Tashkin Donald, Kesten Steven
Pulmonary Division, David Geffen School of Medicine at the University of California at Los Angeles, 90095, USA.
Chest. 2003 May;123(5):1441-9. doi: 10.1378/chest.123.5.1441.
To determine whether long-term symptomatic improvement occurs in COPD patients with maintenance bronchodilator therapy despite a nonsignificant short-term improvement in FEV(1) following bronchodilator inhalation obtained at a single time point.
Data obtained during two identical 1-year, placebo-controlled trials of tiotropium, 18 micro g once daily, were analyzed retrospectively to determine the associations of long-term improvements in lung function and patient health status with short-term improvements in FEV(1), as measured on the first day of treatment. Based on the presence or absence of a short-term improvement in FEV(1) of > or = 12% and > or = 200 mL, respectively, patients who had been treated with tiotropium were characterized as being responsive to tiotropium (TIO-R) or poorly responsive to tiotropium (TIO-PR).
Baseline characteristics were similar other than baseline FEV(1), which was higher in the TIO-R group than in both the TIO-PR and placebo groups (p < 0.05). Baseline FEV(1) was 1.08 L in the TIO-R group (n = 263), 0.95 L in the TIO-PR (n = 255), and 0.99 L in the placebo group (n = 328). The mean (+/- SD) morning predose FEV(1) at 1 year significantly (p < 0.001) improved in patients in both of the tiotropium treatment subgroups (TIO-R group, 212 +/- 17 mL; TIO-PR group, 94 +/- 17 mL) relative to those treated with placebo. Statistically significant improvements in both tiotropium-treated groups also were noted over 1 year for dyspnea (p < 0.001), as assessed by the transition dyspnea index (TDI) [TIO-R group, 1.36 +/- 0.23 L; TIO-PR group, 0.86 +/- 0.23 L] relative to the placebo group. Patient health status assessed by the St. George Respiratory Questionnaire (SGRQ) showed statistically significant improvements over placebo for the TIO-R and TIO-PR groups (-3.96 +/- 0.99 and -3.05 +/- 1.00 L, respectively; p < 0.005). There was a significant correlation of the first-dose short-term FEV(1) response to the end-of-trial trough response (r = 0.43), but there was only a weak correlation to TDI focal score (r = 0.17) or SGRQ total score (r= -0.12).
Tiotropium was effective in the treatment of patients with COPD, irrespective of the presence or absence of a short-term response on the first day of treatment. The short-term bronchodilator response should not be used as a definitive criterion for prescribing long-term treatment with inhaled bronchodilators.
确定慢性阻塞性肺疾病（COPD）患者接受维持性支气管扩张剂治疗后，尽管在单次吸入支气管扩张剂后第1秒用力呼气容积（FEV₁）的短期改善不显著，但长期症状是否会改善。
回顾性分析在两项相同的为期1年、使用噻托溴铵（每日1次，18μg）的安慰剂对照试验中获得的数据，以确定肺功能和患者健康状况的长期改善与治疗第1天测量的FEV₁短期改善之间的关联。根据FEV₁分别是否有≥12%和≥200 mL的短期改善，将接受噻托溴铵治疗的患者分为对噻托溴铵反应良好（TIO-R）或对噻托溴铵反应不佳（TIO-PR）。
除基线FEV₁外，基线特征相似，TIO-R组的基线FEV₁高于TIO-PR组和安慰剂组（p<0.05）。TIO-R组（n = 263）的基线FEV₁为1.08 L，TIO-PR组（n = 255）为0.95 L，安慰剂组（n = 328）为0.99 L。相对于接受安慰剂治疗的患者，两个噻托溴铵治疗亚组（TIO-R组，212±17 mL；TIO-PR组，94±17 mL）的患者在1年时的平均（±标准差）晨起给药前FEV₁显著改善（p<0.001）。在1年期间，通过过渡性呼吸困难指数（TDI）评估，两个噻托溴铵治疗组的呼吸困难也有统计学显著改善（p<0.001）[TIO-R组，1.36±0.23 L；TIO-PR组，0.86±0.23 L]，相对于安慰剂组。通过圣乔治呼吸问卷（SGRQ）评估的患者健康状况显示，TIO-R组和TIO-PR组相对于安慰剂组有统计学显著改善（分别为-3.96±0.99和-3.05±1.00 L；p<0.005）。首剂短期FEV₁反应与试验末期谷值反应有显著相关性（r = 0.43），但与TDI焦点评分（r = 0.17）或SGRQ总分（r = -0.12）仅有微弱相关性。
噻托溴铵对COPD患者有效，无论治疗第1天是否有短期反应。短期支气管扩张剂反应不应作为吸入性支气管扩张剂长期治疗处方的决定性标准。
