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[JAMA最新论文]:茶碱不应作为吸入激素的辅助治疗措施减少COPD急性加重
2018年10月20日 时讯速递, 进展交流 暂无评论

Original Investigation

October 16, 2018

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD: A Randomized Clinical Trial

Graham Devereux, Seonaidh Cotton, Shona Fielding, et al

JAMA. 2018;320(15):1548-1559. doi:10.1001/jama.2018.14432

Abstract

Importance 背景

Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD.

COPD是重要的全球健康问题,茶碱的使用非常普遍。临床前研究显示,低浓度(1-5 mg/L)茶碱能够提高皮质激素对COPD的抗炎作用。

Objective 目的

To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD.

研究吸入皮质激素的基础上加用小剂量茶碱对COPD患者的疗效。

Design, Setting, and Participants 设计,场景及研究人群

The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites.

TWICS研究是一项实效性、双盲、安慰剂对照的随机临床试验,2014年2月6日至2016年8月31日之间纳入COPD患者。最后随访日期为2017年8月31日。入选患者FEV1/FVC < 0.7,前一年至少2次急性发作(接受抗生素和[或]口服皮质激素治疗)且正在使用吸入皮质激素治疗。研究在121个英国的初级及二级医疗中心进行,纳入1578名患者。

Interventions 干预措施

Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787).

研究人群进行随机分组,分别接受小剂量茶碱(200 mg qd或bid)以保证血浆浓度1-5 mg/L(根据理想体重及吸烟状况决定) (n = 791) 或安慰剂 (n = 787)。

Main Outcomes and Measures 主要预后指标

The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period.

在一年治疗期间,自行报告发生中重度急性加重(接受抗生素和[或]口服皮质激素治疗)的患者数。

Results 结果

Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, −0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%).

纳入分析的1567名患者平均 (SD) 年龄 68.4 (8.4) 岁,54% (843) 为男性。1536 名患者 (98%)可以得到主要预后指标(茶碱组772名;安慰剂组764名)。共有3430次急性加重发生:茶碱组1727次(每年平均,2.24 [95% CI, 2.10-2.38] 次急性加重)vs 安慰剂组1703次(每年平均,2.23 [95% CI, 2.09-2.37] 次急性加重);未校正平均差异,0.01 (95% CI, −0.19 to 0.21),校正后发生率比值,0.99 (95% CI, 0.91-1.08)。茶碱组及安慰剂组严重不良事件包括心脏(2.4% vs 3.4%);胃肠道(2.7% vs 1.3%);不良反应包括恶心 (10.9% vs 7.9%) 和头痛 (9.0% vs 7.9%)。

Conclusions and Relevance 结论与意义

Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations.

对于接受吸入皮质激素治疗的COPD急性加重高危成年患者,与安慰剂相比,加用小剂量茶碱不能减少一年期间COPD急性加重次数。这一发现不支持使用小剂量茶碱作为吸入皮质激素的辅助治疗措施预防COPD急性加重。

Trial Registration 试验注册

isrctn.org Identifier: ISRCTN27066620

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