Objective  To systematically review the safety of budesonide inhalation aerosol in the treatment of chronic obstructive pulmonary disease.

Methods  PubMed, Cochrane Library, Web of Science, Embase, CNKI, WanFang Data, VIP and SinoMed databases were electronically searched to collect randomized controlled trials on budesonide inhalation aerosol in the treatment of chronic obstructive pulmonary disease from inception to June 30, 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. The Meta-analysis was performed by using RevMan 5.3 software.

Results  A total of 52 studies with 16,768 patients were included. Meta-analysis results showed that the incidence of respiratory system adverse drug reaction (ADR) was higher in the budesonide group than in the control group, with a statistically significant difference [OR=1.18, 95%CI (1.10, 1.27), P<0.001]. There was no statistically significant difference in the incidence of overall ADR, central and peripheral nervous system ADR, gastrointestinal system ADR, skin ADR, urinary system ADR, infectious disease ADR, and musculoskeletal system ADR between the two groups of patients (P>0.05). According to the subgroup analysis of the treatment course, in the 3-6 month subgroup, the incidence of ADR was higher in the budesonide group than in the control group, with a statistically significant difference [OR=1.43, 95%CI (1.18, 1.74), P<0.001]. In the studies with a treatment duration of more than 6 months, the incidence of ADR was higher in the budesonide group than in the control group, with a statistically significant difference [OR=1.54, 95%CI (1.16, 2.03), P=0.002]. In the study of unknown treatment course, the incidence of ADR in the budesonide group was lower than that in the control group, and the difference was statistically significant [OR=0.39, 95%CI (0.20, 0.76), P=0.005]. In the studies with a treatment duration of less than 3 months, the incidence of ADR in the budesonidegroup was comparable to that in the control group (P>0.05).

Conclusion  The incidence of respiratory ADR caused by budesonide is higher than that of the control group. Although the incidence of overall ADR is not statistically significant, the occurrence of systemic adverse reactions should continue to be closely monitored in the future treatment of chronic obstructive pulmonary disease.

1.王晓曦, 葛渊源, 张景辰,等. 吸入三联药物的研究现状及展望[J]. 中国药事, 2021, 35(10): 1173-1180. [Wang XX, Ge YY, Zhang JC, et al. Research status and prospect of inhaled triple drugs[J]. Chinese Pharmaceutical Affairs, 2021, 35(10): 1173-1180.] DOI: 10.16153/j.1002-7777.2021.10.013.

2.范晓艳. 布地格福吸入气雾剂对慢性阻塞性肺疾病急性加重期患者的疗效分析[J]. 中国药物与临床, 2021, 21(24): 3994-3997. DOI: 10.11655/zgywylc2021.24.016.

3.栾俊旺. 布地格福吸入气雾剂治疗慢性阻塞性肺疾病的临床效果分析[J]. 中外医药研究, 2022, 1(7): 33-35. [Luan JW. Clinical effect analysis of budesonide, glycopyrronium bromide and formoterol fumarate inhalation aerosol in treatment of chronic obstructive pulmonary disease[J]. Journal of Chinese and Foreign Medicine and Pharmacy Research, 2022, 1(7): 33-35.] DOI: 10.3969/j.issn.2096-6229.2022.07.011.

4.Green HH, Ray L, Buchanan J, et al. Urinary retention and mydriasis secondary to topical glycopyrronium for axillary hyperhidrosis[J]. Am J Health Syst Pharm, 2023, 80(18): 1234-1237. DOI: 10.1093/ajhp/zxad141.

5.Mannino DM, Watt G, Hole D, et al. The natural history of chronic obstructive pulmonary disease[J]. Eur Respir J, 2006, 27(3): 627-643. DOI: 10.1183/09031936.06.0024605.

6.Klein R, Klein BEK. The prevalence of age-related eye diseases and visual impairment in aging: current estimates[J]. Invest Ophthalmol Vis Sci, 2013, 54(14): ORSF5-ORSF13. DOI: 10.1167/iovs.13-12789.

7.Warming L, Hassager C, Christiansen C. Changes in bone mineral density with age in men and women: a longitudinal study[J]. Osteoporos Int, 2002, 13(2): 105-112. DOI: 10.1007/s001980200001.

8.朱启城, 陈有华, 黄南华, 等. 布地格福吸入气雾剂对慢性阻塞性肺疾病患者的临床效果[J]. 实用临床医学, 2024, 25(2): 24-26, 31. DOI: 10.13764/j.cnki.lcsy.2024.02.006.

9.朱美君, 孙芳, 涂水余, 等. 噻托溴铵联合布地格福吸入对慢性阻塞性肺疾病急性加重期患者肺功能及血清特异因子的影响[J]. 山西医药杂志, 2023, 52(14): 1083-1086. DOI: 10.3969/j.issn.0253-9926.2023.14.009.

10.郑文风. 布地格福吸入气雾剂对中重度慢性阻塞性肺疾病患者肺功能、血气分析的影响[J]. 北方药学, 2024, 21(1): 160-162. DOI: 10.3969/j.issn.1672-8351.2024.01.054.

11.阿米娜古丽·塔西铁木尔, 祖菲亚·努尔买买提. 布地格福吸入气雾剂治疗中重度慢性阻塞性肺疾病的疗效及安全性研究[J]. 世界最新医学信息文摘, 2021, 21(60): 5-6, 9. [Aminaguri T, Zufia N. Efficacy and safety of budesonide, glycopyrronium bromide and formoterol fumarate inhalation aerosol in the treatment of moderate and severe chronic obstructive pulmonary disease[J]. World Latest Medicine Information (Electronic Version), 2021, 21(60): 5-6, 9.] DOI: 10.3969/j.issn.1671-3141.2021.60.002.

12.Ichinose M, Fukushima Y, Inoue Y, et al. Long-term safety and efficacy of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology in japanese patients with COPD[J]. Int J Chron Obstruct Pulmon Dis, 2019, 14: 2993-3002. DOI: 10.2147/COPD.S220861.

13.Kerwin EM, Ferguson GT, Mo M, et al. Bone and ocular safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in COPD: a 52-week randomized study[J]. Respir Res, 2019, 20(1): 167. DOI: 10.1186/s12931-019-1126-7.

14.汪洋. Cochrane偏倚风险评估工具简介[J]. 中国全科医学, 2019, 22(11): 1322. https://kns.cnki.net/kcms2/article/abstract?v=hzXYN1WNkISKdaN04K3HGUf-q33Ri5qtC7IKwzJHfA6pkrsSj0d9YQXqbJLEvbyN50G-QRX_bCqBszi8oafYRmlt_JXqFEHHqDcrTQcQrpqQxR3-p8gMvYs-K8DnI6c3fEphISlmgHPNK4MLc4x1UGkmGB9Ho77G6vbzsOogHpQhqYs0a8R0Aw==&uniplatform=NZKPT&language=CHS.

15.周迎春. 布地格福吸入对慢阻肺急性加重期肺功能指标、不良反应影响[J]. 中文科技期刊数据库（全文版）医药卫生, 2023, (12): 21-24. [Zhou YC. Effect of budesonide inhalation on lung function indicators and adverse reactions in patients acute exacerbation of chronic obstructive pulmonary disease[J]. Chinese Science and Technology Journal Database (full-text version) for Medicine and health, 2023, (12): 21-24.] http://gfffia5e5c054bd9b44a8h5up6wxk9qp5c6cfx.fffi.dali.cwkeji.cn/Qikan/Article/Detail?id=1000003923068.

16.郑笑红. 布地格福吸入气雾剂治疗重度慢性阻塞性肺疾病的效果研究[J]. 中外医学研究, 2023, 21(9): 13-16. [Zheng XH. Effect of budesonide, glycopyrronium bromide and formoterol fumarate inhalation aerosol on severe chronic obstructive pulmonary disease[J]. Chinese and Foreign Medical Research, 2023, 21(9): 13-16.] DOI: 10.14033/j.cnki.cfmr.2023.09.004.

17.章邱东, 梅晓冬. 布地格福吸入气雾剂治疗中、重度慢性阻塞性肺疾病患者的临床研究[J]. 中国临床药理学杂志, 2022, 38(3): 203-206. [Zhang QD, Mei XD. Clinical trial of budegofol inhaled aerosol in the treatment of patients with moderate-to-severe chronic obstructive pulmonary disease[J]. The Chinese Journal of Clinical Pharmacology, 2022, 38(3): 203-206.] DOI: 10.13699/j.cnki.1001-6821.2022.03.003.

18.张伟荣, 吴柳娇. 布地格福吸入气雾剂联合多索茶碱治疗慢性阻塞性肺疾病稳定期患者的效果[J]. 慢性病学杂志, 2023, 24(4): 600-603. DOI: 10.16440/J.CNKI.1674-8166.2023.04.31.

19.张倩倩, 张艳艳, 聂丽, 等. 细菌溶解产物胶囊分别联合氟替美维与布地格福治疗老年慢性阻塞性肺疾病急性加重期的疗效观察[J]. 中国医院用药评价与分析, 2024, 24(4): 443-446. [Zhang QQ, Zhang YY, Nie L, et al. Efficacy of bacterial lysate capsules combined with futimeiwei or budigefu in the treatment of acute exacerbation of chronic obstructive pulmonary disease in elderly patients[J]. Evaluation and Analysis of Drug-Use in Hospitals, 2024, 24 (4): 443-446.] DOI: 10.14009/j.issn.1672-2124.2024.04.013.

20.张俊, 黄乐. 布地格福对慢性阻塞性肺疾病患者炎症反应及免疫功能的影响[J]. 医学理论与实践, 2024, 37(2): 223-225. DOI: 10.19381/j.issn.1001-7585.2024.02.014.

21.杨金玲, 郭现玲. 布地奈德福莫特罗、布地格福吸入气雾剂治疗中重度COPD的疗效及对肺功能的影响[J]. 哈尔滨医药, 2024, 44(2): 49-52. [Yang JL, Guo XL. The efficacy of budesonide formoterol and breztri aerosphere in the treatment of moderate to severe COPD and their impact on lung function[J]. Harbin Medical Journal, 2024, 44(2): 49-52.] DOI: 10.3969/j.issn.1001-8131. 2024.02.016.

22.徐枝磊, 胡邦丽. 布地格福吸入气雾剂对慢阻肺治疗效果的研究[J]. 当代医药论丛, 2023, 21(7): 121-124. DOI: 10.3969/j.issn.2095-7629.2023.07.039.

23.谢传洪. 布地格福治疗慢性阻塞性肺疾病稳定期的效果研究 [J]. 智慧健康, 2023, 9(10): 85-88. [Xie CH. Effect research of budesonide in treatment of stable chronic obstructive pulmonary disease[J]. Smart Healthcare, 2023, 9(10): 85-88.] DOI: 10.19335/j.cnki.2096-1219.2023.10.021.

24.伍虎, 蒲方华, 丁先志. 布地格福吸入气雾剂联合肺功能康复训练治疗中重度COPD的临床疗效[J]. 临床合理用药, 2023, 16(21): 58-60. DOI: 10.15887/j.cnki.13-1389/r.2023.21.016.

25.吴秋华, 樊荣. 布地格福吸入气雾剂治疗中重度COPD的临床效果分析[J]. 系统医学, 2022, 7(19): 128-131. [Wu QH, Fan R. Clinical effect analysis of budesonide inhalation aerosol in the treatment of moderate to severe COPD[J]. System Medicine, 2022, 7(19): 128-131.] DOI: 10.19368/j.cnki.2096-1782.2022.19.128.

26.王开勤, 赵丽, 张倩倩, 等. 布地格福吸入气雾剂治疗COPD稳定期的效果观察[J]. 现代科学仪器, 2023, 40(5): 108-111. [Wang KQ, Zhao L, Zhang QQ, et al. Observation on the effect of budesonide inhalation aerosol in the treatment of stable COPD[J]. Modern Scientific Instruments, 2023, 40(5): 108-111.] http://d.wanfangdata.f.yyttgd.top/periodical/ChlQZXJpb2RpY2FsQ0hJTmV3UzIwMjMxMjI2Eg94ZGt4eXEyMDIzMDUwMjQaCG1ucXdjMjl6.

27.王洁. 布地格福气雾剂联合氨茶碱对慢阻肺稳定期患者呼吸状况及肺功能的影响[J]. 当代医药论丛, 2023, 21(19): 120-123. DOI: 10.3969/j.issn.2095-7629.2023.19.040.

28.任婷婷, 焦伟, 丁成红, 等. 布地格福吸入气雾剂与氟替美维吸入粉雾剂治疗中重度慢性阻塞性肺疾病稳定期有效性与安全性比较[J]. 中国药业, 2024, 33(11): 84-87. [Ren TT, Jiao W, Ding CH, et al. Comparison of efficacy and safety of budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol combined with fluticasone furoate,umeclidinium bromide and vilanterol trifenatate powder for inhalation in the treatment of moderate to severe chronic obstructive pulmonary disease during stable phase[J]. China Pharmaceuticals, 2024, 33(11): 84-87.] DOI: 10.3969/j.issn.1006-4931.2024.11.019.

29.彭甘霖. 布地格福吸入气雾剂联合肺康复训练对中重度慢性阻塞性肺疾病患者的效果观察[J]. 首都食品与医药, 2022, 29(21): 88-90. [Peng GL. Effect of budesof inhalation aerosol combined with pulmonary rehabilitation training on patients with moderate to severe chronic obstructive pulmonary disease[J]. Capital Medicine, 2022, 29 (21): 88-90.] DOI: 10.3969/j.issn.1005-8257.2022.21.031.

30.穆曼娜, 李雄辉. 布地格福吸入气雾剂治疗中重度慢性阻塞性肺疾病的临床效果及安全性[J]. 临床合理用药, 2023, 16(23): 66-69. DOI: 10.15887/j.cnki.13-1389/r.2023.23.019.

31.孟丹丹. 布地格福吸入气雾剂在老年人慢性阻塞性肺疾病患者中应用疗效与安全性分析[J]. 益寿宝典, 2022, (16): 22-24. http://gfffia5e5c054bd9b44a8hcfupxv0cunu6665x.fffi.dali.cwkeji.cn/Qikan/Article/Detail?id=1000003416100.

32.毛静, 陈国萍. 布地格福治疗慢性阻塞性肺疾病的临床效果观察[J]. 中外医药研究, 2023, 2(34): 57-59. [Mao J, Chen GP. Observation on clinical effect of budesonide, glycopyrronium bromide and formoterol fumarate in treatment of chronic obstructive pulmonary disease[J]. Journal of Chinese and Foreign Medicine and Pharmacy Research, 2023, 2(34): 57-59.] DOI: 10.3969/j.issn.2096-6229. 2023.34.020.

33.卢明海, 刘鸿宇. 布地格福吸入对稳定期COPD患者运动耐力、动脉血气分析指标及肺功能的影响[J]. 药品评价, 2022, 19(12): 727-730. [Lu MH, Liu HY. Effect of budesonide, glycopyrronium bromide and formoterol fumarate inhalation aerosol on exercise tolerance and arterial blood gas analysis in stable COPD patients and lung function[J]. Drug Evaluation, 2022, 19(12): 727-730.] DOI: 10.19939/j.cnki.1672-2809.2022.12.07.

34.廖珍珠, 丘灿明, 刘隽, 等. 布地格福吸入气雾剂与马来酸茚达特罗吸入粉雾剂治疗慢性阻塞性肺疾病疗效及其对肺功能影响的比较研究[J]. 临床合理用药杂志, 2022, 15(30): 91-94. DOI: 10.15887/j.cnki.13-1389/r.2022.30.026.

35.李静飞, 孟晓燕. 布地格福吸入气雾剂治疗慢性阻塞性肺疾病急性加重期患者的效果[J]. 中国民康医学, 2024, 36(10): 47-49, 56. [Li JF, Meng XY. Effects of budesonide, glycopyrronium bromide and formoterol fumarate inhalation aerosol in treatment of patients with acute exacerbation of chronic obstructive[J]. Medical Journal of Chinese People's Health, 2024, 36(10): 47-49, 56.] DOI: 10.3969/j.issn.1672-0369.2024.10.014.

36.康敏, 吴轶, 罗帅, 等. 布地格福与开放三联治疗AECOPD的疗效及安全性分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(2): 248-250. DOI: 10.3877/cma.j.issn.1674-6902.2023. 02.026.

37.金礼, 徐光辉, 张露. 布地格福治疗慢性阻塞性肺病的效果及对FENO的影响[J]. 齐齐哈尔医学院学报, 2023, 44(5): 459-461. [Jin L, Xu GH, Zhang L. Effect of budesonide, glycopyrronium bromideand formoterol fumarate inhalation aerosol on chronic obstructive pulmonary disease and its effect on FENO[J]. Journal of Qiqihar Medical University, 2023, 44(5): 459-461.] DOI: 10.3969/j.issn.1002-256.2023.05.014.

38.接传健, 李红苗. 布地格福气雾剂联合多索茶碱对慢性阻塞性肺疾病稳定期患者治疗效果及肺功能的影响[J]. 黑龙江医学, 2023, 47(17): 2103-2105. [Jie CJ, Li HM. Effect of budegefo aerosol combined with doxorubicin on the efficacy and pulmonary function of stable patients with chronic obstructive pulmonary disease[J]. Heilongjiang Medical Journa, 023, 47(17): 2103-2105.] DOI: 10.3969/j.issn.1004-5775.2023.17.016.

39.贾莉, 雷蓉. 布地格福气雾吸入剂与乌美溴铵维兰特罗吸入粉雾剂治疗重度COPD稳定期患者的疗效对比[J]. 贵州医药, 2023, 47(6): 883-884. DOI: 10.3969/j.issn.1000-744X.2023.06. 023.

40.黄奕荣, 吴骏斌, 杨左泰. 布地格福治疗对慢性阻塞性肺疾病患者肺功能的影响[J]. 中国处方药, 2023, 21(10): 87-90. DOI: 10.3969/j.issn.1671-945X.2023.10.027.

41.黄雪琴. 布地格福吸入气雾剂治疗慢性阻塞性肺疾病的临床效果[J]. 临床合理用药杂志, 2022, 15(32): 40-42. DOI: 10.15887/j.cnki.13-1389/r.2022.32.011.

42.胡小龙, 傅春生, 杨进, 等. 布地格福与布地奈德福莫特罗粉对COPD缓解期患者肺功能、运动耐力的影响对比[J]. 现代生物医学进展, 2023, 23(20): 3874-3878. [Hu XL, Fu CS, Yang J, et al. Comparison on the effects of budesonide glycopyrronium bromide and budesonide formoterol on pulmonary function and exercise tolerance in patients with COPD during remission[J]. Progress in Modern Biomedicine, 2023, 23(20): 3874-3878.] DOI: 10.13241/j.cnki.pmb.2023.20.015.

43.胡春晓, 孙蓉媛, 张利华, 等. 布地格福吸入气雾剂联合茶碱治疗慢性阻塞性肺疾病稳定期的临床研究[J]. 现代药物与临床, 2021, 36(11): 2386-2391. [Hu CX, Sun RY, Zhang LH, et al. Clinical study on glycopyrronium bromide and formoterol fumarate inhalation aerosol combined with theophylline in treatment of chronic obstructive pulmonary disease in stable phase[J]. Drugs & Clinic, 2021, 36(11): 2386-2391.] DOI: 10.7501/j.issn.1674-5515. 2021.11.033.

44.贺李明. 布地格福与布地奈德福莫特罗治疗COPD稳定期效果的对照研究[J]. 上海医药, 2023, 44(24): 37-40. [He LM. A comparative study of the effect of budigfu and budesonide formoterol in the treatment of chronic obstructive pulmonary disease in the stable stage[J]. Shanghai Medicine, 2023, 44(24): 37-40.] DOI: 10.3969/j.issn.1006-533.2023.24.011.

45.代海云, 耿立惠. 布地格福联合乙酰半胱氨酸治疗老年慢性阻塞性肺疾病急性加重期临床观察[J]. 中国药业, 2023, 32(23): 122-125. [Dai HY, Geng LH. Clinical observation of budesonide, glycopyrronium bromide and formoterol fumarate inhalation aerosol combined with acetylcysteine in the treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease[J]. China Pharmaceuticals, 2023, 32(23): 122-125.] DOI: 10.3969/j.issn.1006-4931.2023.23.028.

46.程易, 黄锦宏, 由振华, 等. 布地格福吸入气雾剂治疗COPD稳定期的临床疗效及安全性研究[J]. 中外医疗, 2023, 42(28): 72-76. [Cheng Y, Huang JH, You ZH, et al. Clinical efficacy and safety study of budesonide inhalation aerosol in the treatment of stable COPD phase[J]. China Foreign Medical Treatment, 2023, 42(28): 72-76.] DOI: 10.16662/j.cnki.1674-0742.2023.28.072.

47.陈语嫣. 布地格福吸入气雾剂治疗慢性阻塞性肺疾病急性加重期的疗效观察[J]. 临床医药文献电子杂志, 2024, 11(1): 22-25. http://d.wanfangdata.f.yyttgd.top/periodical/ChlQZXJpb2RpY2FsQ0hJTmV3UzIwMjMxMjI2EhpRS0JKQkQyMDI0MjAyNDAzMDEwMDAwOTU3MxoIbW5xd2MyOXo%3D.

48.陈应南, 黄鑫华, 罗爱清. 布地格福联合氨茶碱对中重度稳定期慢性阻塞性肺疾病肺功能和急性发作的影响[J]. 保健文汇, 2024, 25(2): 81-84. DOI: 10.3969/j.issn.1671-5217.2024.02.021.

49.陈素萍. 布地格福吸入对慢阻肺急性加重期的疗效[J]. 中文科技期刊数据库（全文版）医药卫生, 2022, (7): 31-34. [Chen SP. Effect of budesonide inhalation in the treatment of acute exacerbation of COPD[J]. Chinese Science and Technology Journal Database (full-text version) for Medicine and health, 2022, (7): 31-34.] http://gfffia5e5c054bd9b44a8hcfupxv0cunu6665x.fffi.dali.cwkeji.cn/Qikan/Article/Detail?id=1000003565903.

50.陈秋吕, 李肖. 布地格福吸入气雾剂治疗慢性阻塞性肺疾病急性加重期的疗效观察[J]. 中国现代医生, 2023, 61(9): 65-68, 88. [Chen QL, Li X. Effects of budesonide inhalation aerosol in the treatment of acute exacerbation of COPD[J]. China Modern Doctor, 2023, 61(9): 65-68, 88.] DOI: 10.3969/j.issn.1673-9701.2023.09.016.

51.陈凌燕. 布地格福吸入气雾剂对慢阻肺的治疗效果研究 [J]. 婚育与健康, 2023, 29(20): 67-69. [Chen LY. Study on the therapeutic effect of budesonide inhalation aerosol on chronic obstructive pulmonary disease[J]. Marriage and Childbearing and Health, 2023, 29(20): 67-69.] http://qikan.cqvip.com/Qikan/Article/Detail?id=7109399532.

52.陈荟仿, 张宇璞, 曾义林, 等. 布地格福治疗重度慢性阻塞性肺疾病的临床疗效研究[J]. 中国处方药, 2023, 21(3): 100-103. [Chen HF, Zhang YP, Zeng YL, et al. Clinical studies of budesonide, glycopyrronium bromide and formoterol fumarate inhalation aerosol in treating the severe chronic obstructive pulmonary disease[J]. Journal of China Prescription Drug, 2023, 21(3): 100-103.] DOI: 10.3969/j.issn.1671-945X.2023.03.029.

53.柴景伟, 薛洪刚. 布地格福与双联支气管扩张剂对慢性阻塞性肺疾病患者的疗效及肺功能与炎症因子的影响[J]. 中国药物经济学, 2023, 18(12): 61-65. [Chai JW, Xue HG. Effects of budigovir and dibronchodilator on pulmonary function and inflammatory factors in patients with chronic obstructive pulmonary disease[J]. China Journal of Pharmaceutical Economics, 2023, 18(12): 61-65.] DOI: 10.12010/j.issn.1673-5846.2023.12.014.

54.Wang C, Yang T, Kang J, et al. Efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in chinese patients with COPD: a subgroup analysis of KRONOS[J]. Adv Ther, 2020, 37(4): 1591-607. DOI: 10.1007/s12325-020-01266-5.

55.van den Berge M, De Backer J, Van Holsbeke C, et al. Functional respiratory imaging assessment of budesonide/glycopyrrolate/formoterol fumarate and glycopyrrolate/formoterol fumarate metered dose inhalers in patients with COPD: the value of inhaled corticosteroids[J]. Respir Res, 2021, 22(1): 191. DOI: 10.1186/s12931-021-01772-2.

56.Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD[J]. N Engl J Med, 2020, 383(1): 35-48. DOI: 10.1056/NEJMoa1916046.

57.Muro S, Sugiura H, Darken P, et al. Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-HOC analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts[J]. Respir Res, 2021, 22(1): 187. DOI: 10.1186/s12931-021-01803-y.

58.Ichinose M, Fukushima Y, Inoue Y, et al. Efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology in japanese patients with COPD: a subgroup analysis of the KRONOS study[J]. Int J Chron Obstruct Pulmon Dis, 2019, 14: 2979-2991. DOI: 10.2147/COPD.S220850.

59.Chen SY, Huang CK, Peng H C, et al. Inappropriate peak inspiratory flow rate with dry powder inhaler in chronic obstructive pulmonary disease[J]. Sci Rep, 2020, 10(1): 7271. DOI: 10.1038/s41598-020-64235-6.

60.Bosnic-Anticevich SZ, Cvetkovski B, Azzi EA, et al. Identifying critical errors: addressing inhaler technique in the context of asthma management[J]. Pulm Ther, 2018, 4(1): 1-12. DOI: 10.1007/s41030-018-0051-0.

61.Kawamatawong T, Khiawwan S, Pornsuriyasak P. Peak inspiratory flow rate measurement by using In-Check DIAL for the different inhaler devices in elderly with obstructive airway diseases[J]. J Asthma Allergy, 2017, 10: 17-21. DOI: 10.2147/JAA.S127580.

62.中国医学装备协会呼吸病学专委会吸入治疗与呼吸康复学组. 稳定期慢性气道疾病吸装置规范应用中国专家共识（2023版）[J]. 中华结核和呼吸杂志, 2023, 46(11): 1055-1067. DOI: 10.3760/cma.j.cn112147-20230411-00167.

63.Nicolini G, Scichilone N, Bizzi A, et al. Beclomethasone/formoterol fixed combination for the management of asthma: patient considerations[J]. Ther Clin Risk Manag, 2008, 4(5): 855-864. DOI: 10.2147/tcrm.s3126.

64.Filho FSL, Takiguchi H, Akata K, et al. Effects of inhaled corticosteroid/long-acting beta2-agonist combination on the airway microbiome of patients with chronic obstructive pulmonary disease:a randomized controlled clinical trial (DISARM)[J]. Am J Respir Crit Care Med, 2021, 204(10): 1143-1152. DOI: 10.1164/rccm.202102-0289OC.

65.Knight L, Fletcher J. Growth of candida albicans in saliva: stimulation by glucose associated with antibiotics, corticosteroids, and diabetes mellitus[J]. J Infect Dis, 1971, 123(4): 371-317. DOI: 10.1093/infdis/123.4.371.

66.Ellepola A, Samaranayake L. Inhalational and topical steroids, and oral candidosis: amini review[J]. Oral Dis, 2001, 7(4): 211-216. https://pubmed.ncbi.nlm.nih.gov/11575870/.

67.Yang IA, Ferry OR, Clarke MS, et al. Inhaled corticosteroids versus placebo for stable chronic obstructive pulmonary disease[J]. Cochrane Database Syst Rev, 2023, 3(3): CD002991. DOI: 10.1002/14651858.CD002991.pub4.

68.陶艺文. LABA/LAMA对比 LAMA及 LABA/ICS 治疗COPD 的荟萃分析及成本-效用分析[D]. 沈阳: 中国医科大学, 2021. DOI: 10.27652/d.cnki.gzyku.2021.000524.

69.Lipson DA, Barnacle H, Birk R, et al. FULFIL trial: once-daily triple therapy for patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2017, 196(4): 4384-4446. DOI: 10.1164/rccm.201703-0449OC.

70.Humenberger M, Horner A, Labek A, et al. Adherence to inhaled therapy and its impact on chronic obstructive pulmonary disease (COPD)[J]. BMC Pulm Med, 2018, 18(1): 163. DOI: 10.1186/s12890-018-0724-3.

71.袁薇, 杨明莹, 冯海葵, 等. 慢性阻塞性肺疾病患者稳定期吸入剂治疗依从性的调查分析[J]. 广东医学院学报, 2011, 29(3): 324, 353. DOI: 10.3969/j.issn.1005-4057.2011.03.044.

72.郑孝琴, 陈瑾, 李育霞. 慢性阻塞性肺疾病患者激素吸入治疗依从性及影响因素分析[J]. 护理学报, 2012, 19(8): 29-31. [Zheng XQ, Chen J, Li YX. Compliance of glucocorticoid inhalation of patients with COPD and its influencing factors[J]. Journal of Nursing, 2012, 19(8): 29-31.] DOI: 10.3969/j.issn.1008-9969.2012.08.009.