Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.
Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.
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DOI：
10.1186/s13063-015-0782-2
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发表时间：
2015-06-10
期刊：
影响因子：
2.5
通讯作者：
Price D
中科院分区：
文献类型：
--
作者：
Devereux G;Cotton S;Barnes P;Briggs A;Burns G;Chaudhuri R;Chrystyn H;Davies L;De Soyza A;Fielding S;Gompertz S;Haughney J;Lee AJ;McCormack K;McPherson G;Morice A;Norrie J;Sullivan A;Wilson A;Price D
慢性阻塞性肺疾病（COPD）与高发病率、高死亡率和高保健费用有关。慢性阻塞性肺病患者对吸入皮质类固醇抗炎作用的反应不完全。临床前研究表明，“低剂量”茶碱可改善类固醇反应性。茶碱与吸入皮质类固醇（TWICS）试验研究了在吸入皮质类固醇中添加“低剂量”茶碱是否对慢性阻塞性肺病有临床和成本效益效益。TWICS是一项随机双盲安慰剂对照试验，在英国的初级和二级医疗机构进行。纳入标准如下：COPD的主要呼吸道诊断（支气管扩张剂后第一秒用力呼气量/用力肺活量[FEV1/FVC]小于0.7），年龄至少40岁，吸烟史至少10包年，目前吸入性皮质类固醇使用史，前一年至少有两次需要抗生素或口服皮质类固醇治疗的加重史。计算机化随机化系统将按地区和招募设置（小学和中学）对1424名参与者进行分层，然后以相同的概率随机分配到干预组或对照组。参与者将接受“低剂量”茶碱（Uniphyllin MR 200毫克片剂）或安慰剂治疗52周。给药是基于药代动力学模型，以达到1-5毫克/升的稳态血清茶碱。不吸烟的参与者或吸烟但理想体重（IBW）不超过60公斤的参与者将服用剂量为每日200毫克的茶碱MR（或每日一次的安慰剂）。吸烟且体重超过60公斤的参与者将服用茶碱MR 200毫克，每日两次（或安慰剂每日两次）。参与者将在招聘时、6个月和12个月后接受评估。主要结局是在52周的治疗期间，参与者报告的需要口服皮质类固醇或抗生素的COPD恶化的总人数。“低剂量”茶碱通过减少急性发作发生率而增加吸入皮质类固醇治疗COPD的疗效，这一证明不仅与患者和临床医生有关，而且与英国和全球的卫生保健提供者有关。当前对照试验ISRCTN27066620于2013年9月19日注册，第一名受试者于2014年2月6日随机分配。本文的在线版本（doi:10.1186/s13063-015-0782-2）包含补充材料，仅供授权用户使用。
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that ‘low dose’ theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of ‘low dose’ theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either ‘low dose’ theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1–5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. The demonstration that ‘low dose’ theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014. The online version of this article (doi:10.1186/s13063-015-0782-2) contains supplementary material, which is available to authorized users.
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茶碱恢复了COPD巨噬细胞中组蛋白脱乙酰基酶的活性和类固醇反应。
影响因子：
15.3
作者：
Cosio, BG;Tsaprouni, L;Ito, K;Jazrawi, E;Adcock, IM;Barnes, PJ
通讯作者：
Barnes, PJ
DOI：
10.1111/j.1365-2125.1989.tb05353.x
发表时间：
1989-02-01
影响因子：
3.4
作者：
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通讯作者：
PEAKE, MD
DOI：
10.1111/j.1365-2125.1987.tb03173.x
发表时间：
1987-09-01
影响因子：
3.4
作者：
CHRYSTYN, H;MULLEY, BA;PEAKE, MD
通讯作者：
PEAKE, MD
影响因子：
9.6
作者：
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通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
Blais, Lucie