Long-term Treatment with Corticosteroids/ACTH in Asthmatic Children

ABSTRACT. Skeletal maturation in severe bronchial asthma was studied in 15 children during and after treatment with depot tetracosactrin and in 6 children during treatment with prednisolone. Attained skeletal maturity before treatment was below the reference mean in the majority of children. Skeletal maturation was enhanced during treatment with depot tetracosactrin, which led to more advanced attained skeletal maturity at withdrawal than at start of treatment. There was a tendency towards larger increases of skeletal maturity than of height. The influence of adrenal androgens, released by ACTH-stimulation and good control of the disease are probably relevant factors for the acceleration of skeletal maturation. After withdrawal of depot tetracosactrin the rate of skeletal maturation normalized. During prednisolone treatment there was a delay of skeletal maturation leading to a progressive relative decrease of attained skeletal maturity, and closely related to a delay in linear growth. Treatment with depot tetracosactrin may thus induce enhancement of skeletal maturation, but with the treatment regimen found to be efficacious in bronchial asthma, the effect is not very pronounced and does not perceptibly affect the ultimate outcome of growth.     

Long-term Treatment with Glucocorticoids/ACTH in Asthmatic Children III.

ABSTRACT. The effect on growth of long-term treatment with prednisolone and/or ACTH_1-24 (tetracosactrin) depot preparation was studied in 40 children with severe bronchial asthma. Height velocity was subnormal before treatment. During treatment the group of 17 children primarily treated with ACTH showed a moderate increase in mean velocity. Their height was not significantly altered, and neither was the age at peak height velocity nor adult height. In the group of 23 children treated with prednisolone the mean velocity decreased, resulting in a relative decrease in height. Peak height velocity was delayed by about 2 years in the boys but occurred at the expected time in the girls, as did menarche. Mean adult height was lower than expected after adjustment for mid-parenteral height. In 10 children ACTH was substituted for prednisolone, and their height velocity increased but not enough to affect adult height, which was just as low as in the patients treated with prednisolone only.     

Placebo Controlled Trial of Systemic Corticosteroids in Acute Childhood Asthma

ABSTRACT. In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p < 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p < 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p < 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.     

Adrenal Function in Asthmatic Children Treated with Inhaled Budesonide

Bisgaard, H., Pedersen S., Damkjær Nielsen M and Østerballe O. (Department of Paediatrics, University Hospital of Copenhagen, County of Gentofte, Copenhagen; Department of Paediatrics, County Hospital of Kolding; Department of Clinical Physiology, University Hospital of Copenhagen, County of Glostrup, Copenhagen; Department of Paediatrics, County Hospital of Viborg, Denmark). Adrenal function in asthmatic children treated with inhaled budesonide. Acta Paediatr Scand 80: 213, 1991
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 μg through 400 μg to 800 μg 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 μg budesonide as compared to treatment with 200 μg 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.     

丙酸氟替卡松联合沙美特罗吸入治疗支气管哮喘

目的观察糖皮质激素与长效β2受体激动剂联合吸入治疗支气管哮喘的疗效。方法对47例诊断为支气管哮喘中重度持续的患儿予丙酸氟替卡松及沙美特罗联合吸入治疗。观察病人治疗前、治疗1周及治疗1个月时PEF值、哮喘症状计分、治疗第1周及第4周使用短效β2受体激动剂的天数、患儿对治疗的主观感受(或家长的评价)及治疗过程中的不良事件。结果治疗1周时PEF值、哮喘症状计分与治疗前相比显著缩短(P<0.01),治疗1个月时症状及肺功能均进一步改善。治疗第4周使用短效β2受体激动剂的天数与第1周相比有显著缩短(P<0.01)。结论糖皮质激素与长效β2受体激动剂有互补作用.对于中重度哮喘患儿,两者联合吸入治疗,有显著疗效。     

Studies of Pulmonary Function in Asthmatic Children

Pulmonary functions were studied in 188 asymptomatic children with bronchial asthma and 272 healthy children. Ventilatory function was measured by the spirogram and maximum expiratory flow volume (MEFV) curve. Although the forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were of the same values in normal and asthmatic subjects, the maximal mid-expiratory flow rate (MMF), the maximal flow rate at 50% (V50) and that at 25% (V25) of vital capacity were definitely lower in asthmatic children than those in healthy children, particularly in children with severe asthma. Arterial blood gas tensions and pH were measured in 180 asthmatic children with various clinical symptoms and 102 asthmatic children with disturbance of consciousness. Hypocapnia was detected even in the asymptomatic state, and carbon dioxide tensions (Pco2) were markedly high values only on very severe attacks. There was a linear fall in arterial oxygen tension (Po2) and oxygen saturation (So2) with increasing severity of attack. A complication of metabolic acidosis was frequent in the subjects who suffered from severe attacks. Children with severe asthma had small airways obstruction even in the asymptomatic state. This pulmonary disturbance appears to induce mild sustained hypocapnia and respiratory alkalosis as acceleration of ventilatory drive. Therefore, the development of hypercapnia, even if it is mild, may be considered to represent somewhat severe impairement of the pulmonary function in children with bronchial asthma.     

哮喘患儿Clara细胞分泌蛋白的临床意义

目的探讨Clara细胞分泌蛋白(CCSP)检测在儿童哮喘中的临床意义。方法采用酶联免疫吸附法检测50例哮喘急性发作期患儿血清CCSP水平,其中22例患儿经治疗后于缓解期采血复查,另设20例健康儿童作对照。结果哮喘急性发作期、缓解期患儿血清CCSP水平均较健康对照组显著降低(P<0.001,0.01)。中重度发作哮喘患儿,血清CCSP浓度显著低于轻度发作的哮喘患儿(P<0.001)。病程长的哮喘患儿CCSP水平显著低于病程短者(P<0.05)。结论CCSP具有抗感染作用,CCSP的减少可诱导或加重哮喘儿童的呼吸道炎症。检测血清CCSP是反映小呼吸道Clara细胞受损的一种非侵入性方法;CCSP可作为判断哮喘病情、治疗效果及预后的指标之一。     

不同时期哮喘患儿血清白细胞介素-6变化的意义

目的探讨白细胞介素-6(IL-6)在支气管哮喘中的临床意义。方法采用放射免疫法检测29例哮喘急性发作期患儿、32例缓解期患儿血清IL-6水平,并设20例健康儿童为对照组。结果1.哮喘急性发作期患儿血清IL-6水平明显增高,与缓解期哮喘组及对照组比较,差异均非常显著(P均<0.001)。2.缓解期哮喘患儿IL-6水平仍高于正常对照组(P<0.001)。3.缓解期>3岁哮喘患儿IL-6水平较≤3岁组高(P<0.001)。结论IL-6参与哮喘的发病,在哮喘的各个时期发挥不同的生物学效应。     

危重症时早产儿促肾上腺皮质激素、皮质醇及醛固酮的变化

目的 以血清皮质醇、醛固酮、促肾上腺皮质激素(ACTH)水平作为监测指标,观察危重症对早产儿下丘脑-垂体-肾上腺(HPA)轴相关激素的影响.方法 以出生72 h内的早产儿90例(胎龄<37周)为研究对象,分为胎龄≥34周组及胎龄<34周组,在入院时及日龄7 d、14d行新生儿危重症评分,取最低值进行分组,分为危重组,非危重组;全部患儿分别在入院时及日龄7 d、14d时采血检测血清皮质醇、ACTH、醛固酮水平.结果 (1)危重组血清皮质醇浓度均高于非危重组.日龄≤72 h、胎龄≥34周早产儿危重组与非危重组比较,差异有显著性(t＝-2.263,P=0.029);日龄14 d、胎龄<34周早产儿危重组与非危重组比较,差异有显著性(t=-2.913,P=0.006).(2)在危重组中,日龄≤72 h时,胎龄≥34周组血清皮质醇浓度显著高于胎龄<34周组(t=-2.641,P=0.010);日龄14 d时,胎龄<34周组血清皮质醇浓度显著高于胎龄≥34周组(t=-2.189,P=0.036).(3)胎龄≥34周危重组早产儿血清皮质醇浓度随日龄增加显著下降(F=4.679,P=0.012).(4)ACTH、醛固酮水平危重组与非危重组比较,差异无显著性(P>0.05).结论 早产儿应激发生时机体已具有调节皮质醇分泌的能力,胎龄越大,这种能力越成熟.危重症时早产儿血清皮质醇浓度增高,血清醛固酮、ACTH浓度与疾病的严重程度无显著相关性.     

支气管哮喘4～7岁患儿脉冲振荡肺功能异常与正常分界点的确定

目的探讨4~7岁哮喘患儿脉冲振荡肺功能(IOS)异常与正常值的分界点。方法选择正常患儿124例,发作期哮喘儿童160例,采用Mastscreen IOS肺功能仪进行IOS测定,计算IOS主要参数在不同预计值水平判断肺功能异常的敏感度与特异度。结果哮喘患儿IOS参数与正常儿童显著不同,以呼吸总阻抗(Zrs)≥115%正常预计值作为肺功能异常时,其对哮喘诊断的敏感度和特异度均为0.68;以总呼吸道黏性阻力(R5)≥115%正常预计值作为异常时,其敏感度和特异度则分别为0.61和0.63;而以电抗(X5)≥110%正常预计值作为异常时,其敏感度和特异度分别为0.84和0.81。结论对哮喘患儿进行IOS测试时,应将Zrs、R5≥115%正常预计值,X5≥110%正常预计值作为判断异常指标。     

Growth Response to Human Growth Hormone Treatment in Children with Partial and Total Growth Hormone Deficiency

ABSTRACT. The growth response during the first and second years of human growth hormone (hGH) treatment was studied in 14 prepubertal children with so-called "partial" GH deficiency (peak GH between 8 and 15 mU/1) and compared to 28 prepubertal children with "total" GH deficiency (peak GH less than 8 mU/1). There was no difference in growth acceleration between children with partial and total GH deficiency, when initial covariables were taken into account. In a stepwise multiple regression analysis initial stature, pre-treatment growth velocity and skinfold thickness were shown to be most related to growth response, but after exclusion of 3 children with a genetic form of total GH deficiency and partial TSH deficiency this relationship was lost. GH levels during provocation tests and auxological criteria have a poor predictive value for growth response to hGH therapy.     

Growth Hormone Treatment in Non-Growth Hormone-Deficient Children: Effects of Stopping Treatment

ABSTRACT. Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved CH levels greater than 15 mU/1 following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase. demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period. all children received GH according to the same dose regimen: they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating'catch-down'growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.     

(2) Inspiratory Muscle Hyperreactivity in Children with Severe Asthma

Intercostal EMG's (EMGic) and diaphragmatic EMG's (EMGdi) were studied to evaluate the role of the inspiratory muscles in compensation for an increased load during provocation tests with methacholine. The EMG's were obtained with surface electrodes. Methacholine provocation tests were performed using an Astograph which demonstrated the dose response curve to respiratory resistance (Rrs) on an X-Y recorder. The moving averages were analyzed in terms of the rates of rise (Xp/Ti) and peak activities (Xp). Experiments were performed on 15 asthmatics, aged 11 to 17 yrs, (6 mild and 9 severe asthmatics) and three normal subjects, aged 8 to 13 yrs. Pulmonary function values before provocation tests, except for mid-maximal expiratory flow (MMEF), showed no significant differences among these three groups. Changes in Xp and Xp/Ti were measured at the degree of 1.5 and 2 times the initial respiratory resistance level. In severe asthmatics, the changes in Xp and Xp/Ti were significantly larger than those of mild asthmatics, especially in intercostal Xp/Ti. From our results, the severe asthmatics had respiratory muscle hyper-reactivity compared with mild asthmatics, especially in the intercostal muscles.     

Clinical effects of a Long-term Educational Program for Children with Asthma – Aironet®. A 1-yr randomized controlled trial

Educational self-management programs for children with asthma have now become a routine feature in the management of the disease, as international guidelines underline. We designed this trial to find out whether Aironet^®, an educational program developed for children with asthma, influenced asthma severity and improved parents' knowledge of the disease. In a multicenter, prospective, randomized controlled trial we enrolled 123 children, 72 boys, mean age 8.78 yr (±2.33 s.d.), with intermittent or mild persistent asthma. Participants were randomly assigned to an education group, who received Aironet^® at baseline and 2 months later (60 children), or to a control group who did not (63 children). Follow-up lasted 12 months and included out-patient clinic visits and spirometry at 2, 4 and 12 months. At baseline and at 12 months follow-up, parents were questioned about their knowledge of asthma, and their children's asthmatic attacks, use of systemic corticosteroids, family physician or hospital emergency room visits, hospitalizations and asthma-related school absences. Questionnaire replies at 12-month follow-up reported significantly fewer asthma attacks in patients who received the program than in those who did not (1.65 ± 1.21 vs. 2.34 ± 1.73; p < 0.05). For the subgroup of children who had ≥3 asthma attacks at baseline, parents' knowledge improved significantly more in the educational group than in the control group. The out-patient educational program Aironet^® reduces the number of asthma attacks in children with intermittent or mild persistent asthma and improves knowledge of the disease.     

Two-Year Results of Treatment with Methionyl Human Growth Hormone in Children with Turner Syndrome

ABSTRACT. Methionyl growth hormone (somatrem) in a daily dosage of 4 IU/m² body surface area was administered to 16 girls with Turner syndrome. Low dose ethinyl estradiol (0.1 μg/kg body weight) was added in girls aged 13 years or more. Mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) and 5.3 (1.3) cm/year in the first and second year, respectively. Bone age advanced 1.8 years over 2 years and predicted adult height was increased. Apart from the occurrence of anti-GH antibodies there were no side effects. In conclusion, somatrem is an efficacious and safe therapy for short stature in Turner syndrome over a period of 2 years. Longer follow-up is needed before conclusions about its effect on final height can be drawn.     

重组人生长激素替代治疗对生长激素缺乏症患儿糖代谢的影响

目的观察国产重组人生长激素(r-hGH)替代治疗对生长激素缺乏症(GHD)患儿糖代谢的影响。方法用国产r-hGH对GHD 15例患儿治疗3个月。治疗前后行口服葡萄糖耐量试验(OGTT)及胰岛素(INS)释放试验(IRT)。分别于0、30 mun,1、2 h采静脉血行血浆葡萄糖(PG)及胰岛素(INS)测定。结果治疗前患儿糖耐量均正常,治疗3个月后OGTT空腹PG 无明显增加,但PG 30min(P<0.01)、1 h(P<0.05)、2 h(P<0.05)、血糖曲线下面积(AUCglu)(P<0.01)均明显增加;虽葡萄糖耐量曲线上移,但均未出现糖耐量损伤(IGT)或糖尿病(DM)。IRT空腹INS(P<0.05)、30 min(P<0.05)、1 h(P<0.01)、2 h(P<0.01)、INS曲线下面积(AUCins)(P<0.01)均显著增加,稳态模型胰岛素抵抗指数(Homa IR)明显上升(P<0.05)。结论GHD患儿r-hGH替代治疗3个月后INS敏感性下降,糖耐量降低,提示应用r-hGH替代治疗患儿应监测PG、INS水平     

Growth Hormone Secretion and Growth Hormone Treatment in Children with Intrauterine Growth Retardation

Albertsson-Wikland, K. (Departments of Paediatrics II and Physiology, University of Gothenburg, Gothenburg, Sweden). Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 35, 1989.
Few children with intrauterine growth retardation (IUGR) fail to show catch-up growth during the first year of life. There may he many reasons for this, ranging from disturbances of hormone production to hormonal unresponsiveness of target cells. This report presents preliminary data on growth hormone (GH) secretion and responses to GH treatment in 16 children with IUGR and poor catch-up growth, six of whom had Silver-Russell stigmata. GH secretion was assessed by measurement of the GH response to an arginine-insulin test and determination of spontaneous GH secretion over 24 hours. GH production was heterogeneous hut, more often than expected, children showed both a low response to GH provocation and low spontaneous secretion of GH. Five out of six of the children with Silver-Russell syndrome and seven out of 10 of the children with non-Silver-Russell IUGR gained more than 2 cm in height during 1 year of treatment with GH at a dose of 0.1 IU/kg/day. These results clearly demonstrate that some children with IUGR and poor catch-up growth secrete insufficient amounts of GH, and that many of these very short children show an improvement in growth rate during treatment with physiological doses of GH.     

Growth and Growth Hormone Secretion in Children Following Treatment of Brain Tumours with Radiotherapy

ABSTRACT. We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n= 20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n= 36) from -0.28 to - 1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys.
Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whom were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m²/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to + 1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group.     

支气管哮喘患儿心理学特点及整合性心理治疗对其疗效影响

目的 了解哮喘患儿的心理学特点,探讨整合性心理治疗对哮喘疗效影响.方法 采用个性测试问卷(艾森克个性问卷儿童手册EPQ)、行为量表(Conners父母用量表)、焦虑自评量表(SAS)对哮喘患儿79例和健康对照儿童45例进行个性、行为及焦虑情绪的心理测试;采用随机对照方法,将哮喘患儿分为干预和非干预组均进行规范治疗,干预组同时进行团体整合性心理治疗,每2周1次.3个月后二组患儿重新填写以上量表,进行疗效判断和肺功能检查.结果 哮喘患儿SAS标准分、精神稳定性(EPQ-N分)、因子Ⅱ～Ⅴ得分明显高于健康对照组,差异有显著性(Pa＜0.001).干预组治疗前后SAS标准分、N分及因子Ⅱ～Ⅴ得分均明显下降(Pa＜0.05),而非干预组上述指标无明显变化(Pa＞0.05).干预组肺功能各项指标增加值与非干预组比较差异显著(Pa＜0.001).结论 哮喘儿童情绪不稳定,存在着学习问题、心身问题和焦虑.整合性心理治疗能明显改善患儿情绪障碍、躯体症状和肺功能,是一种有效的辅助治疗方法.