ALLICS在儿童哮喘长期维持治疗中的应用培训课件

1、ALLICS在儿童哮喘长期维持治疗中的应用培训课件1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.2 Rank MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol, 2013,131(3):724

2、-9.3 Castro-Rodriguez GA, et al. The role of inhaled corticosteroids and montelukast in children with mildmoderate asthma: results of a systematic review with meta-analysis. Arch Dis Child, 2010,95:365370.4 Szefler SJ, et al. Budesonide inhalation suspension versus montelukast in children aged 2 to

3、4 years with mild persistent asthma. J Allergy Clin Immunol: In Practice, 2013,1:58-64。5 McLaughlin T, et al. Risk of recurrent emergency department visits or hospitalizations in children with asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications. Current

4、 Medical Research and Opinion, 2007, 23(6): 13191328.6 GINA. 2012: 40.7 Brand PL. Inhaled corticosteroids should be the first line of treatment for children with asthma. Padiatric Respiratory Reviews, 2011,12: 245249.8申昆玲, 等. 糖皮质激素雾化吸入疗法在儿科应用的专家共识. 临床儿科杂志, 2011, 29(1): 86-91.9 Kemp JP, et al. Once-d

5、aily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol, 1999, 83: 231239.10 Baker JW, et al. A Multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of pers

6、istent asthma in young children and infants. Pediatrics, 1999, 103 (2): 414-421.1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断达到并维持症状的控制维持正常活动，包括运动能力使肺功能水平尽量接近正常预防哮喘急性发作避免因哮喘药物治疗导致的不良反应预防哮喘导致的死亡儿童哮喘的治疗目标中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.达到并维持症状的控制儿童哮喘的治疗目标中华医学会儿科学分会呼长期、持续、规范、个体化治疗快速缓解症

7、状防止症状加重和预防复发哮喘的防治原则中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.总原则急性发作期慢性持续期和临床缓解期长期、持续、规范、个体化治疗哮喘的防治原则中华医学会儿科学分1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.2 Rank MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a s

8、ystematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol, 2013,131(3):724-9.3 Castro-Rodriguez GA, et al. The role of inhaled corticosteroids and montelukast in children with mildmoderate asthma: results of a systematic review with meta-analysis. Arch Dis Child, 201

9、0,95:365370.4 Szefler SJ, et al. Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. J Allergy Clin Immunol: In Practice, 2013,1:58-64。5 McLaughlin T, et al. Risk of recurrent emergency department visits or hospitalizations in children with

10、asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications. Current Medical Research and Opinion, 2007, 23(6): 13191328.6 GINA. 2012: 40.7 Brand PL. Inhaled corticosteroids should be the first line of treatment for children with asthma. Padiatric Respiratory R

11、eviews, 2011,12: 245249.8申昆玲, 等. 糖皮质激素雾化吸入疗法在儿科应用的专家共识. 临床儿科杂志, 2011, 29(1): 86-91.9 Kemp JP, et al. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol, 1999, 83: 231239.10 Baker JW, et al. A Multiple-dosing, p

12、lacebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics, 1999, 103 (2): 414-421.1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断长期规律雾化吸入ICS治疗的必要性一项系统综述纳入7项比较停用和继续使用ICS对哮喘急性发作风险的研究，荟萃分析结果表明，对于哮喘控制良好的哮喘患者来说，与继续使用I

13、CS患者相比，停用ICS可使哮喘急性发作风险增加停药哮喘加重Rank MA,et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol.2013;131(3):724-9.哮喘加重相对风险值增加2.35倍肺功能指标：FEV1降低130mL晨间PEF降低18L/min平均标准哮喘症状评分增加0.4

14、3倍长期规律雾化吸入ICS治疗的必要性一项系统综述纳入7项比较停1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.2 Rank MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol, 2013,131

15、(3):724-9.3 Castro-Rodriguez GA, et al. The role of inhaled corticosteroids and montelukast in children with mildmoderate asthma: results of a systematic review with meta-analysis. Arch Dis Child, 2010,95:365370.4 Szefler SJ, et al. Budesonide inhalation suspension versus montelukast in children age

16、d 2 to 4 years with mild persistent asthma. J Allergy Clin Immunol: In Practice, 2013,1:58-64。5 McLaughlin T, et al. Risk of recurrent emergency department visits or hospitalizations in children with asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications.

17、Current Medical Research and Opinion, 2007, 23(6): 13191328.6 GINA. 2012: 40.7 Brand PL. Inhaled corticosteroids should be the first line of treatment for children with asthma. Padiatric Respiratory Reviews, 2011,12: 245249.8申昆玲, 等. 糖皮质激素雾化吸入疗法在儿科应用的专家共识. 临床儿科杂志, 2011, 29(1): 86-91.9 Kemp JP, et al.

18、 Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol, 1999, 83: 231239.10 Baker JW, et al. A Multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment

19、of persistent asthma in young children and infants. Pediatrics, 1999, 103 (2): 414-421.1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断ICS白三烯调节剂LABA茶碱长效口服2受体激动剂全身用糖皮质激素抗IgE抗体抗过敏药物变应原特异性免疫治疗儿童哮喘长期控制的治疗药物中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.ICS儿童哮喘长期控制的治疗药物中华医学会儿科学分会呼吸学组多项指南推荐ICS用于儿童哮喘的长期维持中国

20、儿童支气管哮喘诊断与防治指南20081 GINA 2012. 2 ICON 2012.3中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.GINA 2012多项指南推荐ICS用于儿童哮喘的长期维持中国儿童支气管哮指南推荐：5岁以下儿童哮喘最有效的长期治疗药物是ICS中国儿童支气管哮喘诊断与防治指南2008对于5岁以下儿童哮喘的长期治疗，最有效的治疗药物是ICS。对于大多数患儿推荐使用低剂量ICS，如果低剂量ICS不能控制症状，增加ICS剂量是最佳选择。无法应用或不愿使用ICS，或伴过敏性鼻炎的患儿可选用白三烯受体拮抗

21、剂（LTRA）中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.指南推荐：5岁以下儿童哮喘最有效的中国儿童支气管哮喘诊断与防与孟鲁司特比较，ICS能显著降低需要使用全身激素的急性发作风险需要使用全身激素的急性发作风险Castro-Rodriguez GA, et al. The role of inhaled corticosteroids and montelukast in children with mildmoderate asthma: results of a systematic review with

22、 meta-analysis. Arch Dis Child 2010;95:365370.在1996年1月-2009年11月发表的18项前瞻性随机对照试验比较了吸入糖皮质激素和孟鲁司特用于治疗轻中度持续性哮喘患者的疗效，荟萃分析结果表明，在18项研究纳入的3757例患者中，与孟鲁司特相比，吸入糖皮质激素可显著降低需要使用全身激素的急性发作风险（RR=0.83，P=0.01）。与孟鲁司特比较，ICS能显著降低需要使用全身激素的急性发作雾化吸入布地奈德用于儿童持续性哮喘控制效果优于口服孟鲁司特Szefler SJ, Carlsson L-G, Uryniak T, Baker JW. Budes

23、onide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. J Allergy Clin Immunol: In Practice 2013;1:58-64一项为期52周的开放、随机、对照的多中心研究纳入202例2-4岁轻度持续性哮喘患儿，给予布地奈德混悬液（n=105）或孟鲁司特（n=97）治疗，主要终点指标是52周内首次急性发作（需加用其他哮喘药物）的时间。结果显示，两组间主要终点指标无差异(183d vs 86d)，但52周时口服激素的患

24、儿比例布地奈德治疗组显著低于孟鲁司特组(21.9%vs37.1%,P=0.022)。布地奈德混悬液(n=105)孟鲁司特(n=97)52周内不需要口服激素治疗的百分比（%）与口服孟鲁司特相比，雾化吸入布地奈德可显著减少哮喘急性发作所需的口服激素治疗时间（月）雾化吸入布地奈德用于儿童持续性哮喘控制效果优于口服孟鲁司特S1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.2 Rank MA, et al. The risk of asthma exacerbation after stopping low-dose i

25、nhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol, 2013,131(3):724-9.3 Castro-Rodriguez GA, et al. The role of inhaled corticosteroids and montelukast in children with mildmoderate asthma: results of a systematic review with meta-an

26、alysis. Arch Dis Child, 2010,95:365370.4 Szefler SJ, et al. Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. J Allergy Clin Immunol: In Practice, 2013,1:58-64。5 McLaughlin T, et al. Risk of recurrent emergency department visits or hospita

27、lizations in children with asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications. Current Medical Research and Opinion, 2007, 23(6): 13191328.6 GINA. 2012: 40.7 Brand PL. Inhaled corticosteroids should be the first line of treatment for children with asth

28、ma. Padiatric Respiratory Reviews, 2011,12: 245249.8申昆玲, 等. 糖皮质激素雾化吸入疗法在儿科应用的专家共识. 临床儿科杂志, 2011, 29(1): 86-91.9 Kemp JP, et al. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol, 1999, 83: 231239.10 Baker JW,

29、et al. A Multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics, 1999, 103 (2): 414-421.1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断pMDI(气雾剂)pMDI+储雾罐DPI(干粉剂)家用Nebulizer(雾化器) 超声雾化器 喷射雾化器不同吸

30、入给药方式的装置pMDI(气雾剂)不同吸入给药方式的装置雾化吸入对患者的配合性、协同性要求少Dolovich MB, Ahrens RC, Hess DR, et al. Device Selection and Outcomes of Aerosol Therapy: Evidence-Based Guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology Chest, 2005,127:335-371.与其他吸入装置相比，雾化吸入：对患者协同性无要求

31、潮式呼吸即有效可使用高剂量可调整剂量不释放CFC可同时辅助供氧可实现联合药物治疗（若药物之间无配伍禁忌）雾化吸入对患者的配合性、协同性要求少Dolovich MB,与储雾罐+MDI相比，雾化器使用正确率更高两种吸入装置使用的总错误率结果两种吸入装置使用的主要错误率结果总错误率（%）主要错误率（%）24.815.915.68.5P0.001P0.001在154例1-6岁的哮喘患儿中调查吸入疗法的使用情况， 其中储雾罐+MDI组110例、雾化吸入组44例，结果表明，与储雾罐+MDI相比雾化吸入装置使用正确率更高Welch MJ, et al. Evaluation of Inhaler Devic

32、e Technique in Caregivers of Young Children with Asthma. Pediatric Allergy, Immunology, and Pulmonology. 2010, 23(2): 113-120. 与储雾罐+MDI相比，雾化器使用正确率更高两种吸入装置使用的雾化吸入装置适合各年龄哮喘患儿使用1.贺孝良,李昌崇.哮喘吸入治疗装置新进展.实用儿科临床杂志.2007;22(4):309-311.吸入装置1适用范围限制使用注意雾化器各年龄段，用于不能正确掌握定量吸入器、严重气促无法做深吸气的患者定量吸入器6-7岁特别强调正确掌握吸入技术，婴幼儿较

33、难完成吸气和喷药动作的协调吸药后必须漱口定量吸入器+储雾罐4岁贮雾罐携带不方便，不能一次喷入多剂量药物吸药后必须漱口干粉剂5岁吸药后必须漱口雾化吸入装置适合各年龄哮喘患儿使用1.贺孝良,李昌崇.哮喘吸雾化吸入布地奈德治疗vs非雾化方式吸入激素治疗哮喘再发风险的风险比95%可信区间相对风险降低4岁哮喘患儿（n=766)0.380.21 - 0.7062%5-8岁哮喘患儿（n=786)0.480.16 - 1.4652%McLaughlin T, et al. Risk of recurrent emergency department visits or hospitalizations in

34、children with asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications. Current Medical Research and Opinion,2007, 23(6): 13191328.与其他哮喘治疗药物和非雾化方式吸入糖皮质激素相比，雾化吸入布地奈德混悬液治疗与哮喘再发风险的显著降低相关一项纵向回顾性研究纳入10176例急诊或住院的哮喘患儿，回顾性调查其过去6个月的用药情况，并记录收治后30天内的用药情况，并据此分组，观察31-180

35、天内患者再次急诊或住院的风险。结果表明，在因哮喘导致急诊或住院的哮喘患儿（年龄8岁）中，与其他哮喘治疗药物和非雾化方式吸入糖皮质激素相比，雾化吸入布地奈德混悬液治疗与哮喘再发风险的显著降低相关。雾化吸入布地奈德治疗哮喘再发风险的风险比95%可信区间相对风1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.2 Rank MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a system

36、atic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol, 2013,131(3):724-9.3 Castro-Rodriguez GA, et al. The role of inhaled corticosteroids and montelukast in children with mildmoderate asthma: results of a systematic review with meta-analysis. Arch Dis Child, 2010,95:

37、365370.4 Szefler SJ, et al. Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. J Allergy Clin Immunol: In Practice, 2013,1:58-64。5 McLaughlin T, et al. Risk of recurrent emergency department visits or hospitalizations in children with asthm

38、a receiving nebulized budesonide inhalation suspension compared with other asthma medications. Current Medical Research and Opinion, 2007, 23(6): 13191328.6 GINA. 2012: 40.7 Brand PL. Inhaled corticosteroids should be the first line of treatment for children with asthma. Padiatric Respiratory Review

39、s, 2011,12: 245249.8申昆玲, 等. 糖皮质激素雾化吸入疗法在儿科应用的专家共识. 临床儿科杂志, 2011, 29(1): 86-91.9 Kemp JP, et al. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol, 1999, 83: 231239.10 Baker JW, et al. A Multiple-dosing, placeb

40、o-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics, 1999, 103 (2): 414-421.1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断GINA指南：长期低剂量ICS对儿童生长发育无显著不良影响GINA 2012: 40.糖皮质激素的使用与儿童生长的关系：控制不佳或严重的哮喘影响儿童的生长发育，未能达到预期的成

41、人身高并无长期对照试验报道ICS（100-200g/d）的长期使用对生长有显著不良影响当高剂量使用ICS时，可能造成生长迟缓在短期和中期研究中，生长迟缓的发生与剂量呈相关性不同年龄的患儿对ICS导致的生长迟缓效应的易感性不同，2-10的儿童比成人更易感在治疗的第一年，糖皮质激素导致的生长率的变化似乎是暂时的。使用ICS治疗的哮喘患儿可在较晚的年龄达到正常的成人身高（根据家庭成员来估计）GINA指南：长期低剂量ICS对儿童生长发育无显著不良影响GINA指南：长期低剂量ICS对儿童骨折和骨密度无显著不良影响GINA 2012: 40.糖皮质激素的使用与儿童骨发育的关系：并无研究报道使用ICS的患儿

42、骨折风险显著升高口服或全身激素可增加骨折的风险，骨折风险的升高与治疗疗程数相关，在4个疗程后增加32%。使用ICS可降低全身激素疗程的需求持续2-5年的有对照的纵向研究和一些横断面调查显示，ICS治疗对骨矿物质密度无不良影响ICS使用可能会导致男孩在进入青春期时骨矿物质增生减少，但这种风险可被降低口服激素用量所带来的获益抵消GINA指南：长期低剂量ICS对儿童骨折和骨密度无显著不良ICS 用于儿童哮喘长期维持安全性数据良好Brand PL. Inhaled corticosteroids should be the first line of treatment for children wi

43、th asthma. Paediatric Respiratory Reviews, 2011,12: 245249.ICS 用于儿童哮喘长期维持安全性数据良好Brand PL.平均基础皮质激素与ACTH诱导皮质激素水平（nmol/L）基础* ACTH*基础* ACTH*基础 * ACTH*基础* ACTH*安慰剂组0.25 mg BID组0.50 mg BID组1.0 mg BID组雾化吸入布地奈德对下丘脑-垂体-肾上腺轴 (HPAA)功能无显著不良影响一项研究纳入178例吸入激素依赖型持续性哮喘患儿，随机分入布地奈德0.25mg、bid治疗组（47例），0.50 mg、bid治疗组（42例

44、），1.0 mg、bid治疗组（45例）和安慰剂组（44例），主要疗效指标为夜间和日间哮喘症状评分与基线（随机分组前7天的平均数）相比的差异，并观察不良事件发生率。结果表明，各剂量布地奈德组与安慰剂组对比，基础皮质醇水平与ACTH刺激的皮质醇水平无显著差异。Shapiro G, et al., Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma. The Jo

45、urnal of allergy and clinical immunology, 1998. 102(5): 789-796.*：基础的皮质醇水平*：ACTH刺激的皮质醇水平平均基础皮质激素与ACTH诱导皮质激素水平基础* AC雾化吸入布地奈德对HPAA功能无明显影响湛洁谊, 等. 雾化吸入糖皮质激素对支气管哮喘患儿下丘脑-垂体-肾上腺轴功能的影响. 实用儿科临床杂志, 2009, 24(16): 1244-6.血清皮质醇（nmol/L）24h尿游离皮质醇与尿肌酐比值（nmol/mmoL）各组间 P=NS各组间 P=NS研究纳入60例已规律雾化吸入布地奈德超过6个月，起始剂量为1000g/d

46、，逐渐减量至250g/d或500g/d并维持该剂量至少3个月的患儿，根据近3个月布地奈德剂量分入BUD-250组（吸入BUD250g）和BUD-500组（吸入BUD500g），并选择30例健康儿童作为对照组，测定血清皮质醇和24h尿游离皮质醇与尿肌酐比值。结果表明，不同剂量布地奈德治疗组和对照组的血清皮质醇和24h尿游离皮质醇与尿肌酐比值的差异均无统计学意义。雾化吸入布地奈德对下丘脑-垂体-肾上腺轴 (HPAA)功能无明显影响1雾化吸入布地奈德对HPAA功能无明显影响湛洁谊, 等. 雾化长期雾化吸入布地奈德治疗对骨矿物质密度无显著影响Agertoft L, Pedersen S. Bone m

47、ineral density in children with asthma receiving long-term treatment with inhaled budesonide. Am J Respir Crit Care Med 1998;157:178183.为了研究长期使用雾化吸入布地奈德对骨代谢的影响，一项研究纳入157例长期使用布地奈德的哮喘患儿，平均使用剂量为504 g/d，平均使用年限为4.5年，111例未使用过外源性糖皮质激素的哮喘患儿作为对照组，结果表明，两组患者的骨矿物质密度无显著差异。骨矿物质密度对照组布地奈德治疗组0.917 g/cm0.915g/cmNS长期雾

48、化吸入布地奈德治疗对骨矿物质密度无显著影响AgertoSTART研究：布地奈德治疗并不增加哮喘患儿的常见副反应Silverman M, et al. Safety and tolerability of inhaled budesonide in children in the Steroid Treatment As Regular Therapy in early asthma (START) trial. Pediatr Allergy Immunol 2006: 17 (Suppl. 17): 1420.不良事件布地奈德联合常规治疗组（n=1004）常规治疗组（n=977）呼吸系统感染

49、440（43.8%）428（43.8%）咽炎290（28.9%）304（31.1%）鼻炎285 (28.4%)267 (27.3%)病毒感染201 (20.0%) 184（18.8%）支气管炎164 (16.3%) 183 (18.7%)发热117 (11.7%) 100 (10.2%)中耳炎112 (11.2%)96 (9.8%)鼻窦炎87 (8.7%) 99 (10.1%)咳嗽88 (8.8%) 81 (8.3%)结膜炎88 (8.8%) 79 (8.1%)头痛86 (8.6%)72 (7.4%)事故/受伤75 (7.5%)79 (8.1%)胃肠炎81 (8.1%) 68 (7.0%)哮喘

50、加重50 (5.0%) 73 (7.6%)肺炎38 (3.8%)57 (5.8%)START研究对纳入的1981例5-10岁轻度持续性哮喘患者进行了安全性研究，所有患者均接受常规哮喘治疗，其中1004例接受布地奈德200 g/d治疗，977例患者接受安慰剂治疗，治疗维持三年，观察两组患者常见副反应的发生率。结果显示，常规治疗加入布地奈德治疗用于新近发病的轻度持续性哮喘患儿是可耐受的。START研究：布地奈德治疗并不增加哮喘患儿的常见副反应Si雾化吸入布地奈德长期控制哮喘不影响儿童身高1 Pedersen S, et al. Growth and adult height in children

51、 treated with budesonide for 5 years in the START study. ATS, 2004, Abstract A37.START研究1：一项为期5年的国际多中心研究纳入2938例5-15岁轻度持续性哮喘患者，11岁以下的儿童接受布地奈德干粉剂吸入200g治疗，11岁以上的儿童接受布地奈德400g治疗，每天一次。治疗3年后均接受布地奈德治疗，持续2年，观察患儿的身高。START研究结果：布地奈德治疗2年及5年后，患儿的身高与未用激素的同龄儿童相比均无显著差异。雾化吸入布地奈德长期控制哮喘不影响儿童身高1 Pederse长期使用ICS安全性数据良好1GI

52、NA 2012: 40.2 Brand PL. Inhaled corticosteroids should be the first line of treatment for children with asthma. Paediatric Respiratory Reviews, 2011,12: 245249.3 Agertoft L, et al. Bone mineral density in children with asthma receiving long-term treatment with inhaled budesonide. Am J Respir Crit Ca

53、re Med, 1998,157:178183.4 Shapiro G, et al, Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma. The Journal of allergy and clinical immunology, 1998, 102(5): 789-796.5湛洁谊, 等. 雾化吸入糖皮质激素对支气管哮喘患儿下丘脑-垂体-肾上腺轴功能的

54、影响. 实用儿科临床杂志, 2009, 24(16): 1244-6.6 Silverman M, et al. Safety and tolerability of inhaled budesonide in children in the Steroid Treatment As Regular Therapy in early asthma (START) trial. Pediatr Allergy Immunol, 2006, 17 (Suppl. 17): 1420.长期使用ICS安全性数据良好1GINA 2012: 40.1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊

55、断与防治指南.中华儿科杂志, 2008, 46(10): 745-753.2 Rank MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol, 2013,131(3):724-9.3 Castro-Rodriguez GA, et al. The role of inhaled c

56、orticosteroids and montelukast in children with mildmoderate asthma: results of a systematic review with meta-analysis. Arch Dis Child, 2010,95:365370.4 Szefler SJ, et al. Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma. J Allergy Clin Im

57、munol: In Practice, 2013,1:58-64。5 McLaughlin T, et al. Risk of recurrent emergency department visits or hospitalizations in children with asthma receiving nebulized budesonide inhalation suspension compared with other asthma medications. Current Medical Research and Opinion, 2007, 23(6): 13191328.6

58、 GINA. 2012: 40.7 Brand PL. Inhaled corticosteroids should be the first line of treatment for children with asthma. Padiatric Respiratory Reviews, 2011,12: 245249.8申昆玲, 等. 糖皮质激素雾化吸入疗法在儿科应用的专家共识. 临床儿科杂志, 2011, 29(1): 86-91.9 Kemp JP, et al. Once-daily budesonide inhalation suspension for the treatmen

59、t of persistent asthma in infants and young children. Ann Allergy Asthma Immunol, 1999, 83: 231239.10 Baker JW, et al. A Multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatric

60、s, 1999, 103 (2): 414-421.1 中华医学会儿科学分会呼吸学组, 等. 儿童支气管哮喘诊断儿童哮喘严重程度分级中华医学会儿科学分会呼吸学组. 中华儿科杂志,2008;46(10):745-753.严重程度日间症状夜间症状/憋醒应急缓解药的使用活动受限肺功能（5岁者适用）急性发作（需使用全身激素治疗）5岁间歇状态（第1级）2d/周，发作间歇无症状无2d/周无01次/年轻度持续（第2级）2d/周，但非每日有症状12次/月2d/周，但非每天使用轻微受限6个月内2次，根据发作的频度和严重度确定分级中度持续（第3级）每天有症状34次/月每天使用部分受限重度持续（第4级）每天持续有症