Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
Lung Clinic Immenhausen, Immenhausen, Germany.
Respir Res. 2019 Aug 16;20(1):186. doi: 10.1186/s12931-019-1163-2.
An important goal of chronic obstructive pulmonary disease (COPD) treatment is to reduce the frequency of exacerbations. Some observations suggest a decline in exacerbation rates in clinical trials over time. A more systematic understanding would help to improve the design and interpretation of COPD trials.
We performed a systematic review and meta-regression of the placebo groups in published randomized controlled trials reporting exacerbations as an outcome. A Bayesian negative binomial model was developed to accommodate results that are reported in different formats; results are reported with credible intervals (CI) and posterior tail probabilities (p).
Of 1114 studies identified by our search, 55 were ultimately included. Exacerbation rates decreased by 6.7% (95% CI (4.4, 9.0); p < 0.001) per year, or 50% (95% CI (36, 61)) per decade. Adjusting for available study and baseline characteristics such as forced expiratory volume in 1 s (FEV) did not alter the observed trend considerably. Two subsets of studies, one using a true placebo group and the other allowing inhaled corticosteroids in the "placebo" group, also yielded consistent results.
In conclusion, this meta-regression indicates that the rate of COPD exacerbations decreased over the past two decades to a clinically relevant extent independent of important prognostic factors. This suggests that care is needed in the design of new trials or when comparing results from older trials with more recent ones. Also a considerable effect of adjunct therapy on COPD exacerbations can be assumed.
PROSPERO 2018 CRD4218118823.
慢性阻塞性肺疾病（COPD）治疗的一个重要目标是减少加重的频率。一些观察结果表明，临床试验中加重的发生率随着时间的推移而下降。更系统的理解将有助于改善 COPD 试验的设计和解释。
我们对发表的随机对照试验中报告加重为结局的安慰剂组进行了系统评价和荟萃回归分析。采用贝叶斯负二项式模型来适应以不同格式报告的结果；结果以可信区间（CI）和后尾概率（p）报告。
通过我们的搜索共确定了 1114 项研究，最终有 55 项研究被纳入。每年加重率下降 6.7%（95% CI（4.4，9.0）；p<0.001），每十年下降 50%（95% CI（36，61））。调整可用的研究和基线特征，如 1 秒用力呼气量（FEV），并没有显著改变观察到的趋势。两个研究子集，一个使用真正的安慰剂组，另一个允许在“安慰剂”组中使用吸入皮质激素，也得出了一致的结果。
总之，这项荟萃回归表明，在过去的二十年中，COPD 加重的发生率下降到了一个临床相关的程度，这与重要的预后因素无关。这表明在设计新试验或比较旧试验与最近试验的结果时需要谨慎。此外，还可以假定辅助治疗对 COPD 加重有相当大的影响。
PROSPERO 2018 CRD4218118823。
