Once-daily inhaled corticosteroids in children with asthma: nebulisation

Current guidelines on the management of childhood asthma have emphasised the important preventive role of inhaled corticosteroids, which should be used at the lowest possible doses that are compatible with good disease control. However, some children do not respond to inhaled corticosteroids, the most common reasons for which are inability to use conventional hand-held inhalers (plus spacers and face masks) effectively or lack of cooperation with them, particularly among infants and young children. In these patients, nebulisers have proved effective in administering corticosteroids, and this form of delivery is often preferred by both the children and their parents, despite their longer administration times (commonly around 10 minutes). Compliance with these devices may therefore be better than with a conventional pressurised metered-dose inhaler plus spacer and face mask. Recent studies with nebulised budesonide have demonstrated that once-daily administration is as effective in maintaining control of asthma symptoms in children as the usual twice-daily administration. In children with moderately severe persistent asthma, the improvement provided by once-daily nebulised doses of 1.0 mg budesonide has been found to be equivalent to that with twice-daily doses of 0.25 or 0.5 mg, indicating that once-daily therapy is an effective option that can be considered in many patients. In view of the time-consuming nature of nebuliser administration, reduction of the frequency of corticosteroid administration from twice to once daily may be useful in simplifying the treatment programme and improving compliance with it. This may be beneficial in reducing under-utilisation of inhaled corticosteroids in children with asthma and improving long term control of the disease.     

Once-daily inhaled corticosteroids in children with asthma: dry powder inhalers

The cornerstone of pharmacological management of asthma in childhood is inhaled corticosteroids. These drugs are intended for long term treatment and, consequently, compliance is a major issue. Once-daily administration of maintenance medication would simplify treatment and it is likely that it would lead to better compliance. Moreover, the excellent safety profile of inhaled corticosteroid treatment tailored to disease severity may, theoretically, be further improved with once-daily administration. Studies comparing inhaled corticosteroids given once or twice daily to patients with asthma indicate that unstable asthma is best treated with at least 2 daily doses. On the other hand, it has been demonstrated that, if the asthma is stabilised, most children can be treated with inhaled corticosteroids once daily without loss of efficacy. Thus, the data suggest that newly diagnosed asthma, or asthma after deterioration, should first be reliably controlled with inhaled corticosteroids divided into at least 2 daily doses. Once-daily maintenance treatment should then be tried with the aim of improving compliance and quality of life. A dry powder inhalation device is probably the best choice for children from the age of 5 years.     

Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma

AIMS: Inhalers combining long acting beta2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma. METHODS: Twenty-nine patients with mean FEV1 (+/- SEM) of 78 +/- 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 microg + formoterol 12 microg (BUD + FM) combination twice daily followed by 1 week of BUD 400 microg alone twice daily, or 4 weeks of fluticasone propionate 250 microg + salmeterol 50 microg (FP + SM) combination twice daily followed by 1 week of FP 250 microg alone twice daily. Measurements were made at baseline and following each randomized treatment. RESULTS: FEV1 increase from pretreatment baseline as mean (+/- SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 +/- 1%) vs BUD (2 +/- 1%), and for FP + SM (8 +/- 1%) vs FP (2 +/- 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 +/- 1%), BUD (24 +/- 1%), FP + SM (23 +/- 1%) and FP (23 +/- 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 +/- 35.5) vs BUD (281.1 +/- 52.8), and with FP + SM (553.1 +/- 34.1) vs FP (368.3 +/- 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments. CONCLUSIONS: Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.     

探讨维生素D水平在哮喘儿童吸入皮质激素治疗中的意义

目的 探讨维生素D水平在哮喘儿童吸入皮质激素治疗中的意义.方法 选择100例哮喘患儿进行研究.所有患儿均进行血清维生素D水平的检测,根据维生素D水平将其分为维生素D缺乏组(维生素D水平＜20 μg·L-1)共10例、维生素D不足组(维生素D水平在20～30 μg·L-1之间)共25例以及维生素D充足组(维生素D水平＞30μg·L-1)共65例.所有患儿均给予布地奈德气雾剂的吸入,每次200μg,每天2次.检测各组患儿治疗前和治疗8个月后进行一秒用力呼气容积(FEV1)以及用药后FEV1的改善率.结果 维生素D缺乏组、不足组和充足组用药前FEV1和用药8个月后FEV1改善率整体比较差异有统计学意义(P＜0.05);多重比较得出维生素D不足组与充足组FEV1之间差异无统计学意义(P＞0.05),而缺乏组则与充足组患儿相比差异有统计学意义(P＜0.05).结论 充足的维生素D水平对于哮喘患儿吸入激素治疗提升肺功能起到重要的作用.检测维生素D水平以及维生素D的补充可作为临床上吸入糖皮质激素治疗患儿的参考指标.     

顺尔宁联合糖皮质激素吸入和单纯糖皮质激素吸入治疗儿童哮喘的效果对比

目的探讨顺尔宁联合糖皮质激素吸入和单纯糖皮质激素吸入治疗儿童哮喘的临床效果。方法将2014年2月~2016年12月在我院接受治疗的60例儿童哮喘患者作为本次研究对象,将其按照随机数字法平均分为两组,30例采用单纯糖皮质激素吸入治疗(对照组),30例给予顺尔宁联合糖皮质激素吸入治疗(研究组)。将两组患者临床疗效、湿啰音消失时间、哮鸣音消失时间、咳嗽消失时间、住院时间、FEV1、PEF、Eos指标及不良反应发生情况进行比较。结果研究组临床总有效率为86.66%,对照组临床总有效率为63.33%,研究组患者临床总有效率显著高于对照组(P<0.05)。研究组患者湿啰音消失时间、哮鸣音消失时间、咳嗽消失时间及住院时间均显著短于对照组(P<0.05)。干预前两组患者FEV1、PEF、Eos指标比较差异无统计学意义(P>0.05),干预后两组患者FEV1、PEF指标均显著升高,Eos指标均显著降低(P<0.05),且研究组较对照组改善显著(P<0.05)。研究组不良反应发生率为6.66%,对照组不良反应发生率为10.00%。两组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论在儿童哮喘患者治疗中选择顺尔宁联合糖皮质激素吸入治疗可显著缩短患者临床症状消失时间及住院时间,提高治疗效果,降低患者经济负担,改善患者肺功能,且不良反应低安全有效,值得在临床上推广使用。     

Underuse of inhaled corticosteroids in adults with asthma

Despite strong evidence that inhaled corticosteroids are beneficial in treating asthma, a number of small studies suggest a use rate of only 34-56%. The primary objective of this study was to determine patterns of prescribing inhaled corticosteroids for high-risk patients with asthma. Secondary objectives were to assess patterns of practice with respect to other agents prescribed before and at hospital discharge, and to determine if an emergency room asthma care map at one of the study hospitals was being followed. We retrospectively reviewed charts of 1022 patients with an acute attack of asthma treated in the emergency rooms of the Royal Alexandra Hospital and University of Alberta Hospital from January 1, 1996, to March 31, 1997. A forward stepwise logistic regression analysis was performed with the dependent variable defined as whether or not the patient was using an inhaled or oral corticosteroid during the index visit, and the independent variable being all major demographic variables. Inhaled corticosteroids were prescribed for 460 patients (52.0%) at the index visit. Overall, antiinflammatory drugs were prescribed for 548 patients (62.1%). An asthma care map was followed for 107 (16.8%) patients treated at the Royal Alexandra Hospital at the index visit. Logistic regression analysis showed that women and patients with more than one emergency room visit most likely were to be using inhaled or inhaled plus oral corticosteroids at the index visit. Documentation of drug therapy at discharge was poor for 42% of patients; therefore, analysis of practice patterns in this group was not attempted. This study shows that inhaled corticosteroids were prescribed for only about one-half of patients with an acute asthma attack. Given this low use by high-risk patients, the need for programs designed to improve asthma therapy is evident.     

The use of inhaled corticosteroids in childhood asthma

In the UK around 1 in 5 children will have been diagnosed as having asthma at some stage before they reach 15 years old. The use of inhaled corticosteroids has done much to reduce morbidity in these children and current British Guidelines recommend the use of inhaled corticosteroids in all but mild childhood asthma. However, there are concerns about the long-term safety of such treatment in growing children, and the benefits and risks of their use need careful evaluation. In this article we review the place of inhaled corticosteroids in childhood asthma.     

孟鲁司特纳治疗小儿轻、中度持续性哮喘分析

目的研究孟鲁司特纳治疗小儿轻、中度持续性哮喘的效果。方法根据双盲随机分组原则将2016年8月～2017年7月本院接收的轻、中度持续性哮喘患儿104例分为对照组(常规对症治疗)和观察组(加用孟鲁司特纳治疗),每组52例。将两组的临床效果、实验室指标、肺功能指标、不良反应发生情况、复发情况进行比对。结果观察组轻、中度持续性哮喘患儿的临床总有效率、治疗后的IL-12、FEV1高于对照组(P 0.05),治疗后的IL-4、Ig E水平以及复发率低于对照组(P 0.05);治疗后的肺功能指标明显优于治疗前(P 0.05),两组均无明显不良反应发生。结论孟鲁司特纳应用于小儿轻、中度持续性哮喘治疗中安全有效。     

孟鲁斯特治疗小儿轻中度持续哮喘的临床疗效

目的探讨孟鲁斯特治疗小儿轻中度持续性哮喘的临床效果。方法选取2012年5月～2013年7月收治的轻中度持续哮喘患儿98例,随机分为两组,对照组46例患儿给予布地奈德气雾剂进行常规治疗,观察组52例在对照组常规治疗的基础上,再给予口服孟鲁斯特钠片进行治疗。比较两组患儿的治疗效果。结果观察组患儿的临床总有效率为94．2％,显著高于对照组的76．1％,差异有统计学意义（P〈0．05）;经治疗跟踪观察,对照组患儿嗜酸性粒细胞及血清IgE水平均显著高于观察组,差异具有统计学意义（P〈0．05）。结论孟鲁司特在治疗小儿轻中度持续性哮喘时效果显著。     

Smoking influences response to inhaled corticosteroids in patients with asthma: a meta-analysis

Abstract

Objective:

To determine the effects of smoking on efficacy of inhaled corticosteroids in asthmatics.     

Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma

AIMS: To compare the pharmacokinetic profiles of beclometasone, budesonide, fluticasone and mometasone following inhalation in patients with asthma, and explore the relationship between lung function and plasma drug concentrations. METHODS: Thirty subjects with asthma and a forced expiratory volume in 1 s (FEV(1)) ranging from 36 to 138% predicted, inhaled 800 microg beclometasone, budesonide and mometasone and 1000 microg fluticasone in random order. Plasma drug concentrations were measured over 8 h and the relationship between the area under the plasma concentration-time curve (AUC(0-8)) and lung function was modelled using linear regression. Estimated AUC(0-8) values at 50 and 100% predicted FEV(1) were compared for each drug. RESULTS: Pharmacokinetic profiles differed markedly between the drugs. Correlation coefficients for the relation between FEV(1)% predicted and AUC(0-8) values for beclometasone, budesonide, fluticasone and mometasone were 0.37 (P = 0.05), 0.33 (P = 0.08), 0.25 (P = 0.2) and 0.52 (P = 0.004), respectively, and estimated AUC(0-8) values were 1.3 [95% confidence interval (CI) 1.0, 1.8], 1.3 (95% CI 1.0, 1.8), 1.4 (95% CI 0.9, 2.2) and 2.2 (95% CI 1.3, 3.5) times higher for the four drugs, respectively, at 100 compared with 50% predicted FEV(1.) CONCLUSION: The higher plasma concentrations of inhaled corticosteroids in patients with a higher FEV(1)% predicted suggests that, for any given dose, these patients will be at greater risk of developing adverse systemic effects with long-term use.     

Safety of the newer inhaled corticosteroids in childhood asthma

Inhaled corticosteroids (ICS) remain a vital part of the management of persistent asthma, but concerns have been raised about their potential adverse effects in children. This review examines the safety data on three new ICS - fluticasone propionate, mometasone, and extrafine beclomethasone in hydrofluoroalkane (HFA-134a) propellant (QVAR The use of tradenames is for product identification purposes only and does not imply endorsement. formulation) in relation to the older corticosteroids. Topical adverse effects such as thrush and dysphonia are rare, but dental erosion is a possibility with powder forms of ICS because of their low pH. Thus, it is important to stress mouth rinsing after administration and maintaining good dental hygiene to minimize this risk. Biochemical adrenal suppression can be readily demonstrated, particularly with high doses of all ICS. The clinical relevance of this was uncertain in the past, but there have now been >50 reported cases of acute adrenal crises in children receiving ICS, most of whom were on fluticasone propionate. In order to minimize the risk of symptomatic adrenal suppression, it is important to back-titrate the ICS dose and alert families of children receiving high-dose ICS of this potential adverse effect. A pediatric endocrine opinion should be sought if adrenal suppression is suspected. The older ICS cause temporary slowing of growth velocity, but the limited data available do not show any significant compromise of final adult height. The effect on growth of fluticasone propionate may not be as great as with the older ICS, but the studies have been short term and only used low doses of fluticasone propionate. There have been case reports of growth suppression in children receiving high doses of fluticasone propionate. The limited studies performed on the effect of ICS on bone mineral density in children did not show any adverse effects, but there may be an increased risk of fractures. Hydrofluoroalkane beclomethasone (QVAR) is essentially the same drug as chlorofluorocarbon beclomethasone, but with double the lung deposition owing to the smaller particle size. Thus, it could be expected that any adverse effects seen with chlorofluorocarbon beclomethasone would be the same with hydrofluoroalkane beclomethasone. However, some of the published data, particularly in adults, suggest that hydrofluoroalkane beclomethasone may be less systemically active than chlorofluorocarbon beclomethasone, even at equipotent doses. As yet, there are no long-term data on mometasone, but initial studies in adults suggest there may be less suppression of the hypothalamic-pituitary-adrenal axis, although further studies are required, particularly in children.ICS will remain a cornerstone in the management of persistent pediatric asthma, provided that the diagnosis of asthma is secure. It is very important to use ICS appropriately and to ensure the lowest possible doses are used to achieve symptom control, thus minimizing the risk of serious adverse effects.     

Daily versus intermittent corticosteroids for the treatment of mild persistent asthma

Asthma is a chronic disease of the airways in which inflammation causes bronchial hyper-reactivity and attacks of wheezing, dyspnea and chest tightness that are triggered by various agents. It requires both acute treatment of the paroxistical respiratory symptoms with reliever medications and maintenance treatment, which is aimed at achieving an optimal disease control and consists of controller medications with regimens and dosages that are tailored according to disease severity. Inhaled steroids represent the main controller medication and are recommended to be given even in mild asthma on a daily basis in order to improve lung function, reduce asthma exacerbations and symptoms, and improve the quality of life. Intermittent regimens could also be used and the currently discussed study compares these two regimens in terms of clinical efficacy.     

The use of inhaled corticosteroids in adults with asthma

Inhaled corticosteroids have now been used for the treatment of asthma for over 25 years. They have largely replaced oral corticosteroids for the prevention of asthma symptoms and asthma attacks, and for most patients they have become the first line of preventive drug therapy. We recently discussed the role of inhaled corticosteroids in the management of childhood asthma. Here, we review their place in the management of adults with asthma. A forthcoming article will review the various types of inhaler now available for delivering drugs for asthma.     

赛庚啶加二氧丙嗪辅助治疗轻中度支气管哮喘的疗效观察

目的探讨分析赛庚啶加二氧丙嗪辅助治疗轻中度支气管哮喘的疗效。方法将2009年6月～2011年6月间在笔者所在医院进行治疗的84例轻中度支气管哮喘患者,按治疗方法分为治疗和对照组,每组42例。治疗组在对照组治疗基础上加服赛庚啶和盐酸二氧丙嗪。治疗7d后,对两组患者的治疗效果进行观察。结果经过7d的治疗后,治疗组患者总有效率为92.86%,显著高于对照组的73.81%(P<0.05)。结论在吸入普米克都保及支气管舒张治疗的基础上,用赛庚啶和盐酸二氧丙嗪辅助治疗轻中度支气管哮喘具有良好疗效。     

Once-daily lisinopril compared with twice-daily captopril in the treatment of mild to moderate hypertension: assessment of office and ambulatory blood pressures

This multicenter, double-blind, parallel-group study compared the antihypertensive effects of two angiotensin-converting enzyme inhibitors, lisinopril and captopril, in 70 patients (35 lisinopril, 35 captopril) with mild-to-moderate essential hypertension. Doses of 10, 20, and 40 mg once-daily lisinopril or 25, 50, and 100 mg bid captopril were increased at biweekly intervals until patients responded to treatment, as defined by a decrease in office diastolic pressure to less than 90 mm Hg or at least a 10 mm Hg decrease from baseline. Patients who responded to a 2-week titration dose remained at that dose for another 2 weeks. Blood pressure assessments were made using both office and ambulatory blood pressure monitoring. Area under the curve analysis of ambulatory blood pressure reductions showed significant differences between treatment groups for both systolic (P = .023) and diastolic (P = .007) blood pressures, with lisinopril-treated patients showing the most significant reduction in pressure. Greater reductions (P less than .05) were also noted in patients receiving lisinopril at hours 10 to 12, suggesting two blood pressure troughs for those receiving captopril. Both drugs were well tolerated, and no patients withdrew from either treatment group. The authors concluded that after at least 4 weeks of therapy, once-daily lisinopril administration was more effective than twice-daily captopril administration in reducing blood pressure, when measured by 24-hour ambulatory blood pressure monitoring.     

大剂量吸入糖皮质激素治疗儿童哮喘急性发作的研究进展

支气管哮喘是儿童常见的慢性疾病之一．它的基本病理生理改变为气道慢性炎症反应。糖皮质激素可以抑制气道粘膜下炎症反应的各个环节。在哮喘治疗中起到举足轻重的作用。目前临床大多采用哮喘急性发作期全身应用激素缓解症状,缓解期长期吸入糖皮质激素预防复发。儿童尤其是婴幼儿常因病毒性呼吸道感染频繁诱导哮喘急性发作。频繁口服或静脉应用