哮喘儿童吸入糖皮质激素疗效与白三烯水平的相关性探讨

目的：探讨哮喘儿童半胱氨酰白三烯合成与分泌水平与吸入糖皮质激素（ICS）疗效个体差异的相关性。方法：32例5～12岁已规律使用ICS 6个月以上非急性发作期哮喘儿童,按病情控制程度分为ICS控制良好组（14例）与ICS控制不良组（18例）,取10例健康儿童作为对照组,比较3组儿童外周血多形核白细胞(PMNL)白三烯C4合成酶（LTC4S ）mRNA表达与尿白三烯E4（LTE4）分泌水平。LTC4S mRNA表达水平以qCt值表示,qCt值与基因表达水平呈负相关。结果：哮喘儿童组PMNL LTC4S mRNA 表达（qCt值:1.12±0.27）明显高于对照组（qCt值:1.42±0.12）,P<0.05。ICS控制不良组PMNL LTC4S mRNA表达水平最高（qCt值:1.03±0.17）,与ICS控制良好组（qCt值:1.24±0.33）和健康对照组(qCt值:1.42±0.12)比较差异均有显著性意义（分别P<0.05和P<0.01）。3组间尿LTE4比较差异无显著性意义。结论：哮喘儿童外周血LTC4S mRNA表达水平增高,且规范使用ICS控制不良患儿显著高于ICS控制良好患儿,提示体内白三烯水平增高可能与ICS控制不良有关。［中国当代儿科杂志,2009,11（6）：441-444］     

吸入糖皮质激素对哮喘儿童骨龄及生长发育的影响

目的：长期吸入糖皮质激素是哮喘的首选治疗方法,但国内外对于年幼儿童长期吸入糖皮质激素治疗的安全性仍有争议,本研究旨在探讨支气管哮喘患儿吸入糖皮质激素对骨龄及生长发育的影响。方法：73例支气管哮喘患儿给予丙酸氟替卡松吸入治疗,剂量250 μg/d,3个月后减量1/3续用3个月,再减为125 μg/d续用6个月,治疗后观察疗效,治疗前后分别测量骨龄、身高、体重。结果：入选患儿治疗后身高、体重及RUS骨龄增长与正常儿童差异无统计学意义（P>0.05）;体重指数(BMI)治疗前后差异无统计学意义（P>0.05）;治疗前后C骨龄与年龄差值分别为-0.2（-0.6,0.8）岁、-0.5（-1.0、0.6)岁,治疗后明显比治疗前延迟（P<0.05）。结论：哮喘患儿吸入糖皮质激素治疗 1年对C骨龄发育有一定抑制作用,对RUS骨龄、身高、体重及BMI无明显影响;长期糖皮质激素治疗的患儿应监测生长发育状况。     

Behaviour problems in children with language impairment

BACKGROUND: Language impairment is often associated with behaviour problems. However, detailed relations between different types of language impairment and specific behaviour problems in children have yet to be demonstrated. The present study attempted to do just this with an eye to the implications to identify foci for early intervention. METHODS: The language abilities of 71 five-year-old children with language impairment were assessed via the administration of an extensive battery of language tests. The children's behaviour profile was assessed via administration of the Child Behaviour Checklist. RESULTS: Factor analyses confirmed the presence of four language factors: speech, syntax, semantics and phonology. Forty percent of the children displayed serious significant behaviour problems. The most frequently occurring behaviour problems were: withdrawn behaviour, somatic complaints, thought problems and aggressive behaviour. Behaviour problems were associated with three of the four language factors but not strongly associated with speech problems. CONCLUSIONS: Differential relations between specific types of language impairment and specific behaviour problems already exist at a young age. Phonological problems showed broad relations to problem behaviour; semantic language problems were especially related to internalizing behaviour problems. This finding suggests the need for specific therapies for both different types of language problems and different types of behaviour problems.     

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...     

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.     

Use of inhaled corticosteroids decreases hospital admissions for asthma in young children

Background  An active use of inhaled corticosteroids for asthma has been associated with less asthma exacerbations and hospital admissions in children aged more than 2 years. The present study aimed to investigate hospital admission rates in young children from two populations in relation to the age-specific use of maintenance medication for asthma. Methods  Annual data on children aged less than 24 months treated for asthma, including data on the use of maintenance medication based on the purchases of prescribed medications, and annual numbers of admissions to hospital and proportions of readmissions, were collected from 1995 to 1999 in two provinces of Finland. The inclusion criteria, three or more doctor-diagnosed wheezing episodes, were individually checked by the authors in each case. The mean number of children aged less than 24 months during the years of the study was 5490 in Kuopio and 9914 in Oulu area. Results  In the Kuopio area, during the years of the study, 16.5/1000 children aged less than 24 months were on maintenance medication for asthma, and 90% of them were receiving inhaled corticosteroids. In the Oulu area, the respective figures were 13.5/1000 (P<0.001) and 99%. The average admission rate was 7.9/1000 in the Kuopio area and 8.7/1000 in the Oulu area (P<0.05). The readmissions indicated the higher admission rates in the Oulu (40% of all admissions) than in the Kuopio (28%) area (P<0.01). Conclusion  Active use of maintenance therapy by inhaled corticosteroids was associated with a decreased need of hospital treatment in young children <24 months old with asthma, mainly because of less readmissions.     

Maternal intimate partner violence and behavioural problems among Pacific children living in New Zealand

Aims: To examine (1) the association between maternal intimate partner violence (IPV) perpetration and victimisation and behavioural problems among two‐ and four‐year‐old Pacific children, and (2) the socio‐demographic and parenting factors that may impact on this association. Design: Mothers of the Pacific Islands Families (PIF) cohort of Pacific infants born in New Zealand during 2000 were interviewed when the children were two and four years of age. This data set was based on mothers who were cohabiting in married or de‐facto partnerships (N = 920) and who completed measures of IPV at the two‐year assessment point and the Child Behaviour Checklist (CBCL) at the two‐or four‐year assessment points. Of these, 709 mothers completed the CBCL at both assessment points. Results: There were no significant associations between IPV and the prevalence rates of clinically relevant cases of behavioural problems in the two‐year‐old child cohort. However, the prevalence rates of clinically relevant internalising, externalising and total problem cases were significantly higher among four‐year‐old children of mothers who reported severe perpetration of IPV. The odds of being in clinical range of internalising were 2.16 times higher for children of mothers who were perpetrators of severe physical violence than for those children of mothers who were not, and for externalising and total problems they were 2.38 and 2.36 times higher respectively. Socio‐demographic and parenting factors did not significantly influence the association between IPV and child behaviour problems. Conclusion: These findings contribute to the complex picture of the consequences that exposure to parental violence may have on the behaviour of young children. The effectiveness of preventative strategies may be maximised if implemented in these early years before such problems become entrenched and lead on to future behavioural problems and impaired family relationships.     

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.     

达良好控制哮喘患儿停用低剂量吸入性糖皮质激素的临床随访研究

目的 通过随访达良好控制哮喘患儿停用低剂量吸入性糖皮质激素（ICS）后哮喘急性发作情况,以及实验室指标的动态变化,以期为哮喘患儿的长期控制最佳方案提供依据。方法 根据家长意愿,将63例达到良好控制的哮喘患儿分为ICS治疗组（n=35）和停药组（n=28）,进行18个月随访,每3个月进行评估,观察哮喘急性发作情况,并动态监测两组患儿肺功能和呼出气一氧化氮（FeNO）浓度,以及儿童哮喘控制测试（C-ACT）评分等指标进行分析。结果 随访第3、6、9、12个月时,FeNO在两组间比较差异无统计学意义（P > 0.05）;但在随访第15、18个月时,停药组FeNO显著高于治疗组（P < 0.05）。6次随访时点内C-ACT在两组间比较差异无统计学意义（P > 0.05）。随访第3、6、9、12个月时,第1秒用力呼气容积占预计值的百分比（FEV1%）、第1秒用力呼气量占用力肺活量比值（FEV1/FVC%）、最大呼气中期流速占预计值百分比（MMEF%）、最大呼气50%肺活量的瞬间流速（MEF50%）等指标在两组间比较差异无统计学意义（P > 0.05）;但在随访第15、18个月时,治疗组MMEF%、MEF50%显著高于停药组（P < 0.05）。治疗组随访期间有3例（9%）患儿哮喘发作,停药组有8例（29%）患儿哮喘发作,停药组哮喘复发率高于治疗组（P=0.0495）。结论 持续吸入低剂量ICS可维持哮喘患儿肺功能稳定,减少哮喘发作。     

Prevalence of hypothalamic-pituitary-adrenal axis suppression in children treated for asthma with inhaled corticosteroid

OBJECTIVE:

To determine the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression in asthmatic children on inhaled corticosteroids (ICS).

METHODS:

Clinical and demographic variables were recorded on preconstructed, standardized forms. HPA axis suppression was measured by morning serum cortisol levels and confirmed by low-dose adrenocorticotropic hormone stimulation testing.

RESULTS:

In total, 214 children participated. Twenty children (9.3%, 95% CI 5.3% to 13.4%) had HPA axis suppression. Odds of HPA axis suppression increased with ICS dose (OR 1.005, 95% CI 1.003 to 1.009, P<0.001). All children with HPA axis suppression were on a medium or lower dose of ICS for their age (200 μg/day to 500 μg/day). HPA axis suppression was not predicted by drug type, dose duration, concomitant use of long-acting beta-agonist or nasal steroid, or clinical features.

CONCLUSION:

Laboratory evidence of HPA axis suppression exists in children taking ICS for asthma. Children should be regularly screened for the presence of HPA axis suppression when treated with high-dose ICS (>500 μg/day). Consideration should be given to screening children on medium-dose ICS.     

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.     

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.     

Treatment adherence and level of control in moderate persistent asthma in children and adolescents treated with fluticasone and salmeterol

Objective

There is a scarcity of studies that assessed the association between adherence to combination therapy and asthma control in pediatric patients. The authors investigated the association between adherence to fluticasone propionate/salmeterol xinafoate combination-metered aerosol and the level of asthma control in children.

吸入变应原sIgE在不同气道过敏性疾病儿童中的分布特征

目的了解不同气道过敏性疾病患儿吸入变应原血清特异性Ig E(slg E)的分布特征。方法应用Uni CAP250变应原定量Ig E检测系统的荧光酶联免疫法,对256例3~14岁气道过敏疾病患儿测定9种常见吸入变应原的血清slg E。256例患儿按临床诊断分为:变应性鼻炎组(简称"鼻炎组",37例)、支气管哮喘组(简称"哮喘组",82例)和变应性鼻炎合并支气管哮喘组(简称"鼻炎并哮喘组",137例)。比较3组患儿9种吸入变应原阳性检出率的分布差异,并比较3组患儿变应原致敏级别和致敏种类数的差异。结果哮喘组、鼻炎组和鼻炎并哮喘组患儿吸入变应原血清s Ig E的阳性检出率分别为57.3%(47/82)、86.5%(32/37)、82.5%(113/137),3组间比较差异有统计学意义(P0.05)。哮喘组、鼻炎组、鼻炎并哮喘组患儿常见变应原均依次为霉菌类(32.9%、54.1%、48.9%)、尘螨类(30.5%、45.9%、46.0%)、花粉类(26.8%、35.1%、32.8%)、宠物类(12.2%、27.0%、18.2%)、蟑螂(9.8%、5.4%、5.8%)。鼻炎组和鼻炎并哮喘组患儿霉菌混合的阳性检出率均高于哮喘组,差异有统计学意义(均P0.0166)。3组患儿9种变应原的致敏级别和致敏种类数比较差异无统计学意义。结论支气管哮喘、变应性鼻炎或二者合并患儿前3位吸入变应原均依次是霉菌类、尘螨类、花粉类;与支气管哮喘相比,霉菌致敏可能与变应性鼻炎关系更密切;这3种常见气道过敏性疾病吸入变应原的致敏分布具有相似性。     

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.     

Six-year follow-up of an intervention to improve the management of preschool children with asthma

Aims:  In a randomized controlled study involving 60 preschool children with asthma, an intervention with extra information and support to parents in the form of group discussions was performed. An earlier follow-up after 18 months revealed an improved adherence and a reduction of exacerbation days. This is a 6-year follow-up.
Methods:  Fifty-four children performed clinical examinations, blood tests, measurements of exhaled nitric oxide, spirometry, bronchial provocation with dry air and skin prick tests. Data from the patients' records and questionnaires were obtained.
Results:  Twenty-nine per cent had no current signs of asthma, whereas 43% exhibited persistent and 28% intermittent asthma. The burden on the healthcare system was minimal. Intermittent inhaled corticosteroid (ICS) therapy was used by 81%. The intervention group (IG) had fewer contacts with nurses. Their parents had a better quality of life. Interviewing children separately contributed in identification of children needing treatment. More children in the IG had to restart ICS as they had signs of worse asthma control.
Conclusion:  Straightforward and timely support to parents of children with asthma can have long-term positive effects by strengthening the ability of parents to treat their children at home, although parents may also develop an underestimation of mild symptoms. It is important to directly ask children about their disease and to maintain regular follow-up visits.