1 Clinical Science Centre, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.
2 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
Ann Am Thorac Soc. 2018 Feb;15(2):200-208. doi: 10.1513/AnnalsATS.201703-194OC.
There is continuing debate about whether to define airflow obstruction by a post-bronchodilator ratio of forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) below 0.70, or by ratio values falling below the age-dependent lower limit of normal (LLN) derived from general population data.
To determine whether using the LLN criterion affects the classification and outcomes of patients previously defined as having chronic obstructive pulmonary disease by the fixed FEV/FVC ratio.
We applied the LLN definition to pooled data from the Tiotropium Safety and Performance in Respimat study that used the fixed FEV/FVC ratio for the clinical diagnosis of chronic obstructive pulmonary disease.
A total of 17,072 patients were analyzed; of these, 1,807 (10.6%) patients had a ratio greater than or equal to LLN. Patients with a ratio greater than or equal to LLN had similar risks of death from any cause and fatal major adverse cardiovascular (CV) event as those below LLN. Patients with a ratio below LLN had a significantly lower risk of major adverse CV events (hazard ratio = 0.69; 95% confidence interval [CI] = 0.55-0.86; P = 0.001), and had significantly greater risks of moderate to severe exacerbation (rate ratio = 1.48; 95% CI = 1.36-1.61; P < 0.0001) and severe exacerbation (rate ratio = 2.01; 95% CI = 1.68-2.40; P < 0.0001) when compared with patients greater than or equal to LLN. Study outcomes by treatment arm (5 μg tiotropium Respimat vs. 18 μg HandiHaler) were comparable.
Using the LLN to define airflow obstruction would have excluded patients in the Tiotropium Safety and Performance in Respimat study with a higher risk of nonfatal major adverse CV events and a lower risk of exacerbation; study outcomes by treatment arm (2.5 μg/5 μg tiotropium Respimat vs. 18 μg HandiHaler) remained similar. Clinical trial registered with www.clinicaltrials.gov (NCT01126437).
目前，关于气流受限的定义，究竟是采用支气管扩张剂后一秒用力呼气容积（FEV1）与用力肺活量（FVC）的比值＜0.70，还是采用基于一般人群数据得出的年龄依赖性正常值下限（LLN）＜比值，仍存在争议。
明确采用 LLN 标准是否会影响既往根据固定 FEV1/FVC 比值诊断为慢性阻塞性肺疾病（COPD）患者的分类和结局。
我们对噻托溴铵 Respimat 安全性和疗效研究的汇总数据进行了 LLN 定义分析，该研究采用固定 FEV1/FVC 比值进行 COPD 的临床诊断。
共分析了 17072 例患者；其中 1807 例（10.6%）患者比值≥LLN。比值≥LLN 的患者无论死因或致命性主要不良心血管（CV）事件的风险均与 LLN 患者相似。比值＜LLN 的患者发生主要不良 CV 事件的风险显著降低（风险比=0.69；95%置信区间[CI]：0.550.86；P=0.001），且中重度加重（率比=1.48；95%CI：1.361.61；P＜0.0001）和重度加重（率比=2.01；95%CI：1.68~2.40；P＜0.0001）的风险显著升高。与比值≥LLN 的患者相比，各治疗组（5μg 噻托溴铵 Respimat 与 18μg HandiHaler）的研究结局相似。
如果采用 LLN 来定义气流受限，噻托溴铵 Respimat 安全性和疗效研究中的患者会被排除在外，这些患者发生非致命性主要 CV 事件的风险更高，发生加重的风险更低；各治疗组（2.5μg/5μg 噻托溴铵 Respimat 与 18μg HandiHaler）的研究结局仍相似。该研究已在 www.clinicaltrials.gov 注册（NCT01126437）。
