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Volume 39 Issue 5
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HAO Xiuli, XIE Fang, YAN Xueping. The therapeutic effect of budesonide on childhood asthma and its influence on growth and development 1 to 2 years after the treatment[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 479-482. doi: 10.12206/j.issn.1006-0111.202101013
Citation: HAO Xiuli, XIE Fang, YAN Xueping. The therapeutic effect of budesonide on childhood asthma and its influence on growth and development 1 to 2 years after the treatment[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 479-482. doi: 10.12206/j.issn.1006-0111.202101013

The therapeutic effect of budesonide on childhood asthma and its influence on growth and development 1 to 2 years after the treatment

doi: 10.12206/j.issn.1006-0111.202101013
  • Received Date: 2021-01-12
  • Rev Recd Date: 2021-04-22
  • Available Online: 2021-09-28
  • Publish Date: 2021-09-25
  •   Objective  To explore the effect of budesonide suspension for inhalation in the treatment of childhood asthma and its influence on growth and development in 1-2 years.  Methods  The 68 children with asthma admitted to our hospital from October 2016 to January 2017 were selected. Every patient had acute attacks and received continued medication. 34 patients treated with salbutamol sulfate inhaled aerosol were used as the control group. 34 patients treated with budesonide suspension combined with salbutamol sulfate aerosol were classified as the observation group. The interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), high-sensitivity-C-reactive protein (hs-CRP), maximum respiratory flow, IS maximum expiratory volume, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, wet rales disappearing time, cough disappearing time, and the two year follow-up indicators of growth and development were compared.  Results  After medication, IL-6, TNF-α, hs-CRP, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, moist rales disappearance time, and cough disappearance time were lower in the observation group(P<0.05). The maximum respiratory flow and IS maximum expiratory volume in the observation group were higher than those in the control group (P<0.05). The GH level, height, and weight obtained from two year follow up in the observation group were lower than those in the control group (P<0.05).  Conclusion  Budesonide suspension combined with salbutamol sulfate aerosol inhalation therapy can alleviate the inflammatory reaction, improve the lung function and immune function of children, and accelerate the disappearance of clinical symptoms, but it will affect the growth and development of children to a certain extent.
  • [1] 田晓曦. 小儿咳嗽变异性哮喘患儿实施布地奈德联用孟鲁司特钠治疗的效果观察[J]. 山西医药杂志, 2018, 47(10):1168-1170. doi:  10.3969/j.issn.0253-9926.2018.10.023
    [2] 盛玮, 田玉珍. 孟鲁斯特联合布地奈德治疗咳嗽变异性哮喘的疗效及对肺功能的影响[J]. 药物评价研究, 2018, 41(4):620-623.
    [3] 李秋珍. 异丙托溴铵联合沙丁胺醇雾化吸人治疗慢性阻塞性肺病的疗效[J]. 中国急救医学, 2018, 38(z2):144. doi:  10.3969/j.issn.1002-1949.2018.z2.144
    [4] 中华医学会儿科学分会呼吸学组, 《中华儿科杂志》编辑委员会. 儿童支气管哮喘诊断与防治指南(二)(2008年修订)[J]. 中华医学信息导报, 2009, 24(2):22.
    [5] 牟京辉, 邵明军, 刘传合, 等. 中国城市支气管哮喘儿童与非支气管哮喘儿童食物过敏患病情况比较[J]. 中华实用儿科临床杂志, 2018, 33(9):684-687.
    [6] 刘调侠, 李延琴. 孟鲁司特钠联合布地奈德治疗小儿毛细支气管炎的临床疗效及其对炎症因子的影响[J]. 儿科药学杂志, 2017, 23(6):27-30.
    [7] 管锡富. 布地奈德雾化吸入联合孟鲁司特治疗小儿哮喘急性发作的疗效观察[J]. 中国妇幼保健, 2017, 32(4):759-761.
    [8] 林寒梅. 孟鲁司特钠联合布地奈德治疗儿童咳嗽变异性哮喘临床疗效及对炎症因子的影响[J]. 中国妇幼保健, 2015, 30(5):796-797.
    [9] 蒋俊, 刘挺. 健脾化痰汤联合布地奈德治疗缓解期儿童哮喘的临床疗效及对炎症因子水平的影响[J]. 中华中医药学刊, 2015, 33(12):3056-3059.
    [10] 张龙英, 姚其娟. 孟鲁司特钠口服联合布地奈德吸入治疗儿童咳嗽变异性哮喘疗效[J]. 江苏医药, 2015, 41(10):1221-1222.
    [11] 唐钧, 林建伯. SAA、hs-CRP在小儿感染性疾病早期鉴别诊断中的价值[J]. 检验医学, 2018, 33(6):499-502. doi:  10.3969/j.issn.1673-8640.2018.06.008
    [12] 吴玲玲. 布地奈德吸入联合孟鲁司特钠对小儿哮喘疗效及炎症因子的影响[J]. 中国妇幼保健, 2017, 32(1):191-194.
    [13] 王跃飞, 林邦长, 何哲航, 等. T淋巴细胞亚群与调节性B细胞在儿童手足口病中的表达及临床意义[J]. 中华医院感染学杂志, 2017, 27(14):3319-3322.
    [14] 郑桂芬, 乔晓红, 卢双龙, 等. 雾化吸入布地奈德治疗儿童肺炎支原体感染后慢性咳嗽的临床疗效[J]. 中华实用儿科临床杂志, 2017, 32(22):1705-1708. doi:  10.3760/cma.j.issn.2095-428X.2017.22.008
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The therapeutic effect of budesonide on childhood asthma and its influence on growth and development 1 to 2 years after the treatment

doi: 10.12206/j.issn.1006-0111.202101013

Abstract:   Objective  To explore the effect of budesonide suspension for inhalation in the treatment of childhood asthma and its influence on growth and development in 1-2 years.  Methods  The 68 children with asthma admitted to our hospital from October 2016 to January 2017 were selected. Every patient had acute attacks and received continued medication. 34 patients treated with salbutamol sulfate inhaled aerosol were used as the control group. 34 patients treated with budesonide suspension combined with salbutamol sulfate aerosol were classified as the observation group. The interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), high-sensitivity-C-reactive protein (hs-CRP), maximum respiratory flow, IS maximum expiratory volume, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, wet rales disappearing time, cough disappearing time, and the two year follow-up indicators of growth and development were compared.  Results  After medication, IL-6, TNF-α, hs-CRP, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, moist rales disappearance time, and cough disappearance time were lower in the observation group(P<0.05). The maximum respiratory flow and IS maximum expiratory volume in the observation group were higher than those in the control group (P<0.05). The GH level, height, and weight obtained from two year follow up in the observation group were lower than those in the control group (P<0.05).  Conclusion  Budesonide suspension combined with salbutamol sulfate aerosol inhalation therapy can alleviate the inflammatory reaction, improve the lung function and immune function of children, and accelerate the disappearance of clinical symptoms, but it will affect the growth and development of children to a certain extent.

HAO Xiuli, XIE Fang, YAN Xueping. The therapeutic effect of budesonide on childhood asthma and its influence on growth and development 1 to 2 years after the treatment[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 479-482. doi: 10.12206/j.issn.1006-0111.202101013
Citation: HAO Xiuli, XIE Fang, YAN Xueping. The therapeutic effect of budesonide on childhood asthma and its influence on growth and development 1 to 2 years after the treatment[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 479-482. doi: 10.12206/j.issn.1006-0111.202101013
  • 儿童哮喘是一种可分为临床缓解期、急性发作期、慢性持续期3个阶段的临床常见呼吸道疾病[1],其中,以扩张患儿气管、减轻患儿支气管痉挛症状为主要治疗原则的哮喘阶段为急性发作期,常会致使患儿出现胸闷、咳嗽等问题[2]。频繁的急性发作会导致哮喘患儿的生活、学习等均受到影响,并会引起全身炎症反应,甚至导致肺功能损伤,影响机体发育。为解决儿童哮喘急性发作期患者的以上问题,常采用吸入用布地奈德混悬液联合硫酸沙丁胺醇吸入气雾剂雾化吸入疗法进行治疗,吸入用布地奈德混悬液是一种可减少患者抗体合成、增强患者抗炎能力等作用的吸入型糖皮质激素,而硫酸沙丁胺醇吸入气雾剂则是一种可用于治疗肺气肿、支气管哮喘及支气管炎(喘息型)所致支气管痉挛的选择性β2-受体激动剂[3]。笔者为系统分析吸入用布地奈德混悬液联合硫酸沙丁胺醇吸入气雾剂方法在哮喘急性发作期患儿治疗中的效果,并探究其是否会对患儿生长发育造成影响,作以下内容阐述。

  • 收集北京市第一中西医结合医院于2016年10月至2017年1月收诊的儿童哮喘急性发作期患者68例,分为两组:34例应用硫酸沙丁胺醇吸入气雾剂治疗的患者为对照组,34例应用吸入用布地奈德混悬液联合硫酸沙丁胺醇吸入气雾剂治疗的患者为观察组。纳入标准:①入组对象均符合《儿童支气管哮喘诊断与防治指南》[4](中华医学会儿科学分会呼吸学组2008年修订)中有关于小儿哮喘的疾病标准。②对硫酸沙丁胺醇吸入气雾剂、吸入用布地奈德混悬液等本次研究药物无过敏反应者。③14 d内未曾使用过支气管扩张剂、激素等药物。排除标准:①先天性心脏病患者或严重脏器功能受损者。②其他呼吸系统疾病。③意识、视听、交流、理解等障碍者。④支气管异物者。观察组:女16例,男18例;年龄4~13岁,平均(8.47±1.15)岁;急性发作时间1~8 h,平均为(5.47±0.52)h。对照组:女15例,男19例;年龄4~14岁,平均(8.75±1.09)岁;急性发作时间1~9 h,平均为(5.32±0.54)h。比较以上资料,P>0.05,差异无统计学意义。入组患者临床资料齐全,经本院伦理委员会批准,且均已知情同意。

  • 医务工作者对两组儿童哮喘急性发作期患者均行传统治疗,包括祛痰、止咳、吸氧、抗感染、解痉挛等。

  • 硫酸沙丁胺醇吸入气雾剂治疗。方法:对患儿予硫酸沙丁胺醇吸入气雾剂(批准文号:H20090514;GlaxoSmithKline Australia Pty Ltd)进行相应雾化吸入治疗,每次1揿,若患儿病情较重或效果不佳可增至每次2揿,每日3次,单次维持吸入时长为5 min。疗程4周,之后患儿继续进行传统治疗。

  • 吸入用布地奈德混悬液联合硫酸沙丁胺醇吸入气雾剂雾化吸入治疗。方法:患儿吸入用布地奈德混悬液(批准文号:H20090903;Astrazeneca pty ltd)和硫酸沙丁胺醇吸入气雾剂进行相应雾化吸入治疗,其中,硫酸沙丁胺醇吸入气雾剂的用法用量与对照组患儿一致,吸入用布地奈德混悬液每次0.5 mg,若患儿症状严重或效果不佳时可增至每次1 mg,每日3次,单次维持吸入时长为5 min。疗程4周,之后对患儿继续进行传统治疗。

  • 观察评测两组儿童哮喘急性发作期患者的IL-6、TNF-α、hs-CRP、最大呼吸流量、IS最大呼气量、调节性B细胞比例、喘憋消失时间、气促缓解时间、湿啰音消失时间、咳嗽消失时间。

    用药前、用药4周后于患者晨起(9点前)空腹时作肘静脉血抽取及血清分离操作,IL-6、TNF-α、hs-CRP均应用武汉博士德公司提供的试剂盒、全自动生化分析仪(日立7600型)与酶联免疫吸附试验(ELISA)作相应检测。

    最大呼吸流量、IS最大呼气量均应用肺功能测试仪作有效检测;通过CD19-efluro450 设门,应用全血直接计数法对调节性B细胞比例进行分析。

    跟踪随访两组患者2年,观察患儿治疗前和随访结束后的生长发育指标[生长激素(GH)、身高和体重],其中,GH采用ELISA法和美国DRG公司提供的相关试剂进行检测,所有操作均严格按照试剂盒的说明书进行。

  • 本次研究统计学分析应用SPSS 21.0软件,两组儿童哮喘急性发作期患者的IL-6、TNF-α、hs-CRP、最大呼吸流量、IS最大呼气量、调节性B细胞比例、喘憋消失时间、气促缓解时间、湿啰音消失时间、咳嗽消失时间和生长发育指标均为计量资料,以($\overline x \pm s$)的形式表示,进行t检验;以P<0.05为差异有统计学意义。

  • 观察组用药4周后的IL-6、TNF-α、hs-CRP均低于对照组(P<0.05),见表1

    组别例数IL-6(ng/ml)TNF-α(pg/ml)hs-CRP(mg/L)
    治疗前
      观察组n=34174.56±24.3524.26±2.8314.45±2.27
      对照组n=34174.21±24.7424.71±2.6914.37±2.25
      t0.0590.6720.146
      P>0.05>0.05>0.05
    治疗后
      观察组n=34127.84±15.378.23±1.218.14±1.42
      对照组n=34145.62±19.4815.51±1.6211.18±1.75
      t4.17820.9947.866
      P<0.01<0.01<0.01
  • 观察组治疗4周后的最大呼吸流量、IS最大呼气量均高于对照组(P<0.05),见表2

    组别例数最大呼吸流量(V/L)IS最大呼气量(V/L)
    治疗前
      观察组n=3472.54±8.1772.65±3.45
      对照组n=3472.76±8.1472.91±3.34
      t0.1110.316
      P>0.05>0.05
    治疗后
      观察组n=3494.75±9.9194.55±6.94
      对照组n=3487.74±9.5387.58±5.57
      t2.9734.567
      P<0.01<0.01
  • 观察组用药4周后的调节性B细胞比例低于对照组(P<0.05),见表3

    组别例数调节性B细胞比例(%)
    治疗前
      观察组n=3414.07±2.45
      对照组n=3414.22±2.43
      t0.253
      P>0.05
    治疗后
      观察组n=3411.42±1.41
      对照组n=3413.08±1.95
      t4.022
      P<0.01
  • 观察组用药4周后的喘憋消失时间、气促缓解时间、湿啰音消失时间、咳嗽消失时间均低于对照组(P<0.05),见表4

    组别喘憋消失
    时间
    气促缓解
    时间
    湿啰音消失
    时间
    咳嗽消失
    时间
    观察组(n=34)2.75±0.472.28±0.424.05±0.725.27±0.48
    对照组(n=34)5.04±0.783.11±0.676.17±0.947.17±0.65
    t14.6636.12010.44013.711
    P0.0000.0000.0000.000
  • 观察组随访结束后的生长激素水平、身高和体重均低于对照组(P<0.05),见表5

    生长发育
    指标
    观察组(n=34)对照组(n=34)
    治疗前随访结束后治疗前随访结束后
    生长激素
    (ng/ml)
    12.97±3.5910.34±2.19*#13.08±3.6311.55±2.42*
    身高
    l/cm)
    105.29±9.63112.26±9.92*#105.37±9.52117.61±10.57*
    体重
    m/kg)
    26.29±2.1732.01±3.82*#26.41±2.0834.29±4.76*
    * P<0.05,与治疗前比较;# P<0.05,与对照组比较
  • 儿童哮喘是一种病因多与环境问题、过敏食物、自身免疫异常、内分泌、遗传、感染等因素有关的儿科常见病[5],急性发作时的轻度反应一般以胸闷、发作性咳嗽、呼吸困难、喘息等症状为主[6]。针对儿童哮喘急性发作期患者,以往医务工作者常予以化痰、止咳、抗感染、吸氧等基础治疗[7]。如本文表2表4所示,单独应用硫酸沙丁胺醇吸入气雾剂改善患儿临床症状的效果不如吸入用布地奈德混悬液与硫酸沙丁胺醇吸入气雾剂的联用治疗。

    吸入用布地奈德混悬液是一种可对患儿局部气道产生直接作用的高效糖皮质激素,可减轻患儿呼吸困难、咳嗽、支气管充血、支气管水肿等症状,减少患儿气管过敏活性介质的释放,并有助于平滑肌细胞和内皮细胞的稳定。而硫酸沙丁胺醇吸入气雾剂则是一种可在短时间内减轻患儿哮喘症状的选择性β2受体激动剂,可增强患儿的激素效能,改善激素受体活性,提升其肺功能[8]。以上两种药物均为现阶段治疗儿童哮喘急性发作期患者的首选用药,临床常通过雾化吸入方式应用吸入用布地奈德混悬液、以及硫酸沙丁胺醇吸入气雾剂来控制患儿的哮喘症状。该方法具有口咽部刺激小、不良反应少、持续时间长、起效快等特点[9],可迅速达到解痉平喘、消炎祛痰等的治疗目的[10]。与儿童哮喘发展过程有关的炎性细胞因子一般包括IL-6、TNF-α、hs-CRP等,IL-6是一种可对生物机体炎症、免疫力造成影响的多效性细胞因子;TNF-α是一种可对机体产生免疫调节、炎症、细胞毒性、血管生成、生长抑制等影响的多效性细胞因子;hs-CRP是一种由肝细胞分泌、可对机体炎症状态进行敏感反应的急性期反应蛋白[11]。如本文表1所示,观察组用药4周后的IL-6、TNF-α、hs-CRP均低于对照组(P<0.05)。由结果可知,经吸入用布地奈德混悬液联合硫酸沙丁胺醇吸入气雾剂治疗后,可有效减轻患儿的炎症反应,降低患儿的气道高反应性。此结论与吴玲玲一文[12]中的结论基本一致。

    同时应用吸入用布地奈德混悬液联合硫酸沙丁胺醇吸入气雾剂还可提升患儿的免疫功能,改善患儿的免疫学指标。如文中表3所示,观察组用药4周后的调节性B细胞比例低于对照组(P<0.05)。调节性B细胞是一种可对患儿体内免疫功能动态平衡进行参与维持的B细胞亚群,其负向调节作用显著,可对患儿免疫调节功能产生间接作用,一旦比例下降,说明其免疫功能活化效果提升[13]。但是观察组随访结束后的GH水平、身高和体重均低于对照组(P<0.05)。其原因可能与吸入用布地奈德混悬液是糖皮质激素药物有关,该类药物可抑制人体的生长激素分泌和表达,并可对患者胶原蛋白与软骨细胞增生合成产生影响,其中,生长激素是患儿生长发育的主要激素,且有研究指出糖皮质激素的使用剂量与对儿童生长发育的影响程度呈正相关[14]

    综上所述,将吸入布地奈德混悬液用于儿童哮喘治疗中,可改善患儿的肺功能与免疫功能,但是会对患儿治疗结束后2年内的生长发育造成一定影响,与2012年儿童哮喘管理项目研究得出的新结论较为一致,同时该研究指出吸入糖皮质激素并不会影响儿童成年后的身高,因此,上述治疗方案的临床应用价值值得肯定。

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