Effect of Fluticasone With and Without Salmeterol on Pulmonary Outcomes in Chronic Obstructive Pulmonary Disease A Randomized Trial
Effect of Fluticasone With and Without Salmeterol on Pulmonary Outcomes in Chronic Obstructive Pulmonary Disease A Randomized Trial
复制标题
DOI：
10.7326/0003-4819-151-8-200910200-00004
复制
发表时间：
2009-10-20
影响因子：
39.2
通讯作者：
Sterk, Peter J.
中科院分区：
文献类型：
--
作者：
Lapperre, Therese S.;Snoeck-Stroband, Jiska B.;Sterk, Peter J.
背景：吸入皮质类固醇（ICSs）和长效β(2)-激动剂（LABAs）被用于治疗中重度慢性阻塞性肺疾病（COPD）。目的：确定长期ICS治疗（含或不含LABAs）是否能减轻COPD患者的炎症并改善肺功能。设计：随机、安慰剂对照试验。（ClinicalTrials.gov注册号：NCT00158847）研究地点：荷兰两所大学医学中心。患者：114例患有中度至重度COPD的未接受类固醇治疗的当前或既往吸烟者。测量方法：支气管活检和痰中细胞计数（主要转归）；基线、6个月和30个月的甲胆碱反应性；以及每3个月的临床结果。干预：采用最小化法随机分配，给予丙酸氟替卡松500 μ g，每日2次，疗程为6个月（n = 31）或30个月（n = 26）；氟替卡松，500 μ g，每日2次，沙美特罗，50 μ g，每日2次，疗程30个月（单吸入器，n = 28）；或安慰剂每日两次（n = 29）。结果：101例患者治疗依从性大于70%。氟替卡松治疗降低粘膜CD3（+）细胞计数（-55% [95% CI， -74%至-22%]，P = 0.004）， CD4（+）细胞计数（-78% [CI， -88%至60%]，P < 0.001）， CD8（+）细胞计数（-57% [CI， -77%至-18%]，P = 0.010），肥大细胞计数（-38% [CI， -60%至-2%]，P = 0.039），降低高反应性（P = 0.036）， 30个月后效果维持。氟替卡松治疗30个月可减少肥大细胞计数，增加嗜酸性粒细胞计数和完整上皮百分比，并伴有痰中性粒细胞、巨噬细胞和淋巴细胞计数的减少，改善FEV1下降、呼吸困难和生活质量。炎症细胞的减少与临床改善相关。停止氟替卡松治疗6个月后，CD3（+）细胞（120% [CI， 24%至289%]；P = 0.007）、肥大细胞（218% [CI， 99%至407%]；P < 0.001）和浆细胞（118% [CI， 9%至336%]；P = 0.028）的计数增加，临床结果恶化。沙美特罗可改善FEV1水平。局限性：该研究的目的不是评估临床结果。24%的患者在30个月时无法测量主要结局。结论：ICS治疗可减轻中度至重度COPD初治患者的炎症反应，并可减轻肺功能下降。添加LABAs不会增强这些效果。
Background: Inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD).Objective: To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD.Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847)Setting: 2 university medical centers in The Netherlands.Patients: 114 steroid-naive current or former smokers with moderate to severe COPD.Measurements: Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months.Intervention: Random assignment by minimization method to receive fluticasone propionate, 500 mu g twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 mu g twice daily, and salmeterol, 50 mu g twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29).Results: 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3(+) cells (-55% [95% CI, -74% to -22%]; P = 0.004), CD4(+) cells (-78% [CI, -88% to 60%]; P < 0.001), CD8(+) cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV1 decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3(+) cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV1 level.Limitations: The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months.Conclusion: ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects.