氯雷他定治疗儿童哮喘的疗效与安全性评价

目的：评价新一代抗组胺药物氯雷他定治疗儿童哮喘的疗效和安全性,为儿童哮喘的治疗提供临床依据。方法：采用计算机及手工检索方式检索PubMed、MEDLINE、EMBASE、Cochrance、CNKI、CBMdisc等数据库（1990年1月至2010年12月）。对文献质量进行内部真实性评价,并按Cochrane协作网推荐的方法进行系统评价和分析。结果：检索到文献179篇,最终纳入11篇随机对照研究,共有317例哮喘儿童,其中氯雷他定治疗组159例,安慰剂治疗组（对照组）158例。所有纳入文献质量为B级。Meta分析的结果表明,治疗后氯雷他定组的临床评分、4周和8周的一秒用力呼气容积（FEV1）、8周的呼吸流速峰值（PEFR）均明显优于对照组（P<0.01）,差异均有统计学意义。而氯雷他定组乏力和心动过速及心悸的发生比率均低于对照组,差异有统计学意义。结论：采用氯雷他定治疗儿童哮喘安全有效,值得在临床进行推广。     

氯雷他定对哮喘儿童P-选择素表达的抑制作用及临床意义

为评价氯雷他定对哮喘儿童血浆Ｐ－选择素表达的抑制作用及临床应用的意义。应用＾１２５Ｉ－ＳＺ－５１标记的特异性单克卫生抗体放免法。测定６０例急性发作期和缓解期哮喘患儿血浆Ｐ－选择互水平。随机分成治疗组（３０组）,采用吸入激素＿氯均较对照组明显下降和改善,差异显著（Ｐ均〈０．０１）。提示氯雷他定具有抵抑制Ｐ－选择素表达的作用,能有效地减轻变应性炎症,改善哮喘儿童的临床症状和肺功能,可能作为辅佐治疗儿童     

联合降阶梯方案治疗婴幼儿喘息临床研究

目的观察联合降阶梯方案治疗婴幼儿喘息的有效性及安全性。方法采用分层随机、开放、平行对照试验,于2013年2月至2015年1月,从上海交通大学医学院附属新华医院等4家医院选择轻中度急性发作期的喘息患儿206例,分为观察组106例、对照组100例。(1)观察组采用联合降阶梯方案:醋酸泼尼松片,0.5 mg/(kg·d),晨顿服,疗程3 d;阿奇霉素干混悬剂,10 mg/(kg·d),1次/d,疗程3 d;妥洛特罗贴剂,0.5 mg/d,1次/d,疗程7 d;氯雷他定糖浆,3 mg/d,1次/d,疗程14 d;孟鲁司特钠,4 mg/d,1次/d,疗程28 d。给药途径为口服或外用。(2)对照组采用常规治疗方案:甲泼尼龙琥珀酸钠,1 mg/(kg·d),1次/d,疗程3 d;头孢类抗生素,用药剂量参照说明书,疗程3 d;口服氨溴特罗口服液,每次2.5~7.5 m L,每12 h 1次,疗程遵医嘱(药物连续服用不超过7 d);前两者为静脉给药。观察治疗前后症状、体征积分、疗效及喘息反复情况。结果治疗后7 d的分析结果显示,观察组、对照组的症状体征积分和下降均值分别为5.89、4.84,治疗总有效率分别为98.11%、92.00%(P0.05)。治疗后28 d的分析结果显示,对照组、观察组的喘息反复发生率分别为24.00%、12.26%(P0.05)。结论联合降阶梯方案治疗婴幼儿喘息(轻中度急性发作期)疗效优于常规治疗方案,且可减少喘息反复发作风险,临床应用安全。     

氯雷他定对哮喘豚鼠白细胞介素5及嗜酸性粒细胞凋亡的影响

目的研究氯雷他定对哮喘豚鼠支气管肺泡灌洗液(BALF)和血清IL-5的表达及肺组织嗜酸性粒细胞(EOS)凋亡延迟状态的影响。方法豚鼠32只随机分为正常对照组、哮喘组、氯雷他定低剂量组、氯雷他定高剂量组。经3次20 g·L-1卵清蛋白(OVA)腹腔注射致敏后,10 g·L-1OVA雾化吸入40 min诱发哮喘发作。氯雷他定低、高剂量组豚鼠分别予2 mg·kg-1·d-1、10mg·kg-1·d-1氯雷他定灌服14 d,每天1次;哮喘组、正常对照组给予9 g·L-1盐水作对照。ELISA法检测其血清和BALF中IL-5水平,罗氏TUNEL原位细胞凋亡检测试剂盒检测其凋亡细胞,HE染色切片随机计数每张切片下200个EOS中凋亡细胞数。结果1.正常对照组、哮喘组、氯雷他定低剂量组、氯雷他定高剂量组血清IL-5水平分别为(0.27±0.04)ng·L-1、(0.41±0.03)ng·L-1、(0.38±0.02)ng·L-1、(0.31±0.03)ng·L-1;BALF中IL-5水平分别为(0.10±0.01)ng·L-1、(0.38±0.04)ng·L-1、(0.33±0.05)ng·L-1、(0.23±0.09)ng·L-1,血清及BALF中IL-5水平4组间两两比较差异均有统计学意义(Pa<0.05)。2.正常对照组、哮喘组、氯雷他定低剂量组、氯雷他定高剂量组豚鼠肺组织EOS发生凋亡的细胞数分别为33个、95个、129个、182个,两两比较差异有统计学意义(χ2=114.5,P<0.05)。其中哮喘组与氯雷他定低剂量组间差异无统计学意义(χ2=10.0,P>0.008 3)。结论氯雷他定对IL-5相关的EOS凋亡延迟状态有抑制作用,能改善肺组织变应性炎症状态,对哮喘的控制具有潜在的积极作用。     

抗生素降阶梯治疗在临床应用的再探讨

抗生素降阶梯治疗(ADE)是指停止使用经验性联合抗生素治疗方案中的一种或几种药物,和(或)用较窄谱抗生素替代广谱抗生素。ADE是重症监护病房最为常用的抗生素管理策略之一。本文就ADE的临床应用现况及困窘作一综述。     

婴幼儿喘息的药物治疗

发生喘息的婴幼儿是一个异质性群体，可由多种原因引起。婴幼儿喘息的治疗因病因而异，原则上包括病因治疗（抗感染、取异物、抗反流治疗、解除腔外压迫）、祛痰解痉平喘（化痰药物、β2受体激动剂、抗胆碱药等）、控制气道炎症（激素、白三烯调节剂）及其他对症支持治疗（吸氧、纠正酸中毒、补液、湿化气道）。本文将针对婴幼儿喘息的主要治疗药物讨论如下。     

氯雷他定对哮喘豚鼠肺泡灌洗液及血清白细胞介素-5和嗜酸性粒细胞计数的影响

目的 观察氯雷他定对支气管肺泡灌洗液(BALF)和血清IL-5表达以及嗜酸性粒细胞(EOS)计数的影响,探讨氯雷他定对哮喘豚鼠模型呼吸道高反应性的作用.方法 将32只豚鼠随机分为正常对照组、哮喘组、氯雷他定低剂量组及氯雷他定高剂量组.经鸡卵白蛋白(OVA)致敏后,给予OVA雾化吸入,诱发哮喘发作制作哮喘模型,氯雷他定低剂量组和氯雷他定高剂量组分别给予氯雷他定2 mg·kg-1和10 mg·kg-1灌服.在末次雾化吸入OVA后,经动物呼吸机测定豚鼠呼吸道压力,用酶联免疫法检测其血清和BALF中IL-5水平,并计数外周血及BALF中EOS.结果 正常对照组、哮喘组、氯雷他定低剂量干预组及高剂量干预组血清IL-5水平分别为(0.27±0.04) ng·L-1、(0.41±0.03) ng·L-1、(0.38±0.02) ng·L-1及(0.31±0.03) ng·L-1,BALF中IL-5水平分别为(0.10±0.01) ng·L-1、(0.38±0.04) ng·L-1、(0.33±0.05) ng·L-1及(0.23±0.09) ng·L-1;外周血EOS计数分别为(4.0±0.6)×108L-1、(54.6±7.6)×108L-1、(44.5±3.9)×108L-1及(29.0±5.8)×108L-1;BALF中EOS计数分别为(3.0±0.5)×108L-1、(33.7±3.9)×108L-1、(27.1±3.2) ×108L-1及(18.6±3.3) ×108L-1.以上各指标任意2组比较差异均有统计学意义(Pa＜0.05,0.01).当吸入组胺质量浓度为10 mg·L-1和20 mg·L-1时,哮喘组与氯雷他定低剂量组比较差异无统计学意义,其余任意2组比较差异均有统计学意义(Pa＜0.05).结论 氯雷他定低、高剂量均能改善哮喘模型中豚鼠呼吸道高反应性,并对血清及BALF中IL-5的表达有抑制作用,同时使血清、BALF中EOS计数减少.     

硫酸特布他林注射液治疗婴幼儿喘息性疾病的有效性和安全性临床研究

目的　探讨硫酸特布他林注射液雾化吸入治疗婴幼儿喘息性疾病的疗效和安全性。方法　选择2016年12月至2018年4月在苏州大学附属儿童医院、 成都市妇女儿童中心医院及大连医科大学附属大连市儿童医院呼吸科住院的440例以咳嗽、 喘息为主要表现的下呼吸道感染婴幼儿为研究对象。所有患儿随机分为硫酸特布他林注射液组（A组）、 硫酸特布他林雾化液组（B组）和对照组（C组）。比较三组患儿的疗效、 不良反应发生情况。结果　A组、 B组患儿住院期间喘息症状评分改善显著快于C组（P＜0.05）。A组和B组对心率均有一定的影响，在雾化后30 min及60 min的心率均高于C组。除了对心率的影响外， A组和C组未发现其他不良反应； B组有1例患儿出现手臂震颤， 停药后消失。结论　硫酸特布他林注射液雾化吸入治疗婴幼儿喘息性疾病可以缩短治疗时间， 有效提高临床治疗效率， 临床疗效与硫酸特布他林雾化液相当， 同时安全性高， 值得在临床上推广和运用。     

特布他林联合氨茶碱治疗78例小儿喘息性疾病的临床观察

从2001年11月-2006年11月以来，盘县第二人民医院儿科结合过去实践经验，采用特布他林联合氨茶碱治疗小儿喘息性疾病获得较满意的疗效，现总结报告如下。     

婴幼儿喘息性社区获得性肺炎患儿血清炎症因子的变化

目的 通过测定婴幼儿喘息性社区获得性肺炎(CAP)患儿血清炎症因子的变化,了解婴幼儿喘息性肺炎是否与哮喘有相似的免疫机制。方法 喘息性CAP 47例、非喘息性CAP 42例、正常对照30例婴幼儿纳入该研究。比较3组间外周血C反应蛋白、降钙素原、可溶性髓系细胞触发受体-1、γ干扰素、白细胞介素4、白细胞介素10及骨膜蛋白水平。结果 喘息性和非喘息性肺炎组血降钙素原、可溶性髓系细胞触发受体-1、白细胞介素4、白细胞介素10 含量均高于正常对照组(PPP结论 婴幼儿喘息性肺炎存在γ干扰素/白细胞介素4比值失衡,存在气道嗜酸性粒细胞炎症,提示婴幼儿喘息性肺炎与哮喘有相似的免疫机制。     

外周血CD23表达阳性B淋巴细胞对婴幼儿喘息预后的早期预测作用

目的　探讨外周血CD2 3表达阳性B淋巴细胞 (CD2 3 /CD19 )在婴幼儿哮喘中的表达及对婴幼儿喘息预后的早期预测价值。方法　用流式细胞术测定 5 3例喘息性支气管炎 (喘息组 )、17例婴幼儿哮喘 (哮喘组 )、18例婴幼儿肺炎患儿 (肺炎组 )及 2 2例正常对照组儿童的外周血淋巴细胞CD2 3 /CD19 表达。并对 5 3例喘息性支气管炎做进一步随访。结果　 (1) 5 3例喘息性支气管炎患儿在随访 3年后 ,最终发展为儿童哮喘的有2 0例 (喘息Ⅰ组 ) ,喘息终止 33例 (喘息Ⅱ组 )。 (2 )婴幼儿哮喘组CD2 3 /CD19 表达较婴幼儿肺炎组、对照组增高 ,差异有显著性 (P <0 0 1) ;婴幼儿肺炎组与对照组比较差异无显著性 (P >0 0 5 )。 (3)喘息Ⅰ组CD2 3 /CD19 表达较婴幼儿肺炎组和对照组升高 (P <0 0 1) ,与婴幼儿哮喘组比较差异无显著性 (P >0 0 5 ) ;喘息Ⅱ组CD2 3 /CD19 表达与肺炎组、对照组比较差异无显著性 (P >0 0 5 )。 (4)喘息Ⅰ组CD2 3 /CD19 表达与喘息Ⅱ组比较差异有显著性 (P <0 0 1)。结论　婴幼儿哮喘及最终发展为哮喘的喘息性支气管炎患儿喘息早期表达CD2 3 /CD19 增高 ,CD2 3 /CD19 对婴幼儿喘息预后早期预测可能有重要价值。     

急诊科反复喘息婴幼儿需要住院并接受呼吸支持治疗的预测因素

目的 反复喘息患者多为2岁以下的婴幼儿。在热带国家,对该人群住院期间接受呼吸支持治疗的风险的临床预测模型研究较少。该研究旨在评估就诊于哥伦比亚急诊科的反复喘息婴幼儿需要住院并接受呼吸支持治疗的临床预测因素。方法 该研究是一项回顾性队列研究,纳入了2019年1~12月期间在哥伦比亚Rionegro的两个三级中心医院就诊的所有患有2次或2次以上喘息发作的婴幼儿（年龄均小于2岁）。主要结局指标是住院加呼吸支持治疗。采用多因素logistic回归模型确定需要住院并接受呼吸支持治疗的独立预测因素。结果 共85名婴幼儿住院并接受呼吸支持治疗,其中34名（40%）予以高流量鼻导管吸氧,2名（2%）予以无创通气,6名（7%）予以机械通气,43名（51%）予以常规氧疗。多因素logistic回归模型分析显示,早产（OR=1.79,95% CI：1.04~3.10）、喂养困难（OR=2.22,95% CI：1.25~3.94）、鼻煽和/或咕噜声（OR=4.27,95% CI：2.41~7.56）和既往有1次以上喘息发作需要住院治疗（OR=3.36,95% CI：1.86~7.08）是需要住院并接受呼吸支持治疗的预测因素。该模型特异度高（99.6%）,鉴别度中等,曲线下面积为0.70（95% CI：0.60~0.74）。结论 该研究表明,早产、喂养困难、鼻煽和/或呼噜声,以及有1次以上需要住院治疗的喘息发作史,是急诊科就诊的反复喘息婴幼儿需要住院并接受呼吸支持治疗的独立预测因素。然而,还需收集更多的其他热带国家的证据来验证这个结论。     

肥胖对哮喘预测指数阳性喘息婴幼儿治疗效果的影响

目的 探讨肥胖对哮喘预测指数（API）阳性喘息婴幼儿治疗效果的影响。方法 选取API 阳性的喘息婴幼儿208 例,按Kaup 指数分为肥胖组（93 例）和非肥胖组（115 例）。在急性喘息发作期给予综合治疗,缓解期给予吸入性糖皮质激素（ICS）布地奈德混悬液压缩泵雾化吸入治疗。根据临床控制情况调整ICS治疗用量,共治疗6 个月。治疗后2 周随访1 次,之后每月随访1 次。结果 治疗后2 周、1 个月肥胖组的临床症状缓解率分别为35.5% 及75.3%,低于非肥胖组的53.0% 和87.8%（P P 结论 肥胖可抑制API 阳性喘息婴幼儿对ICS 治疗的反应。     

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??Objective??To evaluate the efficacy and safety of combined de-escalation therapy in the treatment of infant wheezing. Methods??Stratified random??open??parallel control method was adopted. A total of 206 cases of infant wheezing??mild-to-moderate at acute exacerbation?? were recruited from 4 clinical research centers from Feb. 2013 to Jan. 2015??and were divided into the experiment group??n??106?? and the control group??n??100??. ??The experiment group was given the combined de-escalation therapy??prednisone acetate tablets 0.5 mg/??kg·d????QD for 3 d??azithromycin suspension 10 mg/??kg·d????QD for 3 d??tulobuterol tape 0.5 mg/d??QD for 7 d??loratadine syrup 3 mg/d??QD for 14 d??montelukast sodium 4 mg/d??QD for 28 d. The drugs were taken orally or used externally. ??The control group was given the conventional therapy??methylprednisolone 1 mg/??kg·d????QD for 3 d??cephalosporin??medication dosage referring to the drug instructions?? for 3 d??ambrocol oral solution??2.5-7.5 mL each time??Q12 h??taken as prescribed but not more than 7 d??. Both methylprednisolone and cephalosporin were administered by intravenous drip. Before and after treatment??observe the symptom and sign improvement??the treatment effect and the repeatedness of wheezing. Results??After 7 d of treatment??the mean decreased value of symptom score was 5.89 in experiment group and 4.84 in control group??the total effective rate was 98.11% in experiment group and 92.00% in control group??P??0.05??. After 28 d of treatment??the experiment group has lower rate of recurrent wheezing incidence??12.26%?? than the control group??24.00%????P??0.05??. Conclusion??The efficacy of combined de-escalation therapy for infant wheezing??mild-to-moderate at acute exacerbation?? is superior to conventional therapy with good clinical safety. The combined de-escalation therapy may achieve good social and economic benefits by reducing the risk of recurrent wheezing.     

Risk factors associated with wheezing in infants

Objectiveto identify possible risk factors associated with wheezing in infants (12-15 months-old) in the state of Mato Grosso, Brazil.Methodsthis was a cross-sectional study performed by applying a standardized written questionnaire from the international study on wheezing in infants (Estudio Internacional de Sibilancia en Lactantes - EISL), phase 3. Parents and/or guardians of infants were interviewed at primary health care clinics or at home from August of 2009 to November of 2010. Factors associated to wheezing were studied using bivariate and multivariate analysis (using the Statistical Package for Social Sciences [SPSS] v.18.0), and expressed as odds ratios (OR) and 95% confidence intervals (95% CI).Resultsthe written questionnaire was answered by 1,060 parents and/or guardians. The risk factors for wheezing were: history of asthma in the family [mother (OR = 1.62; 95% CI = 1.07-2.43); father (OR = 1.98; 95% CI = 1.22-3.23); siblings (OR = 2.13; 95% CI = 1.18-3.87)]; history of previous pneumonia (OR = 10.80; 95% CI = 4.52-25.77); having had more than six upper respiratory tract infections (URTIs) (OR = 2.95; 95% CI = 2.11-4.14); having had first URTI before the third month of life (OR = 1.50; 95% CI = 1.04-2.17); living in a moderately polluted area (OR = 1.59; 95% CI = 1.08-2.33); paracetamol use for URTI (OR = 2.13; 95% CI = 1.54-2.95); and antibiotic use for skin infection (OR = 2.29; 95% CI = 1.18-4.46).Conclusionsthe study of risk factors for wheezing in the first year of life is important to help physicians identify young children at high risk of developing asthma and to improve public health prevention strategies in order to reduce the morbidity of wheezing in childhood.     

Faecal microbiota in breast-fed infants after antibiotic therapy

Aim: To evaluate modifications of gut microbiota after antibiotic therapy in breast‐fed infants. Study design: Twenty‐six exclusively breast‐fed infants younger than 5 months hospitalized for pneumonia treated with ceftriaxone (50 mg per kilo per day administered intramuscularly) were recruited. Intestinal microbiota at day 0 – before starting antibiotic administration – at the end of the therapy (5 days after) and after 15 days after the stop was analysed. Stool samples were collected and immediately diluted and cultured on selective media to detect total bacteria, Enterobacteriaceae, enterococci and lactobacilli. Statistical analysis was performed by using Wilcoxon test. Results: After 5 days of antibiotic therapy, we observed a significant reduction in total faecal bacterial count (p = 0.003) in Enterobacteriaceae (p = 0.001) and enterococci (p < 0.001), in comparison with day 0. After 5 days of therapy, lactobacilli are no longer detected. Conversely, bacterial count values for all bacteria detected after 15 days from the end of therapy are significantly increased and similar to day 0. Conclusion: Our findings showed that gut microbiota was significantly modified after 5 days of antibiotic therapy; exclusively, breast‐feeding may be relevant in promoting the re‐establishment of gut microbiota composition in early infancy.     

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??Abstract??Wheeze is a common symptom in infants and pre-school children characterized by chronic inflammation of the airway. The management of infantile wheeze focuses on anti-inflammatory agents including corticosteroids?? bronchodilators?? leukotriene receptor antagonists?? antihistamine drugs and macrolides. Here we reviewed the current medications of infantile wheeze and propose a de-escalation combined therapy based on our long-term practice.     

哮喘高危婴幼儿喘息发作期病毒病原及过敏原检测分析

目的分析哮喘高危婴幼儿喘息发作期病毒病原学、过敏原分布，为喘息患儿的早期诊断与干预治疗提供帮助。方法选取2016年4月至2017年8月因喘息性支气管炎和喘息性支气管肺炎住院的135例哮喘高危婴幼儿为研究对象。采用荧光探针PCR法检测患儿鼻咽部抽吸物标本甲型流感病毒（Flu-A）、呼吸道合胞病毒（RSV）、腺病毒（ADV）、副流感病毒（PinF）、人鼻病毒（HRV）、人偏肺病毒（hMPV）、博卡病毒（HBoV）感染情况；采用ImmunoCAP技术检测患儿吸入性变应原、食物性变应原及总IgE浓度。结果 135例患儿中，鼻咽部抽吸物标本病毒检出阳性率为49.6%，各病毒检出阳性率由高到低依次为HRV 25.2%、HBoV 9.6%、RSV 8.1%、PinF 5.9%、Flu-A 3.7%、ADV 1.5%、hMPV 0.7%。HRV在1~3岁年龄组检出率高于<1岁组（P < 0.05）。过敏原筛查试验阳性率为59.3%，吸入性过敏原阳性率为44%，食物性过敏原阳性率为89%；吸入性过敏原中阳性率由高到低依次为尘螨77%、霉菌37%、花粉26%、动物皮屑9%；食物性过敏原中阳性率由高到低依次为鸡蛋白73%、牛奶68%。<1岁组吸入性过敏原阳性率大于1~3岁组（P < 0.05）；1~3岁组T-IgE水平明显高于<1岁组（P < 0.05）。病毒检出组吸入性过敏原阳性率大于病毒未检出组（P < 0.05）。第2次喘息患儿吸入性、食物性过敏原阳性率及T-IgE水平均高于第1次喘息患儿（P < 0.05）；吸入性过敏原尘螨、霉菌在第2次喘息患儿中阳性率高于第1次喘息患儿（P < 0.05）。结论早期HRV感染和吸入性过敏原阳性与哮喘高危婴幼儿喘息发生密切相关。     

Treatment of recurrent acute wheezing episodes in infancy with oral salbutamol and prednisolone

The aim of this study was to investigate the role of oral salbutamol and prednisolone in the treatment of acute episodes of wheezing in infants under 15 months of age. Sixty-two acute episodes of wheezing were studied in 59 babies (age range 3–14 months; mean 7 months), who had all suffered at least one previous wheezy episode. Patients were randomised to receive either salbutamol and prednisolone, salbutamol and placebo or double placebo. Parents were requested to keep a diary card record of twice daily scoring of their baby's symptoms over the next 14 days. A significantly greater number of treatment failures occurred in the placebo group compared to babies treated with oral salbutamol (relative risk 2.51; 95% confidence intervals for relative risk 1.09–5.79). There was no difference in the number of treatment failures between babies treated with a combination of salbutamol and placebo and those treated with salbutamol and prednisolone (relative risk 0.71; 95% confidence intervals for relative risk 0.18–2.80).Conclusion This study demonstrates that oral salbutamol is beneficial in the treatment of acute episodes of wheezing in infancy. A combination of oral salbutamol and oral prednisolone appeared to have no additional benefit over treatment with oral salbutamol alone.