The insulin–like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide

Serum concentrations of growth hormone–dependent insulin–like growth factor I (IGF–I) and insulinlike growth factor binding protein–3 (IGFBP–3), the carboxy terminal propeptide of type I procollagen (PICP), the carboxy terminal pyridinoline cross–linked telopeptide of type I collagen (ICTP) and the amino terminal propeptide of type III procollagen (PIIINP) were studied in 14 prepubertal children with asthma (mean age 9.7 years) during treatment with inhaled budesonide. The study design was a randomized, crossover trial with two double–blind treatment periods (200 and 800 μg) and one open, non–randomized treatment period (400 μg ). All periods were 18 days'duration. Budesonide treatment was associated with a dose–related suppressive trend in serum concentrations of PIIINP when the 400 μg period was included (p < 0.01; z =–2.7) and when it was excluded from the calculations (p < 0.01; z =–2.6), indicating reduced synthesis of type III collagen. A similar trend was observed in ICTP levels when the 400 μg period was excluded from the calculations (p = 0.05; z =–1.9). No other statistically significant variations were seen.     

雾化吸入布地奈德治疗婴幼儿哮喘急性发作的多中心临床观察

目的 观察不同起始剂量布地奈德混悬液雾化吸入(budesonide inhalation,BI)治疗婴幼儿中重度哮喘急性发作的疗效和安全性.方法 2008年9月至2010年4月,上海交通大学附属第一人民医院儿内科、上海交通大学医学院附属新华医院儿内科及复旦大学附属儿科医院呼吸科共收集6个月～3岁的中重度哮喘急性发作的住院患儿150例,随机分为高起始剂量BI组和常规起始剂量BI组.高起始剂量BI组给予雾化吸入BI 1 mg/次,每8小时1次,连用2d.常规起始剂量BI组给予雾化吸入BI 0.5 mg/次,每8小时1次,连用4 d.两组均按需给予博利康尼雾化吸入2.5 mg/次.主要疗效指标为入院时(0 h)及入院后8、16、24、48、72 h的临床症状评分;次要疗效指标为β2受体激动剂、全身糖皮质激素使用情况、住院总天数及医疗费用.结果采用 SPSS 13.0统计软件进行分析.结果 (1)两组组内治疗后各时间点的临床症状评分与入院时比较均明显降低,差异有统计学意义(P＜0.05);高起始剂量BI组较常规起始剂量B1组在治疗后8h、16h能更快地改善症状,提高临床症状评分(2.87±1.60 vs4.48 ±2.24,2.48±1.56 vs 3.25±1.82)(P＜0.01).(2)高起始剂量BI组特布他林的使用量、全身激素的累积使用量均明显减少[(16.27±12.99) mg vs (22.90±18.27) mg,(4.54±18.18) mg vs (11.16±21.34) mg](P＜0.05);而平均住院天数、住院总费用两组比较差异无统计学意义(P＞0.05).(3)全部受试对象未见鹅口疮、声音嘶哑等与吸入激素相关的不良反应.结论 对于中重度哮喘急性发作的婴幼儿,高起始剂量BI治疗能更快地控制症状,减少全身激素的使用量,具备较好的安全性,值得临床推广.     

Changes in bone markers in children with asthma during inhaled budesonide and nedocromil treatments

We evaluated serum and urinary markers of bone turnover in 14 children with asthma during inhaled budesonide and nedocromil treatments. Both the markers of formation (serum carboxy- and aminoterminal propeptides of type I procollagen and serum osteocalcin) and the markers of degradation (serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links) decreased (p < 0.05) during budesonide treatment for 6 months. During inhaled nedocromil treatment (for the following 6 months), the markers returned to the normal levels. These transient decreases in the markers of both formation and degradation of bone suggest that inhaled budesonide may slightly decrease the bone turnover rate. However, normal “coupling” between formation and degradation seemed to operate, e.g. a change in one resulted in a corresponding change in the other, so that net bone loss did not necessarily occur.     

Adrenal function in asthmatic children treated with inhaled budesonide

The effect of the inhaled topical steroid budesonide on adrenal function was evaluated in 33 children (aged 7-15 years) with moderate bronchial asthma. The trial was designed as a prospective single-blind study of the effect of budesonide in daily doses of 200 microgram through 400 microgram to 800 micrograms in three randomized consecutive periods of 8 weeks. The unstimulated diurnal production of cortisol was assessed by measurement of free cortisol in 24-hour urine samples at the end of each period. No significant dose-related suppression was found. The cortisol production did not differ significantly during treatment with 800 microgram budesonide as compared to treatment with 200 microgram budesonide (95% confidence interval: 74%-112%). It is concluded, that budesonide is a topical steroid with a favourable ratio between topical and systemic effects in asthmatic children.     

Glucocorticoids and growth in asthmatic children

The effects of asthma and oral and inhaled glucocorticoid therapy on growth in children are reviewed. Previous reports have shown that asthma itself may delay the onset of puberty, an effect which may masquerade as growth suppression. Oral glucocorticoids appear to impair growth; however, lower doses and alternate-day therapy may have less risk of this effect. While a controversial topic, inhaled glucocorticoids in lower doses appear to be associated with a small risk of adverse effects on growth. Minimal data are available for higher doses. Knemometry, a relatively new technique used for measuring small changes in growth, has detected short-term effects with both oral and inhaled glucocorticoids therapy. However, a number of limitations are associated with short-term growth studies. Clinicians should be aware of the potential for growth impairment with glucocorticoid therapy so adequate monitoring can be undertaken and appropriate intervention introduced when deemed necessary.     

孟鲁司特治疗儿童支气管哮喘的临床疗效观察

目的孟鲁司特联合布地奈德气雾剂吸入治疗合并过敏性鼻炎的轻、中度哮喘儿童临床疗效的前瞻性研究。方法将80例合并有过敏性鼻炎的轻、中度哮喘儿童随机分为治疗组和对照组。治疗组在吸入布地奈德气雾剂的同时加用孟鲁司特片，对照组则在吸入布地奈德气雾剂基础上加安慰剂，其余治疗相同。两组布地奈德气雾剂递减至最适有效剂量（无哮喘症状体征，β2激动剂吸入量无增加，呼气峰流速达预计值的8096以上，或变异率小于20％），并进行统计学分析。结果治疗组在加用孟鲁司特前后布地奈德吸入量减少差异有统计学意义（P〈0．05），对照组在加用安慰剂前后布地奈德吸入量减少差异有统计学意义（P〈0．05），而且两组比较差异亦有统计学意义（P〈0．05）。结论孟鲁司特片联合布地奈德气雾剂治疗儿童合并过敏性鼻炎的哮喘，不仅能明显缓解哮喘和鼻炎的症状，还可以减少糖皮质激素、β2激动剂吸入量，取得了满意的疗效且无明显的不良反应。     

Systemic effects of a short course of betamethasone compared with high-dose inhaled budesonide in early childhood asthma

Forty children aged 1-3 y completed a placebo-controlled study on the effects of 10 d of inhaled budesonide for asthma caused by respiratory tract infection. The effects on symptoms were significantly better in the active than in the placebo group. In 20 of these children the systemic effects of high-dose inhaled budesonide for 10 d and the effect of a 3-d course of oral betamethasone on asthma exacerbation were evaluated. Systemic effects were evaluated by measuring morning cortisol in serum and urine, and the bone markers osteocalcin, ICTP (the C-terminal telopeptide region of type I collagen) and PIIINP (an N-terminal propeptide of type III procollagen) in serum before and at the end (d 7-10) of treatment (1600 microg budesonide d(-1) for 3 d and 800 microg for 7 d). In 9 children, measurements were taken on d 3 of a 3-d course of betamethasone (6, 4 and 2 mg) for asthma exacerbation and 14 d later. There were no signs of systemic effects after 7-10 d of budesonide. After 3 d of betamethasone, serum cortisol decreased from a median of 263 to 26 nmol l(-1), urine cortisol/creatinine from 19.9 to 7.2 nmol l(-1), osteocalcin from 31.4 to 5.5 microg l(-1), ICTP from 19.4 to 8.5 microg l(-1) and PIIINP from 12.3 to 5.9 microg l(-1). Two weeks later, the levels were back to normal. In conclusion, short courses of oral betamethasone have pronounced systemic effects, whereas 10 d of high doses of budesonide do not produce significant systemic effects.     

Prospective study of lung volumes in young asthmatic children

In a 9-y prospective study, the occurrence and duration of lung volume abnormalities in 21 young asthmatic children (median age at recruitment 4y, range 3–8 y) was determined. The median functional residual capacity (FRC) at recruitment was 135% of that predicted for height (range 79–187%) and 13 children were hyperinflated. The median FRC decreased significantly after 3 y of follow-up and by 9 y only one child remained hyperinflated. We conclude that persistent elevation of lung volume in young asthmatic children appears to be uncommon.     

Linear growth in early treated children with congenital hypothyroidism

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment ( r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine <40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment ( r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year ( r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.     

孟鲁司特治疗儿童支气管哮喘的临床疗效观察

目的孟鲁司特联合布地奈德气雾剂吸入治疗合并过敏性鼻炎的轻、中度哮喘儿童临床疗效的前瞻性研究。方法将80例合并有过敏性鼻炎的轻、中度哮喘儿童随机分为治疗组和对照组。治疗组在吸入布地奈德气雾剂的同时加用孟鲁司特片,对照组则在吸入布地奈德气雾剂基础上加安慰剂,其余治疗相同。两组布地奈德气雾剂递减至最适有效剂量(无哮喘症状体征,β2激动剂吸入量无增加,呼气峰流速达预计值的80%以上,或变异率小于20%),并进行统计学分析。结果治疗组在加用孟鲁司特前后布地奈德吸入量减少差异有统计学意义(P<0.05),对照组在加用安慰剂前后布地奈德吸入量减少差异有统计学意义(P<0.05),而且两组比较差异亦有统计学意义(P<0.05)。结论孟鲁司特片联合布地奈德气雾剂治疗儿童合并过敏性鼻炎的哮喘,不仅能明显缓解哮喘和鼻炎的症状,还可以减少糖皮质激素、β2激动剂吸入量,取得了满意的疗效且无明显的不良反应。     

Influence of budesonide on the response to inhaled terbutaline in children with mild asthma

The aim of this study was to evaluate if continuous treatment with budesonide or salmeterol influences the bronchodilator response to terbutaline in children with asthma; 23 children, aged 7 to 16 years (mean = 11 years), with mild asthma were treated with inhaled budesonide 100 μg b.i.d. and placebo for three weeks in a randomized, double blind crossover study. These treatments were followed by treatment with inhaled salmeterol 50 μg b.i.d. for 3 weeks. On the last day of each period a cumulative dose-response experiment with terbutaline in the doses 50, 100, 250 and 500 μg (cumulative dose 900 μg) was performed. Lung function was measured before and 20 min after each terbutaline inhalation. Baseline pulmonary functions after budesonide treatment were significantly higher than the baseline measured after the two other treatments (p < 0.05). After budesonide treatment, the dose-response curve was shifted vertically upwards but otherwise parallel to the dose-response curve after placebo. The increase from baseline after the first cumulative dose of terbutaline was significantly lower after salmeterol treatment than after the two other treatments (p < 0.01). Maximal lung functions after 900 μg terbutaline also differed significantly between the three dose-response days; budesonide being significantly higher and salmeterol significantly lower than placebo (p = 0.02 and p < 0.001, respectively). It is concluded that budesonide treatment does not enhance the brochodilator response to terbutaline. Further studies are needed to assess if long-term continuous salmeterol treatment reduces the response to terbutaline.     

Prediction of the growth response of short prepubertal children treated with growth hormone

The aim of this study was to identify predictors of the growth response to growth hormone (GH) during the first 2 years of GH treatment, using auxological data and the maximum GH response (GH_max) to provocation tests. The patients were 169 prepubertal short children (27F, 142M), with Gmax values ranging from 0 to 65 mU/1. Their mean age (± SD)was8.3 ± 2.4 years (range 3-13 years), mean height SDS –3.0 ± 0.7 (range –1.5 to –6.0SDS) and mean pretreatment height velocity was normal (± 0.0 SDS) (range -1.6 to + 0.9 SDS). The increase in height SDS during the first 2 years of GH treatment (0.1 U/kg/day) varied from 0.10 to 3.75 SDS, with younger children having a better growth response. Individual growth responses correlated (p < 0.001) with GH_max (r =–0.37), age (r= -0.35), 1-year pretreatment delta SDS (r = -0.25), mid-parental height SDS (r = 0.34), height SDS at start of treatment (r =–0.22) and difference between height SDS of an individual child at the onset of GH treatment and mid-parental height expressed in SDS (diff SDS) (r = –0.43). In a multiple stepwise linear regression model, diff SDS and log GH_max were found to be the strongest predictors of the magnitude of the growth response. In the short children in this study who exhibited a broad range of GH_max values, 33% of the growth response during the first 2 years of treatment could be predicted.     

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1–11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.     

布地奈德混悬液雾化吸入治疗婴幼儿哮喘急性发作疗效观察

目的 评价布地奈德和博利康尼雾化溶液联合应用治疗婴幼儿哮喘急性发作的疗效。方法 采用随机对照，对15例婴幼儿哮喘急性发作进行布地奈德（0．5mg/ml)加博利康尼雾化溶液（2．5mg/ml)雾化吸入治疗，另18例用甲基强的松龙（1－2mg/kg)静点加博利康尼雾化溶液（2．5mg/ml)吸入治疗，进行疗效观察。结果 治疗组和对照组显效率分别为60％和77．78％，两组疗效无显著性差异。结论 雾化吸入布地奈德和博利康尼雾化溶液联合应用与静点甲基强的松龙加雾化吸入博利康尼雾化溶液疗效相同。     

Differential effects of inhaled budesonide on serum osteocalcin in children and adolescents with asthma

In recent years, measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogeneous glucocorticoids. Studies in children with asthma on inhaled glucocorticoids, however, have shown inconsistent results. The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide using three different osteocalcin assays: the Pharmacia Osteocalcin CAP FEIA, the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays. Two studies were conducted: 1) a randomised double blind two-period crossover study of 22 prepubertal children aged 5-12 years. In one period 800 μg budesonide was given once in the morning, in the other 400 μg was given twice daily; 2) a randomised double blind placebo controlled two period crossover study of inhaled budesonide 400 μg twice daily in fourteen 13-16 year old adolescents with pubertal stages II-V. In both studies, treatment periods were of four weeks duration, and blood samples were collected at the last day of each period. In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods. In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment. The suppression reached statistical significance with the CAP FEIA (P = 0.03) and the OSTK-PR (P =0.01) assays, but not with the ELSA-OSTEO assay (P = 0.06). Correlation analyses showed statistically significant correlation coefficients varying between 0.58 and 0.91 (P=0.03 and P < 0.0001, respectively). The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied, and inhaled glucocorticoids have differential effects in children and adolescents.     

Effects of nebulized corticosteroids therapy on hypothalamic–pituitary–adrenal axis in young children with recurrent or persistent wheeze

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic–pituitary–adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6–24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 μg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.     

Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma.

We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. Conclusion: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.     

小剂量阿奇霉素对哮喘儿童气道反应性的影响

目的 探讨小剂量阿奇霉素对哮喘儿童气道反应性的影响.方法 中重度持续哮喘患儿104例分为A组(56例)和B组(48例).所有患儿均应用沙美特罗替卡松(50/100μg/剂)2剂/d,吸人4周,重度持续哮喘患儿加服孟鲁司特5 mg/d,合并过敏性鼻炎者加糠酸莫米松100～200μg/d喷鼻,然后进入观察期.A组继续吸入沙美特罗替卡松(剂量同前),并加口服阿奇霉素7.5 mg/( kg·d)(最大剂量250 mg/d),每周服药2d;B组仅继续吸入沙美特罗替卡松(剂量同前).观察期为12周.试验结束两组分别评定观察期内有症状天数;开始及结束时,两组分别检测一秒钟用力呼气量( FEV1)、最大呼气峰流量(PEF)占预计值的百分率,观察期第15天及结束时检测使FEV1下降20％的组胺激发剂量(PD20-FEV1);观察开始前24h及结束后24h分别检测24h尿17-羟皮质醇(17-OHCS)和17-酮皮质醇(17-KS);试验结束后2周检测血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST).结果 (1)A、B两组有症状天数分别为(2.13±1.18)d、(2.25±1.19)d,差异无统计学意义(t =0.54,P=0.59).(2)观察前、后PEF占预计值百分率:A组分别为(49.77±15.02)％、(82.73±7.81)％,差异有统计学意义(t=16.59,P=0.000),B组分别为(52.69±13.90)％、(81.15+7.28)％,差异有统计学意义(t=12.37,P=0.000);观察前、后FEV1占预计值百分率:A组分别为(50.48±15.08)％、(83.18±6.61)％,差异有统计学意义(t=16.25,P=0.000),B组分别为(53.29±13.89)％、(82.73±6.10)％,差异有统计学意义(t=12.83,P=0.000).(3)观察期第15天、结束时PD20-FEV1水平:A组分别为(65.13±26.08) μg、(460.79± 221.72) μg,差异有统计学意义(t=13.54,P=0.000),B组分别为(65.27±25.75) μg、(65.66±25.09) μg,差异无统计学意义(t=1.45,P=0.15);观察期结束时A、B两组间PD20 - FEV1水平比较,差异有统计学意义(t=13.29,P=0.000).(4)观察前、后24h尿17 -OHCS水平A组分别为(14.27±3.41) nmol/L、(14.43±3.69) nmol/L,B组分别为(14.31±3.66) nmol/L、(14.56±3.37)nmol/L,两组比较差异均无统计学意义;观察前、后24h尿17-KS水平A组分别为(22.43±5.69)nmol/L、(22.07±5.21) nmol/L,B组分别为(22.40±5.04)nmol/L、(22.54±4.74)nmol/L,两组比较差异均无统计学意义.(5)观察期结束后2周血清ALT水平A、B两组分别为(20.39±9.12)U/L、(20.83±7.83) U/L,差异无统计学意义(t=0.26,P=0.79);AST水平A、B两组分别为(20.68±8.67) U/L、(21.44±8.60) U/L,差异无统计学意义(t=0.45,P=0.66).结论 小剂量阿奇霉素口服12周,并联合沙美特罗替卡松吸入可降低哮喘患儿的支气管高反应性,但未减少患儿的有症状天数,也未使FEV1、PEF较单独应用沙美特罗替卡松改善明显,对患儿肾上腺功能及肝功能无影响.     

Prediction of growth response in prepubertal children treated with growth hormone for idiopathic growth hormone deficiency

Several multiple regression models have been developed to predict the first-year growth response to human growth hormone (hGH) in children with growth hormone deficiency (GHD). It was the aim of this study to analyse the significance of various growth parameters for a height prediction model. Data from 148 prepubertal children with idiopathic GHD were evaluated. The prediction model was developed by means of univariate and stepwise linear regression analysis and an “all possible” regression approach using Mallow's C(p) statistics. Six out of eight selected variables had a significant influence on the first-year growth rate. The most important parameter was the difference between target height SDS and height SDS at the start of therapy (THSDS - HSDSC0), accounting for 23.95% and 25.74% of the variability. No other single variable or combination of variables was more informative than the variable THSDS - HSDSC0 alone. From these data, growth velocity for the first year of hGH treatment was estimated as 1.106 (THSDS - HSDSC0) + 6.8 cm/y ± 2.2 cm (SE), allowing a prediction for different intervals between THSDS and HSDSC0. This equation was validated in a small group of 18 GHD patients demonstrating a predicted vs. observed first-year growth rate of 9.4 ± 1.1 vs. 9.5 ± 2.6 cm/y. We conclude that the difference between THSDS and height SDS at the start of therapy is an important predictor of the first-year growth response in children treated with hGH for idiopathic GHD. Unlike in previous studies, additional parameters did not increase predictability.     

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目的研究布地奈德雾化液(BIS)吸入治疗儿童咳嗽变异性哮喘(CVA)的疗效。方法 2008-04-04—2009-03-22期间,采用开放性、多中心非干预性调研,在全国39个中心入选了903例5岁及5岁以下CVA患儿。雾化吸入(BIS)1～2mg/d,共7周。研究期间共有5次访视,评估雾化吸入BIS治疗后CVA患儿症状评分改变、缓解药物的使用、依从性和疾病控制情况等。结果 7周的观察期间,患儿总退出率8.97%(81/903)。雾化吸入BIS治疗后患儿的症状总评分(第1周4.0分vs第7周0.5分),白天症状评分(第1周2.4分vs第7周0.3分),夜间症状评分(第1周1.5分vs第7周0.2分)均明显下降(P均<0.0001)。使用支气管舒张剂的患儿比例明显降低(第1周39.42%vs第7周2.99%,P<0.0001),使用支气管舒张剂的中位数从第1周的5.8d/周减少到治疗终点时的3.9d/周。第7周时仍有87.49%的患儿依从性良好。依从性良好的患儿达到有效控制的可能性是依从性较差患儿的2.698倍,而且CVA复发可能性较低(OR=0.439)。没有自发不良事件报告。结论 BIS雾化吸入治疗能改善CVA患儿的症状评分,减少支气管舒张剂的应用,患儿依从性和安全性良好。