ALLICS在兒童哮喘長(zhǎng)期維持治療中的應(yīng)用培訓(xùn)課件

1、ALLICS在兒童哮喘長(zhǎng)期維持治療中的應(yīng)用培訓(xùn)課件1 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 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. 糖皮質(zhì)激素霧化吸入療法在兒科應(yīng)用的專(zhuān)家共識(shí). 臨床兒科雜志, 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 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷達(dá)到并維持癥狀的控制維持正?；顒?dòng)，包括運(yùn)動(dòng)能力使肺功能水平盡量接近正常預(yù)防哮喘急性發(fā)作避免因哮喘藥物治療導(dǎo)致的不良反應(yīng)預(yù)防哮喘導(dǎo)致的死亡兒童哮喘的治療目標(biāo)中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 2008, 46(10): 745-753.達(dá)到并維持癥狀的控制兒童哮喘的治療目標(biāo)中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼長(zhǎng)期、持續(xù)、規(guī)范、個(gè)體化治療快速緩解癥

7、狀防止癥狀加重和預(yù)防復(fù)發(fā)哮喘的防治原則中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 2008, 46(10): 745-753.總原則急性發(fā)作期慢性持續(xù)期和臨床緩解期長(zhǎng)期、持續(xù)、規(guī)范、個(gè)體化治療哮喘的防治原則中華醫(yī)學(xué)會(huì)兒科學(xué)分1 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 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. 糖皮質(zhì)激素霧化吸入療法在兒科應(yīng)用的專(zhuān)家共識(shí). 臨床兒科雜志, 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 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷長(zhǎng)期規(guī)律霧化吸入ICS治療的必要性一項(xiàng)系統(tǒng)綜述納入7項(xiàng)比較停用和繼續(xù)使用ICS對(duì)哮喘急性發(fā)作風(fēng)險(xiǎn)的研究，薈萃分析結(jié)果表明，對(duì)于哮喘控制良好的哮喘患者來(lái)說(shuō)，與繼續(xù)使用I

13、CS患者相比，停用ICS可使哮喘急性發(fā)作風(fēng)險(xiǎn)增加停藥哮喘加重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.哮喘加重相對(duì)風(fēng)險(xiǎn)值增加2.35倍肺功能指標(biāo)：FEV1降低130mL晨間PEF降低18L/min平均標(biāo)準(zhǔn)哮喘癥狀評(píng)分增加0.4

14、3倍長(zhǎng)期規(guī)律霧化吸入ICS治療的必要性一項(xiàng)系統(tǒng)綜述納入7項(xiàng)比較停1 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 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. 糖皮質(zhì)激素霧化吸入療法在兒科應(yīng)用的專(zhuān)家共識(shí). 臨床兒科雜志, 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 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷ICS白三烯調(diào)節(jié)劑LABA茶堿長(zhǎng)效口服2受體激動(dòng)劑全身用糖皮質(zhì)激素抗IgE抗體抗過(guò)敏藥物變應(yīng)原特異性免疫治療兒童哮喘長(zhǎng)期控制的治療藥物中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 2008, 46(10): 745-753.ICS兒童哮喘長(zhǎng)期控制的治療藥物中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組多項(xiàng)指南推薦ICS用于兒童哮喘的長(zhǎng)期維持中國(guó)

20、兒童支氣管哮喘診斷與防治指南20081 GINA 2012. 2 ICON 2012.3中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 2008, 46(10): 745-753.GINA 2012多項(xiàng)指南推薦ICS用于兒童哮喘的長(zhǎng)期維持中國(guó)兒童支氣管哮指南推薦：5歲以下兒童哮喘最有效的長(zhǎng)期治療藥物是ICS中國(guó)兒童支氣管哮喘診斷與防治指南2008對(duì)于5歲以下兒童哮喘的長(zhǎng)期治療，最有效的治療藥物是ICS。對(duì)于大多數(shù)患兒推薦使用低劑量ICS，如果低劑量ICS不能控制癥狀，增加ICS劑量是最佳選擇。無(wú)法應(yīng)用或不愿使用ICS，或伴過(guò)敏性鼻炎的患兒可選用白三烯受體拮抗

21、劑（LTRA）中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 2008, 46(10): 745-753.指南推薦：5歲以下兒童哮喘最有效的中國(guó)兒童支氣管哮喘診斷與防與孟魯司特比較，ICS能顯著降低需要使用全身激素的急性發(fā)作風(fēng)險(xiǎn)需要使用全身激素的急性發(fā)作風(fēng)險(xiǎn)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月發(fā)表的18項(xiàng)前瞻性隨機(jī)對(duì)照試驗(yàn)比較了吸入糖皮質(zhì)激素和孟魯司特用于治療輕中度持續(xù)性哮喘患者的療效，薈萃分析結(jié)果表明，在18項(xiàng)研究納入的3757例患者中，與孟魯司特相比，吸入糖皮質(zhì)激素可顯著降低需要使用全身激素的急性發(fā)作風(fēng)險(xiǎn)（RR=0.83，P=0.01）。與孟魯司特比較，ICS能顯著降低需要使用全身激素的急性發(fā)作霧化吸入布地奈德用于兒童持續(xù)性哮喘控制效果優(yōu)于口服孟魯司特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;1:58-64一項(xiàng)為期52周的開(kāi)放、隨機(jī)、對(duì)照的多中心研究納入202例2-4歲輕度持續(xù)性哮喘患兒，給予布地奈德混懸液（n=105）或孟魯司特（n=97）治療，主要終點(diǎn)指標(biāo)是52周內(nèi)首次急性發(fā)作（需加用其他哮喘藥物）的時(shí)間。結(jié)果顯示，兩組間主要終點(diǎn)指標(biāo)無(wú)差異(183d vs 86d)，但52周時(shí)口服激素的患

24、兒比例布地奈德治療組顯著低于孟魯司特組(21.9%vs37.1%,P=0.022)。布地奈德混懸液(n=105)孟魯司特(n=97)52周內(nèi)不需要口服激素治療的百分比（%）與口服孟魯司特相比，霧化吸入布地奈德可顯著減少哮喘急性發(fā)作所需的口服激素治療時(shí)間（月）霧化吸入布地奈德用于兒童持續(xù)性哮喘控制效果優(yōu)于口服孟魯司特S1 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 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. 糖皮質(zhì)激素霧化吸入療法在兒科應(yīng)用的專(zhuān)家共識(shí). 臨床兒科雜志, 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 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷pMDI(氣霧劑)pMDI+儲(chǔ)霧罐D(zhuǎn)PI(干粉劑)家用Nebulizer(霧化器) 超聲霧化器 噴射霧化器不同吸

30、入給藥方式的裝置pMDI(氣霧劑)不同吸入給藥方式的裝置霧化吸入對(duì)患者的配合性、協(xié)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.與其他吸入裝置相比，霧化吸入：對(duì)患者協(xié)同性無(wú)要求

31、潮式呼吸即有效可使用高劑量可調(diào)整劑量不釋放CFC可同時(shí)輔助供氧可實(shí)現(xiàn)聯(lián)合藥物治療（若藥物之間無(wú)配伍禁忌）霧化吸入對(duì)患者的配合性、協(xié)同性要求少Dolovich MB,與儲(chǔ)霧罐+MDI相比，霧化器使用正確率更高兩種吸入裝置使用的總錯(cuò)誤率結(jié)果兩種吸入裝置使用的主要錯(cuò)誤率結(jié)果總錯(cuò)誤率（%）主要錯(cuò)誤率（%）24.815.915.68.5P0.001P0.001在154例1-6歲的哮喘患兒中調(diào)查吸入療法的使用情況， 其中儲(chǔ)霧罐+MDI組110例、霧化吸入組44例，結(jié)果表明，與儲(chǔ)霧罐+MDI相比霧化吸入裝置使用正確率更高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. 與儲(chǔ)霧罐+MDI相比，霧化器使用正確率更高兩種吸入裝置使用的霧化吸入裝置適合各年齡哮喘患兒使用1.賀孝良,李昌崇.哮喘吸入治療裝置新進(jìn)展.實(shí)用兒科臨床雜志.2007;22(4):309-311.吸入裝置1適用范圍限制使用注意霧化器各年齡段，用于不能正確掌握定量吸入器、嚴(yán)重氣促無(wú)法做深吸氣的患者定量吸入器6-7歲特別強(qiáng)調(diào)正確掌握吸入技術(shù)，嬰幼兒較

33、難完成吸氣和噴藥動(dòng)作的協(xié)調(diào)吸藥后必須漱口定量吸入器+儲(chǔ)霧罐4歲貯霧罐攜帶不方便，不能一次噴入多劑量藥物吸藥后必須漱口干粉劑5歲吸藥后必須漱口霧化吸入裝置適合各年齡哮喘患兒使用1.賀孝良,李昌崇.哮喘吸霧化吸入布地奈德治療vs非霧化方式吸入激素治療哮喘再發(fā)風(fēng)險(xiǎn)的風(fēng)險(xiǎn)比95%可信區(qū)間相對(duì)風(fēng)險(xiǎn)降低4歲哮喘患兒（n=766)0.380.21 - 0.7062%5-8歲哮喘患兒（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.與其他哮喘治療藥物和非霧化方式吸入糖皮質(zhì)激素相比，霧化吸入布地奈德混懸液治療與哮喘再發(fā)風(fēng)險(xiǎn)的顯著降低相關(guān)一項(xiàng)縱向回顧性研究納入10176例急診或住院的哮喘患兒，回顧性調(diào)查其過(guò)去6個(gè)月的用藥情況，并記錄收治后30天內(nèi)的用藥情況，并據(jù)此分組，觀察31-180

35、天內(nèi)患者再次急診或住院的風(fēng)險(xiǎn)。結(jié)果表明，在因哮喘導(dǎo)致急診或住院的哮喘患兒（年齡8歲）中，與其他哮喘治療藥物和非霧化方式吸入糖皮質(zhì)激素相比，霧化吸入布地奈德混懸液治療與哮喘再發(fā)風(fēng)險(xiǎn)的顯著降低相關(guān)。霧化吸入布地奈德治療哮喘再發(fā)風(fēng)險(xiǎn)的風(fēng)險(xiǎn)比95%可信區(qū)間相對(duì)風(fēng)1 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷與防治指南.中華兒科雜志, 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. 糖皮質(zhì)激素霧化吸入療法在兒科應(yīng)用的專(zhuān)家共識(shí). 臨床兒科雜志, 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 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷GINA指南：長(zhǎng)期低劑量ICS對(duì)兒童生長(zhǎng)發(fā)育無(wú)顯著不良影響GINA 2012: 40.糖皮質(zhì)激素的使用與兒童生長(zhǎng)的關(guān)系：控制不佳或嚴(yán)重的哮喘影響兒童的生長(zhǎng)發(fā)育，未能達(dá)到預(yù)期的成

41、人身高并無(wú)長(zhǎng)期對(duì)照試驗(yàn)報(bào)道ICS（100-200g/d）的長(zhǎng)期使用對(duì)生長(zhǎng)有顯著不良影響當(dāng)高劑量使用ICS時(shí)，可能造成生長(zhǎng)遲緩在短期和中期研究中，生長(zhǎng)遲緩的發(fā)生與劑量呈相關(guān)性不同年齡的患兒對(duì)ICS導(dǎo)致的生長(zhǎng)遲緩效應(yīng)的易感性不同，2-10的兒童比成人更易感在治療的第一年，糖皮質(zhì)激素導(dǎo)致的生長(zhǎng)率的變化似乎是暫時(shí)的。使用ICS治療的哮喘患兒可在較晚的年齡達(dá)到正常的成人身高（根據(jù)家庭成員來(lái)估計(jì)）GINA指南：長(zhǎng)期低劑量ICS對(duì)兒童生長(zhǎng)發(fā)育無(wú)顯著不良影響GINA指南：長(zhǎng)期低劑量ICS對(duì)兒童骨折和骨密度無(wú)顯著不良影響GINA 2012: 40.糖皮質(zhì)激素的使用與兒童骨發(fā)育的關(guān)系：并無(wú)研究報(bào)道使用ICS的患兒

42、骨折風(fēng)險(xiǎn)顯著升高口服或全身激素可增加骨折的風(fēng)險(xiǎn)，骨折風(fēng)險(xiǎn)的升高與治療療程數(shù)相關(guān)，在4個(gè)療程后增加32%。使用ICS可降低全身激素療程的需求持續(xù)2-5年的有對(duì)照的縱向研究和一些橫斷面調(diào)查顯示，ICS治療對(duì)骨礦物質(zhì)密度無(wú)不良影響ICS使用可能會(huì)導(dǎo)致男孩在進(jìn)入青春期時(shí)骨礦物質(zhì)增生減少，但這種風(fēng)險(xiǎn)可被降低口服激素用量所帶來(lái)的獲益抵消GINA指南：長(zhǎng)期低劑量ICS對(duì)兒童骨折和骨密度無(wú)顯著不良ICS 用于兒童哮喘長(zhǎng)期維持安全性數(shù)據(jù)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 用于兒童哮喘長(zhǎng)期維持安全性數(shù)據(jù)良好Brand PL.平均基礎(chǔ)皮質(zhì)激素與ACTH誘導(dǎo)皮質(zhì)激素水平（nmol/L）基礎(chǔ)* ACTH*基礎(chǔ)* ACTH*基礎(chǔ) * ACTH*基礎(chǔ)* ACTH*安慰劑組0.25 mg BID組0.50 mg BID組1.0 mg BID組霧化吸入布地奈德對(duì)下丘腦-垂體-腎上腺軸 (HPAA)功能無(wú)顯著不良影響一項(xiàng)研究納入178例吸入激素依賴型持續(xù)性哮喘患兒，隨機(jī)分入布地奈德0.25mg、bid治療組（47例），0.50 mg、bid治療組（42例

44、），1.0 mg、bid治療組（45例）和安慰劑組（44例），主要療效指標(biāo)為夜間和日間哮喘癥狀評(píng)分與基線（隨機(jī)分組前7天的平均數(shù)）相比的差異，并觀察不良事件發(fā)生率。結(jié)果表明，各劑量布地奈德組與安慰劑組對(duì)比，基礎(chǔ)皮質(zhì)醇水平與ACTH刺激的皮質(zhì)醇水平無(wú)顯著差異。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.*：基礎(chǔ)的皮質(zhì)醇水平*：ACTH刺激的皮質(zhì)醇水平平均基礎(chǔ)皮質(zhì)激素與ACTH誘導(dǎo)皮質(zhì)激素水平基礎(chǔ)* AC霧化吸入布地奈德對(duì)HPAA功能無(wú)明顯影響湛潔誼, 等. 霧化吸入糖皮質(zhì)激素對(duì)支氣管哮喘患兒下丘腦-垂體-腎上腺軸功能的影響. 實(shí)用兒科臨床雜志, 2009, 24(16): 1244-6.血清皮質(zhì)醇（nmol/L）24h尿游離皮質(zhì)醇與尿肌酐比值（nmol/mmoL）各組間 P=NS各組間 P=NS研究納入60例已規(guī)律霧化吸入布地奈德超過(guò)6個(gè)月，起始劑量為1000g/d

46、，逐漸減量至250g/d或500g/d并維持該劑量至少3個(gè)月的患兒，根據(jù)近3個(gè)月布地奈德劑量分入BUD-250組（吸入BUD250g）和BUD-500組（吸入BUD500g），并選擇30例健康兒童作為對(duì)照組，測(cè)定血清皮質(zhì)醇和24h尿游離皮質(zhì)醇與尿肌酐比值。結(jié)果表明，不同劑量布地奈德治療組和對(duì)照組的血清皮質(zhì)醇和24h尿游離皮質(zhì)醇與尿肌酐比值的差異均無(wú)統(tǒng)計(jì)學(xué)意義。霧化吸入布地奈德對(duì)下丘腦-垂體-腎上腺軸 (HPAA)功能無(wú)明顯影響1霧化吸入布地奈德對(duì)HPAA功能無(wú)明顯影響湛潔誼, 等. 霧化長(zhǎng)期霧化吸入布地奈德治療對(duì)骨礦物質(zhì)密度無(wú)顯著影響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.為了研究長(zhǎng)期使用霧化吸入布地奈德對(duì)骨代謝的影響，一項(xiàng)研究納入157例長(zhǎng)期使用布地奈德的哮喘患兒，平均使用劑量為504 g/d，平均使用年限為4.5年，111例未使用過(guò)外源性糖皮質(zhì)激素的哮喘患兒作為對(duì)照組，結(jié)果表明，兩組患者的骨礦物質(zhì)密度無(wú)顯著差異。骨礦物質(zhì)密度對(duì)照組布地奈德治療組0.917 g/cm0.915g/cmNS長(zhǎng)期霧

48、化吸入布地奈德治療對(duì)骨礦物質(zhì)密度無(wú)顯著影響AgertoSTART研究：布地奈德治療并不增加哮喘患兒的常見(jiàn)副反應(yīng)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.不良事件布地奈德聯(lián)合常規(guī)治療組（n=1004）常規(guī)治療組（n=977）呼吸系統(tǒng)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%）支氣管炎164 (16.3%) 183 (18.7%)發(fā)熱117 (11.7%) 100 (10.2%)中耳炎112 (11.2%)96 (9.8%)鼻竇炎87 (8.7%) 99 (10.1%)咳嗽88 (8.8%) 81 (8.3%)結(jié)膜炎88 (8.8%) 79 (8.1%)頭痛86 (8.6%)72 (7.4%)事故/受傷75 (7.5%)79 (8.1%)胃腸炎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研究對(duì)納入的1981例5-10歲輕度持續(xù)性哮喘患者進(jìn)行了安全性研究，所有患者均接受常規(guī)哮喘治療，其中1004例接受布地奈德200 g/d治療，977例患者接受安慰劑治療，治療維持三年，觀察兩組患者常見(jiàn)副反應(yīng)的發(fā)生率。結(jié)果顯示，常規(guī)治療加入布地奈德治療用于新近發(fā)病的輕度持續(xù)性哮喘患兒是可耐受的。START研究：布地奈德治療并不增加哮喘患兒的常見(jiàn)副反應(yīng)Si霧化吸入布地奈德長(zhǎng)期控制哮喘不影響兒童身高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1：一項(xiàng)為期5年的國(guó)際多中心研究納入2938例5-15歲輕度持續(xù)性哮喘患者，11歲以下的兒童接受布地奈德干粉劑吸入200g治療，11歲以上的兒童接受布地奈德400g治療，每天一次。治療3年后均接受布地奈德治療，持續(xù)2年，觀察患兒的身高。START研究結(jié)果：布地奈德治療2年及5年后，患兒的身高與未用激素的同齡兒童相比均無(wú)顯著差異。霧化吸入布地奈德長(zhǎng)期控制哮喘不影響兒童身高1 Pederse長(zhǎng)期使用ICS安全性數(shù)據(jù)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湛潔誼, 等. 霧化吸入糖皮質(zhì)激素對(duì)支氣管哮喘患兒下丘腦-垂體-腎上腺軸功能的

54、影響. 實(shí)用兒科臨床雜志, 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.長(zhǎng)期使用ICS安全性數(shù)據(jù)良好1GINA 2012: 40.1 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診

55、斷與防治指南.中華兒科雜志, 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. 糖皮質(zhì)激素霧化吸入療法在兒科應(yīng)用的專(zhuān)家共識(shí). 臨床兒科雜志, 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 中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組, 等. 兒童支氣管哮喘診斷兒童哮喘嚴(yán)重程度分級(jí)中華醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)呼吸學(xué)組. 中華兒科雜志,2008;46(10):745-753.嚴(yán)重程度日間癥狀夜間癥狀/憋醒應(yīng)急緩解藥的使用活動(dòng)受限肺功能（5歲者適用）急性發(fā)作（需使用全身激素治療）5歲間歇狀態(tài)（第1級(jí)）2d/周，發(fā)作間歇無(wú)癥狀無(wú)2d/周無(wú)01次/年輕度持續(xù)（第2級(jí)）2d/周，但非每日有癥狀12次/月2d/周，但非每天使用輕微受限6個(gè)月內(nèi)2次，根據(jù)發(fā)作的頻度和嚴(yán)重度確定分級(jí)中度持續(xù)（第3級(jí)）每天有癥狀34次/月每天使用部分受限重度持續(xù)（第4級(jí)）每天持續(xù)有癥