Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD
Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD
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DOI：
10.1056/nejmoa1407154
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发表时间：
2014-10-02
影响因子：
158.5
通讯作者：
Winning, A.
中科院分区：
文献类型：
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作者：
Magnussen, Helgo;Disse, Bernd;Winning, A.
研究背景对于重度慢性阻塞性肺疾病（COPD）频繁加重的患者，推荐吸入糖皮质激素联合长效支气管扩张剂治疗。然而，除了两种长效支气管扩张剂外，吸入糖皮质激素的益处尚未完全探索。方法在这项为期12个月的双盲平行组研究中，2485例有COPD加重史的患者接受了噻托溴铵三联治疗，（剂量为18 μ g，每日一次）、沙美特罗（50 μ g，每日两次）和吸入糖皮质激素丙酸氟替卡松（500 μ g，每日两次）。然后，患者被随机分配到继续三联疗法或在12周内分三步停用氟替卡松。主要终点是至首次中度或重度COPD加重的时间。与继续使用糖皮质激素相比，停用糖皮质激素与首次中度或重度COPD急性加重的95%置信区间（CI）上限1.20符合预先设定的非劣效性标准（风险比，1.06; 95%CI，0.94 - 1.19）。在第18周，当糖皮质激素完全停用时，糖皮质激素停用组1秒用力呼气量谷值较基线校正平均减少量比糖皮质激素继续组多38 ml（P
BACKGROUNDTreatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored.METHODSIn this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 mu g once daily), salmeterol (50 mu g twice daily), and the inhaled glucocorticoid fluticasone propionate (500 mu g twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored.RESULTSAs compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P