Effects of Regular Inhalation of Beclomethasone Dipropionate and Sodium Cromoglycate on Bronchial Hyperreactivity in Asthmatic Children

ABSTRACT. The efficacy of beclomethasone dipropionate (BDP) was compared with sodium cromoglycate (SCG) and placebo in a double-blind parallel group study of 30 asthmatic children over a two-month period. All the three treatment groups received salbutamol concomitantly. Lung volumes, airway mechanics and the nonspecific bronchial hyperreactivity to carbachol were measured at the beginning and the end of the study. Two patients were excluded because of unequal clinical conditions at the entry and the end of the study and three because of lack of co-operation. Three patients (1 on SCG, 2 on placebo) dropped out because of worsening clinical symptoms. The improvement in airway mechanics shown by the group treated with BDP ( n =7) was significantly greater ( p <0.01) than in the group treated with SCG ( n =8). Nonspecific hyperreactivity to carbachol improved significantly in the BDP group (factor 5.9) compared to the SCG group (factor 1.9). Childhood asthma seems to be better controlled by a combination of BDP and salbutamol, than by SCG and salbutamol.     

丙酸倍氯松气雾剂防治支气管哮喘18年总结

１９７７年珐１９９５年我科应用丙酸倍氯松气雾剂（ＢＤＰ）防治小儿哮喘千余名,平均剂量为３００μｇ·ｄ,疗程２．１６±１．５２年。对其中３９９例患儿进行了长期随访,考核临床疗效,并行肺功能,气道高反应性,外周血淋巴细胞ＣＤ２３表达、肾上腺皮质功能,咽部霉菌和身高体重的测定。     

吸入二丙酸倍氯米松气雾剂治疗小儿哮喘对骨密度影响的研究

目的　探讨长期吸入二丙酸倍氯米松治疗儿童哮喘对骨密度的影响。方法　对 3～ 1 5岁 6 8例哮喘儿童给予吸入二丙酸倍氯米松 ,吸入剂量≤ 4 0 0 μg/d ,分级阶梯治疗 ,定期复查。分别于吸入前、后测骨密度 (BMD)。根据吸入时间将 6 8例患儿分 3组 (随患儿年龄增长 ,将患儿调入相应的年龄组 ) ,A组 6 8例 ,吸入时间≥ 6个月 ;B组 6 5例 ,吸入时间≥ 1年 ;C组 5 6例 ,吸入时间≥ 2年。每组又根据BMD正常参考值分 3～ 6岁组 ,7～ 1 3岁组 ,采用SAS软件对每例哮喘儿童治疗前和治疗中测的BMD均数值分组进行配对资料t检验。结果　经随访观察吸入二丙酸倍氯米松治疗≥ 6个月、≥ 1年、≥ 2年哮喘儿童BMD均数值与治疗前比较均无明显区别。显示吸入二丙酸倍氯米松≤ 4 0 0 μg/d治疗哮喘 ,3年内是安全的。结论　吸入二丙酸倍氯米松每天剂量≤ 4 0 0 μg/d ,3年内应用是安全的 ,对哮喘儿童骨密度无明显影响。     

哮喘儿童呼出气一氧化氮水平的测定

目的：　探讨哮喘儿童呼出气一氧化氮(exhalednitricoxide,eNO)水平及其意义。方法：　设定13～15cmH2O呼出气阻力以关闭软腭,用化学发光法测定34例6～14岁哮喘儿童和36名6～13岁非呼吸道疾病儿童单次呼吸的eNO浓度 ,同时测定一秒钟用力呼气容积占预计值百分比 (FEV1%)。结果：哮喘儿童的eNO浓度为 (89.4± 56 .4) ppb ,较非呼吸道疾病儿童eNO浓度 [(15 .8±5.8) ppb]显著增高 (P<0.01) ;哮喘儿童eNO浓度与FEV1%之间无显著相关性(r=0.06 ,P>0.05)。结论：　哮喘儿童eNO浓度高于正常,其变化与FEV1%无关。     

ACTH in Normal Children and Children with Pituitary and Adrenal Diseases

ABSTRACT. During insulin hypoglycaemia (IH) reference values for plasma ACTH are 10 to 88 pg/ml at 0 min and 50 to 300 pg/ml at 40 min. Plasma Cortisol reference values are above 400 nmol/l at 40 min. A negative correlation between age and ACTH response was found in normal children. ACTH response during IH in 43 children and adolescents with deficient production of one or several pituitary hormones was significantly lower (median 81 pg/ml at 40 min), than the response in normal children (median 149 pg/ml). Thirty-six patients with idiopathic hypopituitarism could be grouped into 21 with normal, 6 with borderline (50 to 70 pg/ml at 40 min), and 9 with abnormal ACTH response. In 7 patients with intracranial tumour 2 had normal, 3 borderline, and 2 abnormal ACTH response. A good correlation between the ACTH peak at 40 min and the Cortisol value at 40 min was found in patients with idiopathic hypopituitarism. ACTH response also correlated well with the plasma growth hormone (GH) response in the patients. It is recommended to study ACTH together with GH when IH is performed, multiple disturbances are often found in children with GH deficiency and demonstration of an ACTH defect has therapeutic implications.     

ACTH in Normal Children and Children with Pituitary and Adrenal Diseases

ABSTRACT. During insulin hypoglycaemia (IH) reference values for plasma ACTH are 10 to 88 pg/ml at 0 min and 50 to 300 pg/ml at 40 min. Plasma Cortisol reference values are above 400 nmol/l at 40 min. A negative correlation between age and ACTH response was found in normal children. ACTH response during IH in 43 children and adolescents with deficient production of one or several pituitary hormones was significantly lower (median 81 pg/ml at 40 min), than the response in normal children (median 149 pg/ml). Thirty-six patients with idiopathic hypopituitarism could be grouped into 21 with normal, 6 with borderline (50 to 70 pg/ml at 40 min), and 9 with abnormal ACTH response. In 7 patients with intracranial tumour 2 had normal, 3 borderline, and 2 abnormal ACTH response. A good correlation between the ACTH peak at 40 min and the Cortisol value at 40 min was found in patients with idiopathic hypopituitarism. ACTH response also correlated well with the plasma growth hormone (GH) response in the patients. It is recommended to study ACTH together with GH when IH is performed, multiple disturbances are often found in children with GH deficiency and demonstration of an ACTH defect has therapeutic implications.     

Adrenal Cortical Function in Asthmatic Children on Alternate Day Steroids

Adrenal cortical function was determined in 16 children receiving prednisolone or prednisolone stearoylglycolate on alternate days. The dosages of the corticosteroids varied from 2·5 to 10 mg prednisolone, or 6·65 to 13·30 mg of its stearoylglycolate ester; the duration of therapy ranged from 2 to 26 months. Adrenocortical function was assessed from the plasma cortisol response to a single injection of β^1-24 tetracosactrin (Synacthen); repeat tests were performed after altering steroid dosages or for reassessment of individual patients.The effects of prednisolone stearoylglycolate are compared with those of prednisolone, and the effects of alternate-day prednisolone therapy are compared with those found when this corticosteroid was given daily to similar (in three cases, the same) children.     

吸入型糖皮质激素治疗儿童哮喘有效性与安全性的临床研究

目的　吸入型糖皮质激素作为儿童哮喘预防性抗炎治疗的第一线药物,其效应性、安全性已成为 医患双方共同关注的焦点。但目前长期吸入治疗对肾上腺皮质功能和生长发育影响的国内研究为数不多,因此我 们进行一项对照研究以观察二丙酸倍氯米松(BDP)治疗儿童哮喘的疗效及副作用。方法　50例哮喘儿童根据病 情严重程度,在快速缓解后给予不同剂量二丙酸倍氯米松吸入,为期6月～2.5年。治疗期间定期随访,观察临床 疗效,监测最高呼气流速(PEFR)值,测量体重、身高及修改吸入剂量,并进行24小时尿游离皮质醇含量测定。结 果　临床总有效率90%(45/50),与对照组[70%(21/30)]相比差异有显著性意义(P<0.05),吸入BDP后6个 月时PEFR值和初诊时相比较差异有显著性意义(P<0.05),患儿身高、体重与同龄正常值比较无异常(P> 0.05);24h尿游离皮质醇在正常范围。结论　吸入二丙酸倍氯米松治疗不同严重程度的儿童哮喘,疗效好,而且 安全。     

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.     

Endocrine Changes of the Hypothalamic, Pituitary and Adrenal Systems in Cyclic Vomiting

Children with cyclic vomiting had high blood ADH, ACTH, cortisol and plasma renin activity (PRA) during vomiting, and urinary excretion of 170HCS, 17KGS, 17KS, norepinephrine (NE), epinephrine (E), normetanephrine (NMN), metanephrine (MN) and vanillylmandelic acid (VMA) was increased. After disappearance of the vomiting, the levels fell to within the normal range. Variation was not observed in blood prolactin (PRL), Na, osmotic pressure or urine dopamine (DA). Normal findings were obtained in the intravenous water loading test, response of anterior pituitary hormones and cortisol to the insulin, TRH and LH-RH loading, the metopirone test and the dexamethasone suppression test which were performed 1 week after the vomiting.     

Effect of "Shoseiryu-to" on Asthmatic Children and Guinea PIG Tracheal Smooth Muscle

Sixty-five asthmatic children were administered with “Shoseiryu-to” for long time and as a result of following the children its effective ratio was 74.8%. After ten asthmatic children were administered with “Shoseiryu-to”, their PEFR had a tendency to increase and their EIA had a tendency to be controled. Spiral sample of tracheal smooth muscle, which was extracted from a guinea pig after its death, was placed in a solution of Tyrode's medium. Various concentration of extracted solution from “Shoseiryu-to” were added in turn to the chamber which contained the spiral sample. Tracheal smooth muscle was relaxed by “Shoseiryu-to” and when it was contracted by histamine, it was also relaxed by “Shoseiryu-to”. Nineteen asthmatic children were administered with “Shoseiryu-to” and their serum cortisol, ACTH and free fatty acid were examined. The results of the examination in the group given “Shoseiryu-to” were as follows: cortisol increased after thirty minutes and then at one hour intervals (P<0.01) and ACTH was found to be increased at every examination period (P<0.01).     

The Influence of Labor and Delivery on Preterm Fetal Adrenal Function

ABSTRACT. The influence of labor and route of delivery upon umbilical cord serum levels of Cortisol and dehydroepiandrosterone sulfate in one hundred sixty-nine preterm infants not exposed prena-tally to corticosteroids was studied. Vaginally born infants (group A, n=89) presented a higher mean cord Cortisol and dehydroepiandrosterone sulfate concentrations than those delivered by cesarean section (group B, n=80). Although there were no differences in Cortisol and dehydroepiandrosterone sulfate levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I, n=42) and those without labor (group B-II, n=38), the mean Cortisol and dehydroepiandrosterone sulfate concentrations were higher in group A than in group B-I. There was a correlation between umbilical cord Cortisol and dehydroepiandrosterone sulfate levels. It is concluded that there is no association between the presence of labor and high cord serum levels of Cortisol and dehydroepiandrosterone sulfate and there is an association between vaginal delivery and high cord Cortisol and dehydroepiandrosterone sulfate levels in preterm infants. It is suggested that the stress of vaginal delivery stimulates the secretion of fetal Cortisol and dehydroepiandrosterone sulfate in preterm infants.     

Systemic activity of inhaled beclomethasone dipropionate: a double-blind comparison of volume spacers

Background: To which extent volume spacers may influence systemic activity of inhaled beclomethasone dipropionate (BDP) has not been evaluated. Aim: To assess whether the AeroChamber Plus? spacer is equivalent to the Volumatic? spacer for administration of inhaled hydroflouroalkane 134a propelled BDP in terms of lower leg growth rate (LLGR). Patients and methods: Prepubertal children with mild asthma (n = 26, aged 6–14 years) were included in a 3‐time periods of 2 weeks duration randomized double‐blind cross‐over study with a single‐blind placebo run‐in and two washout periods. LLGR was measured with the knemometer. Interventions were inhaled BDP hydroflouroalkane 134a pressurized metered dose inhaler 100 μg and 200 μg b.i.d. with the AeroChamber Plus and 200 μg b.i.d. with the Volumatic spacer. Results: Beclomethasone dipropionate 200 μg b.i.d. from the AeroChamber Plus was non‐inferior to BDP 200 b.i.d. from the Volumatic spacer as the lower margin of confidence interval of the difference between treatments (?0.18 to 0.13 mm/week) was greater than the prespecified lower limit for non‐inferiority (?0.20 mm/week). UFC/creatinine data showed no statistically significant variations. Conclusion: The systemic activity of BDP, via the Volumatic?, and AeroChamber Plus? spacers is similar. The AeroChamber Plus spacer may be used in children without risk of increasing systemic activity of BDP.     

小儿紫癜性肾炎的临床病理及远期预后分析

目的：分析小儿紫癜性肾炎的临床、病理与远期预后的关系。方法：比较32例紫癜性肾炎的临床病理变化,随访其中19例,随访期限8～14年,了解临床及病理对远期预后的影响。结果：小儿紫癜性肾炎的临床分型中以急性肾炎综合征型多见,占50%,肾病综合征型次之占40%;病理变化以Ⅱ～Ⅲ级多见。急性肾炎综合征型与肾病综合征型随访比较,痊愈率分别为55.6%(5/9例)和28.6%(2/7例);病理分级Ⅰ～Ⅲ级的痊愈率为43.8%(7/16例),恶化率12.5%(2/16例),Ⅳ～Ⅴ级中66.7%(2/3例)恶化或死亡。结论：急性肾炎综合征型远期预后较肾病综合征型好,远期预后与临床分型及病理分级密切相关。     

长期吸入糖皮质激素对支气管哮喘患儿身高的影响

支气管哮喘(哮喘)是儿童期最常见的慢性疾病,吸入糖皮质激素(ICS)仍是目前哮喘治疗中最有效的方法。但由于本身存在的不良反应,使其在临床应用中受到一定的影响。通过对近年国内外相关文献进行综述,认为短期吸入中小剂量糖皮质激素(GC)对哮喘儿童的身高无显著性影响。对长期吸入者身高的影响与ICS的种类、剂量、疗程、吸入器、吸入技术、不同年龄以及个体对激素的敏感程度等有关,可采取一定的措施预防ICS对身高的影响。     

The effect of beclomethasone dipropionate in ultrafine particles on bronchial hyper-reactivity in young children

Aim: Bronchial hyper‐reactivity (BHR) provides a tool for asthma diagnosis, assessment of severity and response to treatment. The effect of beclomethasone dipropionate in ultrafine particles (BDP‐HFA) on BHR as measured by the adenosine challenge test in young children has not yet been determined. Our aim was to determine the effect of BDP‐HFA (100 μg twice daily) on BHR as evaluated by a reduction of 20% from baseline FEV1 (PC20‐FEV1) values in young asthmatic children. Methods: Twenty‐one young children (13 males), mean age 4.95 ± 1.05 years, with partially controlled or controlled asthma completed a double‐blind randomized, placebo‐controlled, cross‐over study. Each child received 4 weeks of treatment with either 100 μg BDP‐HFA twice daily or placebo, and after a 2‐week washout period the other way around. Primary outcomes were PC20‐FEV1 concentration, and the stage number at which FEV1 values dropped by 20%. Results: Following 4 weeks of treatment, median PC20‐FEV1 was 81.28 mg/mL while on BDP‐HFA, compared with 9.64 mg/mL on placebo (p < 0.001). The median increase in stages required to achieve PC20 on BDP‐HFA compared with placebo was three (95% CI 2.28–4.86). Conclusion: Four weeks of treatment with BDP‐HFA resulted in significantly decreased BHR in young children.     

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.     

长期吸入糖皮质激素对支气管哮喘患儿可溶性细胞间黏附分子-1的影响

目的探讨支气管哮喘患儿长期吸入糖皮质激素后对可溶性细胞间黏附分子-1(sICAM-1)水平的影响。方法采用酶联免疫吸附(ELISA)法检测36例健康儿童(正常对照组)和29例支气管哮喘患儿吸入糖皮质激素(布地奈德气雾剂)治疗前及后(3、6、12个月)血清sICAM-1水平变化。结果1.支气管哮喘患儿治疗前血清sICAM-1水平明显高于对照组,有极显著性差异(q=34.12 P<0.01);2.吸入糖皮质激素后3、6和12个月血清sICAM-1水平逐渐降低,各治疗组间有极显著性差异(P均<0.01),治疗后各组与治疗前比较均有极显著差异(P均<0.01),其中治疗后3、6个月患儿血清sICAM-1水平明显高于对照组(P均<0.01),而12个月与正常对照组比较无显著差异。结论黏附分子在支气管哮喘的发病中起重要作用。糖皮质激素可能通过抑制sICAM-1水平升高而起到缓解及预防哮喘发作的作用。     

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children

Background:

Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well.

Objectives:

The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma.

Patients and Methods:

1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric.

Results:

Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect.

Conclusions:

The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.