Safety and pharmacokinetics of fluconazole in children with neoplastic diseases

To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 15 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8 +/- 2.3 ml/min, volume of distribution 0.87 +/- 0.06 L/kg, and terminal elimination half-life 16.8 +/- 1.1 hours. Similarly, after the last dose, clearance was 19.4 +/- 1.3 ml/min, volume of distribution 0.84 +/- 0.04 L/kg, and terminal elimination half-life 18.1 +/- 1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5 +/- 0.4 microgram/ml and trough levels of 2.7 +/- 0.5 microgram/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186 +/- 16 micrograms.hr per milliliter. Renal clearance of fluconazole was 65% +/- 5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials.     

Dose-related effects of nebulized metaproterenol in asthmatic children

The dose-related effects of inhaled 5% metaproterenol solution in asthmatic children between the ages of six and 12 years with acute bronchospasm were evaluated. Tests included FEV1.0, FEF25-75, and PEFR. For entry into the study, subjects were required to have an FEV1.0 or an FEF25-75 less than 80% of the child's predicted normal value based on height and race. Sixty children were randomly assigned in double-blind fashion to receive one of four different doses of 5% metaproterenol inhalant solution: 0.0 ml (placebo), 0.1 ml, 0.2 ml, or 0.3 ml. Drug efficacy was assessed by spirometry using a DeVilbiss Surveyor I spirometer. Spirometry was performed prior to inhalation of the test dose (baseline) and four times after inhalation: immediately after and 15, 30, and 60 minutes after inhalation. Patients in the three treated groups had significantly higher peak post-dose FEV1.0 and FEF25-75 than the placebo group but were not significantly different from one another. There was a significant relationship between dose and incidence of side effects. These results suggest that 0.1 ml (5 mg) of nebulized metaproterenol may provide as much bronchodilatation as higher doses with fewer side effects.     

节段性肺炎支原体肺炎患儿肺功能检测的临床意义

目的探讨节段性肺炎支原体肺炎(SMPP)患儿肺功能变化及临床意义。方法分别测定55例SMPP患儿急性期和恢复期的肺功能,包括FVC、FEV1、FEV1/FVC、PEF、FEF25%、FEF50%、FEF75%、FEF25%-75%。结果 55例SMPP患儿急性期FVC、FEV1、FEV1/FVC、PEF、FEF25%、FEF50%、FEF75%及FEF25%-75%均有不同程度降低,以FEF25%、FEF50%、FEF75%和FEF25%-75%降低较为明显。恢复期各项指标均有明显改善,两组比较差异有统计学意义(P<0.05)。多部位病变SMPP患儿急性期FVC和FEV1较单个叶段病变患儿下降明显(P<0.05)。结论 SMPP患儿急性期大、小气道功能均有不同程度损伤,多表现为限制性通气障碍,小气道功能受损更明显;恢复期肺功能明显好转。多叶段病变大气道功能受损较单个叶段病变严重。     

昆明市5~14岁儿童肺通气功能参数实测值与Zap

目的 研究昆明市5~14岁健康儿童肺通气功能主要参数实测值占Zapletal方程式预计值的百分比,为临床准确判断肺通气功能提供依据。方法 纳入昆明市5~14岁健康儿童702名,其中男352名,女350名。采用Jaeger肺功能仪测定用力肺活量（FVC）、第1秒用力呼气容积（FEV1）、1秒率（FEV1/FVC）、最大中期呼气流量（MMEF）、用力呼气25%肺活量时瞬时流量（FEF25）、用力呼气50%肺活量时瞬时流量（FEF50）、用力呼气75%肺活量时瞬时流量（FEF75）、最高呼气流量（PEF）、每分钟最大通气量（MVV）,共9项指标,以肺功能仪中提供的Zalpetal预计值公式得出的数值作为所选择儿童的预计值,计算其实测值占预计值的百分比。结果 在702名儿童中,肺通气功能主要参数PEF、FVC、FEV1、FEV1/FVC、MVV实测值占预计值百分比的均值分别波动于102%~114%、94%~108%、98%~113%、98%~107%、141%~183%。气道流速指标功能参数FEF25、FEF50、FEF75、MMEF实测值占预计值百分比分别波动于98%~116%、85%~102%、71%~98%、83%~100%。各参数PEF、FVC、FEV1、FEV1/FVC、MVV、FEF25、FEF50、FEF75、MMEF实测值占Zapletal方程式预计值百分比的下限分别为88.2%、88.4%、92.0%、94.4%、118.5%、82.9%、70.0%、62.1%、70.1%。结论 昆明地区5~14岁健康儿童肺通气功能参数水平与Zapletal方程式提供的正常值存在一定差异;该地区此年龄段的健康儿童肺通气功能参数PEF、FVC、FEV、FEV1/FVC、MVV、FEF25、FEF50、FEF75、MMEF实测值占预计值百分比的正常参考值下限可考虑分别设为88.2%、88.4%、92.0%、94.4%、118.5%、82.9%、70.0%、62.1%、70.1%。     

Adverse pulmonary responses to aspirin and acetaminophen in chronic childhood asthma

Because aspirin (ASA) is often reported to have an adverse effect on pulmonary function in children with chronic asthma, acetaminophen is commonly used as an ASA substitute in these children. To study acetaminophen effects on pulmonary functions, double-blind, oral challenges of ASA (600 mg), acetaminophen (600 mg), or lactose were administered on separate days to 25 chronic asthmatics, ten boys and 15 girls, ranging in age from 8 to 18 years (mean age +/- 1 SD: 12.5 +/- 2.8 years). No patient had a past history of adverse reactions to either drug. Forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEFR), maximal mid-expiratory flow rate (FEF25-75), forced vital capacity (FVC), maximal voluntary ventilation (MVV), and flow volume curves were measured at base line and 1/2, 1, 2, 3, and 4 hours after ingestion of drug or placebo. Persistent decreases from base line FEV1 (greater than 20%) or FEF25-75 (greater than 30%) occurred in four ASA- and two acetaminophen-challenged patients. One ASA-sensitive patient was placebo intolerant; another reacted to acetaminophen. The acetaminophen responses were of less intensity than the ASA responses. Analysis of group mean pulmonary function responses to ASA, acetaminophen, and lactose showed no significant difference among the three agents at any time. Aspirin should be used cautiously in asthmatic children. Acetaminophen appears to be an adequate, although not completely, innocuous ASA substitute.     

What are the best pulmonary function test parameters for early detection of post‐lung transplant bronchiolitis obliterans syndrome in children?

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV1) >or=20% of baseline (B). There have been reports in adults that FEF25-75% (>30% decline from B) is more sensitive than FEV1 for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters - forced expiratory flow rates at 25-75% of vital capacity (FEF25-75%) and maximal expiratory flow rate at 80% (Vmax80%), 70% (Vmax70%) and 60% (Vmax60%) - are more sensitive indicators for early diagnosis of BOS than FEV1 in post-lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 +/- 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post-transplant days when decline in FEV1 >or=20% of B, FEF25-75% >30% of B, and Vmax80%, Vmax70% and Vmax60% from normal occurred (635 +/- 431, 551 +/- 422 and 454 +/- 287 days, respectively; p = 0.4). However, a decline in FEV1 was the first abnormality in only 39% of the patients, while a decline in FEF25-75% and Vmax at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV1 was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post-lung transplant BOS; we speculate that the diagnosis should be based on decreases in FEF25-75% rather than on FEV1.     

昆明市5~14岁儿童肺通气功能参数实测值与Zap

目的 研究昆明市5~14岁健康儿童肺通气功能主要参数实测值占Zapletal方程式预计值的百分比,为临床准确判断肺通气功能提供依据。方法 纳入昆明市5~14岁健康儿童702名,其中男352名,女350名。采用Jaeger肺功能仪测定用力肺活量（FVC）、第1秒用力呼气容积（FEV1）、1秒率（FEV1/FVC）、最大中期呼气流量（MMEF）、用力呼气25%肺活量时瞬时流量（FEF25）、用力呼气50%肺活量时瞬时流量（FEF50）、用力呼气75%肺活量时瞬时流量（FEF75）、最高呼气流量（PEF）、每分钟最大通气量（MVV）,共9项指标,以肺功能仪中提供的Zalpetal预计值公式得出的数值作为所选择儿童的预计值,计算其实测值占预计值的百分比。结果 在702名儿童中,肺通气功能主要参数PEF、FVC、FEV1、FEV1/FVC、MVV实测值占预计值百分比的均值分别波动于102%~114%、94%~108%、98%~113%、98%~107%、141%~183%。气道流速指标功能参数FEF25、FEF50、FEF75、MMEF实测值占预计值百分比分别波动于98%~116%、85%~102%、71%~98%、83%~100%。各参数PEF、FVC、FEV1、FEV1/FVC、MVV、FEF25、FEF50、FEF75、MMEF实测值占Zapletal方程式预计值百分比的下限分别为88.2%、88.4%、92.0%、94.4%、118.5%、82.9%、70.0%、62.1%、70.1%。结论 昆明地区5~14岁健康儿童肺通气功能参数水平与Zapletal方程式提供的正常值存在一定差异;该地区此年龄段的健康儿童肺通气功能参数PEF、FVC、FEV、FEV1/FVC、MVV、FEF25、FEF50、FEF75、MMEF实测值占预计值百分比的正常参考值下限可考虑分别设为88.2%、88.4%、92.0%、94.4%、118.5%、82.9%、70.0%、62.1%、70.1%。     

Pharmacokinetics and adverse effects of amphotericin B in infants and children

The pharmacokinetics and safety of amphotericin B infusion were studied in 13 infants and children (age range 3 weeks to 18 years; median age 11 years) treated with the drug for proved (n = 11) or suspected (n = 2) fungal infections. The dose during the first day was 0.5 mg/kg, followed by a daily dose of 1 mg/kg for the rest of the treatment period in most patients. The drug was infused over 4 to 6 hours. During the first day, serum concentrations were above the target therapeutic level of 0.3 microgram/ml in all patients at 2 and 6 hours from the start of the infusion, in 12 of 13 patients at 12 hours, but in only 6 of 13 patients at 24 hours. On the third day, all concentrations were greater than 0.3 microgram/ml throughout the 24-hour period, and in 12 of 13 patients were greater than 0.5 microgram/ml. The same kinetic profile prevailed on days 7 to 10 of therapy, with a tendency for increasing concentrations. Elimination half-life was 9.93 +/- 1.5 hours (mean +/- SEM), clearance rate 26 +/- 5 ml/kg.hr, and distribution volume 378 +/- 25 ml/kg. The half-life inversely correlated with patient's age. Pharmacokinetic values calculated during the first day were not different from those calculated on day 3. Significant decreases in hemoglobin, platelets, and serum potassium concentration were recorded along with significant increases in serum creatinine, urea, and aspartate transaminase values. Because of the large pharmacokinetic variability and the high rate of serious adverse effects, individualized dosing of amphotericin B based on therapeutic drug monitoring should be considered.     

Effects of passive smoking on lung function in children

BACKGROUND: Passive smoking can have significant effects on lung function with reductions in forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid-expiratory flow rate (FEF25-75%) of between 5 and 10%. METHODS: Fifty non-smoking children aged 6-15 years, who had no history of asthma or atopy and no parental history of atopy, were assessed with respect to their lung functions (FEV1, FEV1/FVC, FEF25-75%). RESULTS: Thirty-three of these children were being exposed to environmental tobacco smoke inside their homes, while 17 children were not exposed. In the 'passive smoker' group the FEV1, FEV1/FVC and FEF25-75% values were found to be significantly lower than the non-smoker control group's values (P = 0.0080, 0.0228 and 0.0003, respectively). The decrease in FEF25-75% was significantly correlated inversely with the number of cigarettes smoked per day (P = 0.0261). CONCLUSION: There is sufficient evidence to support the notion that environmental tobacco smoke is a serious health burden for children. Considering that recent studies suggest that up to 70% of children grow up in homes with at least one smoker, every effort should be made to reduce these children's exposure to environmental tobacco smoke and to give them a chance to grow up in a more healthy environment.     

Lung function tests in asthma: which indices are better for assessment of severity?

Pulmonary function tests are objective evidence of the severity of asthma. A cross-sectional study was carried out to determine the sensitivity of various pulmonary function indices in picking up clinically diagnosed mild and severe asthma. Three groups, each with 60 subjects between 5 and 15 years all of either sex, with mild asthma, severe asthma, and without asthma, respectively, were studied. Pulmonary function tests were performed using a portable spirometer. FEV1 and FVC could differentiate mild asthma from non-asthmatic children in 38 (63 per cent) and 35 (58 per cent), respectively. FEF25% and FEF75% could identify 46 (77 per cent), and 47 (78 per cent) of mild asthmatic children. In children with severe asthma, FEV1, FVC, FEF25%, and FEF75% were abnormal in 54 (90 per cent), 48 (80 per cent), 58 (97 per cent) and 56 (94 per cent), respectively. Peak expiratory flow rate was abnormal in 77 per cent of mild and 87 per cent of severe asthmatics. The FEV1/FVC ratio showed no significant difference between asthmatics and non-asthmatics. It is concluded that FEF25% and FEF75% are better indices for assessment of severity of asthma than FEV1 and FVC. The ratio FEV1/FVC is not useful.     

肺功能检查在儿童难治性肺炎支原体肺炎诊疗中的意义

目的 探讨肺功能检查在儿童难治性肺炎支原体肺炎诊疗中的价值.方法 收集2015年5月至2016年2月期间在中国医科大学附附属盛京医院住院患儿58例,所有患儿均经临床确诊为难治性肺炎支原体肺炎(refractory mycoplasma pneumoniae pneumonia,RMPP),急性期行支气管镜检查及介入治疗并于镜前24h内行肺功能检测,对支气管镜下表现和同期肺功能数值进行分析.按照支气管镜下黏膜是否完整将镜下表现分为轻度组和重度组,记录每个患儿的常规肺通气功能指标.结果 RMPP患儿镜下表现重度组急性期肺功能的大气道通气指标(FVC、FEV1、PEF)和小气道通气指标(FEF25、FEF50、FEF75、FEF25-75)较轻度组均降低,二者有显著统计学差异(P＜0.05).结论 RMPP急性期可出现不同的肺功能表现,包括肺功能正常、限制性或阻塞性或混合性通气功能障碍,最常见的是小气道功能改变,提示肺炎支原体感染后极易引起小气道受累.RMPP急性期镜下表现越重,同期的肺功能指标下降程度越重.通过肺功能检测对预测RMPP的严重程度及早期识别具有一定作用.肺功能指标对判断支气管镜介入治疗指征及评价介入治疗效果提供了更充分的依据.     

Abnormal spirometry in children with persistent allergic rhinitis due to mite sensitization: the benefit of nasal corticosteroids.

Inflammatory processes affecting nasal and bronchial mucosa are similar in nature. The purpose of this study was to examine whether children with perennial allergic rhinitis, without underlying asthma, have impaired pulmonary function. We also investigated whether nasal corticosteroids and loratidine would improve the pulmonary function tests of those children with impaired lung function. Fifty subjects with moderate/severe persistent allergic rhinitis due to exclusively dust mite sensitization and no past medical history suggestive of asthma were assessed. The control group consisted of 26 matched healthy subjects. Subjects with airway obstruction, as detected by forced expiratory volume/1 s (FEV1) or forced expiratory flow from 25/% to 75% (FEF(25-75)) values <80% of those predicted, were treated with loratidine, once a day for 10 days, and daily nasal budesonide for 3 months. We found that 11 of 50 patients (22%) with perennial allergic rhinitis had impaired pulmonary function (FEF(25-75) values <80%), compared to 1/26 (3.8%) of the control group (p < or = 0.05). Reversibility was observed in 9/11 (81.8%), mean 24.7% +/- 10.3%. Within 3 months of treatment, 7/10 had FEF(25-75) > 80% of their predicted values as well as significant improvements in their FEV1 (p = 0.04), and FEV1/FVC (p = 0.04). We conclude that a substantial proportion of children with perennial allergic rhinitis have diminished FEF (25-75) values and reversible airway obstruction. Nasal corticosteroids improve the pulmonary function tests of these children with impaired lung function.     

Significance of transient postnatal hypothyroxinemia in premature infants with and without respiratory distress syndrome

The significance of relatively low thyroxine (T4) levels in preterm infants with and without respiratory distress syndrome (RDS) was assessed by evaluating the free T4 level, the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH), and intellectual development in infants less than or equal to 35 weeks with cord blood T4 concentrations less than 6.5 microgram/100 ml. Fifty-four (19 well, 28 with RDS, and seven without RDS and sick) of 215 premature infants (25%) and 27 of 8,831 term infants (0.3%) had cord T4 levels less than 6.5 microgram/100 ml. Serum T4 levels were measured in 39 surviving preterm infants (20 RDS and 19 well) during the first 5 days of life and at 2, 4, 24, and 52 weeks postnatally. Serum total T4 level during the first week was 4.5 +/- 0.3 microgram/100 ml (mean +/- SEM). Free T4 levels ranged from 1.1 to 2.2 ng/100 ml (normal adult range 0.8 to 2.3 ng/100 ml). Administration of TRH resulted in a clear increase in both TSH and T4 levels in all infants. T4 levels increased significantly (r = .70, P less than .01) with increasing postnatal age, reaching stable levels by 6 to 7 weeks. Developmental quotients obtained in the infants with low T4 levels were no different from those found in a matched control population at 12 months of age. The low T4, free T4, and TSH concentrations and normal TSH responses to TRH found in these infants are characteristic of hypothalamic (tertiary) hypothyroidism, but differ from classic tertiary hypothyroidism in that the disorder was transient. The normal intellectual development at 12 months of age and the spontaneous increase in T4 levels that occurs over the first six weeks of life suggest that the low T4 levels in these infants reflect a benign relative delay in maturation of hypothalamic-pituitary-thyroid control.     

大鼠获得性漏斗胸形成过程中肺功能的观察

目的 观察获得性漏斗胸形成过程中肺功能的变化.方法 4周龄SD大鼠40只按数字随机法分为实验组和对照组各20只.实验组行经胸骨旁切断下位三对肋软骨观察漏斗胸形成,对照组不做任何干预,于术后3d和4周测定动物肺功能指标,包括:吸气阻力(Ri)、呼气阻力(Re)、肺的顺应性(Cl)、每分钟通气量(MVV)、用力肺活量(FVC)、第0.2s用力呼气容积(FEV0.2)、FEV0.2/FVC%、呼出50%FVC量时的流速(FEF50%)及用力最大呼气流速(PEF)等,检测结果在组间进行比较分析.结果 造模术后1周内动物呼吸频率增快,其后漏斗胸逐渐形成并稳定.肺功能检测:术后3d测得Ri在实验组和对照组分别为(1.16±0.21)cmH2O·ml-1·s-1和(0.73±0.26)cmH2O·ml-1·s-1 (P=0.00),Re分别为(0.86±0.30)cmH2O·ml-1·s-1和(0.58±0.16)cmH2O·ml-1·s-1 (P=0.01),Cl分别为(0.05±0.01)cmH2O/ml和(0.09±0.02)cmH2O/ml(P=0.00),FVC分别为(3.69±0.10)ml和(3.89±0.19)ml (P=0.00),FEV0.2分别为(3.28±0.40) ml和(3.58±0.15)ml(P=0.02);术后4周测得Ri在实验组和对照组分别为(0.88±0.17) cmH2O·ml-1·s-1和(0.66±0.10)cmH2O·ml-1·s-1 (P=0.00),FVC分别为(5.76±0.52)ml和(5.47±0.20) ml(P=0.05).Ri在术后3d和4周的检测结果在同龄动物组间比较差异均有显著性,造模术后动物的吸气阻力增加(P<0.05);Re、Cl、FEV0.2和FVC等指标在术后3d的测得值组间差异有显著性,实验组Re增加而另3个指标减小(P<0.05),FVC在术后4周时组间比较P=0.05,而MVV 、FEV0.2/FVC%、PEF25%~75%和PEF等指标不论在术后3d还是4周的检测结果组间比较差异均无统计学意义(P>0.05).结论 通过胸骨旁切断下位三对肋软骨造成模型漏斗胸的形成过程中,幼鼠吸气和呼气阻力增加,胸壁和肺的顺应性均降低,随着漏斗胸的形成和稳定,肺功能重新建立适应,但胸廓的顺应性仍较正常降低.     

The effect of reduction of maintenance treatment on circadian variation in peak expiratory flow rate values in asthmatic children

We investigated in well controlled asthmatic children whether it is possible to predict by measuring daytime forced expiratory volume in one second, the decline in nocturnal peak expiratory flow rate values after withdrawal of maintenance medication. Forced expiratory volume in one second and peak expiratory flow rate were measured in the outpatient clinic, on the last day with medication. Peak expiratory flow rates were then measured every four hours on days 4, 5 and 6 without medication. Seventeen children showed an amplitude in circadian peak expiratory flow rate values of more than 20% (group I) and nine children showed an amplitude of 20% or less on the three study days (group II). Mean values +/- SEM were 34.7 +/- 2.1% and 10.5 +/- 1.5%, respectively. Forced expiratory volume in one second values were comparable in both groups. Daytime peak expiratory flow rate values before and after withdrawal, remained on the same level in both groups. In group I peak expiratory flow rate values of 24.00 and 08.00 hours on day 6 were significantly lower (p less than 0.05) than on day 4. The results indicate that history and daytime pulmonary function measurements alone, are insufficient to assess the clinical situation and suggest that a decrease in early morning peak expiratory flow rate value (08.00 hours) is an early sign of deterioration of the disease state, after reduction of medication.     

Risk factors for reduced lung function in Australian Aboriginal children

AIM: To determine the influence of perinatal and childhood exposures on lung function in a cohort of Australian Aboriginal children. METHODS: This was a cross-sectional study of 547 Northern Territory Aboriginal children, aged 8-14 years, belonging to a birth cohort. Assessment included physical examination and spirometry as well as retrospective review of centralised hospital records. The effect of select perinatal and childhood exposures on lung function outcomes (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and forced expiratory flow between 25 and 75 s (FEF25-75)) adjusted for age, sex, height and other measures of size was examined using multiple regression. RESULTS: Non-urban residence (FEV1 -5% (95% confidence interval, CI 0.91-0.99), FVC -9% (95% CI 0.87-0.95)), current cough (FEV1 -6% (95% CI 0.91-0.97), FVC -4% (95% CI 0.93-0.97), FEF25-75 -8% (95% CI 0.86-0.98)) and hospitalisations for respiratory disease (FEV1 -10% (95% CI 0.86-0.95), FEF25-75 -12% (95% CI 0.70-0.87)) all had significant negative effects on adjusted lung function measures. Children with a non-Aboriginal ancestor had significantly better lung function. No perinatal exposure other than neonatal lung disease had any significant effect on adjusted lung function. CONCLUSIONS: For Northern Territory Aboriginal children factors related to the childhood environment are more important than perinatal factors in determining childhood lung function.     

Impact of acute chest syndrome on lung function of children with sickle cell disease

OBJECTIVE: To test the hypothesis that children with sickle cell disease (SCD) who experienced an acute chest syndrome (ACS) hospitalization episode would have worse lung function than children with SCD without ACS episodes. STUDY DESIGN: Forced expiratory volume in 1 second (FEV(1)); forced vital capacity (FVC); FEV(1)/FVC ratio; peak expiratory flow (PEF); forced expiratory flow at 25% (FEF(25)), 50% (FEF(50)), and 75% (FEF(75)) of FVC; airway resistance (Raw); and lung volumes were compared in 20 children with ACS and 20 aged-matched children without ACS (median age, 11 years; range, 6 to 16 years). Fourteen age-matched pairs were assessed before and after bronchodilator use. RESULTS: The mean Raw (P = .03), TLC (P = .01), and RV (P = .003) were significantly higher in the group with ACS than in the group without ACS. There were no significant differences in the changes in lung function test results in response to bronchodilator administration between the 2 groups, but the children with ACS had a lower FEF(25) (P = .04) and FEF(75) (P = .03) pre-bronchodilator use and a lower mean FEV(1)/FVC ratio (P = .03) and FEF(75) (P = .03) post-bronchodilator use. CONCLUSIONS: Children with SCD who experienced an ACS hospitalization episode had significant differences in lung function compared with those who did not experience ACS episodes. Our results are compatible with the hypothesis that ACS episodes predispose children to increased airway obstruction.     

哮喘和咳嗽变异性哮喘儿童肺常规通气功能的比较

目的：比较哮喘与咳嗽变异性哮喘（CVA）患儿肺常规通气功能的变化。方法：选择2010年 5月至2011年5月确诊为哮喘或CVA的患儿140例,分为哮喘急性发作组（发作组,50例）、哮喘缓解组（缓解组,50例）和CVA组（40例）;同期正常健康体检儿童30例作为对照组。测定4组儿童用力肺活量(FVC)、一秒钟用力呼气容积(FEV1)、最大呼气峰流速(PEF)、用力呼气25%流速(FEF25)、用力呼气50%流速(FEF50)、用力呼气75%流速(FEF75)、最大呼气中期流速(MMEF75/25)等7项肺功能指标。结果：发作组患儿各项肺功能指标如大气道指标FVC、FEV1、PEF、FEF25及小气道指标FEF50、FEF75、MMEF75/25的实际值/预计值平均水平均<80%,且以FEF50、FEF75、MMEF75/25等小气道指标下降为著。CVA组患儿小气道指标FEF75、MMEF75/25实际值/预计值的平均水平<80%。发作组各项肺常规通气功能指标均低于对照组;缓解组、CVA组FVC、FEV1、FEF25及 MMEF75/25实际值/预计值的平均水平低于对照组;发作组各项肺功能指标均明显低于缓解组和CVA组;CVA组与缓解组各项肺功能指标差异均无统计学意义。结论：哮喘急性发作期患儿存在大小气道功能障碍,以小气道功能障碍为主;CVA患儿以小气道功能轻微障碍为主,与哮喘缓解期相似。     

Lack of cardiac effect from repeated doses of albuterol aerosol. A margin of safety

To simulate the pattern of use by some patients at home, we studied the effect of frequently repeated inhalation of albuterol aerosol on cardiac rhythm. Fifteen stable outpatient asthmatic children, ages 9-14 years were treated with two puffs of albuterol aerosol (180 mcg) followed either by hourly placebo or hourly albuterol aerosol for 5 hours (10 puffs = 900 mcg) in a randomized, double-blind crossover study. Cardiac rhythm was Holter monitored and pulmonary function was tested hourly for 5 hours. Heart rate (HR) was analyzed at hourly intervals. Pretreatment heart rate of 95.4 bpm +/- 1.9 SEM declined by 0.4-3 (bpm) after single dose and declined by 2.2-5.6 (bpm) from 99.2 (bpm) +/- 2.3 SEM during multiple doses. No one developed arrhythmia, and side effects were infrequent on either day. Forced expiratory volume in 1 second (FEV1) increased similarly on both regimens. It remained stably elevated on the multiple doses, but it started to decline at 120 minutes after the single dose. Our study shows a substantial margin of safety in administration of albuterol aerosol to asthmatic children.     

Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide

OBJECTIVE: To compare the efficacy and adverse effects of inhaled fluticasone propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800 microgram/d, in children with moderate to severe asthma. METHODS: Three hundred thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were enrolled in a double-blind, double-dummy, randomized, parallel-group study. After a 2-week run-in phase, 166 children received FP and 167 received BUD for 20 weeks. The primary outcome variable was mean morning peak expiratory flow; the 2 treatments were to be regarded as equivalent if the 90% CI for the treatment difference was within +/- 15 L/min. Pulmonary function, height, and diary cards were assessed at each visit; and morning serum cortisol levels were determined before and after treatment. RESULTS: Baseline peak expiratory flow was similar, FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/- 41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =.002). Symptom control and use of rescue medication were the same. Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD) (treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003). CONCLUSION: FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms. Growth was reduced with BUD compared with FP, but there was no difference in serum cortisol suppression or hepatic or renal function.