Increased glycosaminoglycans in the urine of asthmatic children on inhaled corticosteroids

Increased extracellular matrix (ECM) deposition in the airway wall contributes to the airway remodeling in asthmatics. Glycosaminoglycans (GAGs) are polysaccharides attached to a protein core in order to form proteoglycans, a component of the ECM. In this study, we investigated the possible influence of long-term treatment with inhaled corticosteroids (ICS) on urinary GAGs levels of asthmatic children. Seventy asthmatic children (41 boys), aged 6.8-12.5 yr, participated in the study. About 44 were treated with inhaled budesonide via turbuhaler for 2-35 months (median 12 months) and 26 were on relief medications. About 30 healthy controls were also studied. GAGs were precipitated from early morning urine samples, collected, isolated and quantified using uronic acid-carbazole reaction and expressed as uronic acid (UA) in microg/g/Cr(u)/m2. Urinary GAGs values did not differ significantly between controls and asthmatics but significant differences were found between children on ICS and asthmatics on relief medications (p < 0.001). There was a positive correlation between the daily dose of inhaled budesonide and the urinary GAGs values (r = 0.32, p = 0.037) whereas a threshold distinguishing 'low' vs. 'high' doses of ICS was found to be at 300 microg/m2 per day with a significant difference in urinary GAGs secretion (p = 0.006). Our data show that urinary GAGs secretion is reduced in asthmatic children that used only relief medication but it is increased in those on long-term treatment with ICS. A dose dependent effect of ICS was also detected.     

轻-中度哮喘患儿气道炎症类型与病情、糖皮质激素疗效的关系

目的探讨轻-中度支气管哮喘患儿初始治疗前气道炎症类型与病情及吸入糖皮质激素治疗反应的关系。方法以87例轻-中度哮喘患儿作为研究对象,在糖皮质激素吸入治疗(ICS)前进行痰液诱导及诱导痰细胞学分析,酶联免疫荧光法测定痰液嗜酸粒细胞阳离子蛋白(ECP)、ELISA法检测痰液IL-8、TGF-β1,儿童肺功能仪检测基础肺功能和小气道通气指标、乙酰甲胆碱(Mch)支气管激发试验测定气道高反应性(AHR)。20例健康体检儿童作为对照组,应用SPSS13.0软件进行统计学分析。结果87例轻-中度哮喘患儿根据诱导痰液EOS%分为嗜酸性粒细胞哮喘组(EA)64例,非嗜酸性粒细胞哮喘组(NEA)23例,EA与NEA组ICS治疗前痰液细胞学构成比、诱导痰上清液ECP、IL-8差异有统计学意义(P<0.05);两组间FEV1%预测值(FEV1%pred)、PEF%pred、中-重度AHR%、小气道阻塞(%)、痰液TGF-β1水平等指标差异有统计学意义(P<0.05)。ICS治疗4周后EA组基础肺功能指标、气道高反应性、小气道通气功能明显改善,而NEA组改善不明显。多元逐步回归分析结果表明初治痰液EOS%、FEV1%预测值、痰液TG...     

Childhood asthma admissions: Determinants of short stay

The objective of this study was to identify the determinants of short hospital stay (< 24 h) among children admitted because of an acute asthma exacerbation. Computerized health records were used to identify children with a discharge diagnosis of asthma (ICD code 493.0) at the Hospital for Sick Children, Toronto, during the period October 1994 to October 1995. Cases were children with a length of hospital stay of < 24 h (short-stay group) and controls were children with a length of stay of > 24 h (long-stay group). Clinical and demographic data were extracted from the medical record. Over the 12-month period, 485 children were hospitalized because of asthma. Of these, 121 (25%) had short-stay admissions (< 24 h), whereas 364 (75%) had long-stay admissions (> 24 h). Simple random sampling was used to select 85 children from each of the two groups. There were no differences between the two groups regarding language, primary care physician, asthma history, management prior to emergency department (ED) presentation, respiratory rate on presentation, use of the observation unit, and time in the ED. Logistic regression analyses identified three variables associated with short hospital stay: milder asthma (adjusted odds ratio [OR] 4.9), male gender (adjusted OR 2.4), and availability of a delivery device at home (adjusted OR 2.0). In conclusion, many children admitted to hospital because of an asthma exacerbation have short, yet expensive, hospital stays. The results of this study highlight the importance of developing alternative models of health care delivery for asthmatic children requiring short hospital contact.     

Impaired growth in children with asthma during treatment with conventional doses of inhaled corticosteroids

We describe 6 (4F, 2M) prepubertal children with moderate asthma diagnosed at a mean age of 2.8 years. All patients were treated with inhaled corticosteroids in a dose of between 300 and 800 mcg of beclomethasone diproprionate (becotide) daily, given either as an aerosol or rotahaler. Mean height velocity SDS decreased from −0.8(range +0.5 to −2.0)to −3.2(range −1.3 to −4.8) when the dose was increased. Alternatively, when the dose was reduced or stopped, mean height velocity SDS increased from −3.2 (range −2.0 to −4.8) to +0.8 (range −1.2 to +2.7). Careful assessment of height velocity is indicated in all children receiving treatment with inhaled corticosteroids.     

Potential adverse endocrine effects of inhaled corticosteroids

Abstract: Evidence exists for a potential role for inhaled corticosteroids, particularly when used in high dose to cause growth impairment, delayed maturation and adrenal suppression in children and adolescents with asthma. The functional significance of biochemical adrenal suppression remains uncertain. Similarly, there is as yet insufficient evidence to determine whether inhaled corticosteroids may adversely affect bone mineral density in children and adolescents with asthma.     

Early use of inhaled corticosteroids in infancy

The inability to accurately predict the outcome of infants with recurrent wheezy bronchitis makes the early use of inhaled corticosteroids (ICS) controversial. Data from bronchoalveolar lavages and epidemiological surveys suggest a persistent inflammation of the airways in the more severe cases. Prospective studies, mostly with nebulized corticosteroids, have demonstrated clinical efficacy on daytime and nightime symptoms, reduced requirements for rescue bronchodilators and a real steroid sparing effect. In infants with episodic viral-associated wheeze with or without interval symptoms, ICS use carries the risk of overtreatment and of adverse effects. Long-term prospective studies are urgently required to assess the efficacy and safety of ICS and their possible effects on the natural history of infantile asthma.     

Decreasing admissions for childhood asthma to a Swedish county hospital

Hospital admission rates for childhood asthma have increased in many countries. To study if this is also true for Norrköping Hospital, paediatric admission rates for asthma every fifth year were examined for the period 1973 to 1993. Admission rates were found to have fallen over the last 10 years, especially in children of school age. Among the younger age groups (below 5 years of age) a fall in admission rates was also observed over the last 5 years. This fall occurred in spite of reported increases in the prevalence of childhood asthma. The relative risk for admission due to asthma thus decreased from 1 in 1973 to 0.09 in 1993. The readmission rate has been stable. The mean length of stay in hospital for asthma decreased significantly. The observed decreasing trend in hospital admissions for childhood asthma is contrary to that found in many other countries. Possible explanations are discussed.     

Eformoterol Turbohaler® compared with salmeterol by dry powder inhaler in asthmatic children not controlled on inhaled corticosteroids

The aim of the study was to compare the efficacy of the inhaled long‐acting β₂‐agonists eformoterol and salmeterol when added to existing inhaled corticosteroid (ICS) therapy in symptomatic asthmatic children. This randomized, 12‐week, parallel‐group study, performed in a primary care setting, included 156 children and adolescents (aged 6–17 years) with moderate persistent asthma. Patients were randomized to open‐label eformoterol (Oxis^®) Turbohaler^® 9 μg (delivered dose) or salmeterol Accuhaler^® 50 μg, both b.i.d, added to current ICS. Assessments included: changes in daytime reliever β₂‐agonist therapy (primary variable), total 24‐h reliever use, lung function, clinic and diary symptom scores, patient and carer health‐related quality of life (HRQL) and adverse events. Daytime reliever use decreased significantly (p < 0.001) from baseline by 65% and 52%, respectively in the eformoterol and salmeterol treatment groups. Compared with salmeterol, eformoterol produced a greater decrease in daytime (?0.46 inhalations/day; p = 0.081) and 24‐h (?0.70 inhalations/day; p = 0.043) reliever use. The percentage of patients who did not require any reliever medication during the study was significantly higher in the eformoterol group (p < 0.05 vs. salmeterol at weeks 8 and 12). Clinic and diary card peak expiratory flow and symptom measures all improved from baseline in both treatment arms. There was a significantly greater effect in favour of eformoterol for the reduction in clinic‐assessed overall night‐time symptoms (p < 0.05 vs. salmeterol). Clinically relevant improvements in patient‐assessed HRQL occurred during treatment with eformoterol and salmeterol, but carer‐assessed HRQL was improved to a clinically relevant extent, only with eformoterol. Both treatments were well tolerated. In children and adolescents with moderate persistent asthma, add‐on therapy with eformoterol was well tolerated and at least as effective as salmeterol.     

Extra‐fine particle inhaled corticosteroids,pharma‐cokinetics and systemic activity in children with asthma

During recent years, extra‐fine particle inhaled corticosteroids with a median aerodynamic diameter ≤2 μm have been introduced in the treatment of asthma. The aim of this paper was to review pharmacokinetics and systemic activity of extra‐fine particle hydroalkane pressurized metered dose inhaled (pMDI) ciclesonide and beclomethasone dipropionate in children. A literature review was performed. Systemic bioavailability of oral and pulmonary deposition of extra‐fine ciclesonide and beclomethasone dipropionate was 52% and 82%, the half‐life in serum 3.2 and 1.5 h and first‐pass hepatic metabolism >99% and 60%, respectively. Secondary analyses of urine cortisol/creatinine excretion found no effects of ciclesonide pMDI between 40 and 320 μg/day or of beclomethasone dipropionate pMDI between 80 and 400 μg/day. Ciclesonide pMDI 40, 80 and 160 μg/day caused no effects on short‐term lower leg growth rate as assessed by knemometry. Ciclesonide 320 μg/day was associated with a numerically short‐term growth suppression equivalent to 30% which was similar to 25% and 36% suppression caused by beclomethasone dipropionate HFA and CFC 200 μg/day, respectively. Consistent with the differences in key pharmacokinetic features, beclomethasone dipropionate is associated with a systemic activity detected by knemometry at a lower dose than ciclesonide. Whether that correlates with a clinically important difference remains to be explored. Assessments of systemic activity of beclomethasone dipropionate <200 μg/day and of ciclesonide >180 μg/day as well as head‐to‐head comparisons are warranted. Preferably, such studies should apply the sensitive method of knemometry.     

Influence of inhaled corticosteroids on growth: a pediatric endocrinologist''s perspective

Given the increasing advocacy for the use of inhaled corticosteroids as a treatment of choice for persistent asthma, growing numbers of children are being exposed to the possible growth-suppressing effects of glucocorticoids. Recent evidence strongly suggests that, when consistently administered at moderate doses, inhaled corticosteroids (IC) are capable of slowing growth in children. Whether such growth suppression would persist and ultimately affect final adult height remains unknown. Therapeutic goals which aim for uninterrupted inflammatory disease control rather than periodic symptom control may increase the occurrence of growth failure in children treated with IC. In this article, current information about the mechanisms of growth suppression by glucocorticoids and the effects of IC on growth is reviewed, and recommendations for designing studies to investigate the effects of drugs on growth are presented.     

Prophylactic intermittent treatment with inhaled corticosteroids of asthma exacerbations due to airway infections in toddlers

The aim of this study was to investigate whether budesonide, for 10 d, administered at the first sign of an upper respiratory tract infection, could reduce asthma symptoms in 1-3-y-old children with asthma during infections. The primary efficacy variable was symptom scores. The study had a multicentre, randomized, double-blind, placebo-controlled design with parallel groups. Fifty-five children with a mean age of 26 months received either budesonide or placebo via a spacer with a facemask. Each child was monitored for 1 y. Budesonide was given 400 microg q.i.d. for the first 3 d and b.i.d. for 7 d. Symptoms (cough, wheeze, noisy breathing and breathlessness) were scored (0-3) daily by the parents. Asthma symptom scores were lower in children treated with budesonide than in those given placebo. The effect was most pronounced for cough and noisy breathing, but it did not affect the need for hospital care. In conclusion, treatment with budesonide, started at the first sign of a respiratory infection, reduced asthma symptoms in toddlers with episodic asthma.     

Incentive device improves spacer technique but not clinical outcome in preschool children with asthma

Aim: To investigate the influence of an incentive device, the Funhaler, on spacer technique and symptom control in young children with asthma and recurrent wheeze. Methods: Randomised controlled trial where 132 2–6 year old asthmatic children received regular inhaled fluticasone through Aerochamber Plus, or Funhaler. The setting was a research clinic at Princess Margaret Hospital for Children, Perth, Australia. Subjects were followed up for a year. The main outcome measure was asthma symptoms. Proficiency in spacer technique was measured as salbutamol inhaled from spacer onto filter. Quality of life was measured every three months. Groups were compared in terms of spacer technique, symptoms and quality of life. The relationship between spacer technique and clinical outcome was examined. Results: There was no difference between Funhaler and Aerochamber groups in wheeze free days, cough free days, bronchodilator free days or quality of life (P = 0.90, 0.87, 0.74 and 0.11 respectively). Spacer technique was better in the Funhaler group (P = 0.05), particularly in subjects younger than 4 years of age (P = 0.002). Drug dose on filter (as the mean of five 100 mg doses) ranged from zero to 136 mg. Conclusions: Use of Funhaler incentive device does not improve clinical outcome, but improves spacer technique in children younger than 4 years. Variability in drug delivery is large in young children using pressurised metered dose inhalers and spacers.     

Parental concern towards the use of inhaled therapy in children with chronic asthma

BACKGROUND: Parental attitudes towards the use of inhaled therapy in children with chronic asthma influence treatment adherence and outcome. In the present study, we evaluated the perceptions and concerns of parents of children with chronic asthma towards inhaled therapy. METHODS: A self-administered standard questionnaire was distributed to parents of children attending the Paediatric Asthma Clinic. All these children required inhaled steroids for treatment. RESULTS: One-hundred and twelve of 170 parents (66%) surveyed were concerned with inhaled therapy. The most common concern with its use was medication side effects (91%), followed by 'inhaler dependency' (86%), cost of the inhaler (34%) and difficulty in using the inhaler (15%). Parental perception that the oral route was superior to the inhaled route, preference for the oral route for asthma prophylaxis and a higher steroid dose required for prophylaxis were more likely to be associated with concerns towards inhaled therapy. More importantly, these children were also more likely to miss > 25% of their prescribed doses of inhaled steroids (46 vs 22% in the group concerned about inhaled therapy compared with the group that was not concerned, respectively; P = 0.007) and had a higher mean number of nebulization treatments in the last year (3.2 +/- 2.9 vs 1.8 +/- 1.3 in the group concerned about inhaled therapy compared with the group that was not concerned, respectively; P = 0.01). CONCLUSIONS: A significant proportion of parents whose children were on inhaled prophylaxis had concerns towards the use of inhaled therapy. Parental concern towards inhaled therapy appeared to increase the problem of non-adherence to treatment. Education for these parents will need to be addressed to improve asthma management in our patient population.     

Acute childhood asthma in Finland:A retrospective review of hospital admissions from 1976 to 1995

The prevalence of childhood asthma has increased markedly in many Western societies during recent decades. We wanted to study whether the incidence and severity of childhood asthma in Finland had changed during the time-period 1976–95. Hospital admission rates from 1976 to 1995 were obtained from the National Hospital Discharge Register and the individual intensive care unit (ICU) registers of the five university hospitals in Finland. The number and length of treatment periods for childhood asthma in all Finnish hospitals and at the ICUs of the five university hospitals were analyzed. The number of children receiving special reimbursement for asthma medication costs was obtained from the central register of the Social Insurance Institution. The data showed that during the time-period investigated, hospital admissions as a result of asthma had increased by 2.8-fold, but the mean length of hospital stay had more than halved (from 7.3 to 2.6 days). The increase in hospital admissions showed greatest significance in the 0–4-year age-group among both sexes (p < 0.001). In contrast, a significant reduction in hospital admissions was found among the 10–14-year age-group (p < 0.001). No discernible change in admission to ICUs was seen. During the same time-period, the number of children receiving special reimbursement for asthma medication costs increased 7.5-fold. Hence, a major increase has occured in the number of children diagnosed with asthma that has not been paralleled by a proportionate increase in the number of hospital admissions. While the prevalence of mild and moderate asthma has increased, the occurrence of severe asthma has remained essentially unchanged.     

反义寡核苷酸和激素干预对哮喘小鼠GATA-3表达的影响

目的 探讨转录因子GATA-3在支气管哮喘发病中的作用,评价反义寡核苷酸干预及吸入糖皮质激素对其调节作用.方法 40只雌性BALB/c小鼠随机分为正常对照组(A组)、哮喘组(B组)、激素治疗组(C组)及GATA-3反义寡核苷酸治疗组(D组)4组.采用卵清白蛋白致敏、激发建立哮喘小鼠模型,对小鼠血及支气管肺泡灌洗液(BALF)中嗜酸性粒细胞进行计数,并测定小鼠血清IgE含量;采用Western b1ot及RT-PCR技术检测治疗前后哮喘小鼠肺组织中GATA-3蛋白和GATA-3 mRNA的表达.结果 通过小鼠行为学变化、血和BALF嗜酸性粒细胞计数、血清IgE水平以及肺组织病理切片鉴定模型成立.哮喘小鼠气道管壁及伴行动脉周围可见炎性细胞浸润、杯状细胞增生及平滑肌增厚.Western blot结果显示哮喘组小鼠肺组织GATA-3蛋白表达增高,GATA-3反义寡核苷酸治疗组和激素治疗组GATA-3表达均下降,GATA-3反义寡核苷酸治疗组较激素治疗组下降略明显,但差异无统计学意义.RT-PCR结果与Western blot结果一致.结论 蛋白质水平及mRNA水平显示哮喘小鼠模型肺组织GATA-3表达升高,激素和反义寡核苷酸干预可下调GATA-3表达,可能是其抑制气道炎症形成的重要作用机制;应用反义寡核苷酸可能为哮喘治疗提供一种新的方法.     

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目的评价呼出气一氧化氮(FeNO)监测在哮喘控制治疗中的评估指导作用。方法收集深圳市儿童医院哮喘专科门诊的41例患儿,根据抽签分组,20例进入FeNO组,21例进入对照组。控制治疗中,对照组根据儿童哮喘控制水平分级进行调整;FeNO组在此基础上结合FeNO检测结果进行调整。在10个月治疗后,观察两组之间哮喘症状、短效β受体激动剂使用情况、肺功能结果,吸入激素使用量,从而判断FeNO检测在哮喘控制治疗中的作用。结果 FeNO组使用短效β受体激动剂平均天数为(4.3±3)d,对照组为(3.7±2.8)d;FeNO组总发作次数9次,对照组为11次;第1秒用力呼气容积(FEV1)占预计值%在FeNO组为100.96±7.69,对照组为90.37±12.95;达50%用力肺活量时最大呼气流速(MEF50)占预计值%在FeNO组为95.77±9.32,对照组为87.01±13.84。以上指标比较均为P>0.05,差异无统计学意义。FeNO组平均吸入糖皮质激素量为(290±75)μg,对照组为(225±50)μg(P<0.01)。结论在哮喘控制治疗评估中,加入FeNO浓度检测,对吸入糖皮质激素(ICS)有指导作用,但未能显...