未控制哮喘儿童的最佳强化治疗:个体参与者数据的系统回顾和网络荟萃分析
2023/11/23
摘要
背景：吸入皮质类固醇后仍未控制的哮喘儿童/青少年的最佳治疗方案尚不确定，国际指南提出了不同的建议。
目的：我们评估了在吸入皮质类固醇后仍未控制的<18岁患者中减少哮喘加重和症状的药物治疗。
方法：我们检索了 MEDLINE、Cochrane 系统评价数据库、Cochrane 对照试验中央注册库、Embase、Web of Science 平台、NICE 技术评估、NIHRHTA 系列、WHO 国际临床试验注册平台、会议摘要和内部临床试验注册（2014年7月1日至2023年5月5日）对18岁以下受试者进行随机对照试验，这些受试者在筛选时单独使用任何吸入皮质类固醇 (ICS) 剂量但哮喘未得到控制。 2014年7月之前的研究是从之前的系统综述/与作者的联系中检索到的。患者必须随机接受任何剂量的ICS单独治疗或与长效β受体激动剂（LABA）联合治疗或与白三烯受体拮抗剂（LTRA）联合治疗；单独 LTRA；茶碱；安慰剂。主要结局是病情恶化和哮喘控制。评估的干预措施为ICS（低/中/高剂量）； ICS+LABA； ICS+LTRA；单独 LTRA；茶碱；安慰剂。
结果：在确定的4708篇出版物中，有144项试验符合条件。个体参与者数据来自29项试验，汇总数据来自19项试验。与低剂量ICS相比，中剂量ICS+LABA与最低的恶化率(OR 0.44 [95% CrI 0.19-0.90])和增加的FEV (MD 0.71 [95% CrI 0.35-1.06])相关。LTRA治疗是最不可取的。在哮喘控制方面没有发现明显差异。
结论：对于使用低剂量 ICS 且未得到控制的儿童/青少年，应建议改用中等剂量 ICS+LABA，以降低加重风险并改善肺功能。对于仅使用低剂量吸入性皮质类固醇且哮喘无法控制的 6-17 岁患者，使用中等剂量吸入性皮质类固醇和长效β激动剂可降低急性加重的几率并增加 FEV。
Best step-up treatments for children with uncontrolled asthma: A systematic review and network meta-analysis of individual participant data.
Cividini S, Sinha I, Donegan S
Abstrast
Background: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids, and international guidelines make different recommendations.
Objectived：We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients <18 years on inhaled corticosteroids.
Methods: We searched MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Embase, the Web of Science platform, NICE Technology Appraisals, the NIHR HTA series, the WHO International Clinical Trials Registry Platform, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants <18 with uncontrolled asthma on any inhaled corticosteroid (ICS) dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting β-agonists (LABAs) or combined with leukotriene receptor antagonists (LTRAs); LTRAs alone; theophylline; placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (Low/Medium/High dose); ICS+LABA; ICS+LTRA; LTRA alone; theophylline; placebo.
Results: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials, and aggregate data from 19 trials. Compared to ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44 [95% CrI 0.19-0.90]) and with an increased FEV (MD 0.71 [95% CrI 0.35-1.06]). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control.
Conclusions: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.Using medium-dose inhaled corticosteroids with long-acting β-agonists reduces the odds of exacerbation and increases FEV in patients 6 to 17 years whose asthma is uncontrolled on a low dose of inhaled corticosteroids alone.
背景：吸入皮质类固醇后仍未控制的哮喘儿童/青少年的最佳治疗方案尚不确定，国际指南提出了不同的建议。
目的：我们评估了在吸入皮质类固醇后仍未控制的<18岁患者中减少哮喘加重和症状的药物治疗。
方法：我们检索了 MEDLINE、Cochrane 系统评价数据库、Cochrane 对照试验中央注册库、Embase、Web of Science 平台、NICE 技术评估、NIHRHTA 系列、WHO 国际临床试验注册平台、会议摘要和内部临床试验注册（2014年7月1日至2023年5月5日）对18岁以下受试者进行随机对照试验，这些受试者在筛选时单独使用任何吸入皮质类固醇 (ICS) 剂量但哮喘未得到控制。 2014年7月之前的研究是从之前的系统综述/与作者的联系中检索到的。患者必须随机接受任何剂量的ICS单独治疗或与长效β受体激动剂（LABA）联合治疗或与白三烯受体拮抗剂（LTRA）联合治疗；单独 LTRA；茶碱；安慰剂。主要结局是病情恶化和哮喘控制。评估的干预措施为ICS（低/中/高剂量）； ICS+LABA； ICS+LTRA；单独 LTRA；茶碱；安慰剂。
结果：在确定的4708篇出版物中，有144项试验符合条件。个体参与者数据来自29项试验，汇总数据来自19项试验。与低剂量ICS相比，中剂量ICS+LABA与最低的恶化率(OR 0.44 [95% CrI 0.19-0.90])和增加的FEV (MD 0.71 [95% CrI 0.35-1.06])相关。LTRA治疗是最不可取的。在哮喘控制方面没有发现明显差异。
结论：对于使用低剂量 ICS 且未得到控制的儿童/青少年，应建议改用中等剂量 ICS+LABA，以降低加重风险并改善肺功能。对于仅使用低剂量吸入性皮质类固醇且哮喘无法控制的 6-17 岁患者，使用中等剂量吸入性皮质类固醇和长效β激动剂可降低急性加重的几率并增加 FEV。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Eur Respir J 2023 Nov 09;;doi: 10.1183/13993003.01011-2023. IF: 12.339)
(Eur Respir J 2023 Nov 09;;doi: 10.1183/13993003.01011-2023. IF: 12.339)
Best step-up treatments for children with uncontrolled asthma: A systematic review and network meta-analysis of individual participant data.
Cividini S, Sinha I, Donegan S
Abstrast
Background: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids, and international guidelines make different recommendations.
Objectived：We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients <18 years on inhaled corticosteroids.
Methods: We searched MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Embase, the Web of Science platform, NICE Technology Appraisals, the NIHR HTA series, the WHO International Clinical Trials Registry Platform, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants <18 with uncontrolled asthma on any inhaled corticosteroid (ICS) dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting β-agonists (LABAs) or combined with leukotriene receptor antagonists (LTRAs); LTRAs alone; theophylline; placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (Low/Medium/High dose); ICS+LABA; ICS+LTRA; LTRA alone; theophylline; placebo.
Results: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials, and aggregate data from 19 trials. Compared to ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44 [95% CrI 0.19-0.90]) and with an increased FEV (MD 0.71 [95% CrI 0.35-1.06]). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control.
Conclusions: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.Using medium-dose inhaled corticosteroids with long-acting β-agonists reduces the odds of exacerbation and increases FEV in patients 6 to 17 years whose asthma is uncontrolled on a low dose of inhaled corticosteroids alone.
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重症哮喘患者T2相关合并症与生物制剂疗效的关系
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生物治疗对重度哮喘患者的临床缓解：英国重度哮喘登记研究的分析
