Long-term Treatment with Corticosteroids/ACTH in Asthmatic Children

Hypothalamic-pituitary-adrenal (HPA) function was studied in 23 children with severe bronchial asthma during and after long-term treatment with prednisolone and/or ACTH_1-24 (depot tetracosactrin) by means of ACTH stimulation test and insulin tolerance test. In the 14 children primarily treated with depot tetracosactrin, the Cortisol levels in insulin tests were within normal limits both during and after treatment. An enhanced response to ACTH stimulation was found during the treatment period. During treatment with prednisolone a marked impairment of the adrenocortical function was found, with low basal plasma Cortisol levels and subnormal response to ACTH stimulation, more marked the lower the age at the start of treatment and the higher the dose per kg body weight. After substitution with depot tetracosactrin the HPA-function was restituted, with plasma Cortisol levels within normal limits. Growth hormone levels after insulin induced hypoglycemia were ±7 ng/ml during and after treatment with depot tetracosactrin. As long-term treatment with depot tetracosactrin has little side-effects in terms of suppression of the HPA-axis it is a useful alternative to oral prednisolone in severe asthma in children.     

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.     

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.     

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.     

支气管哮喘患儿血清可溶性细胞间黏附分子-1的临床意义

目的探讨可溶性细胞间黏附分子1(sICAM1)在儿童哮喘发病机制中的作用。方法采用ELISA双抗体夹心法测定16例哮喘患儿急性发作期血清中sICAM1水平,以10例健康儿童为对照。结果哮喘患儿发作期血清sICAM1明显高于对照组(P<0.001)。且sICAM1与IgE呈显著正相关(r=0.603P<0.05)。结论sICAM1参与哮喘的发病,并可作为哮喘发病的检测指标。     

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。     

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.     

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。     

不同亚型中重度支气管哮喘患儿白细胞介素-5、免疫球蛋白E水平变化及意义

目的 研究IL-5、IgE水平在不同亚型中重度患儿哮喘发病中的变化及意义.方法 选取2009年9月-2010年3月于本院儿科哮喘专科门诊就诊的中重度哮喘患儿65例(哮喘组),将哮喘组中急性发作期患儿按诱导痰的细胞分类分为嗜酸性粒细胞(EOS)型哮喘(EA)组及非EOS型哮喘(NEA)组.选取20例健康儿童为健康对照组.采用ELISA法检测不同亚型哮喘患儿血清IgE水平.将哮喘组及健康对照组儿童外周血单个核细胞(PBMC)与CD3单克隆抗体及CD28单克隆抗体共培养,ELISA法检测PBMC在抗体刺激下分泌的IL-5水平.并对IL-5表达水平与IgE水平进行相关性分析,了解IL-5、IgE在不同亚型中重度哮喘患儿中的作用.结果 EA组诱导痰EOS百分比明显高于NEA组(P=0.000).哮喘组患儿PBMC表达的IL-5水平显著高于健康对照组,急性发作组明显高于临床缓解组,急性发作重度持续组显著高于中度持续组,EA组显著高于健康对照组及NEA组.EA组血清IgE水平显著高于NEA组(P=0.010).哮喘患儿外周血及EOS诱导痰EOS比例与IL-5、IgE水平呈显著正相关(Pa=0.000);哮喘患儿IL-5水平与IgE水平也呈显著正相关(r=0.482,P=0.001).结论 IL-5、IgE参与哮喘的发病,IL-5、IgE在EA中的作用较NEA更为突出.IL-5水平与哮喘病情分度密切相关.     

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。     

支气管哮喘患儿血T辅助淋巴细胞的变化

目的探索支气管哮喘儿童细胞免疫状况的变化。方法采用流式细胞仪检测支气管哮喘儿童急性期及正常对照组外周血T辅助淋巴细胞1(Th1)和Th2的百分率、CD4 、CD3、CD8、NK细胞、B细胞百分率及CD4/CD8比值。对10例哮喘缓解期患儿复查淋巴细胞亚群。结果支气管哮喘患儿发作期外周血Th1细胞百分率[(16.28±9.83)%]明显低于正常对照组[(20.77±6.89)%](P<0.05);哮喘组Th2细胞百分率[(5.44±1.96)%]较对照组[(4.21±2.12)%]明显增高(P<0.05)。Th1/Th2比值,哮喘组为3.41±2.56,对照组为5.91±3.24,两组比较有非常显著性差异(P<0.01)。但哮喘组B细胞、NK细胞百分率、CD3、CD4、CD8及CD4/CD8与正常对照组比较均无统计学差异(P均>0.05)。10例哮喘缓解期患儿淋巴细胞亚群结果表明,B细胞百分率显著下降(P<0.05),其他各项指标在发作期与缓解期无明显差异。结论支气管哮喘儿童最重要的免疫异常是Th1/Th2细胞比例和功能失衡,主要表现为Th2细胞应答优势存在,Th1/Th2显著降低。     

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.     

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.     

支气管哮喘患儿亚甲基四氢叶酸还原酶基因多态性与血清免疫球蛋白E的关系

目的探讨支气管哮喘(哮喘)患儿亚甲基四氢叶酸还原酶(MTHFR)基因C677位点多态性与血清IgE水平的相关性。方法选择95例哮喘患儿作为病例组,均为急性发作期或临床缓解期哮喘患儿,患病前2周均未使用过肾上腺皮质激素及免疫调节剂。另选择健康儿童113例作为健康对照组。2组儿童年龄及性别比较差异均无统计学意义。采用PCR-限制性片段长度多态性分析法对病例组和健康对照组儿童外周血白细胞MTHFR基因C677位点基因多态性进行研究,应用双抗体夹心ELISA法检测2组儿童血清总IgE水平。结果健康对照组MTHFR 677C/T的3种基因型频率分别CC 35.4%、CT 45.1%、TT 19.5%,病例组分别为CC 24.2%、CT 40.0%、TT 35.8%,677C/T基因型分布频率在哮喘病例组和健康对照组间差异有统计学意义(χ2=7.556 5,P<0.05)。病例组T等位基因的频率为55.3%,健康对照组为42.0%,病例组较健康对照组显著增高,其患哮喘的危险度是健康对照组的1.71倍(χ2=7.254 7,P<0.01;95%CI:1.13～2.57)。病例组血清总IgE水平在各基因型患儿间比较差异有统计学意义(F=3.46,P<0.05),健康对照组血清总IgE水平在各基因型儿童间比较差异无统计学意义(F=0.13,P>0.05)。结论 MTHFRC677位点C→T的基因突变增加了患儿哮喘发病的危险度,TT基因型与哮喘的发生直接相关;哮喘患儿血清总IgE水平升高,该位点基因型并非导致血清总IgE水平升高的直接原因。     

无创正压通气在重症支气管哮喘治疗中的应用

目的 观察在常规治疗的基础上加用无创正压通气(NIPPV)对儿童重症支气管哮喘(哮喘)的治疗作用.方法 选取急性发作期重症哮喘患儿40例.随机分为NIPPV组20例和对照组20例.NIPPV组在解痉平喘、抗感染、祛痰、纠正酸碱和水电解质平衡等综合治疗基础上,于发病24 h内予NIPPV治疗;对照组除上述基础治疗外予鼻导管吸氧.监测2组治疗前及治疗4 h、8 h、12 h 及24 h心率、动脉血pH、动脉血氧分压 [pa(O2)]、动脉血二氧化碳分压[pa(CO2)]、血氧饱和度(SpO2)水平.结果 治疗后对照组和NIPPV组心率、动脉血pH值、pa(O2)、pa(CO2)及SpO2水平均较治疗前明显改善,并且随治疗时间的延长而改善有所增加,差异均有统计学意义(Pa<0.01).治疗后,NIPPV组较对照组改善更明显,NIPPV组在治疗4 h、8 h的心率[(119±10)次·min-1、(97±12)次·min-1]、动脉血pH(7.28±0.06、7.34±0.04)、pa(O2)[(67±6) mmHg、(81±5) mmHg](1 mmHg=0.133 kPa)、pa(CO2)[(40±9) mmHg、(31±9) mmHg]、SpO2[(96.23±1.83)%、(98.04±1.32)%]较对照组心率[(125±11)次·min-1、(104±10)次·min-1]、动脉血pH(7.22±0.08、7.29±0.07)、pa(O2)[62±6) mmHg、(76±4) mmHg]、pa(CO2)[(46±9) mmHg、(37±7) mmHg]及SpO2 [(95.05±1.69)%、(97.01±1.41)%]均明显改善,差异均有统计学意义(Pa<0.05).48 h后NIPPV组患儿全部脱机成功,且无严重并发症发生.结论 早期应用NIPPV配合常规药物治疗有助于减缓重症哮喘的病情恶化,可提高急性发作的治疗效果,是抢救重症哮喘的一种安全有效的方法.     

支气管哮喘患儿血清褪黑素水平检测的意义

目的研究不同病情支气管哮喘患儿血清褪黑素水平变化,探讨影响哮喘患儿血清褪黑素水平变化的因素。方法收集哮喘患儿及健康儿童血清样品75例。其中轻度、中度、重度发作期组及临床缓解期组患儿各15例;健康对照组15例。应用酶联免疫吸附法(ELISA)测其血清样品褪黑素水平。结果血清褪黑素水平轻度发作组[(22.76±5.16)ng/L],中度发作组[(16.79±3.35)ng/L],重度发作组[(11.54±1.45)ng/L],缓解期组[(22.06±3.36)ng/L],对照组[(28.72±4.32)ng/L],5组间进行多重比较,除缓解期组与轻度发作组无显著差异外,余各组间均有显著差异(Pa<0.05);随着病情加重,褪黑素的水平渐降低。结论哮喘患儿血清褪黑素水平明显降低,可能与患儿睡眠紊乱、机体处于应激状态时体内高水平皮质激素对松果腺的抑制有关。     

Tissue Doppler echocardiographic assessment of cardiac function in children with bronchial asthma

BACKGROUND: The aim of the present study was to evaluate the role of tissue Doppler echocardiography in assessment of ventricular function in pediatric patients with bronchial asthma (BA). PATIENTS AND METHODS: Fifty-one pediatric patients with BA and 30 age- and sex-matched healthy subjects were studied. BA patients were divided into two groups: mild BA (n = 33) and moderate to severe BA (n = 18). All subjects were examined on conventional and tissue Doppler echocardiography, and 44 patients had pulmonary function tests on spirometry within 1 week of echocardiographic examination. RESULTS: Conventional echocardiographic parameters were all similar in mild asthmatic patients and control subjects. Tricuspid E velocity, E/A ratio and isovolumetric relaxation time (IVRT) in moderate and severe cases differed significantly from mild cases and control subjects. E', A', E'/A' ratio and IVRT of the lateral tricuspid annulus, and IVRT of the medial and lateral mitral annuli were different between mild cases and control subjects. E' velocity and IVRT of the lateral tricuspid annulus and IVRT of the medial and lateral mitral annuli were also different between mild cases and moderate to severe cases. Pulmonary function tests correlated well with E', E'/A' and IVRT of lateral tricuspid annulus. CONCLUSION: Patients with BA have subclinical right ventricular diastolic dysfunction even in the early stages. The severity of the functional impairment is parallel with the severity of the disease. Tissue Doppler echocardiography has a greater predictive value than conventional imaging, and is useful for evaluating ventricular function in patients with BA.     

哮喘儿童白细胞介素13基因型与表型的关联研究

目的探讨哮喘儿童白细胞介素13(IL-13)Arg130Gln基因型与血清总IgE、IL-13水平及过敏原表型之间的关系。方法采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)法,对130例哮喘患儿和100例健康对照儿童进行IL-13Arg130Gln基因多态性的检测,并用酶免法检测血清总IgE、IL-13水平和空气过敏原。结果基因型分布及等位基因频率哮喘组与对照组比较差异均无显著性,哮喘组突变型个体的Log10IL-13水平高于未突变型个体的水平(P<0.05),哮喘组突变纯合型个体的Log10IgE水平高于突变杂合型及未突变型个体的水平(P<0.05),哮喘组及对照组突变型与未突变型的过敏原阳性率比较差异均无显著性。结论IL-13Arg130Gln突变不是中国长春地区儿童哮喘的易感基因,但此突变可能与血清IL-13蛋白质水平升高有关,突变纯合型可能与血清总IgE水平相关联。     

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.