewed. Of those, 571 subjects (34%) reported use of an inhaled anti-inflammatory medication and met our criteria for persistent asthma. Among those with persistent asthma, 23% (131 parents) misunderstood the role of their child's inhaled anti-inflammatory. Misunderstanding of inhaled anti-inflammatory medication was associated with decreased adherence to its daily use (odds ratio [OR] 0.18, 95% confidence interval [CI], 0.11–0.29). The risk for misunderstanding was lower if the patient had seen a specialist (OR 0.42, 95% CI, 0.24–0.75) or had graduated high school (OR = 0.54, 95% CI, 0.34–0.84). Conclusion.?Misunderstanding of the role of inhaled anti-inflammatory medication is associated with reduced adherence to its daily use.     

Comparative efficacy of once-daily therapy with inhaled corticosteroid, leukotriene antagonist or sustained-release theophylline in patients with mild persistent 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.     

Spotlight on montelukast in asthma in children 2 to 14 years of age

Montelukast is a cysteinyl leukotriene receptor antagonist which is used as a preventive treatment for persistent asthma in patients > or =2 years of age. In children aged 6 to 14 years montelukast (5 mg/day) treatment resulted in a significant increase in FEV1 (forced expiratory volume in 1 second, primary clinical outcome) during an 8-week randomized, double-blind trial. Moreover, significant improvements were observed for a range of secondary endpoints assessing symptoms, exacerbation rates, beta-agonist usage and quality of life. Concomitant administration of montelukast (5 mg/day) and inhaled budesonide (200 microg twice daily) resulted in a trend towards an increase in FEV1 (p=0.06, primary endpoint) and a statistically significant reduction in both as-needed beta2-agonist usage and the percentage of days with asthma exacerbations compared with budesonide plus placebo. No significant differences were observed in asthma-related quality of life between the two groups. During clinical trials both improvements in lung function and reductions in as-needed beta2-agonist usage were generally observed within 1 day after initiation of therapy in children 2 to 14 years of age with persistent asthma. Data from a randomized, nonblind trial in 6- to 11-year-old children and a 6-month extension to this trial suggest that both compliance to therapy and patient satisfaction are greater for montelukast than for either inhaled cromolyn sodium (sodium cromoglycate) or inhaled beclomethasone. In addition, patients and parents preferred oral montelukast over cromolyn sodium. In 2- to 5-year-old children with persistent asthma, montelukast (4 mg/day) treatment resulted in significant improvements in a range of outcomes, such as as-needed beta2-agonist usage, symptom scores and percentage of days with asthma symptoms, as assessed during a randomized, double-blind trial primarily designed to assess tolerability. Data from small randomized, double-blind trials suggest that montelukast reduces exercise-induced bronchoconstriction in 6- to 14-year-old children. Montelukast is generally well tolerated. The frequency of adverse events in montelukast-treated children of all ages was comparable to that in patients receiving placebo. CONCLUSION: Oral montelukast has shown efficacy as a preventive treatment for asthma during clinical trials in children aged 2 to 14 years. The drug offers benefits over more standard therapies such as inhaled cromolyn sodium and nedocromil in terms of compliance and convenience. In addition, the drug offers significant benefits when added to inhaled corticosteroids (according to secondary endpoints). Montelukast offers an effective, well tolerated and convenient treatment option for children with asthma.     

Role of leukotriene receptor antagonists in pediatric asthma

During the past decade, the inflammatory mechanisms that result in the clinical syndrome we call asthma have been emphasized in research, publications, and the various asthma management guidelines. This information clearly emphasizes the treatment of asthma with maintenance controller therapies early after the onset of symptoms in all but the very mildest of patients. Until the advent of the leukotriene receptor antagonists, nearly all of these maintenance therapies needed to be administered by inhalation through a variety of devices and spacers. Inhalation of medication was necessary to either increase the amount of drug reaching the airways or to increase the therapeutic index of drugs such as corticosteroids. Even under the best circumstances, this route of administration is difficult and expensive for many parents whose children have asthma. Now that oral controller therapies (leukotriene receptor antagonists) are available for children, their role in clinical practice needs to be examined. The latest asthma management guidelines classify asthma into four groups of severity, and base treatment recommendations on the intensity of symptoms, need for rescue medications, and pulmonary function as measured by peak expiratory flow and forced expiratory volume in 1 sec (FEV(1)). The categories of mild intermittent, mild persistent, moderate persistent, and severe asthma in children will be addressed in this presentation by reviewing the available data on the use of the leukotriene receptor antagonist montelukast in children. Mild intermittent asthma can be typified by exercise-induced asthma, a common pediatric condition. In this often troublesome condition, montelukast demonstrated effectiveness at the end of a once a day dose by blocking the effects of this naturally occurring challenge. Drug regulatory approval of a new drug also includes patients with more regular symptoms who are usually classified as having persistent or moderate asthma. In these montelukast pediatric studies, approximately 40% of patients were already taking inhaled corticosteroids. Patients had improvements in FEV(1), symptoms, and rescue medication use, clearly showing an effect with once a day dosing. Pediatric data in severe asthma patients are more limited, but in such patients a therapeutic trial of montelukast would seem preferable to using systemic corticosteroids or increasing inhaled steroids to a level where adverse effects have an increasing potential of occurring. Montelukast has been available in the United States since March 1998 and has received excellent acceptance by physicians, parents, and patients. The 5-mg chewable tablet administered once a day in the evening in children aged 6-14 years apparently fills a previously unmet need in the treatment of pediatric asthma.     

Geographic variation in inhaled corticosteroid use for children with persistent asthma in Medicaid

Objective: Geographic variation in the rates of inhaled corticosteroid (ICS) use for children with persistent asthma in Medicaid has been reported, but the source of this variation is unknown. The objective of this study was to quantify the geographic variation in ICS use for children with persistent asthma in Medicaid that remains after adjusting for the characteristics of children in an area. Methods: Data from the 2005–2007 Medicaid Analytic eXtract files were used. Frequent fills of short-acting beta₂-agonist (SABA) were used to identify children 5–18 years of age with persistent asthma across the United States. A child was considered to have used an ICS if the child initially filled an ICS following frequent SABA use. Areas were determined using published methods, and the unadjusted ICS rate and the area treatment ratio for ICS, which adjusted for demographic and clinical characteristics, were calculated for each area. Results: Of 15,917 children, 13% used an ICS. The median unadjusted ICS rate for all areas was 10% but ranged from 0% to 64%. ICS use was less than expected for more than half of the areas based on the characteristics of the children in the area, but use was nearly five times what was expected in some areas. Areas with higher than expected ICS use were found contiguous to areas with lower than expected use. Conclusions: Geographic variation in ICS not attributable to the demographic and clinical characteristics of the children in an area exists and could prove useful in the struggle to reduce asthma exacerbation rates.     

Combination Therapy: Appropriate for Everyone?

The severity of asthma often varies throughout the course of the disease. At times the symptoms and underlying inflammation that are characteristic of asthma can worsen. Thus during an episode of viral-induced asthma or during a seasonal increase in asthma severity, a patient may be directed to increase his or her dosage of asthma controllers (i.e., inhaled corticosteroid) or add a long-acting bronchodilator (or other controller medications such as antileukotrienes) to manage symptoms, as recommended in guidelines published by the National Institutes of Health (NIH). Similarly, when symptoms are stable, decreasing dosages or discontinuing certain medications may be appropriate. The recent introduction of a combination product, of a long-acting bronchodilator formulated in the same dry powder device with an inhaled corticosteroid raises new challenges for the step care approach to asthma management recommended by the NIH in 1997. Although unquestionably more convenient for the patient, a combination formulation has the potential to decrease the flexibility required to successfully manage asthma over long periods. In addition, controversy exists regarding long-acting beta-agonists alone because their regular use may mask inflammation in the lung and decrease responsiveness to the bronchodilating effects of rescue medications (i.e., short-acting beta-agonists). The purpose of this article is to help physicians make informed therapeutic decisions for their patients with asthma. It focuses on the advantages and potential disadvantages of using combination products, which contain both an inhaled corticosteroid and a long-acting beta-agonist in the context of the NIH step care approach. Recent publications outlining the use of other add-on controller medications are also discussed.