Effects of guide-recommended treatment strategies on asthma symptom scores in moderate-to-severe asthma patients aged 5-18 years: a network meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Jianrong ¹ , LIU Fengqi ¹ , LIU Zuoxiang ¹ , PENG Hexiang ¹ , ZENG Xueyang ¹ , CHEN Yahong ² ,  WU Tao ^1,3 ,  SUN Feng ^1,3,4

1. Department of Epidemiology and Health Statistics, School of Public Health, Peking University, Beijing 100191, P. R. China;
2. Department of Respiratory Medicine, Peking University Third Hospital, Beijing 100191, P. R. China;
3. Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, P. R. China;
4. Peking University Center for Evidence Based Medicine and Clinical Research, Beijing 100191, P. R. China;

Corresponding author：

WU Tao, Email: twu@bjmu.edu.cn; SUN Feng, Email: sunfeng@bjmu.edu.cn

Keywords：

Asthma; Children and adolescents; Asthma symptom score; Network meta-analysis

DOI：

10.7507/1672-2531.202309050

Video：

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Objectives To evaluate the improvement of symptoms in patients with moderate to severe asthma aged 5-18 years treated with GINA (Global Initiative for Asthma) guidelines by network meta-analysis. Methods Randomized controlled trials (RCTs) about asthma patients aged 5 to 18 years with reported asthma symptom scores were collected from PubMed, Embase, Cochrane Library, CNKI, WanFang Data, VIP, SinoMed and clinical trial registry platform (ClinicalTrials.gov). The search time limit was from the inception to August 26, 2023. After two researchers independently screened literature, extracted data and evaluated the risk of bias of included studies, Stata 15.0 software was used for network meta-analysis. Results A total of 23 studies were included, 23 of which reported daytime asthma symptom scores. Compared with symptom scores in the low-dose ICS group, there was a statistically significant difference in improvement of daytime symptoms between low-dose ICS+LABA+LTRA (SMD=−1.4, 95%CI −1.99 to −0.81) and low-dose ICS+LABA+SABA (SMD=−1.43, 95%CI −2.48 to −0.39). Symptom scores for nighttime asthma were reported in 20 RCTs, and there was a statistically significant difference in symptom scores for low-dose ICS+LABA+LTRA (SMD=−1.20, 95%CI −2.20 to −0.21) compared with the low-dose ICS group. After the ranking of efficacy, the number one asthma symptom score in both daytime and nighttime was low-dose ICS+LABA+LTRA group. Conclusion Low dose ICS+LABA+LTRA has the best efficacy in improving daytime and nighttime asthma symptom scores.

Citation： LI Jianrong, LIU Fengqi, LIU Zuoxiang, PENG Hexiang, ZENG Xueyang, CHEN Yahong, WU Tao, SUN Feng. Effects of guide-recommended treatment strategies on asthma symptom scores in moderate-to-severe asthma patients aged 5-18 years: a network meta-analysis. Chinese Journal of Evidence-Based Medicine, 2024, 24(9): 1044-1051. doi: 10.7507/1672-2531.202309050 Copy

1.	吴嘉婴, 洪建国. 儿童支气管哮喘诊断和防治指南(2016年版)更新要点. 世界临床药物, 2018, 39(8): 512-517.
2.	Papi A, Brightling C, Pedersen SE, et al. Asthma. Lancet, 2018, 391(10122): 783-800.
3.	中华儿科杂志编辑委员会, 中华医学会儿科学分会呼吸学组, 中国医师协会儿科医师分会儿童呼吸专业委员会. 儿童支气管哮喘规范化诊治建议(2020年版). 中华儿科杂志, 2020, 58(9): 708-717.
4.	Busse WW, Chervinsky P, Condemi J, et al. Budesonide delivered by turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma. J Allergy Clin Immunol, 1998, 101(4 Pt 1): 457-463.
5.	Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J, 2008, 31(1): 143-178.
6.	Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021.
7.	Ahmed H, Turner S. Severe asthma in children-a review of definitions, epidemiology, and treatment options in 2019. Pediatr Pulmonol, 2019, 54(6): 778-787.
8.	Guilbert TW, Bacharier LB, Fitzpatrick AM. Severe asthma in children. J Allergy Clin Immunol Pract, 2014, 2(5): 489-500.
9.	Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019, 28(366): 1756-1833.
10.	Chaimani A, Mavridis D, Salanti G. A hands-on practical tutorial on performing meta-analysis with Stata. Evid Based Ment Health, 2014, 17(4): 111-116.
11.	Veroniki AA, Vasiliadis HS, Higgins JP, et al. Evaluation of inconsistency in networks of interventions. Int J Epidemiol, 2013, 42(1): 332-345.
12.	Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol, 2011, 64(2): 163-171.
13.	Chaimani A, Higgins JP, Mavridis D, et al. Graphical tools for network meta-analysis in STATA. PLoS One, 2013, 8(10): e76654.
14.	Puhan MA, Schünemann HJ, Murad MH, et al. A GRADE working group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ, 2014, 349: g5630.
15.	王琪, 王韵华, 赖鸿皓, 等. 网状Meta分析证据质量分级: CINeMA在线应用程序简介. 中国循证医学杂志, 2020, 20(9): 1111-1116.
16.	蔡勇辉, 卢浩堂, 冯科壬, 等. 吸入糖皮质激素联合小剂量茶碱与联合白三烯调节剂治疗5岁以下儿童哮喘的效果比较. 中国当代医药, 2014, 21(2): 103-106.
17.	陈庆海. 小剂量糖皮质激素联合口服茶碱片治疗小儿哮喘的疗效观察. 中国中西医结合儿科学, 2016, 8(3): 286-289.
18.	付睿, 赵艳飞, 杨慧湘, 等. 沙美特罗替卡松气雾剂治疗重度支气管哮喘患儿的疗效及对肺功能、炎性因子的影响. 中国妇幼保健, 2018, 33(21): 4930-4933.
19.	黄胜奇, 农定猛, 吴昔林, 等. 布地奈德联合沙美特罗对儿童中重度哮喘的治疗分析. 中外医疗, 2013, 32(10): 1-2.
20.	黄肖梅, 黄卫娟, 陈建江, 等. 沙美特罗替卡松单用与丙酸氟替卡松联合孟鲁司特钠治疗儿童中度持续哮喘的疗效比较. 中国药房, 2016, 27(23): 3240-3243.
21.	黄莺. 丙酸氟替卡松联合孟鲁司特钠对中度持续哮喘患儿的肺功能及炎症因子的影响. 慢性病学杂志, 2019, 20(3): 384-386.
22.	黄志刚. 丙酸氟替卡松和沙美特罗联合治疗小儿中、重度哮喘的临床效果分析. 临床医药文献电子杂志, 2014, 1(5): 773-774.
23.	廖翠芳. 沙美特罗替卡松联合孟鲁司特治疗儿童中度哮喘分析. 现代医院, 2007, 3: 27-29.
24.	吕燕芬. 孟鲁司特联合布地奈德治疗儿童中度哮喘疗效观察. 海峡药学, 2006, 6: 105.
25.	梅忠卓. 布地奈德联合沙美特罗治疗儿童中重度哮喘的临床疗效. 医学临床研究, 2012, 29(12): 2328-2329.
26.	谭仕凯. 信必可都保联合孟鲁司特治疗中度、重度哮喘患儿的疗效观察. 吉林医学, 2013, 34(25): 5116-5117.
27.	王素梅, 王大斌. 沙美特罗替卡松与孟鲁司特钠联合治疗中重度支气管哮喘的疗效. 实用儿科临床杂志, 2010, 25(16): 1249-1250.
28.	邬菊花, 徐佩茹, 多力坤, 等. 舒利迭治疗儿童哮喘呼气峰流速及症状评分情况的观察. 新疆医学, 2005, 3: 72-74.
29.	武怡, 路明. 沙美特罗/丙酸氟替卡松干粉与布地奈德干粉吸入治疗儿童哮喘的临床观察. 徐州医学院学报, 2007, 5: 339-341.
30.	谢勇军. 孟鲁司特联合吸入糖皮质激素治疗小儿慢性中度持续支气管哮喘的临床疗效. 临床合理用药杂志, 2016, 9(12): 15-17.
31.	应红霞. 白三烯受体拮抗剂孟鲁司特钠治疗儿童中重度哮喘的疗效观察. 中国全科医学, 2009, 12(3): 245-246.
32.	陈碧香, 李陈. 吸入糖皮质激素联合小剂量茶碱白三烯调节剂治疗5岁以下儿童哮喘的临床研究. 基层医学论坛, 2017, 21(29): 3957-3958.
33.	李志辉, 辛淑君, 王影齐, 等. 孟鲁司特联合吸入糖皮质激素治疗小儿中度持续哮喘的疗效及机制. 中国实用医药, 2008, 3(16): 38-40.
34.	王广俊, 吴庆莉, 林荣军. 布地奈德福莫特罗粉吸入剂与布地奈德粉吸入剂联合富马酸福莫特罗粉吸入剂治疗哮喘的疗效及安全性. 实用儿科临床杂志, 2011, 26(4): 3.
35.	Nawaz S, Ahmed RI, Arzoo K, et al. Comparison of montelukast and ketotifen sodium in management of childhood asthma. Rawal Medical Journal, 2021, 46(3): 500-502.
36.	Olszowiec-Chlebna M, Majak P, Brzozowska A, et al. Effect of inhaled steroid and montelukast on clinical symptoms in children with newly diagnosed asthma: a pilot study. Pediatric allergy immuno, 2010, 21(4 Pt 2): e687-e690.
37.	Murray CS, Custovic A, Lowe LA, et al. Effect of addition of salmeterol versus doubling the dose of fluticasone propionate on specific airway resistance in children with asthma. Allergy Asthma Proc, 2010, 31(5): 415-421.
38.	Płoszczuk A, Bosheva M, Spooner K, et al. Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial. Therapeutic Advances in Respiratory Disease, 2018: 12.
39.	Sheikh SI, Ryan-Wenger NA, Pitts J, et al. Impact of asthma severity on long-term asthma control. J Asthma, 2021, 58(6): 725-734.
40.	邹晓东, 王伟, 黄绍光. 哮喘症状评分临床应用价值. 现代诊断与治疗, 1993, (3): 284-286.
41.	Gater A, Nelsen L, Coon CD, et al. Asthma daytime symptom diary (ADSD) and asthma nighttime symptom diary (ANSD): measurement properties of novel patient-reported symptom measures. J Allergy Clin Immunol Pract, 2022, 10(5): 1249-1259.
42.	Zhao Y, Han S, Shang J, et al. Effectiveness of drug treatment strategies to prevent asthma exacerbations and increase symptom-free days in asthmatic children: a network meta-analysis. J Asthma, 2015, 52(8): 846-857.
43.	Sobieraj DM, Baker WL, Nguyen E, et al. Association of inhaled corticosteroids and long-acting muscarinic antagonists with asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta-analysis. JAMA, 2018, 319(14): 1473-1484.
44.	Kim LHY, Saleh C, Whalen-Browne A, et al. Triple vs dual inhaler therapy and asthma outcomes in moderate to severe asthma: a systematic review and meta-analysis. JAMA, 2021, 325(24): 2466-2479.
45.	Agusti A, Fabbri L, Lahousse L, et al. Single inhaler triple therapy (SITT) in asthma: systematic review and practice implications. Allergy, 2022, 77(4): 1105-1113.
46.	Kaplan A, FitzGerald JM, Buhl R, et al. Comparing LAMA with LABA and LTRA as add-on therapies in primary care asthma management. NPJ Prim Care Respir Med, 2020, 30(1): 50.
47.	Rogliani P, Ritondo BL, Calzetta L. Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies. Eur Respir J, 2021, 58(3): 2004233.
48.	Cazzola M, Puxeddu E, Matera MG, et al. A potential role of triple therapy for asthma patients. Expert Rev Respir Med, 2019, 13(11): 1079-1085.
49.	van der Mark LB, Lyklema PHE, Geskus RB, et al. A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four. Bmc Pulmonary Medicine, 2012, 12: 63.

1. 吴嘉婴, 洪建国. 儿童支气管哮喘诊断和防治指南(2016年版)更新要点. 世界临床药物, 2018, 39(8): 512-517.
2. Papi A, Brightling C, Pedersen SE, et al. Asthma. Lancet, 2018, 391(10122): 783-800.
3. 中华儿科杂志编辑委员会, 中华医学会儿科学分会呼吸学组, 中国医师协会儿科医师分会儿童呼吸专业委员会. 儿童支气管哮喘规范化诊治建议(2020年版). 中华儿科杂志, 2020, 58(9): 708-717.
4. Busse WW, Chervinsky P, Condemi J, et al. Budesonide delivered by turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma. J Allergy Clin Immunol, 1998, 101(4 Pt 1): 457-463.
5. Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J, 2008, 31(1): 143-178.
6. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021.
7. Ahmed H, Turner S. Severe asthma in children-a review of definitions, epidemiology, and treatment options in 2019. Pediatr Pulmonol, 2019, 54(6): 778-787.
8. Guilbert TW, Bacharier LB, Fitzpatrick AM. Severe asthma in children. J Allergy Clin Immunol Pract, 2014, 2(5): 489-500.
9. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019, 28(366): 1756-1833.
10. Chaimani A, Mavridis D, Salanti G. A hands-on practical tutorial on performing meta-analysis with Stata. Evid Based Ment Health, 2014, 17(4): 111-116.
11. Veroniki AA, Vasiliadis HS, Higgins JP, et al. Evaluation of inconsistency in networks of interventions. Int J Epidemiol, 2013, 42(1): 332-345.
12. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol, 2011, 64(2): 163-171.
13. Chaimani A, Higgins JP, Mavridis D, et al. Graphical tools for network meta-analysis in STATA. PLoS One, 2013, 8(10): e76654.
14. Puhan MA, Schünemann HJ, Murad MH, et al. A GRADE working group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ, 2014, 349: g5630.
15. 王琪, 王韵华, 赖鸿皓, 等. 网状Meta分析证据质量分级: CINeMA在线应用程序简介. 中国循证医学杂志, 2020, 20(9): 1111-1116.
16. 蔡勇辉, 卢浩堂, 冯科壬, 等. 吸入糖皮质激素联合小剂量茶碱与联合白三烯调节剂治疗5岁以下儿童哮喘的效果比较. 中国当代医药, 2014, 21(2): 103-106.
17. 陈庆海. 小剂量糖皮质激素联合口服茶碱片治疗小儿哮喘的疗效观察. 中国中西医结合儿科学, 2016, 8(3): 286-289.
18. 付睿, 赵艳飞, 杨慧湘, 等. 沙美特罗替卡松气雾剂治疗重度支气管哮喘患儿的疗效及对肺功能、炎性因子的影响. 中国妇幼保健, 2018, 33(21): 4930-4933.
19. 黄胜奇, 农定猛, 吴昔林, 等. 布地奈德联合沙美特罗对儿童中重度哮喘的治疗分析. 中外医疗, 2013, 32(10): 1-2.
20. 黄肖梅, 黄卫娟, 陈建江, 等. 沙美特罗替卡松单用与丙酸氟替卡松联合孟鲁司特钠治疗儿童中度持续哮喘的疗效比较. 中国药房, 2016, 27(23): 3240-3243.
21. 黄莺. 丙酸氟替卡松联合孟鲁司特钠对中度持续哮喘患儿的肺功能及炎症因子的影响. 慢性病学杂志, 2019, 20(3): 384-386.
22. 黄志刚. 丙酸氟替卡松和沙美特罗联合治疗小儿中、重度哮喘的临床效果分析. 临床医药文献电子杂志, 2014, 1(5): 773-774.
23. 廖翠芳. 沙美特罗替卡松联合孟鲁司特治疗儿童中度哮喘分析. 现代医院, 2007, 3: 27-29.
24. 吕燕芬. 孟鲁司特联合布地奈德治疗儿童中度哮喘疗效观察. 海峡药学, 2006, 6: 105.
25. 梅忠卓. 布地奈德联合沙美特罗治疗儿童中重度哮喘的临床疗效. 医学临床研究, 2012, 29(12): 2328-2329.
26. 谭仕凯. 信必可都保联合孟鲁司特治疗中度、重度哮喘患儿的疗效观察. 吉林医学, 2013, 34(25): 5116-5117.
27. 王素梅, 王大斌. 沙美特罗替卡松与孟鲁司特钠联合治疗中重度支气管哮喘的疗效. 实用儿科临床杂志, 2010, 25(16): 1249-1250.
28. 邬菊花, 徐佩茹, 多力坤, 等. 舒利迭治疗儿童哮喘呼气峰流速及症状评分情况的观察. 新疆医学, 2005, 3: 72-74.
29. 武怡, 路明. 沙美特罗/丙酸氟替卡松干粉与布地奈德干粉吸入治疗儿童哮喘的临床观察. 徐州医学院学报, 2007, 5: 339-341.
30. 谢勇军. 孟鲁司特联合吸入糖皮质激素治疗小儿慢性中度持续支气管哮喘的临床疗效. 临床合理用药杂志, 2016, 9(12): 15-17.
31. 应红霞. 白三烯受体拮抗剂孟鲁司特钠治疗儿童中重度哮喘的疗效观察. 中国全科医学, 2009, 12(3): 245-246.
32. 陈碧香, 李陈. 吸入糖皮质激素联合小剂量茶碱白三烯调节剂治疗5岁以下儿童哮喘的临床研究. 基层医学论坛, 2017, 21(29): 3957-3958.
33. 李志辉, 辛淑君, 王影齐, 等. 孟鲁司特联合吸入糖皮质激素治疗小儿中度持续哮喘的疗效及机制. 中国实用医药, 2008, 3(16): 38-40.
34. 王广俊, 吴庆莉, 林荣军. 布地奈德福莫特罗粉吸入剂与布地奈德粉吸入剂联合富马酸福莫特罗粉吸入剂治疗哮喘的疗效及安全性. 实用儿科临床杂志, 2011, 26(4): 3.
35. Nawaz S, Ahmed RI, Arzoo K, et al. Comparison of montelukast and ketotifen sodium in management of childhood asthma. Rawal Medical Journal, 2021, 46(3): 500-502.
36. Olszowiec-Chlebna M, Majak P, Brzozowska A, et al. Effect of inhaled steroid and montelukast on clinical symptoms in children with newly diagnosed asthma: a pilot study. Pediatric allergy immuno, 2010, 21(4 Pt 2): e687-e690.
37. Murray CS, Custovic A, Lowe LA, et al. Effect of addition of salmeterol versus doubling the dose of fluticasone propionate on specific airway resistance in children with asthma. Allergy Asthma Proc, 2010, 31(5): 415-421.
38. Płoszczuk A, Bosheva M, Spooner K, et al. Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial. Therapeutic Advances in Respiratory Disease, 2018: 12.
39. Sheikh SI, Ryan-Wenger NA, Pitts J, et al. Impact of asthma severity on long-term asthma control. J Asthma, 2021, 58(6): 725-734.
40. 邹晓东, 王伟, 黄绍光. 哮喘症状评分临床应用价值. 现代诊断与治疗, 1993, (3): 284-286.
41. Gater A, Nelsen L, Coon CD, et al. Asthma daytime symptom diary (ADSD) and asthma nighttime symptom diary (ANSD): measurement properties of novel patient-reported symptom measures. J Allergy Clin Immunol Pract, 2022, 10(5): 1249-1259.
42. Zhao Y, Han S, Shang J, et al. Effectiveness of drug treatment strategies to prevent asthma exacerbations and increase symptom-free days in asthmatic children: a network meta-analysis. J Asthma, 2015, 52(8): 846-857.
43. Sobieraj DM, Baker WL, Nguyen E, et al. Association of inhaled corticosteroids and long-acting muscarinic antagonists with asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta-analysis. JAMA, 2018, 319(14): 1473-1484.
44. Kim LHY, Saleh C, Whalen-Browne A, et al. Triple vs dual inhaler therapy and asthma outcomes in moderate to severe asthma: a systematic review and meta-analysis. JAMA, 2021, 325(24): 2466-2479.
45. Agusti A, Fabbri L, Lahousse L, et al. Single inhaler triple therapy (SITT) in asthma: systematic review and practice implications. Allergy, 2022, 77(4): 1105-1113.
46. Kaplan A, FitzGerald JM, Buhl R, et al. Comparing LAMA with LABA and LTRA as add-on therapies in primary care asthma management. NPJ Prim Care Respir Med, 2020, 30(1): 50.
47. Rogliani P, Ritondo BL, Calzetta L. Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies. Eur Respir J, 2021, 58(3): 2004233.
48. Cazzola M, Puxeddu E, Matera MG, et al. A potential role of triple therapy for asthma patients. Expert Rev Respir Med, 2019, 13(11): 1079-1085.
49. van der Mark LB, Lyklema PHE, Geskus RB, et al. A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four. Bmc Pulmonary Medicine, 2012, 12: 63.

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Chinese Journal of Evidence-Based Medicine

Effects of guide-recommended treatment strategies on asthma symptom scores in moderate-to-severe asthma patients aged 5-18 years: a network meta-analysis

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